SAMJ Vol 106, No 1 (2016)

JANUARY 2016

VOL. 106 NO. 1

CME Cardiology REVIEW Treatment of type 2 diabetes: The challenges of hyperglycaemia and hypoglycaemia GUEST EDITORIAL mHealth EDITORIAL World Bank smoke and mirrors IN PRACTICE Kangaroo mother care Lower limb weakness: Screen for porphyria!

RESEARCH Failure to administer fibrinolytic therapy for AMI Four-dose HBV vaccination for SA’s babes!

JANUARY 2016

VOL. 106 NO. 1

GUEST EDITORIAL

SAMJ

3 Using mobile technology to improve maternal, child and youth health and treatment of HIV patients

J Peter, P Barron, Y Pillay

EDITOR-IN-CHIEF Janet Seggie, BSc (Hons), MD (Birm), FRCP (Lond), FCP (SA) DEPUTY EDITOR Bridget Farham, BSc (Hons), PhD, MB ChB

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EDITOR’S CHOICE

IZINDABA

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Long-awaited autonomy in sight for SA’s doctors High-risk specialties threatened by runaway legal costs Basson’s private ECG tutoring sets pulses racing

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BOOK REVIEW Being Mortal – Illness, Medicine, and What Matters in the End

EDITORIALS

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Understanding healthcare and population mobility in southern Africa: The case of South Africa H L Walls, J Vearey, M Modisenyane, C M Chetty-Makkan, S Charalambous, R D Smith, J Hanefeld

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The poverty of the concept of ‘poverty eradication’ S R Benatar

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

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South African Guideline Excellence (SAGE): What’s in a name?

T Kredo, S Machingaidze, Q Louw, T Young, K Grimmery

NEWS EDITOR Chris Bateman | Email: chrisb@hmpg.co.za

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Acute heart failure: Can modern therapy delay or prevent death?

L Opie, G Deshpande

PRODUCTION MANAGER Emma Jane Couzens

CONTINUING MEDICAL EDUCATION

DTP AND DESIGN Carl Sampson

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GUEST EDITORIAL Cardiovascular medicine in primary healthcare in sub-Saharan Africa: Minimum standards for practice (part 1) G Ogunbanjo, N A B Ntusi

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REVIEW Heart failure in sub-Saharan Africa: A clinical approach S Kraus, G Ogunbanjo, K Sliwa, N A B Ntusi

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ARTICLES Dyspnoea: Pathophysiology and a clinical approach C B I Coccia, G H Palkowski, B Schweitzer, T Motsohi, N A B Ntusi

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An approach to the young hypertensive patient P Mangena, S Saban, K E Hlabyago, B Rayner

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An approach to the diagnosis and management of valvular heart disease B J Cupido, F Peters, N A B Ntusi

EDITORS EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon) JP de V van Niekerk, MD, FRCR ASSOCIATE EDITORS Q Abdool Karim, A Dhai, N Khumalo, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman HMPG

IN PRACTICE

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ISSUES IN MEDICINE Red meat, processed meat and cancer in South Africa D C Stefan

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CLINICAL ALERT Severe porphyric neuropathy – importance of screening for porphyria in Guillain-Barré syndrome C-M Schutte, C H van der Meyden, L van Niekerk, M Kakaza, R van Coller, V Ueckermann, N M Oosthuizen

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HEALTHCARE DELIVERY Comparison of two text message (mHealth) campaigns for the Deaf: Contracted out v. conducted in-house D Hacking, Y K Lau, H J Haricharan, M Heap

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CEO AND PUBLISHER Hannah Kikaya | Email: hannahk@hmpg.co.za MANAGING EDITOR Ingrid Nye

HEAD OF SALES AND MARKETING Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za JOURNAL ADVERTISING Charles William Duke Benru de Jager Reneé van der Ryst Ladine van Heerden Azad Yusuf ONLINE SUPPORT Gertrude Fani FINANCE Tshepiso Mokoena HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Dr M J Grootboom, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574 SAMA website: www.samedical.org Journal website: www.samj.org.za

January 2016, Vol. 106, No. 1

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Ă&#x; RESTORE cardiac function CARVEDILOL: - is indicated twice daily for mild to moderate stable symptomatic congestive heart failure - is indicated once daily for essential mild to moderate hypertension - has a positive effect on metabolic parameters.1

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For further product information contact PHARMA DYNAMICS P O Box 30958 Tokai Cape Town 7966 Tel 021 707 7000 Fax 021 701 5898 Email info@pharmadynamics.co.za CUSTOMER CARE LINE 0860 PHARMA (742 762) www.pharmadynamics.co.za Carvetrend 6,25 mg. Each tablet contains 6,25 mg carvedilol. Reg. No.: RSA S3 37/7.1.3/0276 NAM NS2 08/7.1.3/0105 BOT S2 BOT1101790. Carvetrend 12,5 mg. Each tablet contains 12,5 mg carvedilol. Reg. No.: RSA S3 37/7.1.3/0277 NAM NS2 08/7.1.3/0104 BOT S2 BOT1101791. Carvetrend 25 mg. Each tablet contains 25 mg carvedilol. Reg. No.: RSA S3 37/7.1.3/0278 NAM NS2 08/7.1.3/0103 BOT S2 BOT1101792. For full prescribing information, refer to the package insert approved by the Medicines Control Council, 16 September 2004. 1) Panagiotis C Stafylas, Pantelis A Sarafidis. Carvedilol in hypertension treatment. Vascular Health and Risk Management 2008;4(1):23-30. CDC81/04/2015.

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Taking kangaroo mother care forward in South Africa: The role of district clinical specialist teams U Feucht, E van Rooyen, R Skhosana, A-M Bergh

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DIAGNOSIS Diagnosis of iron deficiency anaemia in hospital patients: Use of the reticulocyte haemoglobin content to differentiate iron deficiency anaemia from anaemia of chronic disease E Schapkaitz, S Buldeo, J N Mahlangu

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CARDIOVASCULAR MEDICAL DEVICES Focus areas of cardiovascular medical device research in South Africa C Chimhundu, K de Jager, T S Douglas

REVIEW

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Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia J Wing, D Jivan

RESEARCH

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The impact of an electronic clinical decision support for pulmonary embolism imaging on the efficiency of computed tomography pulmonary angiography utilisation in a resource- limited setting* C Murthy, R Davis, C F N Koegelenberg, E M Irusen, R D Pitcher

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The relationship between stunting and overweight among children from South Africa: Secondary analysis of the National Food Consumption Survey – Fortification Baseline I* E A Symington, G J Gericke, J H Nel, D Labadarios

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The socioeconomic and environmental health situation of international migrants in Johannesburg, South Africa* A Mathee, N Naicker

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South African medical schools: Current state of selection criteria and medical students’ demographic profile* L J van der Merwe, G J van Zyl, A St Clair Gibson, M Viljoen, J E Iputo, M Mammen, W Chitha, A M Perez, N Hartman, S Fonn, L Green-Thompson, O A Ayo-Ysuf, G C Botha, D Manning, S J Botha, R Hift, P Retief, B B van Heerden, J Volmink

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Implementation of a new ‘community’ laboratory CD4 service in a rural health district in South Africa extends laboratory services and substantially improves local reporting turnaround time* L M Coetzee, N Cassim, D K Glencross

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HLA typing: Conventional techniques v. next-generation sequencing* J Mellet, C M Gray, M S Pepper

92

Time to fibrinolytics for acute myocardial infarction: Reasons for delays at Steve Biko Academic Hospital, Pretoria, South Africa* R Meel, R Gonçalves

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Antenatal screening for hepatitis B virus in HIV-infected and uninfected pregnant women in the Tshwane district of South Africa* Q Diale, R Pattinson, R Chokoe, L Masenyetse, S Mayaphi

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Prevalence of anaemia in pregnancy in a regional health facility in South Africa* K Tunkyi, J Moodley

PART 2

RECOMMENDATIONS 105-122 Appropriate indications for positron emission tomography/computed tomography, 2015

M Vorster, A Doruyter, A Brink, S Mkhize, J Holness, N Malan, N Nyakale, J M Warwick,

M Sathekge, on behalf of the College of Nuclear Physicians of South Africa

*Full article available online only.

CAREERS & CLASSIFIEDS

CPD QUESTIONS

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January 2016, Vol. 106, No. 1

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Subscriptions: Tel. 012 481 2071 Email: members@samedical.org The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA. HEAD OFFICE Health and Medical Publishing Group (Pty) Ltd Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 Tel. 012 481 2069 Email: dianes@hmpg.co.za EDITORIAL OFFICE Suites 9 & 10, Lonsdale Building, Gardener Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za Please submit all letters and articles for publication online at www.samj.org.za © Copyright: Health and Medical Publishing Group (Pty) Ltd, a subsidiary of the South African Medical Association Use of editorial material is subject to the Creative Commons Attribution – Non-commercial Works Licence. http://creativecommons.org/licenses/by-nc/3.0 Printed by TANDYM PRINT

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GUEST EDITORIAL

Using mobile technology to improve maternal, child and youth health and treatment of HIV patients Case study: Stock-out of iron supplements in pregnancy

In February 2015, the South African (SA) National Department of Health (NDoH) was notified of a short­age of iron tablets at a clinic in Kenneth Kaunda District in North West Province. Similar reports emerged from two other clinics in the same district around the same time. Iron supple­ ments are routinely provided to pregnant women in SA to prevent maternal anaemia. Maternal anaemia is a risk factor for mortality from obstetric haemorrhage, which accounts for more than 200 maternal deaths annually.[1] These reports resulted in a broader enquiry encompassing the whole of the province, revealing widespread stock-outs. With this insight, the provincial Department of Health met with staff to re-emphasise ordering procedures and what to do if drugs are out of stock.

Notably, the earliest reports of iron stock-outs were received not from clinic staff but from pregnant women themselves, using the help desk function of a new mobile phone-based system called MomConnect.

MomConnect

This case study illustrates the potential of mobile health (mHealth) to improve the health system. MomConnect[2] was the first, HIV treatment guidelines the second, and B-Wise the third of a series of NDoH initiatives, launched by the Minister of Health, that use mobile technology. These uses include engaging with users and providers of health services, providing accessible health information, and capturing feedback on the quality of care.

The highest cellphone penetration in Africa

These initiatives take advantage of SA’s extremely high rate of mobile telephone use. According to a recent Pew Research Center report, 90% of South Africans own a cell phone.[3] In addition, we have the highest smartphone ownership on the continent (34%) and are the only African country among those surveyed in the Pew report that did not have a gender gap in phone ownership, with equal numbers of males and females reporting cell phone ownership and use.

What is MomConnect?

MomConnect was conceptualised with four components, which are at various stages of implementation: 1.

A USSD-based registration system to enroll every pregnant woman in the country into a national pregnancy register, using her ID number as a unique identifier. (Unstructured Supplementary Service Data (USSD) is a text-based system that works on even the most basic cell phone. In SA, a majority of cell phone users regularly use USSD for airtime top-ups and checking airtime balances.) This is seen as one of the elements of the macro plan towards adoption of a national electronic medical record.

2. Weekly text messages with information on healthy pregnancy and care of a newborn, timed according to estimated date of delivery and later the age of the infant, are sent to the registered woman.

3. A help desk to allow women to ask additional questions, submit compliments or complaints, or rate the quality of care received.

4. A supportive and empowering SMS (text message) and mobile web component for midwives and nurses that will provide them with

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clinical updates and enable them to interact with each other as well as give feedback to managers.

The programme was launched by Minister of Health Aaron Motsoaledi in August 2014, and registered over 500 000 women in its first year. In the same timeframe, more than 34 000 health workers were trained to register mothers on MomConnect in 95% of public health facilities. Over 3 000 mothers complimented the services and 500 complained, a ratio of six compliments to every complaint. More than 180 000 questions were answered through the help desk. All patient feedback captured via MomConnect is clinicspecific (each clinic has been assigned a unique code that is captured during patient registration), and is routed to the clinic in question via assigned district focal persons. This provides a near real-time view of service delivery quality around the country, allowing rapid detection of remediable problems such as the iron shortages described above.

How does MomConnect work?

Women who suspect they may be pregnant are able to self-subscribe (by dialling *150*550#) for a limited set of text messages that provide information on the MomConnect service and the importance of receiving antenatal care as early as possible. These messages encourage women to go to an antenatal clinic.

Once a pregnancy has been confirmed by a health worker at the first antenatal visit, the woman can opt to be formally registered using her ID number or her passport number as an identifier, and including a clinic code to associate her registration with the particular health facility where she is receiving care. Each registered woman receives two SMS messages a week throughout her pregnancy and for the first year of her child’s life. These messages are timed to correspond with the woman’s stage of pregnancy and the age of her child. Messages cover priority topics such as antenatal nutrition, testing for HIV, warning signs of maternal hypertension, preparation for labour, exclusive breastfeeding, postpartum depression and the immunisation schedule.

They also include information on patient rights and responsibilities and how to provide feedback on the quality of care received.

Mothers are able to reply to any text message or ask questions by phoning *150*550#. The help desk is currently staffed by a professional nurse who deals with complicated issues and is assisted by two clerical workers who deal with routine questions to which they pull automated answers from a suite of possible responses. Women can opt out of the service at any time by phoning *150*550*1#. At around the due date of delivery the messages automatically switch to the infant messaging.

As MomConnect targets all women, including those at the low end of the socioeconomic spectrum, all these services are provided free of charge to the mother.

The evidence for mobile messaging to mothers

MomConnect builds upon a growing body of work around using mobile phones to support improvements in maternal and child health.

Programmes such as Aponjon in Bangladesh, Wazazi Nipendeni in Tanzania, Chipatala Cha Pa Foni in Malawi, Text4Baby in the USA and MAMA in SA (a precursor to MomConnect) have all provided regular SMS and/or voice-based messages to pregnant women and new mothers to support the adoption of healthy behaviours and increase the uptake of health services. Impact evaluations in

January 2016, Vol. 106, No. 1

GUEST EDITORIAL

Malawi and Bangladesh have demonstrated statistically significant improvements in behaviours such as early breastfeeding, use of a bed net and antenatal attendance.[4,5] Operational research on MomConnect suggests overwhelming support by pregnant women. In a sample of nearly 10 000 women telephonically surveyed, with a response rate of over one in five (n=1 999), 98% found the messages helpful, 77% felt better prepared for delivery, 81% shared their messages with family and friends, and 70% wanted more messages per week (M van den Heuvel, market research report on experience of mothers using MomConnect (Johannesburg, Praekelt Foundation, October 2015) – unpublished). However, MomConnect is unique in that it provides two-way interaction rather than simple one-way messaging. By providing channels for patient feedback, it generates useful information to inform and strengthen the quality of health services. For example, in its first year MomConnect received 78 916 completed surveys ranking the quality of the first antenatal visit according to four criteria: cleanliness, staff friendliness, privacy and wait times. The help desk also receives specific compliments and complaints.

Naturally the complaints get more attention from managers than do the compliments, so in addition to improving the supply side from this feedback mechanism, the NDoH is implementing a support mechanism to empower frontline nurses and midwives. They will be registered with their personal cell phones on MomConnect and will receive regular information to increase knowledge of guidelines and support adherence to protocols. A mobile-based learning portal will allow health workers to complete in-service training modules and form peer-to-peer learning and support networks.

HIV treatment guidelines on a mobile application

On the sidelines of the SA AIDS Conference in June 2015, the Minister of Health launched the first-ever mobile application to make HIV treatment guidelines available on a mobile phone to clinicians.

The app was developed in partnership with the private sector and includes a range of functions. Besides the guidelines for treatment of HIV in children and adults, the app provides information on every antiretroviral drug that is part of the national guidelines and their side-effects, contraindications and possible adverse events. In addition, the app assists clinicians to calculate paediatric dosages and report medicine stock-outs.

Clinicians who use either an iPhone or an Android phone can download the app through either the Apple iStore or Google Play store. The app does not require internet access once downloaded.

Revisions of the guideline are downloaded automatically when the phone is connected to the internet. This means that clinicians have the latest clinical guidelines literally at their fingertips.

The NDoH is in the process of developing (with the same private sector company) a similar app for the treatment of drug-susceptible as well as drug-resistant tuberculosis.

Extending health information to the youth: B-Wise

The Minister of Health launched a mobile website named B-Wise (accessible at b-wise.mobi) in August 2015 to specifically address challenges faced by the youth of SA. These health risks include bullying, obesity, unwanted and unplanned pregnancy, and being infected with HIV. B-Wise provides information in easily accessible language, gives practical information about where to get support, and will soon have a more interactive chat facility where experts on various topics will interact with the youth. In the first month after the launch, 20 927 users logged onto B-Wise and 40 580 pages were accessed (Jesse Coleman, Wits Reproductive Health and HIV Institute – personal communication).

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Vision for the future

Technology creates the potential to match demand for health services with supply, and to create linkages between individuals, communities, frontline health workers, health facilities, laboratories and health management. A connected health system is efficient, responsive and patient centred.

MomConnect, the HIV treatment guidelines app and B-Wise are existing examples of the role of technology in linking patients and communities with health workers and the health system, and increasing access to guidelines for health workers. This work serves as an important foundation that can be built upon to reach new audiences.

Processes are in place to extend MomConnect to provide additional support to HIV-positive mothers and partners and to lengthen the period of messaging until children reach age 5. MomConnect is also being extended to the private sector, as there is anecdotal evidence that many women first book with private general practitioners but then deliver in public health facilities. Private practitioners wishing to learn more about MomConnect and ways to engage can contact MomConnect programme manager Antonio Fernandes (fernaa@ health.gov.za).

These efforts will strengthen the continuum of care between reproductive, maternal, new­ born, child and youth health, while facilitating the development of high-quality, accountable health services.

Joanne Peter Advisor to Johnson & Johnson Worldwide Corporate Contributions, Digital Health Portfolio, Cape Town, South Africa

Peter Barron School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa pbarron@iafrica.com

Yogan Pillay National Department of Health, Pretoria, South Africa 1. National Committee for Confidential Enquiry into Maternal Deaths. Saving Mothers 2011-2013: Sixth report on the Confidential Enquiries into Maternal Deaths in South Africa. Department of Health, 2014.

2. Bateman C. Using basic technology – and corporate social responsibility – to save lives. S Afr Med J 2014;104(12):839-840. [http://dx.doi.org/10.7196/SAMJ.9118] 3. Pew Research Center. Cell Phones in Africa: Communication Lifeline. Washington, DC, Pew Research Center, 2015 http://www.pewglobal.org/2015/04/15/cell-phones-in-africa-communication-lifeline/ (accessed 15 October 2015).

4. Watkins, SC, Robinson, A, Dalious, M. Evaluation of the Information and Communications Technology for Maternal, Newborn and Child Health Project Known locally as ‘Chipatala Cha Pa Foni’ (Health Center by Phone). Balaka District, Malawi: Invest in Knowledge Initiative, 2013.

5. Chowdhury, ME. Key Findings of MAMA Study, TRAction-supported study conducted by the International Center for Diarrheal Disease Research, Bangladesh. Dhaka, Bangladesh, icddr,b, 2015. http://www.tractionproject.org/resources/key-findings-mama-study-traction-supprted-studyconducted-international-center-diarrheal (accessed 17 November 2015).

S Afr Med J 2016;106(1):3-4. DOI:10.7196/SAMJ.2016.v106i1.10209

January 2016, Vol. 106, No. 1

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Sun Pharma began the integration of Ranbaxy’s business following the successful closure of its merger on March 25, 2015. The integration, planned by Sun Pharma over many months, focuses on supporting strong growth. The historic merger fortified Sun Pharma’s position as the world’s fifth largest specialty generic pharmaceutical company and the top ranking Indian Pharma company with significant lead in market share. The combined entity’s manufacturing footprint covers 5 continents with products sold in over 150 nations with a stronger presence in US, India, Asia, Europe, South Africa, CIS & Russia and Latin America. Sun Pharma now offers a large basket of specialty and generic products encompassing a broad range of chronic and acute prescription drugs as well as a ready foray into the global consumer healthcare market. The integrated culture theme, “Growing Together”, represents the core objective of this merger focusing on improving productivity, compliance commitment; focus on quality and sustainable growth. Through this merger Sun Pharma emerges as India’s first truly global pharmaceutical company.

It is an important milestone in the history of Sun Pharma as it enters into a new phase of growth. The company will continue to focus on gaining trust of 2

the Regulators globally while continuing to develop products based on patient needs and leverage them to become brand leaders globally. The combined entity capitalizes on the expanded global footprint and enhances its dominance as a world leader in the specialty generics landscape. Sun Pharma remains committed to uncompromised product quality, 100% compliance and promotes innovation to create the most dynamic global specialty generics pharmaceutical company. The company believes that its shareholders, customers and employees share its excitement in the potential of this combination.

This merger strengthens Sun Pharma’s foundation with a strong & multi-cultural team of over 30,000 employees representing over 50 global cultures making the combined entity a truly global corporation in spirit & scale.

The combined entity comprises best intellectual capital, capability of nearly 2000 scientists and the ability to invest significantly in R&D. The focus of R&D investments will be to harness multiple capabilities and technologies for developing complex products in addition to the combined entity’s core business of offering affordable generic medicines. The combined entity will continue developing innovative and complex generics that boast of technical differentiators.

January 2016, Vol. 106, No. 1

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January 2016, Vol. 106, No. 1

EDITOR’S CHOICE

CME: Cardiology

Cardiovascular disease (CVD) accounts for approximately 30% of deaths worldwide, with 80% of this burden in developing countries.

The epidemiological transition occurring in sub-Saharan Africa (SSA) has the consequence of economic and social transformation, resulting in dramatic shifts in disease spectrum from communicable diseases and malnutrition to CVD and cancer. South Africa (SA) is faced with the challenge of four colliding epidemics: (i) poor child and maternal health; (ii) high rates of interpersonal violence; (iii) infectious diseases, including HIV/AIDS and tuberculosis; and (iv) non-communicable diseases (NCDs), including CVD. In SA, NCDs are prevalent in both rural and urban areas, most prominently in poor persons living in urban and periurban settings, resulting in increasing pressure on acute and chronic healthcare services.

A major driver of this NCD burden is the demographic change in the country, leading to an increase in the proportion of people aged over 60 years despite the negative effect of HIV/AIDS on life expectancy. Contributions to the CVD burden in the country include hypertension, cardiomyopathies, rheumatic valvular heart disease, pericardial disease and coronary artery disease, among others. In this issue of SAMJ, the clinical approaches to these common cardiovascular problems are reviewed with the dual aim of empowering the doctors who manage these conditions in primary care settings around the country as well as improving the care of CVD in primary care settings and in emergency departments. This outstanding series of articles represents the collaborative effort of primary health/family physicians and cardiologists from around the country. The authors have synthesised and presented the most current, evidence-based and practical approaches to management of common CVDs. The series will be split over January and February, as the CME articles are now printed in full.

Kangaroo mother care

Our guest editorial[1] informs of the National Department of Health’s use of mobile technology – mHealth – to improve maternal, child and youth health and treatment of HIV patients.

More than 20 million infants are born weighing less than 2 500 g every year – over 96% of them in developing countries – and are at increased risk of early growth retardation, infectious disease, developmental delay and death during infancy and childhood.[2] Kangaroo mother care (KMC)[3] is a safe and effective alternative to conventional neonatal care, which is expensive and needs both highly skilled personnel and permanent logistic support.

Feucht et al.[4] report on how the district clinical specialist team, in conjunction with experienced local KMC implementers, embarked on a quality improvement initiative from 2013 to 2015 to facilitate KMC scale-up in the context of the Tshwane district’s increase in deliveries, the strain on obstetric and neonatal services at the larger secondary and tertiary hospitals, and neonatal bed shortages in SA. Taking technology one step further, Chilean ‘techies’ calling themselves ‘Team BabyBe’ have designed a bionic mattress for a premature infant in an incubator in the neonatal intensive care unit.

The mattress feels like real human skin, and is teamed with a turtlelike sensor worn on the parent’s chest to detect his or her heartbeat and breathing patterns. Information from the sensor is sent to a control module that transmits the information to a pneumatic pump in the mattress that makes the mattress move – so that the baby feels the parent’s heartbeat and breathing.[4]

Treating type 2 diabetes mellitus (DM)

Type 2 DM, set to increase by more than 100% over the next decade in SSA and with its prevalence in SA’s over-30s having doubled, has

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the potential to be as disruptive as the HIV pandemic in lowering life expectancy and reversing previous healthcare gains. Against this background, Wing and Jivan[5] present a review entitled ‘Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia’. We well recognise diabetic complications. In SA these are reckoned to account for 78 900 years lost to disability (YLD), 8 000 new cases of blindness, 2 000 new amputations, 7 000 strokes and 5 500 YLD attributable to ischaemic heart disease. According to the WHO Multinational Study of Vascular Disease in Diabetes, half of all deaths in type 2 DM are attributable to cardiovascular disease.

While intensive glucose control reduces the overall risk of diabetesrelated sequelae such as diabetic retinopathy, the downside is an increased risk of hypoglycaemia and weight gain. Additionally, the ACCORD study – among others – as outlined in this review has identified the increased mortality linked to intensive glucose control in patients with multiple cardiovascular risk factors. Hypoglycaemia has the potential to prompt episodes of syncope, ventricular tachyarrhythmias and cardiac arrest, induces a procoagulant and prothrombotic state, and, counterintuitively, creates a favourable environment for the development of atherosclerosis. New incretinbased therapies, such as the glucagon-like peptide 1 analogues and the di-peptidyl peptidose-4 inhibitors, carry an overall lower risk of hypoglycaemia than the sulphonylureas and insulin and are favoured agents to minimise the extent of hypoglycaemia while still ensuring that patients reach appropriate glucose control targets.

Importance of screening for porphyria

In ‘Severe porphyric neuropathy – importance of screening for porphyria in Guillain-Barré syndrome’, Schutte et al.[6] remind us to consider an acute porphyric attack in patients who present with progressive quadriparesis, characterised by weakness and reduced reflexes, and in whose history there has been a recent change in medication. In two patients in this case series, the attack was probably precipitated by antiretroviral medication – one patient was started on highly active antiretroviral therapy before the onset of the symptoms, and the other took antiretroviral medication for post-exposure prophylaxis. The therapy of choice in an acute porphyric attack is haemin, which limits or reverses the toxic effects of haem precursors on the peripheral nerves. The weakness then resolves rapidly.

Unfortunately haemin was not readily available in the authors’ public sector hospital setting.

Antenatal screening for hepatitis B virus (HBV) in HIV-infected and uninfected pregnant women in Tshwane[7]

In SA, there is a significantly higher HBV prevalence in HIV-infec­ted as opposed to HIV-uninfected women. The risk of vertical perinatal transmission of HBV to the infant is 10 - 20% in pregnant women who are seropositive for hepatitis B surface antigen (HBsAg) but seronegative for hepatitis e antigen (HBeAg); however, perinatal transmission rises to 90% if a mother is seropositive for both HBsAg and HBeAg. Currently pregnant women are not screened for HBV in the public sector, placing neonates at risk of acquiring HBV infection from exposure to maternal blood and secretions during delivery. In the current national vaccination schedule, HBV vaccination is only started at 6 weeks. The authors call, as Spearman and Sonderup[8] already have in this journal, for SA to implement a four-dose HBV vaccination schedule with the addition of the birth-dose vaccine within 24 hours of delivery. This would increase costs slightly but be easy to implement; moreover, it would not disrupt the current HBV vaccination schedule.

January 2016, Vol. 106, No. 1

EDITOR’S CHOICE

Fibrinolytic therapy for acute myocardial infarction

Fibrinolytic therapy for acute myocardial infarction (AMI) became standard of care fully three decades ago, the best approach being to administer thrombolytic therapy as soon as possible to all patients without contraindications who present within 12 hours of symptom onset and have ST-segment elevation on the ECG or new-onset left bundle-branch block, unless an alternative reperfusion strategy is planned. Looking at reasons for delays in administering fibrinolytics to patients with AMI at Steve Biko Academic Hospital, Meel and Gonçalves[9] convey the dismaying news that the majority of patients (67%) presenting to the capital’s academic hospital did not receive fibrinolytic therapy at all. Even those who did received it after the ‘golden’ 60 - 90 minutes when lysis of infarct artery thrombi may achieve reperfusion, thereby reducing infarct size, preserving left ventricular function and improving survival.

A large number of eligible patients arrived at a facility in Pretoria capable of providing fibrinolytic therapy but did not receive any treatment! These missed opportunities will clearly result in excess mortality and morbidity, including heart failure, which would otherwise be preventable.

Migrant health

Climate change, as addressed in last month’s editorial and review,[10,11] is likely to result in the migration of human populations, especially in Africa, affecting disease transmission patterns, burdening healthcare systems and pressurising demand for healthcare services.

An editorial[12] and a research article[13] touch on issues of migrant health. As the authors of the former point out, ‘Migration provides opportunities for health and economic benefits, and has the potential to positively and negatively affect health systems. To maximise positive impact, and mitigate against potential negative consequences, requires attention and engagement of policy-makers from health and other sectors, including public health researchers and health workers.’

It is postulated that a healthy migrant effect exists – studies con­ ducted in several parts of the world point to a pattern of better health in migrant groups compared with their compatriots who decide not to emigrate. Looking at the socioeconomic and environmental heath situation of international migrants in Johannesburg, Mathee and Naicker[13] show unexpectedly that, after controlling for socioeconomic status and area of residence, the health of migrants into SA was quite as bad as that of native citizens in respect of chronic diseases, mental ill health, and communicable and acute ill health, with a similar exposure to violence … probably because intra-African migration may not self-select high levels of health to the same degree as in people migrating from Africa to high-income countries.

Climate change

Returning to the issue of climate change, the COP21 conference is in session as I write, with the aim of achieving an international

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consensus on how the world will keep global warming below 2oC. I suggested last month that we should not hold our respective breaths regarding consensus, or the pledge by developed countries to provide USD100 billion annually to developing nations to enable them to seek renewable energy sources.

In this context, India’s prime minister Narendra Modi, speaking at COP21, has said that the choices for developing countries are not easy: ‘The prosperous still have a strong carbon footprint and the world’s billions in countries at the bottom of the development ladder are seeking space to grow.’ (Of India’s 1.25 billion people, 300 million do not yet have access to energy.) Our own President Zuma drew a distinction between the roles of developed and developing countries‚ emphasising that the latter were already feeling the effects of global warming‚ much of the responsibility for which lay with the developed world.[14] In the midst of the worst drought in SA in decades, half a million people in KwaZulu-Natal are already facing hunger.[15] Perhaps, predictably, the pledges made so far will result in global warming of at least 2.7oC, short of the 2oC goal. Moreover, negotiators seem to have given up on the idea that any pledges should be legally binding and there will be no real sanction, other than opprobrium, for those countries that renege on their undertakings in Paris.

JS 1. Peter J, Barron P, Pillay Y. Using mobile technology to improve maternal, child and youth health and treatment of HIV patients. S Afr Med J 2016;106(1):3-4. [http://dx.doi.org/10.7196/SAMJ.2016. v106i1.10209] 2. World Health Organization. Kangaroo mother care to reduce morbidity and mortality and improve growth in low-birth-weight infants. http://www.who.int/elena/titles/kangaroo_care_infants/en/ (accessed 4 December 2015).

3. World Health Organization. Kangaroo mother care: A practical guide. 2003. http://apps.who.int/iris/ bitstream/10665/42587/1/9241590351.pdf (accessed 4 December 2015).

4. Domanico A. Invention lets newborns in incubators feel mom’s heartbeat. http://www.cnet.com/news/ invention-lets-premature-babies-in-incubators-feel-moms-heartbeat/ (accessed 27 October 2015).

5. Wing J, Jivan D. Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia. S Afr Med J 2016;106(1):57-61. [http://dx.doi.org/10.7196/SAMJ.2016.v106i1.10284] 6. Schutte C-M, van der Meyden CH, van Niekerk L, et al. Severe porphyric neuropathy – importance of screening for porphyria in Guillain-Barré syndrome. S Afr Med J 2016;106(1):44-47. [http://dx.doi. org/10.7196/SAMJ.2016.v106i1.10118] 7. Diale Q, Pattinson R, Chokoe R, Masenyetse L, Mayaphi S. Antenatal screening for hepatitis B virus in HIV-infected and uninfected pregnant women in the Tshwane district of South Africa. S Afr Med J 2016;106(1):97-100. [http://dx.doi.org/10.7196/SAMJ.2016.v106i1.9932] 8. Spearman CWN, Sonderup MW. Preventing hepatitis B and hepatocellular carcinoma in South Africa: The case for a birth-dose vaccine. S Afr Med J 2014;104(9):610-612. [http://dx.doi.org/10.7196/ SAMJ.8607] 9. Meel R, Gonçalves R. Time to fibrinolytics for acute myocardial infarction: Reasons for delays at Steve Biko Academic Hospital, Pretoria, South Africa. S Afr Med J 2016;106(1):92-96. [http://dx.doi. org/10.7196/SAMJ.2016.v106i1.9801] 10. Wright CY, Norval M, Albers PN. Climate change, public health and COP21 – a South African perspective. S Afr Med J 2015;105(12):997-998. [http://dx.doi.org/10.7196/SAMJ.2015.v105i12.10232] 11. Sweijd NA, Wright CY, Westwood A, et al. Climate change is catchy – but when will it really hurt? S Afr Med J 2015;105(12):1018-1023. [http://dx.doi.org/10.7196/SAMJ.2015.v105i12.10332] 12. Walls HL, Vearey J, Modisenyane M, et al. Understanding healthcare and population mobility in southern Africa: The case of South Africa. S Afr Med J 2016;106(1):14-15. [http://dx.doi.org/10.7196/ SAMJ.2016.v106i1.10210] 13. Mathee A, Naicker N. The socioeconomic and environmental heath situation of international migrants in Johannesburg, South Africa. S Afr Med J 2016;106(1):70-75. [http://dx.doi.org/10.7196/SAMJ.2016. v106i1.10210] 14. Dlamini P, Smillie S, Cornelius J. #RainMustFall. 27 October 2015. http://www.timeslive.co.za/ thetimes/2015/10/27/RainMustFall (accessed 3 December 2015).

15. Rich countries must play ball‚ Zuma tells COP21. http://www.timeslive.co.za/scitech/2015/11/30/ Rich-countries-must-play-ball%E2%80%9A-Zuma-tells-COP21 (accessed 3 December 2015).

January 2016, Vol. 106, No. 1

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Long-awaited autonomy in sight for SA’s doctors The long-awaited extrac­ tion of doctors – and possi­ bly dentists – from the dys­ functional and shock­ ingly administered Health Professions Council of South Africa (HPCSA), the defiant leadership of which face the sack, will not lack a helping hand from the country’s largest doctor body.

South African Medical Association (SAMA) Chairperson Dr Mzukisi Groot­ boom told Izindaba that SAMA immediately began drawing up a legal white paper for a new autonomous, self-regulatory body in 2012, when the Parliamentary Portfolio Committee on Health recommended this as the most pragmatic way forward. ‘So the paper is obviously ready and we’ll now hit the ground running and support the health minister to return to Parliament and change the Health Professions Act,’ he said. He was speaking just weeks after the damning report on the HPCSA by a ministerial task team led by Prof. Bongani Mayosi, head of medicine at the University of Cape Town. Grootboom said his 17 500-member organisation had always believed that the independence, autonomy and self-regulation of doctors in any jurisdiction was to the benefit of the patient.

‘It’s an important ethical principle – any government that wants to take over control of any profession will never be doing it in the best interests of the patient,’ he stressed.

He was referring to the controversial

Prof. Bongani Mayosi, who led the ministerial task team probe of the HPCSA.

Health Professions Act, which puts control directly in the hands of the national health minister by allowing him to appoint the majority of the 32-member HPCSA, which is 90% funded by the registration fees of doctors and dentists. This forces doctors and dentists to rely on the largesse of the incumbent minister when it comes to their and their patients’ best interests. While Dr Aaron Motsoaledi has arguably proved the most physician- and patient-friendly health minister yet, when added to HPCSA’s current administrative chaos, the legal set-up is a recipe for failure and controversy. There are 12 professional health boards in the HPCSA, the Medical and Dental Professions Board (MDPB) being the largest, but with hugely diluted political and practical clout.

HPCSA President Dr Kgosi Letlape.

SAMA chair shares his own HPCSA experiences

Outlining his own experience of the HPCSA, Grootboom said that early every January he received scores of calls from irate parents wanting to know when their newly graduated children would be registered.

‘They don’t draw a distinction between SAMA and the HPCSA, so it reflects on us.

It’s mind-boggling how this situation was allowed [to get so bad]. To get registered is like pulling an elephant’s tooth.’ When it came to the HPCSA’s statutory duty to oversee the accreditation of hospitals as training institutions, committee after committee drew up reports giving the facilities reprieves with the excuse that they were ‘still suffering from the effects of apartheid’ and promising to return for a follow-up assessment the following year.

‘Yet the truth is the facilities are getting worse – people need to be honest enough to say such low standards shouldn’t be allowed.’

Doctors (and their patients) faced with a professional conduct complaint to the HPCSA had to wait up to 3 years or more before the matter was heard and/or resolved, with clinical input seldom if ever prioritised.

As for foreign-qualified physicians, they never knew where they stood, as clearly outlined, country-specific registration and vetting procedures were inconsistently applied, resulting in sorely needed, wellqualified doctors either giving up or living in limbo doing menial jobs. Izindaba is aware of several cases of HPCSA administrative

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clerks committing fraud or submitting false documentation to the MDPB’s foreign qualifications vetting committee – in one foreign neurosurgeon’s case, the committee chaired by Mayosi him­ self. Ironically, ensuing internal probes inevitably choke the doctor supply pipeline even further, as every application automatically becomes suspect.

Leadership trio ‘unfit for office’

Mayosi’s fact-finding probe – widely and corr­ ectly predicted to be hard-hitting and with­out fear or favour – comes after the HPCSA Board failed to act on damning earlier forensic reports, or to claim hefty court-ordered legal fees from its Chief Operating Officer, Advocate Tshepo Boikanyo. Boikanyo, along with Chief Executive Officer Buyiswa Mjamba-Matshoba and Head of Legal Services Phelelani Khumalo, refused to give evidence to the ministerial task team that found them ‘unfit for office’. Boikanyo had earlier taken the HPCSA to court for not accepting his application to be CEO – losing with costs. The money was never recouped from him, while a KPMG forensic report concluding that he was involved in ‘unauthorised, irregular and/or fruitless and wasteful expenditure’ was ignored. The KPMG findings centred on the purchase of an Oracle Information Technology system, the cost of which ballooned from ZAR14 million to around ZAR40 million. Mayosi’s task team said that Mjamba-Matshoba’s refusal to appear before them ‘justifies the

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drawing of an inverse inference against her’, and could amount to ‘insubordination’ given that she was appointed by the self-same minister who tasked them. Their report found that the HPCSA was suffering from ‘multisystem organisational dysfunction’.

It recommended that the Council be unbundled into at least two entities: the historic MDPB, which constitutes a third of the current HPCSA membership, and a Health and Rehabilitation Council for the rest of the professional membership. The new councils would join the South African Pharmacy Council, the South African Nursing Council and other autonomous councils in a ‘Forum of Statutory Health Professions Councils’.

While Motsoaledi has arguably proved the most physician- and patient-friendly health minister yet, when added to the HPCSA’s current administrative chaos, the legal set-up is a recipe for failure and controversy.

Said Dr Mark Sonderup, Deputy Chairman of SAMA: ‘Nobody is more delighted about this recommendation than SAMA, which has been increasingly frustrated by the medical and dental board of the HPCSA’s cavalier attitude towards doctors.

We’ve been lobbying for this for the past six years.’ The MDPB’s response to repeated SAMA petitions was that matters could be resolved ‘in-house’ (i.e. within the HPCSA’s existing structures). A former deputy chairperson of the MDPB, Prof. Marietjie de Villiers, reflected this to Izindaba: ‘The Board itself [MDPB] is fine. It’s the HPCSA administration that is dysfunctional. The number of boards is not the problem – it’s the admin culture.’ She served as deputy to Prof. Thanyani Mariba on the MDPB in 2010, and said that when the original South African Medical and Dental Council was dismantled for absorption into the HPCSA ‘we all rejoiced that we were now all together. I’m astounded that they now want to go back.’ De Villiers, Deputy Dean of Education in the Faculty of Medicine and Health Sciences at Stellenbosch University, said that she served as Dean’s Representative on the HPCSA’s Postgraduate Education and Training Committee, ‘but our decisions were not implemented’.

Leadership remains in place

Dr Kgosi Letlape, newly appointed Presi­dent of the HPCSA, said he met with Motsoaledi to hand him an interim report compiled after he convened a special Council meeting just after the task team findings. ‘I cannot reveal the contents, but due process requires us to respect the rights of the people involved,

and the processes of the Council,’ he said.

He added that the leadership trio so severely criticised would therefore remain in place – at least until the Council had compiled an interim report on how it would respond to the task team’s findings, due within 6 months.

‘We have to deal with the issues raised.

These are not things you deal with in one day. These challenges are things that came about over many years,’ Letlape added. A sign of things to come may lie in the changes Motsoaledi rang in his annual appointment of a new Council just weeks after Mayosi’s report. Of the 32 members, 24 are new appointees. When it was put to Letlape that the task team report was ‘pretty damning’, he responded: ‘It’s not for me to agree with that.

The report speaks for itself.’

The HPCSA’s stated mission is ‘to protect the public and guide the professions’, something increasingly satirised by members of both key stakeholder groups over the past 15 years.

As newly appointed SAMA President Dr Denise White observed hopefully: ‘The key will be whether they carry out the task team’s recommendations.’

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(1):7-8.

DOI:10.7196/SAMJ.2016.v106i1.10414

Dear Doctor The South African Medical Association SAMA recognises the seriousness of the current climate change emergency and aims to position itself to spearhead the involvement of doctors in national efforts to address of climate change in South Africa. As of November 2015, five South African provinces — KwaZuluNatal, Mpumalanga, North West, Limpopo and Free State — have been declared drought disaster areas, as dry conditions and heat waves of above 40oC maximum temperatures persistently affect many areas. This has dire consequences on health and calls for urgent, practical measures.

The world is at a sensitive stage with regard to climate change, facing one of the greatest global threats amidst failing international negotiations. The upcoming twenty-first session of the Conference of the Parties (COP21) will take place from 30 November to 11 December 2015, in Paris, France.

SAMA looks forward to positive outcomes from the COP21, whose objective is to achieve, for the first time in over 20 years of United Nations negotiations, a binding and universal agreement on climate, from all the nations of the world.

Although SAMA will not be attending the COP21, SAMA calls upon all its doctors to remain interested in the event and to take serious recognition of climate change related health consequences, while upholding the recommendations of the World Medical Association as outlined in the WMA Declaration on Climate Change. In the interest of “green medicine”, medical professionals must take personal responsibility in exercising good environmental stewardship. Resources on practicing “green medicine” is available from http://www.mygreendoctor.org.

More information on the COP21, WMA Declaration on Climate Change and a plea to physicians to green office space are found in the links below: http://www.cop21paris.org/about/cop21 http://www.wma.net/en/30publications/10policies/c5/ http://www.wma.net/en/40news/20archives/2015/2015_41/index.html.

SAMA Corporate Communication, 24 November 2015

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High-risk specialties threatened by runaway legal costs It’s hoped that it will take less than a decade, but legal and other reforms urgently needed to address the runaway costs of protecting physicians against clinical negligence – which threaten the very existence of higherrisk specialties – now have a starkly clear outline. This emerged after a workshop sponsored by the Medical Protection Society (MPS), in which a review of pertinent global tort reform prompted animated and largely consensual discussion between almost equally represented doctors and lawyers.

The 10 November MPS meeting in Gauteng last year came 8 months after national health minister Dr Aaron Motsoaledi convened a medicolegal summit to address the explosion of litigation against doctors and hospitals, which is costing the state tens of billions of rands and forcing specialists, most alarmingly obstetricians and gynaecologists, to avoid certain procedures, migrate to less litigious climates, or give up practising altogether. This has prompted expert insiders to predict that if the current trend of obs/gynae specialists leaving the private sector continues for 5 or 6 years, there will be ‘no one left to deliver our babies’.

Already too thinly spread even to staff the pivotal specialist-led district outreach teams (one of the pillars of the impending National Health Insurance (NHI)), obstetricians and gynaecologists, followed by neurosurgeons, neonatologists and orthopaedic surgeons, pay up to ZAR45 000 per month in MPS subscriptions to avoid potential financial ruin. Data from MPS indicate that between 2009 and 2015 there has been an escalation in the likely value of claims being brought against doctors, with claim sizes increasing by over 14% on average each year during that period. Their data also indicate that the estimation of the long-term average claim frequency for doctors in 2015 was around 27% higher than in 2009.

No drop in professional standards

The MPS does not believe that the deteri­ orating claims environment in recent times reflects a deterioration in professional standards, although it does consider that there is scope for standardisation of treatments and processes that could ensure

Mark Doepel, an associate professor at the School of Law, University of Notre Dame, Emma Hallinan, MPS Director of Claims, and Dr Graham Howarth, MPS Head of Medicolegal Services for Africa..

a more consistent approach to healthcare.

Rather, the litigation climate has changed, with patients more aware and lawyers taking increasing advantage of both environmental factors and the adversarial local model of tort law.

Both Motsoaledi and John Tiernan, Executive Director of the MPS’s Member Engagement Division, pointed to the litigation-bankrupted Road Accident Fund as having potentially redirected lawyers’ energies at vulnerable healthcare practitioners. The Contingency Fee Act (of 1977) permitting attorneys to offer clients ‘free’ legal help in pursuing a suit against a medical practitioner (25% of the settlement or double their usual fee, whichever is the lesser) is another driver of claims.

Emma Hallinan, MPS Director of Claims and Litigation, told delegates that the current South African (SA) legal framework does not facilitate the efficient and fair resolution of disputes. Damages and costs were soaring and there was no requirement for advance notification of claims and little incentive to reach a solution before proceedings were issued, while the legal system encouraged an adversarial approach that was virtually irreversible once proceedings began. There was also no requirement for clinical experts to meet, and little incentive to exchange expert

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evidence until shortly before trial. Motsoaledi pulled no punches at his medicolegal summit as to how the current system was being cynically manipulated. He claimed to know of syndicates with members in state hospital managements and various State Attorney’s offices respectively tipping off mercenary lawyers and deliberately mismanaging cases to ensure that the state lost. He threatened criminal action against anyone suspected of doing this, adding that a jail term would send out a clear message. Motsoaledi warned that, collectively, his task team, appointed after his 9 March summit, the White Paper on the NHI and the outcome of Chief Justice Mogoeng’s enquiry into soaring healthcare costs would ‘change the health system as we know it today’.

The MPS’s main proposals, based on what has been learnt globally but particularly on Australian legal tort reform, which has left that country with arguably the world’s most stable healthcare litigation environment, centre on early expert mediation and filtering out frivolous and/or vexatious claims, which prove hugely costly and time-consuming.

Hallinan said that the initial complaints process needed to be ‘consistent, efficient, aligned and patient centred’, allowing for local resolution. A powerful handbrake would be a certificate of merit requiring the

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complainant’s lawyer to sign formal court documents saying that he/she believed the case had a reasonable chance of success, with the inbuilt prospect of court censure – including the lawyer paying for both parties’ legal fees – should the judge find otherwise.

Hallinan said that all other early alternative dispute resolution measures should be considered, including a prelitigation resolution framework. Proce­ dural changes should include an exchange of factual witness statements, an early exchange of expert notices and summaries, and mandatory meetings with experts. The MPS proposes that a tariff of general damages be created in law, including limits on general damages, future care costs and loss of future earnings.

Australia side-steps medicolegal ruin – now a global model

Mark Doepel, an associate professor at the School of Law, University of Notre Dame, said that ever-increasing damages awards ‘almost brought the Australian healthcare system to its knees’ before extensive reforms were made about a decade ago. A federal government tort reform commi­ttee, headed by an SA-born judge and New South Wales High Court appeal judge, David Ipp, ‘completely rewrote’ the Australian tort landscape. Adopted were provisions encouraging early apologies and expressions of regret, proportionate liability (paying in ratio to the amount of damage caused), threshold caps, meritorious caps (or certificate of merit), and protection for Good Samaritans (blanket immunity from being sued for anyone, such as an off-duty doctor, acting in good faith during an emergency). Doepel said there were obvious risky recreational activities (such as bungee jumping or swimming in the ocean) for which providers or authorities had been held liable for damages in the past.

‘I was recently asked to give an opinion on a cerebral palsy case, and a Down syndrome patient walked through the door – it’s not surprising that things go wrong’ – medical geneticist He told a ‘partly true’ story (compiled from real-life case studies) to compare ‘the new world order’ with previous legal regimes when it came to tort law and the balancing of rights and personal responsibility. Under Australia’s previous tort regime, an Irish backpacker rendered tetraplegic by rough

three- to four-metre waves in which he was drunkenly swimming on Bondi Beach in Sydney was awarded 20 million Australian dollars. The backpacker and his Australian mates were drinking beer in a picnic area, and he was last seen walking towards the water.

An off-duty medic found him lying face down in the waves, pulled him out and called an ambulance. The backpacker contended that the medic did not use sufficient care by throwing him onto the sand, and submitted that he ‘must have’ entered the water between the red flags demarcating the ‘safe’ swimming area.

Doepel told his audience that in today’s legal environment the lawyer representing the ill-fated backpacker would first have to ensure that he had a reasonable case.

‘I’d say he doesn’t. The victim cannot give evidence that he entered the water between the flags, and the doctor was doing his best under the circumstances. Now we’d have to resolve matters in negotiations, and if it gets to court, the scope of duties is prescribed. If you’ve been drinking there is a significant reduction in damages. Even if he saw the flags, they’re only a representation that this is a control area. In today’s world he’d probably get nothing.’

When teaching can ruin you …

A delegate who described himself as an experi­ enced laparoscopic surgeon with a history of very few patient complications said that when he sought out the most respected legal advice in the country, he was told that he would be culpable for any mistakes made by a registrar while he was teaching him or her a practical procedure. ‘We want to make surgery safer, but in doing so we’re exposing ourselves to risk,’ he complained. Doepel responded that the surgeon’s input had ‘a real flavour of fear to it’, something he and his international colleagues were very familiar with. ‘As South Africans you’re trying to do your very best but you’re still going to get sued – that’s what tort reform will change.

It’s a fundamental paradigm shift that sets up a tort system with protections. It’s not about putting lawyers back in their box.’

At least two neurosurgeons and a retired judge commented on the ‘striking similarity’ between Motsoaledi’s medicolegal summit and the MPS workshop, urging the MPS to slot in with the health minister’s task team in making urgent recommendations to the SA Law Reform Commission. One neurosurgeon said that the MPS should collate data to show ‘where we are falling down and why’, so that in addition to tort reform the profession could identify what intrinsic common mistakes

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were being made, and geographically identify their locations. Dr David Bass, legal advisor to the Western Cape Department of Health, said his administration was building in early complaints procedures and mediation capacity (something several other provinces are now slowly following). ‘We’re trying to introduce an element of disinterest and a non-partisan approach to disputes. Doing this early and promptly can cut down a number of serious cases,’ he said.

The estimation of the long-term average claim frequency for doctors in 2015 was around 27% higher than in 2009.

Retired Gauteng High Court Judge Neels Claasen said that he wholeheartedly supp­ orted the MPS suggestions for tort reform and preventing litigation through early mediation and negotiation. He gave the example of his recently being asked by the National Department of Health to deal with two rural families who suffered ‘severe trauma and damage’ as a result of clear negligence by staff at two national hospitals.

‘We explained to them the benefits of mediation v. the disadvantages of litigation, and they agreed to mediation. Both matters were finalised in a single day, costing almost nothing.’ Elaborating, he said one mother of a victim was so traumatised she could not speak, while her jobless husband also initially remained silent. The mediators creatively asked representatives of nearby national hospitals whether they had a job for the man. ‘As it turned out, one of their heads of security had just resigned and the hospital said that if our client qualified, he could have the job.’ The man was subsequently employed and the bereaved family given a steady income stream. Judge Claasen said that both matters would have taken 2 - 5 years for resolution in court. ‘In SA we have demonstrations for lack of service delivery, students protesting that fees must fall and all of it easily erupting into violence. The health crisis is very serious and we need to join forces and work as a block if we are to resolve these issues,’ he added.

Come clean, apologise – and live to work another day

The MPS presenters repeatedly cited cases in which early and genuine expressions of regret to patients by doctors following an adverse event had had a major impact, hugely

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mitigating the outcome. Said Doepel: ‘Once the writ is served, strap yourself in – it’s almost impossible to parachute out. Early empathy and understanding can make a huge difference.’ Lawyers around the world seemed to have forgotten ‘who they are and what their obligations are. We are professional advisors.

One of the troubling things I see every day is: “I will act because I think there’s a buck in it”.

The certificate of merit [for a case] brings them back to what their obligation is,’ he added.

Medical geneticist Prof. Arnold Christianson said that he was working in a province where litigation had reached ZAR5 billion, adding that it was ‘now virtually impossible to do a decent job’. He said some of the claims coming through were ‘preposterous’. ‘I was recently asked to give an opinion on a cerebral palsy

case, and a Down syndrome patient walked through the door – it’s not surprising that things go wrong.’ He said that provincial governments were now also looking to see if their doctors could be held liable if their Health MECs were found culpable. ‘I think you [i.e. the MPS] are limiting yourselves if you’re addressing only the private sector – it’s a disaster out there.’

Tiernan replied that while the MPS did not indemnify in the public sector, the remedies being suggested were for the entire system, and only South Africans could drive them forward.

Doepel was highly critical of ‘no-fault’ compensation schemes, saying they would almost certainly fail for financial reasons and had almost bankrupted the New Zealand

healthcare system. ‘Lawyers hate a vacuum and will re-enliven personal actions. It’s like the rental car being the fastest car around.

As a philosophical, financial and regulatory mechanism, I’m no great fan of no-fault compensation schemes,’ he said. Hallinan said that the House of Parliament’s Health Committee reported in 2011 that they had heard evidence that the National Health Service bill in the UK would increase by between 20% and 80% were a no-fault compen­sation scheme to be introduced.

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(1):9-11.

DOI:10.7196/SAMJ.2016.v106i1.10415

Basson’s private ECG tutoring sets pulses racing Professionally disgraced apart­ heid-era architect of chemi­cal and biological ‘dirty tricks’ weaponry Dr Wouter Basson continued to tutor Stellenbosch University medical students at a private medical hospital for 11 months after being convicted of unethical conduct.

The maverick clinician’s involvement with young medical minds has drawn fire from top ethicists and the official campus student medical body. The latest twist in the tortuous 14-yearplus drama surrounding the unrepentant cardiologist, found guilty of unethical conduct in December 2013 by a Medical and Dental Professionals Board (MDPB) conduct tribunal, prompted belated but vigorous debate on the Stellenbosch medical campus. His second appeal to the Supreme Court to have the MDPB tribunal recuse itself on grounds of its being ‘biased’ by having failed to disassociate itself from a South African Medical Association (SAMA) statement supporting a petition calling for the ‘strongest possible censure’ of him is due to be heard on 9 February. Basson’s lawyers walked out of what would have been the start of his sentencing in December 2014, claiming that tribunal members Profs Jannie Hugo and Eddie Mhlanga were members of SAMA and therefore inherently biased. Basson’s team returned in April last year, bearing a High Court-approved order that the tribunal hear their application for recusal. The tribunal complied, but turned it down flat, chairperson Hugo saying that

he and his colleague were inactive in SAMA management, with their association confined to academic and professional work. Hugo assured Basson that he and Mhlanga were ‘acutely aware of our duties in this matter’, and pledged to ensure that he continued to experience a fair trial. Undeterred, Basson and his lawyers then applied to the High Court to overrule the MDPB response.

Ethicists speak out

Meanwhile Prof. Keymanthri Moodley, head of the Centre for Medical Ethics and Law at Stellenbosch University, criticised both students and her own Faculty of Medicine and Health Sciences for allowing Basson’s continued tutelage at the Durbanville MediClinic for 11 months after he was found guilty.

His tutorials to 4th-year undergraduates around interpreting electrocardiograms were part of a public-private initiative to increase early exposure of students to private sector practice. Upon hearing of this, the Stellenbosch medical faculty (in an unprecedented step) revoked Basson’s teaching rights on 4 November 2014, a full 11 months after the MDPB guilty finding – his tutelage reportedly having rendered several students ‘acutely uncomfortable’. Prof. Ames Dhai, Director of the Steve Biko Centre for Bioethics at the University of the Witwatersrand, asked what responsible parent would want their child taught by a man dubbed ‘Dr Death’. She said it was ‘shocking that in this day and age

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Prof. Jannie Hugo.

and with our [SA’s] history of human rights abuse, Stellenbosch would not have taken a decision immediately in terms of his guilty finding. Going through all those committees is not a reasonable sort of explanation for an 11-month-long delay.’

Tygerberg Student Council chairperson Nick Wayne said that his council stood by its call that no student should be taught by Basson. While no one was forced to take his class, there were students who did not want to be taught by him and believed he should not be practising at all, let alone

IZINDABA

teaching. ‘Teachers instil certain qualities of themselves in their students, and his lack of remorse and involvement in apartheid warfare makes students very uncomfortable.

They would rather have other tutors,’ he added. Prof. Marietjie de Villiers, Deputy Dean of Education in the Faculty of Medicine and Health Sciences at Stellenbosch University, described the anomaly as ‘a technical difficulty’. ‘There’s a difference between being appointed and being on the teaching staff, and being accredited as a clinical supervisor,’ she explained, adding that Basson had never taught on campus.

While Medi-Clinic had been accredited as a ‘group’, the individuals giving tutorials also had to be named, she confirmed. ‘People use the word “taught” loosely,’ she said.

Explaining the 11-month delay in revoking Basson’s teaching rights after he was found guilty, she said the process began after the 2013/14 festive season academic break.

The un­ precedented revocation followed a quality assurance process that began with the MB ChB Programme Committee, moving to the Faculty Undergraduate Committee, to the Faculty Board and finally to the Uni­ versity Senate – all of which had student representation. She conceded that the student representatives at the time would not have been Wayne or any of his current committee.

Initial student silence on Basson’s teaching questioned

Moodley questioned why the student body had allowed Basson to continue tutoring for so long without speaking up. ‘Perhaps it is because student protests around the country have empowered and liberated students to freely express their views,’ she speculated, expressing concern that ‘a subset of students had no discomfort with his apartheid-related

Ex-SAMA President Prof. Ames Dhai.

activities that transgressed the foundational principles of the profession and basic respect for human rights’. Yet other students ‘showed a profound dialectical capability in sharing the same space with someone they respected as a clinician, yet deplored as a health professional and human being’. De Villiers said that there was a well-publicised and regularly used complaints procedure for students, emphasising that there was no complaint on record about Basson’s tutelage.

Attendance at his tutorials was voluntary, she reaffirmed. Dhai, who is Chairperson of SAMA’s Human Rights and Ethics Committee, said: ‘It boils down to a question of trust.

Clearly, through everything that’s happened and what he was convicted of by the HPCSA, there’s been a real erosion of integrity on his part. Medical students are in their formative years of study. They learn not only from the formal curriculum but the informal one. Bad habits have been picked up from the hidden curriculum and the behaviour patterns of our teachers. The Remunerative Work outside the Public Service abuse is an excellent example of this. Is he worthy of our trust? In my opinion he’s lost people’s trust and is not worthy of it, not only because of what he did, but the manner in which he’s conducted himself subsequently. His lack of remorse and continuous opposing of Council is absolutely cynical.’ Basson said he had ‘no idea what the fuss is about. I teach many groups of people and have received no complaints, related to either the giving thereof or the quality thereof, at all over the years, from any of my students.

My lectures are a given – the attendees are there of their own volition.’ Many doctors and specialists regularly received continuing professional development points by attending his lectures, he added. Moodley challenged the student and lecturer bodies to ‘examine the extent to which we idolise and exaggerate the competence of Wouter Basson, perhaps because his worldview of human rights abuses parallels our own worldviews about racism – or conversely, what we find reprehensible about him may reflect a poignant sense of injustice induced by the apartheid regime and the institutional culture of some tertiary educational institutions.’ She hoped that institutions of higher learning would in future ensure that ‘such debate is encouraged contemporaneously and that safe spaces are created for face-to-face discussion, in addition to social media discussions’.

Dr Kgosi Letlape, President of the Health Professions Council of South Africa, said that there were no limitations on Basson’s registration with the MDPB. No healthcare practitioner could be restricted in his or her practice until the last legal word had been

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January 2016, Vol. 106, No. 1

Associate Professor and Head of the Centre for Medical Ethics and Law at Stellenboch University, Prof. Keymanthri Moodley.

spoken. ‘He has rights like any other citizen, and the laws of the country still prevail,’ he stressed.

SAMA Chair: ‘don’t lean on the private sector’

SAMA Chairperson Dr Mzukisi Groot­ boom said he understood what MediClinic was ‘trying to drive towards’, but dis­agreed with ‘the constant call among the leadership of academic health centres to allow a private practice platform to teach medical students’.

‘I don’t think it’s appropriate. What we need is for these same leaders to advocate for government to do what is correct, and that is to equip and capacitate academic hospitals to cater for and be accessible to the majority of people. The unintended consequence of this [private sector] approach is that it perpetuates the perception that the system has failed. Academic teaching platforms should meet the requirements of teaching medical students. If they allow the situation to deteriorate any further, we won’t have a teaching platform.’ Focusing on primary healthcare was vital, but not at the expense of tertiary health centres, he added.

Izindaba has learnt that the Tygerberg/ Boland branch of SAMA supported Basson in complaining about the petition against the cardiologist (launched by the People’s Health Movement, not SAMA). However, SAMA refused to apologise for supporting the petition, responding that its predecessor (the Medical Association of South Africa, MASA) was a founding member of the World Medical Association, formed in direct response to Nazi atrocities performed by doctors on living human beings. The same

IZINDABA

‘covenant’, which held that even in times of war no doctor should use their training to kill instead of heal, was abused by MASA when black consciousness leader Steve Biko was murdered in 1977. Basson only recently withdrew his membership of SAMA. The MDPB found Basson guilty of co-ordinating the large-scale production of illegal psychoactive drugs (including Ecstasy), arming mortars with teargas and providing military operatives with disorientating substances to make illegal cross-border kidnappings easier. He also made cyanide capsules available to apartheid-era military spies so that they could commit suicide if captured – a slow and painful death, the antithesis of ‘quick and painless’ James Bond-type spy suicides.

Hugo said in his judgment that medical ethics were ‘especially important’ in times of war and conflict. Basson had ‘defiled the unique and sacred position’ of trust in doctors by society that impelled them to stay true to the ethical values of ‘beneficence, non-malificence, justice and autonomy’.

South African Military Health Service Sur­ g­ e on General, Lt.-Gen. A P Sedibe, said that Basson was no longer on their payroll, but declined to answer questions on how long he had been. Head of Communications in the national defence ministry, Siphiwe Dlamani, confirmed that the South African National Defence Force (SANDF) was footing Basson’s hefty legal bill, ‘by virtue of his having been in the SANDF in the past’. The State is paying

both the HPCSA’s and Basson’s legal bills – but no state official will reveal or even estimate what this has cost so far. The professional conduct hearing has dragged on six times longer than the corruption trial of the late former police commissioner, Jackie Selebi (2009 - 2012) – and that cost ZAR17 million. Basson was acquitted in a lengthy criminal trial that predated the current ethics-related hearing. When he will be sentenced remained an open ques­ tion at the time of writing.

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(1):11-13.

DOI:10.7196/SAMJ.2016.v106i1.10416

BOOK REVIEW Being Mortal – Illness, Medicine, and What Matters in the End

By Atul Gawande. Newton, MA: Wellcome Collection, 2014. ISBN 978-1-84668-582-8 Atul Gawande, a surgeon and professor at Harvard Medical School and a staff writer for the New Yorker, is the author of three previous books focusing on difficult issues doctors face.

In Being Mortal he takes a clear-eyed view of issues that have to be dealt with in an era when many people are living longer, often into debility, and when dying of old age is not a rarity. Gawande uses the stories of patients, friends and family to make important points.

Modern medicine is primed to fix even what

is unfixable: we mortals fear debility and death. In the attempt to extend life at all costs, unnecessary suffering is inflicted and personal finances and healthcare budgets are crippled.

As Gawande says, ‘We’ve been wrong about what our job is in medicine. We think our job is to ensure health and survival. But really it is larger than that. It is to enable well-being.’

In the chapter ‘A better life’, Gawande dis­ cusses interesting studies where using simple measures – three square meals a day, reporting falls, adjusting medications – dramatically reduced the amount of time the elderly spent in hospital, so improving the quality of the last period of their lives. These interventions do not generate the revenue that actively treating patients does. The fields of gerontology and geriatric medicine in the USA are therefore unpopular, underfunded and understaffed.

Several clinical trials have shown that stopping treatment in cancer patients when previous lines of treatment have failed, together with the early institution of palliative care, results in their living a better quality and, more surprisingly, a longer life. That we do not often discuss this with our patients shows what happens when we confuse care with treatment.

The chapter titled ‘Hard conversations’ cuts to the heart of this. Here Gawande deals with those candid discussions that are difficult for both patient and caregiver but crucial to ensuring that illusions are removed and achievable goals are looked at realistically and compassionately. Excellent pointers are given in negotiating this crucial interaction.

Patient priorities are more than prolonging life and include avoiding suffering, mental

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alertness, improving relationships with family and friends, not being a burden, and feeling that their lives have not been a waste of time.

‘Endings matter’, says Gawande. The current system of high-tech medical care is failing our patients in meeting these needs, and the cost of this failure is enormous, financially and also in causing unnecessary suffering.

He movingly charts his own journey from being an ‘informative’ to an ‘interpretive’ doctor: from one who merely enumerates treatment options, often when this risks doing harm with little hope of benefit, to one who assists patients in managing the latter stages of their lives in a way that is meaningful to them.

This interpretive approach requires spending the time to learn what the patient’s goals are, understanding what risks and trade-offs they are prepared to accept in exchange for their independence, comfort and dignity, and then assisting them in realising this.

In the last chapter, titled ‘Courage’, Gawande looks at our personal responsibility in planning ahead for our inevitable ageing and death. It takes courage to confront this reality and to act on it. The reality is that if we do not do it, it will be left to others to take those decisions on our behalf, and with that the last vestige of our independence. It is up to us to ensure that our last days are more comfortable and meaningful. As this thought-provoking book shows, it is our dignity and humanity that matter in the end.

David Eedes Clinical oncologist, Three Anchor Bay, Cape Town daveed@mweb.co.za

EDITORIAL

Understanding healthcare and population mobility in southern Africa: The case of South Africa The impact of global increases in human mobility on health systems is a little understood but highly political issue in recipient countries.[1] South Africa (SA) is the greatest recipient of migrants from the Southern African Development Community (SADC), a region with high levels of migration, a high communicable disease burden and struggling public healthcare systems.[2] There is a policy of free primary healthcare for all in SA, as outlined in the Constitution and the National Health Act, but its interpretation is less inclusive within implementation guidelines and practice. As a result, non-nationals face access challenges, and healthcare responses have engaged with migration to a limited extent only. Migration provides opportunities for health and economic benefits, and has the potential to positively and negatively affect health systems.

To maximise positive impact and mitigate against potential negative consequences requires attention and engagement of policy-makers from health and other sectors, including public health researchers and health workers. We outline our current research and existing responses to migration and health in southern Africa.

Despite clear evidence of considerable migration within and into SA,[3] its impact on the healthcare system is unclear and controversial, with assumptions and popular rhetoric often driving responses in lieu of data and evidence.[4] The basic human right of access to health services is incorporated in the SA Constitution, with an acknowledgment of the progressive realisation of this right given limited resources.[5] This is in line with the 2008 World Health Assembly resolution on the issue of migrants, which calls upon member states to promote equitable access to health promotion, disease prevention and care for migrants.[6,7] The Constitution is interpreted within the National Health Act (2004) [8] to include provisions relating to access to public healthcare services for all in SA, with no mention of nationality or legal status. This involves free healthcare services for all pregnant and lactating women and for children under 6 years of age, free primary healthcare for all, and free emergency care at the point of use for all. The Act also states that these rights to access are subject to any provisions prescribed by the Minister. The Uniform Patient Fee Schedule (Appendix H) of the National Health Act provides a fee schedule where a sliding scale of income-dependent co-payments for users of public healthcare services beyond primary healthcare level (e.g. hospitals and specialised services) are outlined; it is this document that outlines differential access to healthcare through user fees being dependent on nationality and documentation status. The result is a complicated system that can lead to confusion for providers and users. Problems are compounded by the politicisation of migration in wider society[9,10] – a challenge in SA and elsewhere in recent years. [9,11-13] Estimates of cross-border migration in SA vary widely, but national census data from 2011 suggest that there are approximately 1.7 million migrants in the country,[3] which at 3.3% of the population reflects global norms.[2] Available data suggest that the numbers of international migrants in SA requiring healthcare, including antiretroviral therapy, are relatively low.[4] Migrants are often (at least initially) more healthy than non-migrant populations in their host countries, known as the ‘healthy migrant effect’.[14] However, while human mobility is not inherently risky,[15] some migrant groups face challenges to their health, often associated with living and working conditions in their destinations, which include unsafe, overcrowded living spaces, poor food security, limited livelihood opportunities and (fear of) violence. [16] These challenges are exacerbated

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by the social exclusion and socioeconomic hardships resulting from xenophobia and barriers to accessing social services, including healthcare.

Maintaining the good health of migrants has been shown to bring economic benefits to the socioeconomic development of both countries of origin and destination.[17] However, these wider societal benefits of migration and health are often overlooked, particularly in the context of a resource-constrained health system.[4] Discussions and research on migration and health have often focused on the issue of migrants’ health and associated costs. Less attention has been paid to the health systems and economic impact of patient mobility, which would enable a more holistic understanding of migration and health.

Governance of migration and health in southern Africa, whether migration with the explicit purpose of medical travel or through general population mobility, should be evidence-informed and based on robust data and their interpretation, including on the cost-effectiveness of healthcare provision for migrants. Such analysis requires better measurement of the numbers of migrants in countries, and of those accessing healthcare services, and will assist the SADC and national, regional and local government policy-makers to ensure that appropriate resources for health and migration are budgeted and planned for.

Responses to addressing migration and health in southern Africa, including current research responses, are worth outlining.

Responding to migration and health in the SADC region

Addressing migration and health in the SADC is an issue gaining momentum, albeit slowly. Just as in many other regions, there is increasing recognition from regional and national policy-makers and practitioners that, in order to address communicable diseases in the region effectively, prevention and treatment responses must engage with migration.[2] This has resulted in considerable policy activity,[18-19] including the SADC Declaration on Tuberculosis in the Mining Sector, ratified in 2012,[19] and the 2009 SADC Draft Policy Framework on Population Mobility and Communicable Diseases in the SADC Region, which is currently being revitalised with the finalisation of a regional needs assessment and the development of proposed regional financing mechanisms (not yet online). Furthermore, health ministers from SA and a range of SADC member states have signed bilateral agreements that aim to address collaboration on a range of health issues, including the treatment of patients, between countries.[20]

Current research responses

Research on population mobility and health is increasing in the south­ ern Africa region. However, there remain considerable knowledge gaps, including a better understanding of the user, provider and policy-maker experiences of policy (development and) implementation, and the impacts of migration and patient mobility – including by type of migrant status – on health systems. Such understanding would guide the development and implementation of practical responses within health systems.

Our current research is examining whether and how patient mobility affects the SA public healthcare system, with a focus on maternal and child health (MCH). This includes exploring the impact of non-nationals living and working in SA on the public healthcare system, and their experiences, and understanding the impact and experience of patients who move with the explicit intention of accessing public healthcare (patient mobility). MCH, a pressing public health issue in SA, serves as an indicator for assessing the health impact of patient mobility, MCH services being an indicator of health system functioning.[21] This

January 2016, Vol. 106, No. 1

EDITORIAL

research is the first of its kind in the SADC region. The work is being undertaken collaboratively by an international group of researchers based at the African Centre for Migration and Society at the University of the Witwatersrand, Johannesburg, the Aurum Institute, Johannesburg, and the London School of Hygiene and Tropical Medicine. An advisory group involving a range of key players has been established to guide the research process.

More specifically, this research will compare health outcomes and patient and health worker experiences in facilities situated in areas where non-national populations are known to be located. This ‘place-based’ research approach will help to inform understanding of the local context in which diverse migrant groups access healthcare. It will examine whether patients are travelling to SA with the intention of accessing the public healthcare system, and if they are, the extent to which this affects perceived and actual quality of public services, or may lead to ‘crowding out’ of domestic patients, including those accessing the private sector. Equally, the research will examine the potential positive contribution of migrants to the health system. The perspectives on these issues of policy-makers, academics and representatives of key non-governmental organisations will also be explored, with the aim of improving understanding of the governance arrangements regarding health, migration and patient mobility between SA and neighbouring countries. Additionally, we will establish what data are routinely collected and available to monitor health systems impact with regard to MCH, and analyse these data alongside the qualitative data obtained. Importantly, the research will inform the development of a larger comparative research project, which will further explore health system impacts of patient mobility.

Conclusion

SA’s migration policy needs further development in relation to documented and undocumented migrants. Current health system responses do not adequately engage with and address patient mobility and migration.[2] While SA’s Constitution includes the human right of access to health services for all, its interpretation into policy emphasises differential rights on the basis of nationality and documentation status. This leads to administrative confusion. As a result, some non-nationals face challenges in accessing healthcare.

Until migration is better considered in health systems planning, the health of people in southern Africa and developmental benefits associated with the movement of people will be compromised.

Accurate and consistent policy implementation, and an improved consideration of migration in health systems policy and its application, are needed at SADC, national, provincial and local government levels, including within healthcare facilities. Improved data collection and research on these issues will greatly assist with the enactment of evidencebased responses to migration and health in the southern African region.

We urge public health practitioners and researchers to embed migration as a central consideration in their work, and, along with policy-makers from health and other sectors, to advocate for improved responses to the movement of people and health in southern Africa.

Acknowledgements. This work is supported by a grant from the Health Systems Research Initiative (MR/M002160/1), jointly supported by the Department of International Development, the Economic and Social Research Council, the Medical Research Council and Wellcome Trust.

Helen L Walls Anthropology, Politics and Policy Group, Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK, Leverhulme Centre for Integrative Research on Agriculture and Health, London, UK, and African Centre for Migration and Society, University of the Witwatersrand, Johannesburg, South Africa

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Jo Vearey African Centre for Migration and Society, University of the Witwatersrand, Johannesburg, South Africa Moeketsi Modisenyane School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, South Africa Candice M Chetty-Makkan, Salome Charalambous Research Department, The Aurum Institute, Johannesburg, South Africa Richard D Smith Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK, and Leverhulme Centre for Integrative Research on Agriculture and Health, London, UK Johanna Hanefeld Anthropology, Politics and Policy Group, Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, UK, and African Centre for Migration and Society, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: H Walls (helen.walls@lshtm.ac.uk) 1. Hanefeld J, Smith D, Lunt N, Horsfall D. What do we know about medical tourism – a review of the literature with discussion of its implications for the UK NHS as an example of a public health care system. J Travel Med 2014;21(6):410-417. [http://dx.doi.org/10.1111/jtm.12147] 2. Vearey J. Healthy migration: A public health and development imperative for south(ern) Africa. S Afr Med J 2014;104(10):603-604. [http://dx.doi.org/10.7196/SAMJ.8569] 3. Statistics South Africa. Census 2011: Census in Brief. Pretoria: Statistics South Africa, 2012. http:// www.statssa.gov.za/census/census_2011/census_products/Census_2011_Census_in_brief.pdf (accessed 10 November 2015).

4. Vearey J. Learning from HIV: Exploring migration and health in South Africa. Glob Public Health 2012;7(1):58-70. [http://dx.doi.org/10.1080/17441692.2010.549494] 5. Republic of South Africa. The Constitution of the Republic of South Africa – No. 108 of 1996. 1996. http://www.gov.za/sites/www.gov.za/files/images/a108-96.pdf (accessed 10 November 2015).

6. Ghent A. Overcoming migrants’ barriers to health. Bull World Health Organ 2008;86(8):583-584. [http://dx.doi.org/10.2471/BLT.08.020808] 7. World Health Assembly. Resolution 61.17 ‘Health of Migrants’. A61/VR/8 Sixty-first World Health Assembly. Geneva: WHA, 2008. http://apps.who.int/gb/ebwha/pdf_files/A61/A61_R17-en.pdf (accessed 10 November 2015).

8. Republic of South Africa. National Health Act – Act No. 61. Government Gazette 2004;469(23): No. 26595. http://www.chr.up.ac.za/undp/domestic/docs/legislation_55.pdf (accessed 10 November 2015).

9. Crush J, Tawodzera G. Medical xenophobia and Zimbabwean migrant access to public health services in South Africa. J Ethn Migr Stud 2014;40(4):655-670. [http://dx.doi.org/10.1080/1369183X.2013.830504] 10. Zihindula G, Meyer-Weitz A, Akintola O. Access to healthcare services by refugees in southern Africa: A review of literature. S Afr J Demogr 2015;16(1):7-35.

11. Delamothe T. Migrant healthcare: Public health versus politics. BMJ 2012;344:e924. [http://dx.doi. org/10.1136/bmj.e924] 12. Kirshner J. ‘We are Gauteng people’: Challenging the politics of xenophobia in Khutsong, South Africa.

Antipode 2012;44(4):1307-1328. [http://dx.doi.org/10.1111/j.1467-8330.2011.00953.x] 13. Frankel A. The intersection of gender, race and ethnicity in South Africa: How xenophobia affects immigrant and refugee women in Cape Town. 2014. Spring 2014. Paper 143. http://openscholarship. wustl.edu/cgi/viewcontent.cgi?article=1142&context=wushta_spr2014 (accessed 10 November 2015).

14. Malmusi D, Borrell C, Benach J. Migration-related health inequalities: Showing the complex interactions between gender, social class and place of origin. Soc Sci Med 2010;71(9):1610-1619. [http://dx.doi.org/10.1016/j.socscimed.2010.07.043] 15. Zimmerman C, Kiss L, Hossain M. Migration and health: A framework for 21st century policymaking. PLoS Med 2011;8(5):e1001034. [http://dx.doi.org/10.1371/journal.pmed.1001034] 16. International Organization for Migration. Migration and Health in South Africa: A Review of the Current Situation and Recommendations for Achieving the World Health Assembly Resolution on the Health of Migrants. Pretoria: IOM Regional Office for Southern Africa, 2010. http://southafrica.iom. int/publication/migration-and-health-in-south-africa/ (accessed 10 November 2015).

17. Landau L, Kabwe-Segatti A. Human development impacts of migration: South Africa case study.

United Nations Development Programme, 2009. (http://core.ac.uk/download/pdf/6569650.pdf (accessed 10 November 2015).

18. Southern African Development Community Directorate for Social and Human Development and Special Programs. Policy Framework for Population Mobility and Communicable Diseases in the SADC Region: Final Draft. Gaborone, Botswana: SADC Secretariat, April 2009. http://www.arasa.info/ files/6613/7574/3254/SADC_Policy_Framework_FINAL.pdf (accessed 10 November 2015).

19. Southern African Development Community. SADC Declaration on Tuberculosis in the Mining Sector.

Gaborone: Botswana: SADC, 2012. http://www.stoptb.org/assets/documents/news/Declaration%20 on%20Tuberculosis%20in%20the%20Mining%20Sector2012English.pdf (accessed 10 November 2015).

20. Crush J, Chikanda A. South-South medical tourism and the quest for health in southern Africa. Soc Sci Med 2015;124(Jan):313-320. [http://dx.doi.org/10.1016/j.socscimed.2014.06.025] 21. UN Millennium Project. Who’s Got the Power? Transforming Health Systems for Women and Children. Task Force on Child Health and Maternal Health. 2005. http://www.unmillenniumproject. org/documents/maternalchild-complete.pdf (accessed 10 November 2015).

S Afr Med J 2016;106(1):14-15. DOI:10.7196/SAMJ.2016.v106i1.10210

January 2016, Vol. 106, No. 1

EDITORIAL

The poverty of the concept of ‘poverty eradication’ Much has been written about ‘poverty eradication’ in recent years. The extent of poverty is of great concern in South Africa (SA) and globally, given the social implications of so many people living under atrocious conditions.[1] Three Carnegie conferences over several decades have addressed poverty in SA. The most recent attracted a large audience, and most of the presentations were on microeconomic approaches to poverty alleviation.[2] Macroeconomic problems and tentative solutions received minimal attention.

Despite the complexity and magnitude of the macroeconomic task, there is evidence that ‘alleviation of extreme poverty’ can be achieved both locally and globally if the goal of doing so is limited to the current parsimonious World Bank (WB) definitions of poverty and economic groups. The swing towards optimism that extreme poverty can be significantly reduced has been boosted by what are (dubiously) deemed by some to be signs of ‘global convergence’ in wealth and health outcomes.[3] Such optimism was also expressed at the recent Davos meeting, where the goals of ‘action 2015’ to ‘end poverty in all its forms’ was discussed.[4] It is, however, clear that the WB definition of poverty is outdated and requires revision.[5] A brief review of how poverty and income levels are defined is offered here to provide insight into the shortcomings of such definitions and into what ‘eradicating poverty in all its forms’ would mean if considered within more realistic boundaries.

The WB’s definition of extreme poverty in 1991 was USD1 per day, rising to USD1.08 per day in 1993, USD1.25 per day in 2005 and most recently USD1.9 per day. These levels of extreme poverty are calculated from standards of absolute poverty in the world’s poorest countries and from consumer price indices that take into account purchasing power parity in various countries – a process not without complications.[6] The lowest income group described by the WB has an annual per capita gross national income (GNI) of USD1 025 or less in 2011.[3] Most in this category are considered to be living in extreme poverty, defined as ‘a condition characterized by severe deprivation of basic human needs, including food, safe drinking water, sanita­tion facilities, health, shelter, education and information’. The reduction in the number of people living in this category from 3.1 billion in 1990 to 0.82 billion by 2011 is what has been described as ‘lifting billions out of poverty’![3] In SA, social grants to 16 million people have similarly reduced the number of people living in ‘extreme poverty’. However, 45% of South Africans continue to live on about USD2 per day, with over 10 million of these under the food poverty line of USD1 per day. Relative poverty in SA, as reflected in the Gini coefficient, has increased from 0.6 in 1995 to almost 0.7 in 2009[7] – the widest in the world.

Such relative poverty is damaging to social wellbeing over and above absolute levels of poverty.[8] It was predicted many years ago that the civil unrest and conflict over political power that was curtailed by SA’s transition would recrudesce if socioeconomic disparities were not adequately addressed in the new SA.[9] Sadly this is now evident, and it is also of global relevance.

The next level in the WB definitions is the low-middle income group that comprises those with annual per capita GNI between USD1 045 and USD4 124 (a four-fold range). In 1990, 0.67 billion people were in this category. By 2011, 1.76 billion had been added, increasing the number to 2.5 billion.[3] This group does not meet the criteria for extreme poverty, and raising their incomes is not part of the poverty eradication endeavour. It does not take much

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imagination to wonder what the standard of living must be like for those living at the lower levels in this category. What does their diet comprise? What housing conditions do they live under? To what standard of healthcare do they have access? What level of education can they reach, and what work can they hope for or do?

The upper-middle income category includes those with annual per capita GNI of between USD4 036 and USD12 475 (a three-fold range).

The number of people herein increased from 0.74 billion in 1990 to 2.5 billion in 2011.[3] Many in this group are probably clustered at the lower end of the range. It should be noted that before they went on strike demanding almost a doubling of their earnings, Lonmin’s Marikana miners were earning about USD7 000 per year.[10] By WB criteria this would (incredibly!) locate them in the upper-middle income category!

The high-income category, defined as an annual per capita GNI of over USD12 474, included 0.87 billion people in 1990, increasing to 1.1 billion by 2011.[3] The distribution of income in this category ranges from USD36 per day to many thousands – a minimum of an eighty-fold difference. The USA is a high-income country, yet 20 million people there live on less than USD2 per day!

In the absence of data regarding the distribution of income within each of the above categories, one could speculate that all of the changes between 1990 and 2011 could have been achieved by annual per capita increments of as little as USD400 - 800 at the upper end of each category. These increases do elevate more people into the lower part of the range in the next-highest category. However, such ‘economic advancement’ cannot be credibly labelled as ‘lifting out of poverty’, other than in terms of the ludicrously low levels of income defined as poverty by the WB. Since the 2008 global economic crisis, it is becoming more widely acknowledged that efforts to address diverse critical local and global problems, including poverty, are frustrated by a misguided, inadequate development ideology and agenda.[11] While global institutional efforts in support of international development targets have been stepped up, current economic trends globally and in SA are preserving privilege for a minority of people while simultaneously intensifying inequality, poverty, starvation, violence and abuse of the environment.[12] In SA, 20% of people earn 75% of the total annual national income, with heads of parastatals and government officials (in particular the President[13]) receiving bloated salaries, while the bottom 80% earn 25%.[14] Similarly, at a global level 20% of people acquire 76% of annual global income while 80% survive on 24%. In SA, 54% of people are food insecure while an estimated 795 million people globally in 2012 - 2014 were chronically undernourished.[15] This is surely an intolerable situation in a world with enough food, and in which human rights are hailed as highly valued!

Poverty should also be viewed in the context of its causal pathways, determined inter alia by the distorted structure of the global political economy,[11,12] one effect of which is a net flow of resources from the global south to the global north. For every USD1 of so-called development aid, USD6 is extracted – much of this is payment towards total debt that can never be repaid.[16] Aid to subSaharan Africa (SSA) amounted to USD21.2 billion in 2000. This is counterbalanced by debt repayments insufficient to reduce total debt, with resulting increase in total SSA debt from USD275.6 billion in 2002 to USD413 billion by 2013. The combined stock of developing countries’ external debt rose from USD4.4 trillion in 2010 to USD4.9 trillion at the end of 2011.[17]

January 2016, Vol. 106, No. 1

EDITORIAL

Claims that significant improvements have been made in lifting people out of poverty, when increments in income have been unimpressive, reflects ways of thinking about the lives of others that lack moral imagination and are dominated by the ideology of longaccepted, but now discredited, economic dogma.[11,18] Such thinking prevents us from recognising the gravity of the economic and ecological situations we all face and from acknowledging the causal role played by those with high levels of entitlement and wasteful consumer lifestyles in sustaining pervasive poverty, conflict and other complex 21st-century global crises.[11] Now that the WB is setting up a new commission on poverty,[19] this is an appropriate time to embark on a ‘truth and reconciliation’ process to examine the role the WB has played in creating and sustaining poverty, and in underestimating the severity of poverty through its parsimonious definitions. Arguably such a process could foster acknowledgment of the poverty of the WB’s conception of poverty and consequently lead to increases in the upper levels of income in each income category. For example, the upper annual GNI limits could become about USD2 500 for extremely poor, USD7 500 for poor, USD20 000 for low-middle income, and USD20 000 - 80 000 for high-middle income (a four-fold range), and there could be two new categories of high income and very high income, USD80 000 - 120 000 and over USD120 000, respectively. This reclassification would increase the challenge of significantly lifting many out of poverty.

In a world with limited renewable resources and a severely threatened natural environment, we should be critical of optimism about success in ‘ending poverty in all its forms’ that afflicts the majority of the world’s people, while continuing to define poverty parsimoniously, and promoting excessively high incomes for a small proportion of people whose consumption patterns adversely impact on human security, climate change and environmental degradation.

Seeking and finding innovative ways of making progress towards the goal of more tolerable lives for many more people is not beyond human ingenuity and ability. Changes to the defining levels of poverty and wealth, together with innovation in generating and distributing income, including appropriate taxation, are defensible and implementable goals that could credibly reduce poverty and promote steps towards meaningful ‘convergence’ of wealth and health outcomes.[11,20, 21]

Solomon R Benatar Bioethics Centre, University of Cape Town, South Africa, and Joint Centre for Bioethics and Dalla Lana School of Public Health, University of Toronto, Canada Corresponding author: S Benatar (solomon.benatar@uct.ac.za) 1. Re-Thinking Poverty: Report on the World Situation 2010. New York: United Nations, 2009. http:// www.un.org/esa/socdev/rwss/docs/2010/fullreport.pdf (accessed 24 November 2015).

2. Carnegie 3. Strategies to overcome poverty and inequality. http://www.carnegie3.org.za/conferencepapers (accessed 22 November 2015).

3. Jamison DT, Summers LH, Alleyne G, et al. Global health 2035: A world converging within a generation. Lancet 2013;382(9908):1898-1955. [http://dx.doi.org/10.1016/S0140-6736(13)62105-4] 4. Global coalition targets key climate change summits. Cape Times 2015; 26 January, p. 7. https://www. highbeam.com/doc/1G1-398748472.html (accessed 22 November 2015).

5. Global poverty, middle-income countries and the future of development aid. http://recom.wider. unu.edu/article/global-poverty-middle-income-countries-and-future-development-aid (accessed 22 November 2015).

6. Jolliffe DM, Prydz EB. The international poverty line has just been raised to $1.9 per day, but global poverty is basically unchanged. Let’s Talk Development. World Bank. http://blogs.worldbank.org/ developmenttalk/international-poverty-line-has-just-been-raised-190-day-global-poverty-basicallyunchanged-how-even (accessed 21 November 2015).

7. Poverty Trends in South Africa: An Examination of Absolute Poverty Between 2006 and 2012.

Statistics South Africa, 2014. http://beta2.statssa.gov.za/publications/Report-03-10-06/Report-03-1006March2014.pdf (accessed 22 November 2015).

8. Wilkinson R, Pickett K. The Spirit Level: Why Equality is Better for Everyone. London: Penguin, 2010.

9. Benatar SR. Health care reform in the new South Africa. N Engl J Med 1997;336(12):891-895.

10. Steyn L. Miners earn a R7000 ‘pittance’. http://mg.co.za/article/2012-08-24-miners-earn-a-r7000pittance/ (accessed 26 November 2015).

11. Gill S, Bakker IC. The global crisis and global health. In: Benatar S, Brock G, eds. Global Health and Global Health Ethics. Cambridge: Cambridge University Press, 2011:221-238.

12. Benatar SR, Gill S, Bakker IC. Global health and the global economic crisis. Am J Public Health 2011;101(4):646-653. [http://dx.doi.org/10.2105/AJPH.2009.188458] 13. Van Onselen G. How much does Jacob Zuma cost us? Politicsweb 19 August 2012. http://www. politicsweb.co.za/news-and-analysis/how-much-does-jacob-zuma-cost-us (accessed 23 November 2015).

14. Leibbrandt M, Woolard I. Trends in inequality and poverty over the post-apartheid era: What kind of a society is emerging? OECD/NPC/TIPS Policy Forum. http://www.oecd.org/els/soc/48228332.pdf (accessed 1 December 2015).

15. Food and Agriculture Organization, United Nations. State of Food Insecurity in the World 2014. http://www.fao.org/publications/sofi/2014/en/?%255C%255C%255C%255C%255C%255C%255C%2 55C=%2503%2504 (accessed 22 November 2015).

16. Rudin J, Sanders D. Debt, structural adjustment and health. In: Benatar SR, Brock G, eds. Global Health and Global Health Ethics. Cambridge: Cambridge University Press, 2011:155-165.

17. World Bank. International Debt Statistics 2013. Washington, DC: World Bank, 2013.

18. Mueller A. What’s behind the financial market crisis? Mises Daily, Ludwig von Mises Institute. http:// mises.org/daily/3111 (accessed 8 January 2011).

19. World Bank chief economist sets up new commission on global poverty. http://www.worldbank.org/ en/news/press-release/2015/06/22/world-bank-chief-economist-sets-up-new-commission-on-globalpoverty (accessed 22 November 2015).

20. Atkinson A. Inequality: What Can Be Done. Cambridge, MA: Harvard University Press, 2015.

21. Piketty T. A practical vision of a more equal society. New York Review of Books. 25 June 2015. http:// www.nybooks.com/articles/2015/06/25/practical-vision-more-equal-society/ (accessed 2 December 2015)

S Afr Med J 2016;106(1):16-17. DOI:10.7196/SAMJ.2016.v106i1.10417

This month in the SAMJ ...

Prof. Jeffrey Wing* is Clinical Head of Medicine at Charlotte Maxeke Johannesburg Academic Hospital. In addition to his many administrative duties, he practises as an endocrinologist in the Division of Endocrinology and Metabolism and participates in clinical trial research in the area of type 2 diabetes mellitus.

Dr Daksha Jivan* is an endocrinologist in the Division of Endocrinology at Charlotte Maxeke Johannesburg Academic Hospital and lectures at the University of the Witwatersrand. She participates in clinical trial research in the area of type 2 diabetes mellitus. She is an active member of the Society of Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) and has previously served on its Executive Committee.

* Wing J, Jivan D. Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia. S Afr Med J 2016;106(1):57-61. [http://dx.doi.org/10.7196/SAMJ.2016.v106i1.10284]

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January 2016, Vol. 106, No. 1

EDITORIAL

South African Guidelines Excellence (SAGE): What’s in a name?

South Africa (SA) remains one of the most unequal societies in the world.[1] Addressing the various challenges we face requires multidisciplinary, multipronged approaches, including consideration of strategies for improving the delivery of healthcare.

Quality of healthcare can be understood to encompass a number of dimensions, including effectiveness, efficiency, accessibility, patientcentredness, equity and safety.[2] SA’s call for primary healthcare re-engineering suggests an acute awareness of local challenges. The planned restructuring, including the National Health Insurance initiative, is a means for reducing inequality in the provision of healthcare, which will require new approaches to healthcare delivery, with greater emphasis on health promotion and preventive activities.[3,4] These changes necessitate a collaborative approach for achieving improvements in key health processes and outcomes, as well as changes in clinician and patient behaviours, all underpinned by innovative interventions.[5] In the changing healthcare system, healthcare providers need clear, trustworthy guidance on how best to care for their patients so that all can reasonably reach the ideals of quality in healthcare. High-quality, evidence-informed clinical practice guidelines (CPGs) are potentially reassuring tools for healthcare providers, as they are a means of bridging the gap between policy, best practice, local contexts and patient choice.

CPGs have long been upheld as an essential part of quality medical practice. ‘Clinical guidelines are statements that include recommendations intended to optimise patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.’[6] CPGs have a range of purposes, intended to improve the efficiency and cost-effectiveness of health system utilisation and to decrease costly and preventable mistakes. They generally include statements of expected practice, and provide benchmarks or standards against which individuals may audit and potentially improve their practices, or guidance with regard to undertaking particular tasks.[7] Internationally, over the past decade there has been a growing volume of research evidence around CPGs, including the processes of guideline development, adaptation, contextualisation, implementation and evaluation. There are detailed processes available for the development of CPGs, but there is no standard approach. Notably, there are well-credentialled international and national guideline development groups, including the World Health Organization,[8] the Scottish Intercollegiate Guidelines Network,[9] the National Institute for Health and Care Excellence[10] and the National Health and Medical Research Council,[11] each with its own approach to guideline construction and writing, usually described in a guideline development manual.

Globally and locally, potentially many hundreds more groups (such as health departments, insurers and other healthcare organisations, professional associations, hospitals, specialty colleges and even small unaffiliated groups of individuals) have attempted the task of producing guidelines with the purpose of improving or standardising local clinical practice. They often use their own interpretations of the best way to construct and write clinical guidelines. Historically, CPGs were built mostly on expert opinion, which included variable (and often selective) reference to research evidence.[12,13] Such guidelines are still found today, albeit in decreasing numbers. Better and more transparently constructed evidence-informed approaches integrated with expert opinion and patient values have gained acceptance as the best approach to clinical guideline development. To support this

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progress, in 2011 the Institute of Medicine (IOM) introduced eight standards for guideline development (IOM 2011), the Guidelines International Network produced 11 relatively similar standards,[14] and McMaster University compiled a checklist of 18 topics and 146 items to guide developers.[15] SA has been a contributor to CPG development and implementation for several decades. Guideline development occurs at national, provincial and hospital levels. In addition, professional societies have played an important role, developing guidance based on their areas of expertise. For example, the National Department of Health spearheads an Essential Medicines Programme that drives the development of standard treatment guidelines to inform rational prescription at all levels of care (primary, secondary and tertiary, quaternary) in an equitable, cost-effective manner throughout the country. Regionally, there is evidence that SA is a node of technical expertise in this field, with the quality of our guideline development exceeding that of our regional neighbours in the Southern African Development Community.[16] However, against a global backdrop SA’s guidelines do not yet demonstrate all the aspects of expected guideline quality indicators according to recognised global standards.

To address concerns with the quality of CPGs, the SAMJ has introduced a Guideline Review Committee to provide peer review before publication in the Journal.[17] In addition to contributions to guideline development, SA researchers are global leaders in research into implementation, conducting high-quality cluster trials of complex interventions evaluating guideline uptake. For instance, the Knowledge Translation Unit at the University of Cape Town has conducted pragmatic trials evaluating outreach education and task shifting of care from doctors to other health professionals, compared with standard care for implementing guidelines for respiratory conditions, including tuberculosis and more recently HIV.[18-20] The guidelines, developed and implemented by this team for SA, are now being rolled out to other settings in Botswana and Malawi, where a similar trial to contextualise the effectiveness of the educational intervention has been tested.[21] This research team is currently expanding its work to include guideline implementation for a package of primary care conditions, the results of which are impacting on clinical care at primary care level throughout SA,[22] and has recently gone into partnership with the British Medical Journal.[23] Despite these innovative SA research activities into CPG development and implementation, there is still limited knowledge of the overall context and processes of guideline development, adherence by clinicians to clinical guidelines, and factors that could improve accessibility and use of guidelines in the local healthcare context.

Our work is based on the premise that high-quality, evidenceinformed CPGs offer a cogent and persuasive way of bridging the gap between evidence and best practice, local contexts and health provider behaviour. Understanding the current state of play in SA primary care CPG development and implementation can therefore pave the way for better-focused and more effective and efficient interventions to improve healthcare. Project SAGE (South African Guidelines Excellence) is a 3-year research project, funded by the South African Medical Research Council through the Flagship Project scheme (http:// www.mrc.ac.za/cochrane/sage.htm).[24] The overarching goal of the Flagship Projects is to support large-scale, innovative, interdisciplinary research projects to address health problems in SA. Project SAGE is an innovative research partnership between Cochrane South Africa, the Centre for Evidence-based Health Care

January 2016, Vol. 106, No. 1

EDITORIAL

MAPPING PHASE

DEVELOPMENT PHASE

CAPACITY PHASE

Outcome 1: Who is playing, how and why?

GOAL 1 SA guideline stakeholder & agenda mapping

GOAL 2 Outcome 2: PHC guideline What PHC guidelines identification & are available? Are they useful for SA? appraisal

GOAL 4 Guideline writing & implementation manual for SA

GOAL 5 Capacity building, dissemination, training & development

Outcome 4: A comprehensive ‘how to do it’ guideline manual for SA

Outcome 5: Capacity building and rolling out the findings

GOAL 3 Guideline stakeholder Outcome 3: requirement What help do SA guidemapping line stakeholders need?

1 - 18 months

12 - 24 months

24 - 36 months

Fig. 1. South African Guideline Excellence (SAGE) – project outline. (PHC = primary healthcare.)

and the Department of Physiotherapy in the Faculty of Medicine and Health Sciences, Stellenbosch University, and the International Centre for Allied Health Evidence, University of South Australia.

Project SAGE has five goals that aim to improve the quality and reach of SA primary care CPGs (Fig. 1). Using stakeholder-driven processes, SAGE will provide tools to assist effective SA CPG activities in developing, adapting, adopting, contextualising and implementing primary care CPGs.[24] In a resource-limited setting such as SA, where access to resources for health is limited, ensuring the best use of effective and costeffective primary care diagnostics and treatments is key to reducing waste, improving access and hence improving quality of care.[25] CPGs should be seen to transparently and systematically consider best research evidence to produce believable recommendations, which can then be credible vehicles for knowledge translation.

Once there is agreement on what constitutes SA best practices in CPG development, implementation and evaluation, primary care clinicians can be assured that the CPGs developed and implemented in SA will support best practice, are achievable by all end users, and will lead to improved patient care.

Tamara Kredo, Shingai Machingaidze Cochrane South Africa, South African Medical Research Council, Tygerberg, Cape Town, South Africa Quinette Louw Department of Physiotherapy, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa, and Cochrane South Africa, South African Medical Research Council, Tygerberg

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Taryn Young Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa, and South African Medical Research Council, Tygerberg Karen Grimmer International Centre for Allied Health Evidence, University of South Australia, Adelaide, Australia, and Department of Physiotherapy, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa Corresponding author: T Kredo (tamara.kredo@mrc.ac.za) 1. Lehlola P. Statistics South Africa. Poverty Trends in South Africa: An Examination of Absolute Poverty Between 2006 and 2011. Pretoria: SSA, 2014.

2. World Health Organization. Quality of Care – A Process for Making Stratetic Choices in Health Systems. Geneva: WHO, 2006.

3. National Department of Health. The 10 Point Plan Medium Term Strategic Framework 2009-2014.

2009. http://www.healthlink.org.za/publications/874 (accessed 15 August 2015).

4. Matsoso P, Fryatt R. National Health Insurance: The first 16 months. S Afr Med J 2013;103(3):156-158. [http://dx.doi.org/10.7196/SAMJ.6601] 5. Mayosi BM, Flisher AJ, Lalloo UG, et al. The burden of non-communicable diseases in South Africa.

Lancet 2009;374(9693):934-947. [http://dx.doi.org/10.1016/S0140-6736(12)61814-5] 6. Graham R, Mancher M, Wolman D, Greenfield S, Steinberg E. Clinical Practice Guidelines We Can Trust. Washington, DC: Institute of Medicine Committee on Standards for Developing Trustworthy Clinical Practice Guidelines/National Academies Press, 2011:15.

7. Woolf SH, Grol R, Hutchinson A, et al. Clinical guidelines: Potential benefits, limitations, and harms of clinical guidelines. BMJ 1999;318(7182):527-530. [http://dx.doi.org/10.1136/bmj.318.7182.527] 8. World Health Organization. WHO Handbook for Guideline Development. Geneva: WHO, 2008.

9. Scottish Intercollegiate Guidelines Network. SIGN 50: A Guideline Developer’s Handbook. 2008. http://www.sign.ac.uk/methodology/index.html (accessed 7 January 2011).

10. National Institute for Health and Clinical Excellence. The Guidelines Manual. November 2008. London: National Institute for Health and Clinical Excellence. www.nice.org.uk (accessed 15 August 2015).

11. National Health and Medical Research Council. A Guide to the Development, Implementation and Evaluation of Clinical Practice Guidelines. Canberra, Australia: National Health and Medical Research Council, 1999.

12. Shaneyfelt TM, Mayo-Smith MF, Rothwangl J. Are guidelines following guidelines? The methodo­ logical quality of clinical practice guidelines in the peer-reviewed medical literature. JAMA 1999;281(20):1900-1905.

January 2016, Vol. 106, No. 1

EDITORIAL

13. Grilli R, Magrini N, Penna A, Mura G, Liberati A. Practice guidelines developed by specialty societies: The need for a critical appraisal. Lancet 2000;355(9198):103-106. [http://dx.doi.org/10.1016/S01406736(99)02171-6] 14. Qaseem A, Forland F, Macbeth F, Ollenschläger G, Phillips S, van der Wees P; Board of Trustees of the Guidelines International Network. Guidelines International Network : Toward international standards for clinical practice guidelines. Ann Intern Med 2012;156 (7):525-531. [http://dx.doi. org/10.7326/0003-4819-156-7-201204030-00009] 15. Schünemann HJ, Wiercioch W, Etxeandia I, et al. Guidelines 2.0: Systematic development of a comprehensive checklist for a successful guideline enterprise. CMAJ 2014;186(3):E123-E142. [http:// dx.doi.org/10.1503/cmaj.131237] 16. Kredo T, Gerritsen A, van Heerden J, et al. Clinical practice guidelines within the Southern African Development Community: A descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases. Health Res Policy Syst 2012;10(1):1. [http:// dx.doi.org/10.1186/1478-4505-10-1] 17. Wiseman R, Cohen K, Gray A, et al. AGREE to disagree: Critical appraisal and the publication of practice guidelines. S Afr Med J 2014;104(5):345-346. [http://dx.doi.org/10.7196/smaj.8215] 18. Fairall LR, Zwarenstein M, Bateman ED, et al. Effect of educational outreach to nurses on tuberculosis case detection and primary care of respiratory illness: Pragmatic cluster randomised controlled trial. BMJ 2005;331(7519):750-754. Erratum in: BMJ. 2005;331(7525):1120. Myers, Pat [corrected to Mayers, Pat] [http://dx.doi.org/10.1136/bmj.331.7519.750] 19. Zwarenstein M, Fairall R, Lombard C, et al. Outreach education for integration of HIV/AIDS care, antiretroviral treatment, and tuberculosis care in primary care clinics in South Africa: PALSA PLUS

pragmatic cluster randomised trial. BMJ 2011;342:d2022. [http://dx.doi.org/10.1136/bmj.d2022] 20. Fairall LR, Bachmann MO, Lombard C, et al. Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): A pragmatic, parallel, cluster-randomised trial.

Lancet 2012;380(9845):889-898. [http://dx.doi.org/10.1016/S0140-6736(12)60730-2] 21. Schull MJ, Cornick R, Thompson S, et al. From PALSA PLUS to PALM PLUS: Adapting and developing a South African guideline and training intervention to better integrate HIV/AIDS care with primary care in rural health centers in Malawi. Implement Sci 2011;6:82. [http://dx.doi.org/10.1186/1748-59086-82] 22. Knowledge Translation Unit. Evidence on the effectiveness of the Primary Care 101 guideline. http:// knowledgetranslation.co.za/research/current-research-trials/primary-care-101-trial/ (accessed 15 August 2015).

23. Providing guidance to empower LMIC heath teams. http://www.bmj.com/company/partner-with-us/ providing-local-health-guidelines-to-improve-patient-care-in-south-africa/ (accessed 10 February 2015).

24. Machingaidze S, Kredo T, Louw Q, Young T, Grimmer K. South African Guidelines Excellence (SAGE): Clinical practice guidelines – quality and credibility. S Afr Med J 2015;105(9):743-745. [http:// dx.doi.org/10.7196/SAMJnew.7697] 25. Chinnock P, Siegfried N, Clarke M. Is evidence-based medicine relevant to the developing world? PLoS Med 2005;2(5):e107. [http://dx.doi.org/10.1371/journal.pmed.0020107]

S Afr Med J 2016;106(1):18-20. DOI:10.7196/SAMJ.2016.v106i1.10286

Acute heart failure: Can modern therapy delay or prevent death?

Acute heart failure in sub-Saharan Africa

Conclusion

Acute heart failure (AHF) is a common mechanism of death in sub-Saharan Africa (SSA).[1] The most common cause is untreated hypertension, which as elsewhere in the world, including Europe, the USA, India, China, Africa and South Africa (SA), has a dire prognosis associated with high mortality.

The treatment of this common condition in SSA is not well documented. However, it is likely that, as in North America, loop diuretics are usually tried early in the course of therapy. In North America, patients with decompensated AHF are given loop diuretics as an essential component of therapy,[2] yet there are few randomised prospective data to guide their use. There were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as opposed to continuous infusion, or at a high dose as opposed to a low dose.

Hypertension as a cause of heart failure

Hypertension is common in Africa, as is heart failure.[1] Establishing the cause of AHF would enable specific therapy to be started as a matter of urgency. For example, a patient with hypertensive AHF needs urgent intravenous therapy to reduce the blood pressure.

Besides the typical clinical presentation of cardiomegaly and often atrial fibrillation, AHF may first manifest itself indirectly as left ventricular systolic dysfunction, especially in the elderly and in people with diabetes.[3] Analysis of gender differences in AHF shows that modifiable lifestyle risk factors are prominent in men, while women more commonly have rheumatic heart disease and nutritional deficiencies, as shown in the Sub-Saharan Africa Survey of Heart Failure (THESUSHF) study on 1 006 subjects.[4] This study found that the causes of AHF in Africa were typically non-ischaemic, with hypertension a prominent cause. In contrast, in North America and in European countries the typical cause of AHF is ischaemic heart disease rather than hypertension.[5]

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With regard to the treatment of AHF, there are both clinical and research messages. Neglected hypertension, although relatively easy to treat, is a frequent source of AHF. The problem in rural African communities in SSA is that hypertension is seldom diagnosed and appropriate therapy is seldom instituted, so that a crisis is likely to occur after years of neglect. Ideally, the populations of sub-Saharan countries such as Nigeria, Kenya, Tanzania, SA and Mozambique should have much better access to mobile clinics that can reach the non-urban population.

The clinical message is that not only are the complications of significant hypertension susceptible to therapy, but preventive measures such as salt reduction, mobile clinics and workplace blood pressure measurements would help to counter the disease earlier.

The research message is that laboratory research should focus on preventive therapy directed at preservation of the threatened myocardium, including much wider use of angiotensin-converting enzyme inhibitors or even novel metabolic therapy such as reducing the elevated cardiotoxic blood free fatty acids.

Lionel Opie, Gaurang Deshpande Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: L Opie (lionel.opie@uct.ac.za) 1. Damasceno A, Mayosi BM, Sani M, et al. The causes, treatment, and outcome of acute heart failure in 1006 Africans from 9 countries. Arch Intern Med 2012;172(18):1386-1394. [http://dx.doi.org/10.1001/ archinternmed.2012.3310] 2. Ojji D, Atherton J, Sliwa K, Alfa J, Ngabea M, Opie L. Left ventricular systolic dysfunction in asymptomatic black hypertensive subjects. Am J Hypertens 2015;28(7):924-929. [http://dx.doi. org/10.1093/ajh/hpu247] 3. Ogah OS, Davison BA, Sliwa K, et al. Gender differences in clinical characteristics and outcome of acute heart failure in sub-Saharan Africa: Results of the THESUS-HF study. Clin Res Cardiol 2015;104(6):481-490. [http://dx.doi.org/10.1007/s00392-015-0810-y] 4. Sliwa K, Davison BA, Mayosi BM, et al Readmission and death after an acute heart failure event: predictors and outcomes in sub-Saharan Africa: Results from the THESUS-HF registry.

Eur Heart J 2013;34(40):3151-3159. [http://dx.doi.org/10.1093/eurheartj/eht393] 5. Opie LH. Cardioprotection from metabolism to molecules to certainties. S Afr Med J 2012;102(6):491-492.

S Afr Med J 2016;106(1):20. DOI:10.7196/SAMJ.2016.v106i1.10208

January 2016, Vol. 106, No. 1

CME

GUEST EDITORIAL

Cardiovascular medicine in primary healthcare in sub-Saharan Africa: Minimum standards for practice (part 1) Cardiovascular disease (CVD) accounts for approx­ imately 30% of deaths worldwide, with 80% of this CVD burden occurring in developing countries.[1] The epidemiological transition occurring in sub-Saharan Africa (SSA) has the consequence of economic and social transformation, resulting in dramatic shifts in the disease spectrum from communicable diseases and malnutrition to CVD and cancer.[2] South Africa (SA) is faced with the challenge of four colliding epidemics: (i) poor child and maternal health; (ii) high rates of interpersonal violence; (iii) infectious diseases including HIV/AIDS and tuberculosis; and (iv) non-communicable diseases (NCDs) including CVD. In SA NCDs are prevalent in both rural and urban areas, most prominently in poor persons living in urban and periurban settings, resulting in increasing pressure on acute and chronic healthcare services.[3] A major driver of this NCD burden in SA is the demographic change in the country leading to an increase in the proportion of people older than 60 years, despite the negative effect of HIV/AIDS on life expectancy. Contributions to the CVD burden in the country include hypertension, cardiomyopathies, rheumatic valvular heart disease, pericardial disease and coronary artery disease, among others.[4] In this issue of the journal the clinical approaches to these common cardiovascular problems are reviewed, with the dual objective of empowering doctors who manage these conditions in primary care settings around SA as well as improving the care of CVD in primary care settings and emergency departments. This series of articles represents the collaborative efforts of primary health/family physicians and cardiologists from around the country, who have synthesised and presented the most current, evidence-based and practical approaches to manage common CVDs. In this edition, the important topics of heart failure (HF), dyspnoea, hypertension in the young, and valvular heart disease are reviewed. The following issue will focus on infective endocarditis, pericardial disease, acute coronary syndromes, and chest pain and suspected tachyarrhythmias in the emergency room.

HF in SSA is a prevalent problem that presents varying challenges in resource-constrained countries, and remains one of the most common primary diagnoses for patients on the continent admitted to hospital with heart disease. Kraus et al.[5] review the epidemiology of HF in SSA and the principles of management, focusing on symptom relief, prevention of hospitalisation and improving survival.

There have been no population-based epidemiological studies on HF in Africa, but there have been a number of important hospitalbased studies. The article reviews the classification, aetiology, patho­ physiology and clinical presentation of HF, which represents the final common expression of many cardiovascular disorders. While the diagnosis of HF is a clinical one, the electrocardiogram (ECG) and echocardiogram remain the most useful investigations.

The authors emphasise the importance of patient education and optimisation of medical therapy, especially disease-modifying drugs such as angiotensin-converting enzyme inhibitors, beta-blockers and those that relieve symptoms and keep patients out of hospital, such as digoxin and diuretics. Effective diuresis and complete resolution of congestion are key in improving symptoms and functionality of patients with HF, along with optimal doses of disease-modifying drugs.

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The article by Coccia et al.[6] on dyspnoea reviews the patho­ physiology and management of breathlessness, a complex symptom resulting from cardiovascular, respiratory or other system com­ promise. Almost 90% of cases are due to common and easily manage­ able conditions.

Specifically in SA, with the high burden of HIV infections and high prevalence of interpersonal violence, many patients present with dyspnoea due to either opportunistic infections related to HIV infection or trauma related to violence. A detailed history and careful assessment are imperative, looking for specific red flags that suggest a life-threatening cause such as hypotension, altered mental status and high respiratory rate. The chest radiograph is a useful tool, but has low sensitivity in diagnosis of some of the causes. The utility of other investigations, such as the ECG, cardiopulmonary exercise testing and echocardiography, is concisely discussed.

Management of dyspnoea should focus primarily on treating the underlying disease and relieving symptoms, supported by the use of oxygen where indicated, pharmacological therapy and pulmonary rehabilitation. Although supplemental oxygen improves mortality in chronically hypoxaemic patients with chronic obstructive pulmo­ nary disease, there are conflicting data about its ability to relieve breathlessness. As supplemental oxygen is an expensive form of therapy, the lack of evidence-based data for this intervention should discourage its use. Opioids have been the most widely studied agent in the treatment of dyspnoea. Short-term administration reduces breathless­ness in patients with a variety of conditions. Pulmonary rehabilitation is an integral component of the management of patients with chronic lung disease, and results in decreased ventilatory require­ ments and respiratory rate during ambulation, thereby decreasing the risk of developing dynamic hyperinflation.

Hypertension in the young patient is an important challenge for many primary healthcare clinicians. Mangena et al.[7] review hyper­tension in patients under the age of 40 years. In SA one-third of the population (approximately 17 million persons) are hyper­ tensive and in adolescents and young adults (15 - 24 years) the incidence of hypertension is 10%. The aetiological profile remains the same as in the adult population, where 90% of cases are due to primary hypertension and the remaining 10% are secondary to renal parenchymal and renovascular disease, primary aldosteronism, medications such as oral contraceptives, cocaine or amphetamines, and rare causes such as coarctation of the aorta.

The management approach is opportunistic screening for raised blood pressure, pharmacotherapy, and alcohol and illicit drug cessation. Non-pharmacological approaches to lowering blood pressure include weight loss, exercise and avoidance of junk food.

The SA hypertension guidelines[8] have recently been updated, and provide comprehensive guidance on management. Referral of all young hypertensives for specialist evaluation is recommended.

Cupido et al.[9] review the diagnosis and management of valvular heart disease (VHD), a common but difficult problem in everyday clinical practice. Rheumatic heart disease, a sequela of streptococcal throat infection, remains a common cause of VHD in SA, and often has devastating complications in the young. The causes, clinical presentation, and ECG and chest radiographic features of the common valve lesions are described. Patients with symptomatic valve

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lesions should be referred for cardiological specialist assessment.

In most cases, medical therapy serves as a bridge to definitive mechanical or surgical therapy.

Echocardiography with colour flow and Doppler (not focusassessed transthoracic echocardiography (FATE) scans) plays a pivotal role in confirming the diagnosis and assessing the severity of the valve lesions and concomitant pulmonary hypertension, other valve lesions and haemodynamic consequences. Invasive testing with cardiac catheterisation is reserved for patients in whom there is a discrepancy between clinical findings and echocardiography.

Prosthetic valves are also discussed, including properties of the different types, and the role and management of anticoagulation in patients with VHD. Warfarin is the anticoagulant of choice in patients with metallic prosthetic valves, aiming for an international normalised ratio of 2.5 - 3.5.

Antiplatelet agents such as aspirin do not provide adequate protection and are not recommended without the use of anticoagulants.

It is our sincere hope that this series of articles on common cardiovascular conditions often encountered in primary care settings in SA and SSA will improve the care of patients with CVD. Furthermore, it is our wish that these articles clearly emphasise the minimum standards for management of these common cardiovascular disorders.

Gboyega Ogunbanjo Guest editor Department of Family Medicine and Primary Health Care, Sefako Makgatho Health Sciences University, Pretoria, South Africa profbanjo@gmail.com

Ntobeko A B Ntusi Guest editor Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa ntobeko.ntusi@gmail.com

1. Mathers CD, Fat DM, Inoue M, Rao C, Lopez AD. Counting the dead and what they died from: An assessment of the global status of cause of death data. Bull World Health Organ 2005;83:171-177.

2. Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management.

Circulation 2005;112:3547-3553. [http://dx.doi.org/10.1161/CIRCULATIONAHA.105.591792] 3. Mayosi BM, Flisher AJ, Lalloo UG, Sitas F, Tollman SM, Bradshaw D. The burden of noncommunicable diseases in South Africa. Lancet 2009;374:934-947. [http://dx.doi.org/10.1016/ S0140-6736(09)61087-4] 4. Ntusi NAB, Mayosi BM. Epidemiology of heart failure in sub-Saharan Africa. Expert Rev Cardiovasc Ther 2009;7:169-180. [http://dx.doi.org/10.1586/14779072.7.2.169] 5. Kraus S, Ogunbanjo G, Sliwa K, Ntusi NAB. Heart failure in sub-Saharan Africa: A clinical approach. S Afr Med J 2016;106(1):23-31. [http://dx.doi.org/10.7196/SAMJ.2016.v106i1.10325] 6. Coccia CBI, Palkowski GH, Schweitzer B, Motsohi T, Ntusi NAB. Dyspnoea: Pathophysiology and a clinical approach. S Afr Med J 2016;106(1):32-36. [http://dx.doi.org/10.7196/SAMJ.2016. v106i1.10324] 7. Mangena P, Saban S, Hlabyago KE, Rayner B. An approach to the young hypertensive patient. S Afr Med J 2016;106(1):36-38. [http://dx.doi.org/10.7196/SAMJ.2016.v106i1.10329] 8. Hypertension guideline working group: Seedat YK, Rayner BL, Veriava Y. South African hypertension practice guideline 2014. Cardiovasc J Afr 2014;25:288-294. [http://dx.doi.org/ 10.5830/ CVJA-2014-062] 9. Cupido BJ, Peters F, Ntusi NAB. An approach to the diagnosis and management of valvu足 lar heart disease. S Afr Med J 2016;106(1):39-42. [http://dx.doi.org/10.7196/SAMJ.2016. v106i1.10326]

S Afr Med J 2016;106(1):21-22. DOI:10.7196/SAMJ.2016.v106i1.10372

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Heart failure in sub-Saharan Africa: A clinical approach S Kraus,1 FCP (SA); G Ogunbanjo,2 MFamMed, FCFP (SA); K Sliwa,1,3 MD, PhD; N A B Ntusi,1 FCP (SA), DPhil Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa 2 Department of Family Medicine and Primary Health Care, Sefako Makgatho Health Sciences University, Pretoria, South Africa 3 Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, South Africa 1

Corresponding author: N A B Ntusi (ntobeko.ntusi@gmail.com)

Despite medical advances, heart failure (HF) remains a global health problem and sub-Saharan Africa (SSA) is no exception, with decompensated HF being the most common primary diagnosis for patients admitted to hospital with heart disease. In SSA the in-hospital mortality rate of decompensated HF is up to 8.3%. HF is a clinical syndrome that is caused by a diverse group of aetiologies, each requiring unique management strategies, highlighting the need for diagnostic certainty and a broad understanding of the complex pathophysiology of this condition. While there are a number of advanced medical, device and surgical interventions being tailored for HF internationally, the fundamental basic principles of HF management, such as patient education, effective management of congestion and initiation of diseasemodifying medical therapies, remain a challenge on our continent. This review addresses both the epidemiology of HF in SSA and principles of management that focus specifically on symptom relief, prevention of hospitalisation and improving survival in this population.

S Afr Med J 2016;106(1):23-31. DOI:10.7196/SAMJ.2016.v106i1.10325

Heart failure (HF) is a major public health challenge, accounting for significant morbidity and premature mortality globally, including in sub-Saharan Africa (SSA).[1] Owing to high prevalence and poor clin­ ical outcomes, HF is associated with recurrent hospitalisation and substantial healthcare expenditure.[2] In contrast to Western countries, where HF is considered a disease of older persons, in SSA it affects younger individuals.[1-3] Acute decompensated HF is the most common primary diagnosis for patients admitted to hospital with heart disease in SSA, and it is encountered at all levels of care.[1,3,4] The goals of the clinical approach to HF include: (i) correctly diag­ nosing the clinical syndrome of HF; (ii) identifying the underlying cause; and (iii) implementing an effective management strategy for symptom control, prolonging survival and reversing factors that predispose to precipitation of HF exacerbations.

Classification of HF

Definitions

Aetiology of HF in SSA

HF is a clinical syndrome of effort intolerance characterised by breathlessness and fatigue, due to structural and functional abnormal­ ities of the myocardium, resulting in salt and water reten­tion that is associated with neurohormonal adaptations, mainly in the reninangiotension-aldosterone system (RAAS).

Ejection fraction is the stroke volume (end-diastolic volume minus the end-systolic volume) divided by the end-diastolic volume. Systolic dysfunction is reduced contraction and emptying of the left ventricle, and diastolic dysfunction is impaired relaxation of the left ventricular myocardium resulting in impaired filling of the left ventricle.

Epidemiology of HF in SSA

Although there have been no population-based epidemiological studies of HF in Africa, there have been a number of hospital-based studies that give important insights into the incidence and prevalence of HF in SSA. In contrast to other parts of the world, non-ischaemic aetiologies are predominant, with hypertension, rheumatic heart disease (RHD) and cardiomyopathy accounting for two-thirds of cases of HF in hospitalised patients in the region.[1,5]

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Patients with HF can be divided into two categories: HF with reduced ejection fraction (HF-REF), and HF with preserved ejection fraction (HF-PEF) (Fig. 1). Although there is poor correlation between symptom severity and left ventricular ejection fraction (LVEF), the LVEF carries independent prognostic significance and is considered abnormal when <50%.[2] The diagnosis of HF-PEF is more difficult, and although LVEF is normal or only mildly reduced in this condition, relevant structural heart disease and/or diastolic dysfunction should be present to make this diagnosis. Importantly, HF-PEF is a diagnosis of exclusion where other non-cardiac causes for patients’ symptoms must be considered and discounted.[2] Patients with HF-PEF are older, more often female and obese, and more likely to have hypertension and atrial fibrillation, compared to those with HF-REF, and their prognosis appears to be better overall.[6]

HF is a final common pathway for a number of conditions affecting the heart, and it is useful to classify the aetiology according to the following diseases: (i) hypertension; (ii) primary myocardial disease that includes cardiomyopathies and myocarditis; (iii) valvular heart disease; (iv) ischaemic heart disease; (v) congenital heart disease; (vi) pericardial disease; and (vii) pulmonary hypertension (PH) (Table 1).

It is important to consider alternative causes for fluid retention (e.g. renal or liver disease) and pulmonary oedema (e.g. neurogenic) in the context of a structurally normal heart.

Pathophysiology

Damage to cardiac myocytes and the extracellular matrix after myocardial injury results in pathological remodelling of the left ventricle with dilatation, impaired contractility, perfusion, fibrosis and electrical instability. If left untreated, these changes worsen over time, exacerbated by additional myocardial injury from neurohormonal imbalance resulting from activation of the RAAS and the sympathetic nervous system, increased cytokine expression, immune and inflammatory changes, altered fibrinolysis and oxidative stress. Reduced cardiac output results in arterial

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Heart failure

HF-REF The diagnosis of HF-REF requires 3 conditions to be satisfied 1. Symptoms typical of HF 2. Signs typical of HF 3. Reduced LVEF <50%

Typical symptoms

HF-PEF

Specific signs

• Breathlessness • Orthopnoea • Paroxysmal nocturnal dyspnoea • Reduced exercise tolerance • Fatigue, tiredness, increased time to recover after exercise • Ankle swelling

• Elevated jugular venous pressure • Hepatojugular reflex • Third heart sound (gallop) • Laterally displaced apical impulse • Cardiac murmur

Less typical symptoms • Nocturnal cough • Wheezing • Weight gain (>2 kg/week) • Weight loss (advanced HF) • Bloated feeling • Loss of appetite • Confusion (elderly) • Depression • Palpitations • Syncope

Less specific signs

The diagnosis of HF-PEF requires 4 conditions to be satisfied 1. Symptoms typical of HF 2. Signs typical of HF 3. Normal (or mildly reduced) LVEF 4. Relevant structural heart disease (LV hypertrophy/ LA enlargement) and/or diastolic dysfunction

• Peripheral oedema • Pulmonary crepitations • Reduced breath sounds and dullness at lung bases (pleural effusion) • Tachycardia • Irregular pulse • Tachypnoea • Hepatomegaly • Ascites • Cachexia

Symptom status Compensated HF

Decompensated HF

Rendered asymptomatic with treatment NB: Although signs and symptoms may resolve, patients' underlying cardiac dysfunction may not, and they remain at risk for recurrent decompensation

Worsening HF symptoms NB: Look for precipitant (e.g. inadequate antifailure therapy, anaemia, infection, non-compliance, fluid intake, new arrhythmia, acute coronary syndrome, natural progression of disease, pregnancy, thyrotoxicosis, myocarditis, etc.)

Symptom severity: NYHA functional classification NB: symptom severity correlates poorly with ventricular function NYHA Class II (mild symptoms) Slight limitation in physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue, or palpitations NYHA Class I (asymptomatic) No limitation of physical activity.

Ordinary physical activity does not cause undue breathlessness, fatigue or palpitations

NYHA Class III (moderate, or moderate-severe symptoms) Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in undue breathlessness, fatigue and palpitations NYHA Class IV (severe symptoms) Unable to carry on any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort is increased

Fig. 1. Classification, clinical profile, grading of severity and natural history of heart failure (NYHA = New York Heart Association; LA = left atrial).

underfilling, leading to renal sodium and water retention via activation of the above-mentioned neuro-endocrine systems, in an attempt to restore arterial circulatory integrity (Fig. 2).[7]

Clinical presentation

The history is key in making the diagnosis of HF, grading symptom severity, and establishing not only the underlying

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cause but also identifying factors that may have precipitated decompensation (Table 2). The typical symptoms of HF are breathlessness, orthopnoea, paroxysmal

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Table 1. Diseases causing heart failure

Table 1. (continued) Diseases causing heart failure

Hypertension

Pericardial disease

Essential hypertension

Unknown

Secondary hypertension

Primary aldosteronism (Conn syndrome), Cushing syndrome, phaeochromocytoma, chronic kidney disease, renal artery stenosis, coarctation of the aorta, obstructive sleep apnoea

Pericarditis, pericardial effusion, pericardial constriction

Primary myocardial disease; cardiomyopathies and myocarditis HCM

DCM

ARVC RCM

Familial Sporadic Obesity, infants of diabetic mothers, amyloid, athletes Familial Non-familial Alcohol, pregnancy, tachymyopathy, thyrotoxicosis, myocarditis, nutritional (e.g. thiamine, selenium), drugs (e.g. anthracycline, cocaine), iron overload Familial Non-familial Familial Non-familial Endomyocardial fibrosis, radiation, amyloid, carcinoid

Unspecified cardiomyopathy

Familial (left ventricular non-compaction) Non-familial (Takotsubo cardiomyopathy)

Myocarditis

Infective Viral, HIV, bacterial, fungal, helminths, protozoa, rickettsia, spirochetes Toxic/hypersensitivity Anthracycline chemotherapy, alcohol, methamphetamines, other drugs Immune Lupus, rheumatoid arthritis, sarcoidosis

Pulmonary hypertension Pulmonary arterial hypertension

Idiopathic, heritable, drugs/toxins, associated with connective tissue disease, HIV, portal hypertension, CHD, schistosomiasis, chronic haemolytic anaemia, viral hepatitis

Pulmonary venoocclusive disease

Unknown

PH due to left heart disease

Rheumatic heart disease

PH due to lung disease and/or hypoxia

Post-tuberculous bronchiectasis, chronic obstructive pulmonary disease, occupational lung disease, interstitial lung disease

Chronic thromboembolic PH

Thrombophilia, deep venous thrombosis

PH with unclear and/ or multifactorial mechanism HCM = hypertrophic cardiomyopathy; DCM = dilated cardiomyopathy; ARVC = arrhythmogenic right ventricular cardiomyopathy; PH = pulmonary hypertension; CHD = congenital heart disease; RCM = restrictive cardiomyopathy.

pressure, a tender hepatomegaly and basal crackles indicate congestive HF. Additional features that can be found on examination are listed in Table 3.

Valvular heart disease Rheumatic heart disease, endocarditis (infective and non-infective), degenerative, myxomatous, congenital Ischaemic heart disease Atherosclerosis Spasm Atherothrombosis Coronary artery dissection Congenital heart disease Atrial septal defects, ventricular septal defects, transposition of the great vessels, tetralogy of Fallot, single ventricle, patent ductus arteriosis, etc.

Continued â&#x20AC;Ś

nocturnal dyspnoea, reduced effort tolerance, fatigue, and ankle swelling. The New York Heart Association (NYHA) functional class allows a grading of symptom severity in a standardised manner (Fig. 1).[2] Exploring past medical history, environmental exposures and family history may assist in deciphering a possible aetiology.

The physical examination findings may differ, depending on the underlying aetiology, but pedal oedema, raised jugular venous

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Idiopathic Infectious Viral, tuberculosis, fungal Non-infectious Uraemia, acute myocardial infarction, neoplasm, post-cardiac injury syndrome (trauma, cardiothoracic surgery), systemic auto-immune disease, mediastinal radiation

Diagnostic tests in suspected HF

The baseline investigations recommended in clinical assessment of HF are outlined in Table 4. The electrocardiogram (ECG) and echocardiogram are the most useful investigations, as they confirm the presence of underlying structural heart disease. The likelihood of a normal ECG in a patient presenting with HF is low, making it an extremely helpful screening tool.[2] It is recommended that all patients with a new diagnosis of HF undergo echocardiographic evaluation as it confirms the type of structural heart disease present and provides information on cardiac function.[2] Understanding the aetiology of HF is vital when determining definitive management strategies and prognosis. The pursuit of a correctable cause and identification of reversible factors are central to improving outcomes in these patients. Patients with unexplained HF, particularly those who are not improving on standard therapy, should be referred for specialist review where advanced investigations can be done to establish a diagnosis (Table 4).

Specific aetiologies of HF Hypertension

Hypertension has been reported as the dominant cause of HF in Africa, responsible for up to 46% of cases of HF in hospitalised patients.[4,5,8] Young hypertensive patients should be investigated for secondary causes of hypertension (Table 1). Standard anti-failure therapy and blood pressure control are the mainstays of therapy.

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Increased heart rate

Injury to cardiac myocytes and extracellular matrix Increased cytokine expression, inflammatory changes, apoptosis, oxidative stress, altered gene expression

Neurohormonal imbalance with activation of reninangiotension-aldosterone system and sympathetic nervous system Ventricular remodelling

Reduced arterial filling

Myocyte hypertrophy

Extracellular matrix remodelling leads to fibrosis and activation of collagenolytic enzymes that lead to chamber dilatation

Chamber dilatation, reduced contractility, fibrosis, reduced compliance of the left ventricle and electrical instability

Reduction in cardiac ouput

Sodium and water retention

Heart failure

Fig. 2. Pathophysiology of heart failure.

Cardiomyopathy

Cardiomyopathy accounts for 20 - 30% of heart failure in Africans.[1] Most commonly, patients who present with HF have a dilated phenotype, and potentially treatable causes for dilated cardiomyopathy should routinely be excluded (Table 1). Importantly, patients with other forms of cardiomyopathy (hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), and left ventricular non-compaction) presenting with HF should be referred for specialist review, as the management of these condi­ tions is complex and multi­ disciplinary.[9] Myocarditis should be considered in patients who present with cardiac symptoms and elevated cardiac biomarkers (tropo­nin T or I), ECG abnormalities and/or evidence of functional impairment on echocardiogram, where acute coronary syndrome has been excluded.[10,11] Forty-four percent of HIVassociated cardiomyopathy cases have evidence of myocarditis on endo­ myocardial biopsy, either as a result of HIV or secondary to opportunistic infections,[12] justifying anti­ retroviral therapy in these patients.

Valvular heart disease

In contrast to Western populations, where valvular heart disease is mainly degenerative, in SSA valvular heart disease is predominantly caused by rheumatic fever and infective endocarditis. Despite a reduction in RHD as a cause of HF in SSA in recent years, it remains endemic on our continent.[13] The mainstay of treatment for patients with symptomatic valvular heart disease is surgery, complemented by anti-failure therapy and secondary prevention of rheumatic fever with penicillin in RHD. All patients should be referred for evaluation for surgery.

Ischaemic heart disease

Ischaemic heart disease (IHD) is an uncom­ mon cause of HF in SSA, accounting for only 7.7 - 9% of cases.[3,4,8] Although IHD is considered uncommon among black Africans, there has been a notable rise in risk factors for atherosclerotic vascular disease in both urban and rural communities over the last few decades.[14] Patients presenting with ischaemic left ventricular dysfunction require rigorous risk factor management in addition to conventional HF therapy. Patients

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Table 2. Precipitating factors to consider in acute decompensated heart failure Anaemia Onset of a new arrhythmia (e.g. atrial fibrillation/flutter, supraventricular tachycardia, ventricular tachycardia) Hyperthyroidism Infection Pregnancy Infective endocarditis Recurrence of rheumatic fever Renal failure Malignant hypertension Myocardial infarction Non-compliance on maintenance therapy

with suspected coronary artery disease with ongoing symptoms of angina should be referred to a cardiologist for consideration for revascularisation therapy.[2,15]

Congenital heart disease

Although the prevalence of congenital heart disease (CHD) in SSA is considered to be the lowest in the world, it is likely that this

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reflects the paucity of readily available estimates and that the true number of individuals affected with CHD is grossly underestimated.

While CHD is an important cause of HF in children in SSA, it accounts for only a small percentage of cases of HF in adults.[16] CHD is riddled with complexity and requires management by experienced clinicians.[2]

Pericardial disease

Pericardial disease has a broad aetiology, but tuberculous pericarditis is the commonest cause of pericardial effusion, cardiac tampo足nade, and constrictive pericarditis in SSA, and carries a high mortality rate despite antituberculosis therapy, pericardiocentesis and peri足 cardectomy.[17]

Pulmonary hypertension

PH is a debilitating progressive disease that leads to right HF, and although little is currently known about the epidemiology of PH Table 3. Additional examination findings in heart failure Structural heart disease/ aetiology

Examination findings that could be present

Conditions that result in left ventricular dilatation and systolic dysfunction

Laterally displaced apex, a third heart sound, cardiac murmur

Pulmonary hypertension

Palpable and/or loud pulmonary component of the second heart sound, parasternal heave, pulmonary pathology, cyanosis, clubbing

Pericardial disease

Congenital heart disease

Hypertensive heart disease

in Africa, the reported incidence appears to be higher than in developed countries. The Pan African Pulmonary Hypertension Cohort study hopes to address the paucity of our knowledge.

Importantly, many risk factors associated with PH are endemic in SSA (Table 1).[18] PH (not associated with left heart pathology) requires investigation in the absence of significant pulmonary disease.

Management of HF

Although a significant portion of HF management falls within the realm of the general practitioner and general physician, it is important to be able to recognise which patients require specialist referral, particularly where there is diagnostic uncertainty and/or failure to improve, or deterioration, on anti-failure therapy.

The goals of treatment in patients with established HF are to: (i) relieve symptoms with the aim to improve quality of life and functional capacity; (ii) prevent recur足rent hospitalisations; and (iii) improve survival. In SSA these goals are achieved predominantly through patient education and medical therapy. Despite resource restraints, there is a role for advanced medical, device and surgical interventions, including orthotopic heart transplantation, for HF in SSA. It is important for

Table 4. Investigations in heart failure Baseline investigations

Elevated venous pressure, pedal oedema and ascites, unremarkable precordial examination and clear lung fields Pericardial rub may be present in pericarditis Hypotension, distended neck veins, muffled heart sounds, and pulsus paradoxus are suggestive of pericardial effusion with tamponade Diastolic knock may be present in constrictive pericarditis Depending on underlying cardiac lesion; cardiac murmur, signs of pulmonary hypertension, parasternal heave (right ventri足 cular hypertrophy), fixed split of the second heart sound (atrial septal defect), cyanosis, clubbing, surgical scars Radial-radial delay, radialfemoral delay may be present in coarctation of the aorta Blood pressure may be elevated, or normal in end-stage disease Pressure-loaded apex beat, loud aortic component of the second heart sound, fourth heart sound Evidence of target organ damage (retinopathy, proteinuria)

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Pro-BNP/BNP

Elevated in heart failure Not routinely required

Electrocardiogram

Heart rate and rhythm disturbances (atrial fibrillation/flutter) Electrical conduction abnormalities (left or right bundle branch block, heart block) Cardiac wall and/or chamber abnormalities (ventricular hypertrophy, atrial enlargement, Q-waves)

Chest radiograph

Cardiac size and shape (cardiomegaly) Pulmonary congestion Presence or absence of pulmonary pathology

Echocardiogram

Chamber size Systolic and diastolic function Ventricular wall thickness Valve morphology and function

Advanced investigations Cardiovascular magnetic resonance imaging

Cardiac structure, size and function Tissue characterisation Perfusion imaging Late gadolinium imaging (scar) Velocity-encoded flow imaging Defining anatomy in complex CHD

Cardiac computed tomography

Coronary artery angiography

Nuclear medicine imaging

Cardiac function (right and left ventricular ejection fraction) Myocardial perfusion studies

Angiography

Haemodynamic assessment Coronary artery angiography

Endomyocardial biopsy

Histological diagnosis

BNP = brain natriuretic peptide; CHD = congenital heart disease.

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Table 5. Patient education Patients should be well informed about: What heart failure is and why symptoms occur The underlying cause of their heart failure Prognosis The treatment options available to them Patients must be educated about: Medications, specifically the role of each drug used to treat heart failure Fluid retention and how to manage it (i.e. how to restrict fluids, monitor weight and adjust diuretic therapy accordingly) Remembering the names, doses and frequency of medication they are on or bringing the drugs to hospital with them Patients should be encouraged to make realistic decisions regarding: Their ability to work. Temporary or permanent disability grant applications should be made if anticipated time away from work is ≥6 months Financial implications related to loss of employment or added healthcare costs Legal issues in the event of their death Obtaining medical aid, where possible Patients are at increased risk of depression and may require referral for counselling or antidepressant drug therapy Exercise An active lifestyle should be encouraged Heart rate monitoring can be helpful in guiding patients with regard to safe levels of exercise Aiming for a maximum heart rate of (180 – age – 20) beats/minute during exercise is recommended Excessive alcohol consumption should be discouraged and excessive use of caffeine/stimulants avoided The dangers of illicit drug use should be addressed In women, pregnancy and contraception should be discussed: Contraception is recommended in all patients with cardiac disease Women need to be well informed of the dangers of pregnancy, particularly in the setting of LVEF <45%, pulmonary hypertension or mitral stenosis Patients should be informed that medication used to treat heart failure, such as ACE inhibitors, are teratogenic Patients who strongly desire a pregnancy, or who have fallen pregnant inadvertently, should be referred to a specialist centre for assessment Pregnant patients with underlying cardiac disease are at extremely high risk and require a multidisciplinary team (cardiologist, obstetrician, anaesthetist) to manage them throughout their pregnancy, during delivery and post partum

clinicians to familiarise themselves with the indica­tions and the availability of services.[2]

Patient education

It is the attending clinicians’ responsibility to inform patients about their condition.

Important aspects to consider are listed in Table 5.

Optimising medical therapy

Medical therapy consists of two components: (i) disease-modifying drugs consisting of three neurohormonal antagonists (angiotensinconverting enzyme (ACE) inhibitors (or angiotensin receptor blockers), beta-blockers, and mineralocorticoid receptor antagonists) that are fundamental in modifying the course of disease and improving survival;

and (ii) symptomatic therapies, such as diuretics and digoxin, that relieve congestion, reduce hospitalisation and improve quality of life.

Fig. 3 illustrates an approach for the medi­ cal management of HF. The first step is to manage and alleviate congestion. Diseasemodifying drugs should be introduced at recommended starting doses and titrated up to maximum tolerated doses over a number of weeks (Table 6).[2] Digoxin has been shown to relieve symptoms and reduce hospitalisations,[19] but is associated with an increase in mortality in HF patients.[20] Current guidelines recommend low-dose digoxin in selected patients who remain symptomatic despite optimal ACE inhibitor and betablocker therapy. Hypokalaemia and renal failure predispose patients to digoxin toxicity,

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and its use is contraindicated in these circumstances.[21] The prognosis of acute decompensated HF remains poor, with greater severity of congestion being associated with worse outcomes. Acute decompensated HF is asso­ ciated with an in-hospital mortality rate of up to 8.3% in Africa.[8] Fluid retention and congestion are responsible for 90% of HF hospital admissions, and even with diuretic therapy approximately 40% of patients are discharged with unresolved congestion.[22] The mainstay therapy for the treatment of congestion is loop diuretics. Diuretic resistance is the failure to adequately control salt and water retention despite appropriate dose escalation of loop diuretics. The doseresponse curve for loop diuretics shifts in HF, resulting in the need for increased doses of the drug to achieve a therapeutic effect; thus inadequate dosing must be differentiated from diuretic resistance.

Infrequent dosing can result in rebound salt and water retention, which can be addressed by increasing the frequency of dosing or changing to a continuous intravenous infusion.

Strategies for overcoming diuretic resis­ tance include the addition of thiazide diuretics and/or spironolactone. Importantly, diuretic combinations can result in severe volume depletion and electrolyte disturbances, and should only be used in circumstances where volume status and electrolytes can be monitored. RAAS activation plays an important role in sodium and water retention by increasing distal sodium reabsorption in the kidney. Introducing ACE inhibitors is crucial in managing congestion. The challenge is maintaining adequate arterial blood pressure, as low blood pressure drives plasma renin activity and further activation of RAAS (Fig. 4).[22]

Advanced medical, device and surgical interventions

Heart rate reduction improves clinical out­comes in HF. Beta-blocker dosage should be titrated to maintain a resting heart rate <75 beats/minute.

In instances where patients are unable to tolerate increased doses of beta-blockers, ivabradine can be considered. Ivabradine inhi­bits the If channel in the sinus node and can be used to slow the heart rate in patients in sinus rhythm.[2] Indications for device and surgical interventions are listed in Table 7.[2,23]

Conclusion

HF is a common condition that is caused by a diverse group of aetiologies, representing unique disease entities that require different management strategies. It is for this reason

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Symptoms and signs of congestion

No symptoms and signs of congestion

Diuresis (Fig. 4)

Introduce disease-modifying drugs (Table 6)

Loop diuretics + If renal function is normal, add mineralocorticoid receptor antagonist In cases of diuretic resistance, add thiazide diuretic

ACE inhibitors (or ARB) and beta-blockers can be introduced one at a time, or simultaneously, at low doses. Titrate to maximum tolerated doses over a number of weeks + Mineralocorticoid receptor antagonist

Monitor fluid status and electrolytes

Monitor renal function and potassium

Add low-dose ACE inhibitors (or ARB) Slowly titrate to maximum tolerated dose

Once congestion has resolved, introduce beta-blockers at low dose Slowly titrate to maximum tolerated dose

Persistent symptoms of heart failure NYHA Class II - IV

Consider the following: • Has the underlying aetiology of the heart been adequately addressed?

• Is the patient still congested? Ask about fluid intake • Is the patient compliant on medication? Ask about side-effects • Is the patient on optimal (tolerated) doses of ACE inhibitors, beta-blockers and mineralocorticoid antagonists?

• Are there any exacerbating factors or an alternative pathology causing these symptoms? (Table 2) e.g. anaemia, new arrhythmia, ischaemia, infection, thyroid disease, pregnancy, renal impairment, autoimmune conditions, lung disease, depression, diabetes • Consider low-dose digoxin if renal function is normal

ASSESSMENT BY CARDIOLOGIST CONSIDERATION FOR DEVICE AND/OR SURGICAL INTERVENTION, INCLUDING TRANSPLANTATION (Table 7) Sinus rhythm and heart rate ≥75 beats/minute → consider ivabradine Refractory heart failure, QRS duration >120 ms and LVEF ≤35% → consider cardiac resynchronisation therapy

Fig. 3. Approach to management of heart failure (ARB = angiotensin receptor blocker).

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Heart failure Reduced cardiac output

Loop diuretics

Activation of RAAS

Inhibition of the Na+/CI-/K + co-transporter, resulting in reduced sodium and chloride reabsorption proximally (kidney)

Prostaglandin synthesis

ACE inhibitors

Vascular smooth muscle relaxation and vasodilatation

Secondary hyperaldosteronism

Thiazide diuretics

Increased sodium delivery distally (kidney) Natriuresis and diuresis

Mineralocorticoid receptor antagonists Increased absorption of sodium distally (kidney)

Sodium and water retention

Fig. 4. Mechanisms of action of pharmacotherapy used in heart failure management.

Table 6. Disease-modifying drugs used in heart failure[2] Drugs

Level of evidence

Starting dose

Target dose

Recommendation

6.25 mg 3 × /day 2.5 mg 2 × /day 2.5 - 5.0 mg daily 2.0 mg daily 2.5 mg daily 0.5 mg daily

50 mg 3 × /day 10 - 20 mg 2 × /day 20 - 35 mg daily 4.0 mg daily 5.0 mg 2 × /day 4.0 mg daily

Recommended, in addition to beta-blockers, for all patients with LVEF ≤40% to reduce risk of HF hospitalisation and premature death

IA

1.25 mg daily 3.125 mg 2 × /day 12.5 - 25 mg daily

10 mg daily 25 - 50 mg 2 × /day 200 mg daily

Recommended, in addition to ACE inhibitors, for all patients with LVEF ≤40% to reduce risk of HF hospitalisation and premature death

IA

32 mg daily 160 mg 2 × /day 150 mg daily 80 mg daily

Recommended as an alternative to ACE inhibitors, in patients with LVEF ≤40% to reduce risk of HF, hospitalisation and premature death

IA

25 mg daily

25 - 50 mg daily

IA

25 mg daily

50 mg daily

Recommended for all patients with persisting symptoms and an LVEF ≤35% despite treatment with an ACE inhibitor and a betablocker to reduce risk of HF hospitalisation and premature death

ACE inhibitors Captopril Enalapril Lisinopril Perindopril Ramipril Trandolapril Beta-blockers Bisoprolol Carvedilol Metoprolol succinate

Angiotensin II receptor blockers Candesartan Valsartan Losartan Telmisartan

4 mg or 8 mg daily 40 mg 2 × /day 50 mg daily 20 mg daily

Mineralocorticoid receptor antagonists Spironolactone Eplerenone

that diagnostic certainty is as important as treating the clinical syndrome of HF. Effective diuresis and complete resolution

of congestion is key in improving symptoms and functional capacity, reducing the need for recurrent hospitalisation, increasing

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Table 7. Device and surgical interventions in heart failure[2,23] Intervention

Indication

ICD

Secondary prevention Survivors of cardiac arrest or patients with sustained symptomatic ventricular tachycardia, irrespective of LVEF Good functional status Expected survival >1 year Primary prevention (limited availability in SSA) LVEF ≤35% Symptomatic (NYHA Class II - III) despite ≥3 months on optimal medical therapy Increased risk of SCD in conditions such as ARVC and HCM

CRT

Cardiac resynchronisation therapy should be considered in patients who fulfil the following criteria Typical LBBB (QRS ≥120 ms) Persistent symptoms despite ≥3 months of optimal medical therapy NYHA Class III/IV (ambulatory) LVEF ≤35% and an expected survival >1 year Right bundle branch block and prolonged PR interval are predictors of non-favourable outcomes

Mechanical circulatory support Limited availability in SSA Drug-refractory acute circulatory collapse and at immediate risk of death To sustain life, as a bridge to decision/candidacy for transplantation or as a bridge to transplantation, recovery or destination therapy Heart transplantation

End-stage heart failure with severe symptoms, a poor prognosis, and no remaining alternative treatment option Motivated, well-informed, and emotionally stable Capable of complying with the intense treatment required postoperatively Contraindications to transplantation Active infection, significant comorbidities (e.g. severe peripheral vascular disease, cerebrovascular disease, renal failure, liver disease, systemic multiorgan disease), recurrent thromboembolism, unhealed peptic ulcer, current alcohol or drug abuse, emotional/psychiatric instability, cancer within the previous 5 years High, fixed pulmonary vascular resistance (>4 - 5 Wood units and mean transpulmonary gradient >5 mmHg)

ICD = implantable cardioverter-defibrillator; CRT = cardiac resynchronisation therapy; SCD = sudden cardiac death; HCM = hypertrophic cardiomyopathy.

Funding. This manuscript is not funded. Dr N A B Ntusi acknowledges support from the National Research Foundation and Medical Research Council of South Africa.

References 1. Ntusi NB, Mayosi BM. Epidemiology of heart failure in sub-Saharan Africa. Expert Rev Cardiovasc Ther 2009;7(2):169-180. [http://dx.doi.org/10.1586/14779072.7.2.169] 2. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14(8):803-869. [http://dx.doi. org/10.1093/eurjhf/hfs105] 3. Sliwa K, Wilkinson D, Hansen C, et al. Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): A cohort study. Lancet 2008;371(9616):915922. [http://dx.doi.org/10.16/S0140-6736(08)60417-1] 4. Damasceno A, Mayosi BM, Sani M, et al. The causes, treatment, and outcome of acute heart failure in 1006 Africans from 9 countries. Arch Intern Med 2012;72(18):1386-1394. [http://dx.doi.org/10.1001/ archinternmed.2012.3310] 5. Sliwa K, Mayosi BM. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa. Heart 2013;99(18):1317-1322. [http://dx.doi.org/10.1136/ heartjnl-2013-303592] 6. Meta-analysis Global Group in Chronic Heart Failure. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: An individual patient data meta-analysis. Eur Heart J 2012;33(14):1750-1757. [http://dx.doi.org/10.1093/eurheartj/ehr254] 7. McMurray JJ. Clinical practice. Systolic heart failure. N Engl J Med 2010;362(3):228-238. [http:// dx.doi.org/10.1056/NEJMcp0909392] 8. Callender T, Woodward M, Roth G, et al. Heart failure care in low- and middle-income countries: A systematic review and meta-analysis. PLoS Med 2014;11(8):1001699. [http://dx.doi.org/10.10.1371/ journal.pmed.1001699] 9. Kraus S, Ntusi NA. Specialist multidisciplinary hypertrophic cardiomyopathy clinics: Should they be the standard of care? Intern Med J 2015;45(3):237-238. [http://dx.doi.org/10.10.1111/imj.12686] 10. Cooper LT Jr, Keren A, Sliwa K, Matsumori A, Mensah GA. The global burden of myocarditis. Part 1.

A systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study.

Global Heart 2014;9(1):121-129. [http://dx.doi.org/10.1016/j.gheart.2014.01.007]

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11. Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. J Am Coll Cardiol 2012;59(9):779792. [http://dx.doi.org/10.1016/j.jacc.2011.09.074] 12. Shaboodien G, Maske C, Wainwright H, et al. Prevalence of myocarditis and cardiotropic virus infection in Africans with HIV-associated cardiomyopathy, idiopathic dilated cardiomyopathy and heart transplant recipients: A pilot study: Cardiovascular topic. Cardiovasc J Afr 2013;24(6):218-223. [http://dx.doi.org/10.5830/cvja-2013-039] 13. Sliwa K, Carrington M, Mayosi BM, Zigiriadis E, Mvungi R, Stewart S. Incidence and characteristics of newly diagnosed rheumatic heart disease in urban African adults: Insights from the Heart of Soweto study. Eur Heart J 2010;31(6):719-727. [http://dx.doi.org/10.1093/eurheartj/ehp530] 14. Mayosi BM, Flisher AJ, Lalloo UG, Sitas F, Tollman SM, Bradshaw D. The burden of noncommunicable diseases in South Africa. Lancet 2009;374(9693):934-947. [http://dx.doi.org/10.1016/ S0140-6736(09)61087-4] 15. Task Force on Myocardial Revascularization of the European Society of, Cardiology, et al. Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2010;38(Suppl):S1-S52. [http://dx.doi. org/10.1016/j.ejcts.2010.08.019] 16. Zuhlke L, Mirabel M, Marijon E. Congenital heart disease and rheumatic heart disease in Africa: Recent advances and current priorities. Heart 2013;99(21):1554-1561. [http://dx.doi.org/10.1136/ heartjnl-2013-303896] 17. Mayosi BM, Ntsekhe M, Bosch J, et al. Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis. N Engl J Med 2014;371(12):1121-1130. [http://dx.doi.org/10.1056/NEJMoa1407380] 18. Thienemann F, Dzudie A, Mocumbi AO, et al. Rationale and design of the Pan African Pulmonary hypertension Cohort (PAPUCO) study: Implementing a contemporary registry on pulmonary hypertension in Africa. BMJ Open 2014;4(10):e005950. [http://dx.doi.org/10.1136/bmjopen-2014-005950] 19. Digitalis Investigation. The effect of digoxin on mortality and morbidity in patients with heart failure.

N Engl J Med 1997;36(8):525-533. [http://dx.doi.org/10.1056/NEJM199702203360801] 20. Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: A systematic review and meta-analysis of the literature. Eur Heart J 2015;36(28):1831-1838. [http://dx.doi.org/10.1093/eurheartj/ehv143] 21. Mkoko P, Mokhele N, Ntsekhe M, Ntusi NA, Digoxin therapy in the modern management of cardiovascular disease: An unusual but serious complication. S Afr Med J 2015;105(2):154. [http:// dx.doi.org/10.7196/samj.8638] 22. Felker GM, Mentz RJ. Diuretics and ultrafiltration in acute decompensated heart failure. J Am Coll Cardiol 2012;59(24):2145-2153. [http://dx.doi.org/10.1016/j.jacc.2011.10.910] 23. Dickstein K, Vardas PE, Auricchio A, et al. 2010 focused update of ESC Guidelines on device therapy in heart failure: An update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC Guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur J Heart Fail 2010;12(11):1143-1153. [http://dx.doi.org/10.1093/eurjhf/hfq192]

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ARTICLE

Dyspnoea: Pathophysiology and a clinical approach C B I Coccia,1* MB ChB; G H Palkowski,1* MB ChB; B Schweitzer,2 MB ChB, FCFP (SA); T Motsohi,2 MB ChB, FCFP (SA); N A B Ntusi,1 FCP (SA), DPhil Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa 2 Division of Family Medicine, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa *Joint first author 1

Corresponding author: N A B Ntusi (ntobeko.ntusi@gmail.com)

Dyspnoea, also known as shortness of breath or breathlessness, is a subjective awareness of the sensation of uncomfortable breathing. It may be of physiological, pathological or social origin. The pathophysiology of dyspnoea is complex, and involves the activation of several pathways that lead to increased work of breathing, stimulation of the receptors of the upper or lower airway, lung parenchyma, or chest wall, and excessive stimulation of the respiratory centre by central and peripheral chemoreceptors. Activation of these pathways is relayed to the central nervous system via respiratory muscle and vagal afferents, which are consequently interpreted by the individual in the context of the affective state, attention, and prior experience, resulting in the awareness of breathing. The clinical evaluation and approach to the management of dyspnoea are directed by the clinical presentation and underlying cause. The causes of dyspnoea are manifold, and include a spectrum of disorders, from benign to serious and life-threatening entities. The pathophysiology, aetiology, clinical presentation and management of dyspnoea are reviewed.

S Afr Med J 2016;106(1):32-36. DOI:10.7196/SAMJ.2016.v106i1.10324

Dyspnoea, often known as shortness of breath or breathlessness, is a common and often distressing symp­ tom reported by patients, and accounts for nearly half of hospital admissions in tertiary centres.[1] As dyspnoea is a symptom and not a sign, the patient experiences it subjectively. Dyspnoea varies greatly among individuals exposed to the same stimuli or with similar pathologies. This differential experience of the condition emanates from interactions among multiple physiological, psychological, social and environmental factors that induce secondary physiological and behavioural responses.[2] Dyspnoea not only manifests with respiratory difficulty that embarrasses and limits the patient, but often presents a diagnostic challenge for the busy clinician. In the evaluation and management of a patient with breathlessness, a comprehensive understanding of the pathophysiology of dyspnoea is essential. A structured clinical approach based on a thorough medical history and clinical examination is key to making the correct diagnosis. Special investigations play secondary and supplementary roles in the diagnosis; they are guided by the history and examination and may be useful in confirming the clinical suspicion of the physician.

Disappointingly for both doctors and patients, even when the cause of dyspnoea has been determined, the symptoms may persist despite optimal therapy.

Definition

Dyspnoea is defined as ‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity’, and may either be acute or chronic.[1] The distinct sensations often reported by patients include effort/work of breathing, chest tightness, and air hunger (a feeling of not enough air on inspiration). Dyspnoea should be assessed by the intensity of these sensations, the degree of distress involved, and its burden or impact on instrumental activities of daily living. Dyspnoea is a normal symptom of heavy exertion but may be pathological if it occurs in unexpected situations. It derives from interactions among

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multiple physiological, psychological, social, and environmental factors, and may induce secondary physiological and behavioural responses. Its management typically depends on the underlying cause.

Pathophysiology

Dyspnoea is a complex symptom that arises from physiological impairment and alerts one to the possibility of threatened homeo­ stasis. The discomfort primarily occurs as a result of either cardiovascular or respiratory system compromise, but may also be attributed to metabolic derangements, neuromuscular disorders or psychogenic conditions. The condition is perceived as increased respiratory work/effort, tightness, or air hunger, which are caused by pulmonary ventilation not matching the drive to breathe.[1,3] The dissociation between pulmonary ventilation and respiratory drive arises from a mismatch between afferent receptors in the airways, lungs and chest wall structures, and central respiratory motor activity. Physiological pathways lead to shortness of breath via specific acid-sensing ion channels, mechanoreceptors and lung receptors located in different zones of the respiratory apparatus. Chemoreceptors in the carotid bodies and medulla supply information with regard to the blood gas levels of O2, CO2 and H+. In the lungs, juxtacapillary receptors are sensitive to pulmonary interstitial oedema, while stretch receptors signal bronchoconstriction. Muscle spindles in the chest wall signal the stretch and tension of the respiratory muscles. Efferent signals are the motor neuronal signals descending to the respiratory muscles, the most important being the diaphragm.

Three main components contribute to dyspnoea: afferent signals, efferent signals, and central information processing. The central processing in the brain compares the afferent and efferent signals and dyspnoea results when a mismatch occurs between the two, such as when the need for ventilation (afferent signalling) is not being met by physical breathing (efferent signalling). The afferent receptors allow the brain to assess whether the efferent or motor commands to the ventilatory muscles are effective, meeting

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the required demands of airway pressure, air flow, and/or lung movement. When these respond inappropriately to the command, the intensity of the dyspnoea increases.[4] The sensory cortex is simultaneously activated when motor signals are sent to the chest wall, resulting in the conscious sensation of muscular effort and breathlessness.[5] There is also a strong psychological component to dyspnoea, as some people may become aware of their breathing in such circumstances but not experience the distress typical of the condition.

Table 1. Causes of dyspnoea System

Pathology

Cardiac

Arrhythmia Atrial fibrillation Sinus tachycardia Sick sinus syndrome/bradycardia Ventricular tachycardia/fibrillation Myocardial Cardiomyopathy Hypertensive heart disease Congestive cardiac failure Myocarditis Coronary vessels Myocardial ischaemia Acute myocardial infarction Chronic ischaemic myocardial dysfunction Valvular Aortic stenosis/regurgitation Mitral stenosis/regurgitation Tricuspid regurgitation/stenosis Pulmonic regurgitation/stenosis Pericardial Pericarditis Pericardial effusion Pericardial tamponade Pericardial constriction Congenital Atrial septal defect Tetralogy of Fallot

Respiratory

Obstructive Asthma Chronic obstructive pulmonary disease Bronchitis Bronchiectasis Bronchiolitis obliterans Intrabronchial neoplasm Tracheomalacia Obstructive sleep apnoea Restrictive Interstitial lung disease Sarcoidosis Kyphoscoliosis Obesity Pleural disease/effusion Pneumothorax Alveolar Bronchoalveolar carcinoma Tuberculosis Bacterial pneumonia Pneumocystis pneumonia Eosinophilic pneumonitis Aspiration Hypersensitivity pneumonitis Interstitial Drugs (methotrexate, amiodarone) Radiation therapy Passive congestion/pulmonary oedema Lymphangitic spread of malignancy Vascular Pulmonary embolus (acute/chronic) Idiopathic pulmonary hypertension

Causes of dyspnoea

Dyspnoea is primarily of respiratory or cardiac origin, with almost 90% of all cases being due to asthma, heart failure, myocardial ischaemia, chronic obstructive pulmonary disease (COPD), pneu­ monia, and psychogenic disorders.[6] In the South African (SA) context, where there is a high burden of HIV infection, a broader differential needs to be incorporated that includes infectious diseases such as tuberculosis, Pneumocystis pneumonia, aspergillosis and acute infective exacerbations of bronchiectasis. Furthermore, due to the high prevalence of interpersonal violence in SA, a significant proportion of patients presenting to emergency centres have dyspnoea related to trauma, with the cause dependent on the mechanism of injury and organ system involved. Table 1 highlights important causes of dyspnoea.

Clinical evaluation

A patient presenting with dyspnoea often complains of difficulty breathing or chest discomfort and may present to a general practitioner, community health centre or emergency centre. A problematic aspect of the clinician-patient interface is the complicated use of language in articulating the patient’s experience, which may be a manifestation of biological, social and psychological challenges facing an individual.

A biopsychosocial classification of dyspnoea follows the acronym DYSPNEA: D: Depression Y: Yearning for peace, forgiveness, etc.

S: Social issues P: Physical problems, pain N: Non-acceptance or spiritual/existential distress E: Economic or financial distress A: Anxiety or anger.

There is always a certain degree of concern with regard to understanding the different types of dyspnoea that stem from different neurophysiological pathways (sequentially or in parallel) and viewing them as socioculturally diverse ways of describing the same neurophysiological phenomenon.

In the initial assessment/triage it is essential to establish the degree of urgency by determining the duration of the dyspnoea, the severity of the symptoms and whether the condition is acute or chronic. It is imperative to detect warning signs that require immediate attention, as the patient may have a life-threatening cause of dyspnoea. These ‘red flags’ include hypotension, a high respiratory rate, an altered mental status, hypoxia, cyanosis, stridor, breathing effort without air movement, chest wall retractions, tracheal deviation and unilateral breath sounds (underlying pneumothorax), and an unstable arrhythmia (Table 2).[7] The presence of any of these mandates emergency assessment of the patient, including supplementation of oxygen and consideration of endotracheal intubation.

With regard to the clinical evaluation, there are two major categories of patients: those with new onset of breathing discomfort for whom the underlying cause of dyspnoea has not yet been determined; and those with known cardiovascular,

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Table 1. (continued) Causes of dyspnoea

Table 2. ‘Red flags’ for serious forms of dyspnoea

System

Pathology

Hypotension

Haematological

Anaemia Methaemoglobinaemia Sulfhaemoglobinaemia Carbon monoxide poisoning Thrombotic thrombocytopenic purpura

Respiratory rate >40 breaths/minute

Ascites Gastro-oesophageal reflux disease Peptic ulcer disease

Stridor

Metabolic

Thyroid disease Cushing’s syndrome

Unstable arrhythmia

Psychogenic

Anxiety and panic attacks

Neurological

Amyotropic lateral sclerosis Polio Other acute viral anterior horn infections Guillain-Barré syndrome Myasthenia gravis Paraneoplastic myasthenia syndrome

Physiological

Exercise Normal ageing Deconditioning Obesity

Uncommon causes

Pulmonary contusion Angio-oedema Trauma Foreign body aspiration Retrosternal goitre Vocal cord dysfunction Pulmonary hypertension Hepatopulmonary syndrome Pulmonary arteriovenous malformations Mesothelioma Pleuritis Haemothorax Cardiac drugs Superior vena cava syndrome Pulmonary leukostasis Tetanus Botulism Anaphylaxis

Abdominal

Altered mental status Hypoxia Cyanosis Breathing effort without air movement Tracheal deviation with unilateral breath sounds

Medical history

respiratory, or neuromuscular disease who are experiencing worsening symptoms. For the former, evaluation is focused on discovering an underlying abnormality or diagnosis; for the latter, the goal is to discern whether there is deterioration of a known disorder or emergence of a new problem. In a patient with new onset of dyspnoea, the history and physical examination remain the mainstay of diagnostic evaluation.

Among those for whom diagnosis remains elusive, specialist referral should be considered (e.g. to a pulmonologist, cardio­ logist, or multidisciplinary dyspnoea clinic), which will proba­ bly lead to identification and successful management of the underlying cause. Psychogenic dyspnoea may be a significant challenge for primary care physicians. The typical scenario is a young person without a notable medical history, with normal oxygen saturation in room air, who complains of breathlessness and tingling around the mouth, fingers and toes. Psychogenic dyspnoea responds well to reassurance (and acknowledgement of the underlying problem).

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A complete history should emphasise any coexisting cardiac and pulmonary comorbidities and symptoms, as the cardiac and pulmonary systems comprise the most common causes of dyspnoea. Moreover, the history should determine the character, onset, duration, associations, severity, relation to exertion and any exacerbating/relieving factors.

The presence of cough may imply asthma or chest infection, and cough combined with a change in the appearance of the sputum may be related to an exacerbation of COPD. Chest pain during dyspnoea may be caused by cardiac conditions or pleural disease (the description of the quality of the chest pain is useful). Pleuritic chest pain results from pericarditis, pneumonia, pulmonary embolism, pneumothorax, or pleuritis. Chest pain almost always occurs in spontaneous pneumothorax, while dyspnoea is the second most common symptom. Anginal chest pain accompanied by shortness of breath may signify ischaemia associated with left ventricular dysfunction. Sudden shortness of breath at rest suggests pulmonary embolism or pneumothorax. Spontaneous pneumothorax should be considered in patients with COPD, cystic fibrosis, or AIDS. A history of scuba diving may suggest barotrauma. Vehicle airbag trauma has been reported to cause pneumothorax. The clinician should note a history of penetrating or non-penetrating trauma. Severe respiratory distress continuing over 1 - 2 hours suggests congestive cardiac failure (CCF) or asthma. The presence of comorbidities such as hypertension, hyperlipidaemia, diabetes mellitus, and obstructive sleep apnoea increase the likelihood of developing CCF. Elements of the social history include smoking, alcohol use and illicit drug use. A family history of coronary artery disease, dilated cardiomyopathy, and sudden cardiac death may provide important information regarding the possible aetiology of CCF. Dyspnoea may also present as orthopnoea (breathlessness on assuming the supine position) and paroxysmal nocturnal dyspnoea (attacks of breathlessness that occur at night and may awaken the sleeping patient). Patients with CCF tend to increase the number of pillows on which they sleep to avoid symptoms of orthopnoea: the number of pillows is a marker of the severity of heart failure. Advanced or end-stage heart failure can present with an abnormal pattern of breathing characterised by periods of hyperapnoea and CheyneStokes respiration, which is a marker of poor prognosis.

Non-respiratory causes of dyspnoea should be considered, including anaemia, acidosis and drug poisoning. The attending physician should enquire about indigestion or dysphagia, which may indicate gastro-oesophageal reflux or aspiration. Anxiety symptoms may imply psychogenic causes of dyspnoea, but organic causes should always be excluded first: a diagnosis of hyperventilation syndrome cannot be made before organic disease is ruled out.

Medication use is another important consideration, especially drugs with potential adverse cardiopulmonary effects (e.g. betablockers, eyedrops). Drugs may cause haemolytic anaemia (quinidine

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and penicillin); methaemoglobinaemia (nitrites and nitrates); sulf­ haemoglobinaemia (dapsone and sulfonamides); and acute or chronic fibrosis (nitrofurantoin or amiodarone). Aspirin sensitivity is a cause of asthma in a significant number of patients.

Clinical examination

General appearance and vital signs. To determine the severity of dyspnoea, one should carefully observe respiratory effort, use of accessory muscles, mental status, and ability to speak. Pulsus paradoxus may exist in COPD, asthma, cardiac tamponade or pericardial constriction. Stridor indicates upper airway obstruction.

It may be necessary to obtain a rectal temperature to detect fever, as oral airflow may decrease the oral temperature.

Extremities. The lower extremities should be inspected for oedema and any signs suggestive of deep venous thrombosis, and the digits examined for clubbing or cyanosis.

Neck. Distention of the neck veins may imply cor pulmonale caused by severe COPD, CCF, or cardiac tamponade. The thyroid size should be assessed, as CCF may result from hyper- or hypothyroidism. The trachea should be central and the presence of stridor excluded.

Cardiac and pulmonary disease. Palpate the chest for sub­ cutaneous emphysema and crepitus, and percuss for dullness, an indication of consolidation or effusion. Hyper-resonance on percussion suggests pneumothorax or bullous emphysema. The clinician should always auscultate the heart and lungs for murmurs or extra heart sounds; absent breathing sounds may be consistent with pneumothorax or pleural effusion. Wheezing is usually consistent with obstructive lung disease, but can be caused by pulmonary oedema or pulmonary embolism. Rales are present in pulmonary oedema, pneumonia or restrictive lung pathology. A rapid or irregular pulse may signify a dysrhythmia. An S3 gallop suggests left ventricular systolic dysfunction in CCF, while an S4 gallop may indicate left ventricular dysfunction in hypertension or ischaemia. A loud P2 may be heard in patients with pulmonary hypertension or cor pulmonale. Murmurs can be an indirect sign of CCF or valvular heart disease, and distant heart sounds can point to cardiac tamponade.

Abdomen. The clinician should look for hepatomegaly and ascites.

Assessing for hepatojugular reflux is a valid bedside maneouvre in the diagnosis of CCF in patients with acute dyspnoea.

Relevant special investigations

Chest radiography (CXR). This has a great potential in aiding the diagnosis of many lung disorders that cause acute dyspnoea and chest pain. The physician should be aware that the sensitivity of CXR is rather low in the diagnosis of pneumothorax, pleural effusion and pulmonary oedema, particularly in bedside-acquired images.

Nevertheless, thoracic imaging by means of CXR plays a crucial role in the diagnostic process, because it allows a panoramic view, at the same time being cost-effective, safe and time saving.

Electrocardiography (ECG). In African patients presenting with heart failure common causes include hypertension (43.2%), idio­ pathic dilated cardiomyopathy (21.0%), rheumatic heart disease (17.2%), and ischaemic heart disease (7.7%).[8] The ECG is unlikely to be normal in the presence of structural heart disease. However, in black patients, ECG abnormalities can occur among those without heart disease; up to 13% of these patients may present with significant Q waves in the absence of myocardial ischaemia.

Cardiopulmonary exercise tests. These can be particularly helpful in the evaluation of patients in whom an initial evaluation is unrevealing or in those in whom multiple problems may contribute to dyspnoea. Identifying non-respiratory causes of exercise limitation (e.g. leg discomfort, fatigue or weakness) is important, because these often coexist with breathing discomfort.

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The D-dimer. This is a component of the evaluation of patients with suspected pulmonary embolism. As with many screening tests, the sensitivity of D-dimer is much greater than its specificity, and its positive predictive value is poor. Therefore, its primary value is to rapidly identify patients with a low probability of pulmonary embolism, particularly in outpatient settings. There is evidence that its negative predictive value is poor in hospitalised patients, especially after several days of hospitalisation, or in patients >60 years of age.

Brain natriuretic peptide (BNP). Routine use of BNP in all patients presenting with acute dyspnoea is not recommended. In acute-care settings such as an emergency department, the sensitivity of BNP or N-terminal (NT)-pro-BNP is substantially higher than its specificity, and its use is greatest for ruling out heart failure as a cause of acute dyspnoea in patients with a low to intermediate pretest probability of heart failure. In general, heart failure is unlikely at BNP values <100 pg/mL and is very likely at BNP values >500 pg/mL. Point-of-care ultrasound scans and echocardiography. These may aid clinicians in the diagnosis of acute cardiogenic pulmonary oedema. In patients with a moderate to high pretest probability, a point-of-care ultrasound/echocardiogram can be used to strengthen an emergency physician’s working diagnosis of acute cardiogenic pulmonary oedema. In patients with a low pretest probability, a negative study can almost exclude the possibility of the condition.

A clinical decision rule (pulmonary embolism rule-out criteria).

To exclude pulmonary embolism among patients with a low suspicion a clinical decision rule has been developed.[9] Pulmonary embolism can also be safely excluded on the basis of a Wells score of ≤4, combined with a negative qualitative point-of-care D-dimer test result.[10]

Management

In a patient with dyspnoea, the initial focus should be on optimising treatment of the underlying disease and relieving symptoms.

Supplemental oxygen. Although supplemental oxygen reduces the mortality rate in chronically hypoxaemic patients with COPD, there are conflicting data about its ability to relieve breathlessness.

Beneficial effects of oxygen could be related to changes in chemo­ receptor stimulation, changes in breathing pattern, and/or stimulation of receptors related to gas flow through the upper airway. Oxygen therapy may be useful for patients with advanced heart or lung disease, in particular those who are hypoxaemic at rest. Long-term oxygen therapy (LTOT) may be of great help in patients with COPD. Patients with stable COPD and a resting PaO2 ≤7.3 kPa should be assessed for LTOT. The latter should not be routinely administered to patients who are breathless when there is no evidence of benefit, as it is expensive and may sometimes be associated with increased harm.

Pharmacological therapy. Opioids have been the most widely studied agents in the treatment of dyspnoea. Short-term admin­ istration reduces breathlessness in patients with a variety of condi­ tions, including advanced COPD, interstitial lung disease, cancer, and CCF. However, evidence of long-term efficacy is limited and conflicting. Recent evidence-based clinical guidelines recommend that opioids be considered on an individualised basis for palliation of unrelieved dyspnoea in patients with advanced cardiopulmonary disease despite otherwise adequate treatment of the underlying condition, with due consideration to patient history, comorbid conditions, and risk of respiratory depression.

Pulmonary rehabilitation. This is an integral component of the management of patients with chronic lung disease. Among the beneficial effects of pulmonary rehabilitation are a reduction in exertional dyspnoea during exercise and improved exercise tolerance, as well as a decrease in self-reported dyspnoea with activity. Exercise is the main component of pulmonary rehabilitation responsible for these improvements, but it is less clear whether mechanisms leading to improvement in

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dyspnoea are mainly due to improvements in conditioning, pacing of activities, desensitisation to respiratory sensations or affective distress, or a combination of these effects. Evidence that other components of pulmonary rehabilitation (e.g. education to improve inhaler technique, medication adherence, pacing activities, or breathing techniques) ameliorate dyspnoea independent of exercise is inconsistent, but it is likely that individual characteristics, such as motivation, are relevant.

In COPD, pulmonary rehabilitation may result in decreased ventilatory requirements and respiratory rate during ambulation, thereby decreasing the risk for developing dynamic hyperinflation. There is evidence that patients with COPD who undergo 6 weeks of exercise training experience comparable small decreases in dyspnoea intensity, regardless of whether or not they demonstrate improved exercise capacity.

Other non-pharmacological approaches. Patients with dyspnoea often report that movement of cool air reduces breathlessness, and laboratory studies have shown that cold air directed on the face decreases dyspnoea induced in healthy individuals. Increased respiratory muscle effort, associated with high ventilatory demand relative to respiratory muscle capacity, may contribute to dyspnoea in many patients with chronic respiratory disease. By reducing the demand on the respiratory muscles, non-invasive ventilation might reduce dyspnoea. However, few studies of non-invasive ventilation have used dyspnoea as an endpoint.

Conclusion

Dyspnoea is a common and often distressing symptom and a frequent reason for general practitioner and clinic visits. Dyspnoea is a

symptom, and its experience is subjective and varies greatly among individuals exposed to the same stimuli or with similar pathologies.

This differential experience of dyspnoea among individuals emanates from interactions among multiple physiological, psychological, social, and environmental factors that induce secondary physiological and behavioural responses. The management of dyspnoea will depend on the underlying cause.

Funding. This manuscript is not funded. Dr N A B Ntusi acknowledges support from the National Research Foundation and Medical Research Council of South Africa.

References 1. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society Statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012;185(4):435-453. [http://dx.doi.org/10.1164/rccm.201111-2042ST] 2. Boyars MC, Karnath BM, Mercado AC. Acute dyspnea: A sign of underlying disease. Hosp Phys 2004;40(7):23-27.

3. Oâ&#x20AC;&#x2122;Donnell DE, Banzett RB, Carrieri-Kohlman V, et al. Pathophysiology of dyspnea in chronic obstructive pulmonary disease. Proc Am Thor Soc 2007;4(2):145-168. [http://dx.doi.org/10.1513/pats.200611-159CC] 4. Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N Engl J Med 1995;333:1547-1553. [http://dx.doi.org/10.1056/NEJM199512073332307] 5. Nishino T. Dyspnoea: Underlying mechanisms and treatment. Br J Anaesth 2011;106(4):463-474. [http://dx.doi.org/10.1093/bja/aer040] 6. Zoorob RJ, Campbell JS. Acute dyspnea in the office. Am Fam Phys 2003;68(9):1803-1810.

7. Gopal M, Karnath B. Clinical diagnosis of heart failure. Hosp Phys 2009;45(7):9-15.

8. Ntusi NAB, Mayosi BM. Epidemiology of heart failure in sub-Saharan Africa. Expert Rev Cardiovasc Ther 2009;7(2):169-80. [http://dx.doi.org/10.1586/14779072.7.2.169] 9. Singh B, Mommer SK, Erwin PJ, Mascarenhas SS, Parsaik AK. Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism â&#x20AC;&#x201C; revisited: A systematic review and meta-analysis. Emerg Med J 2013;30:701-706. [http://dx.doi.org/10.1136/emermed-2012-201730] 10. Geersing GJ, Erkens PM, Lucassen WA, et al. Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: Prospective cohort study. BMJ 2012;345:e6564. [http://dx.doi.org/10.1136/bmj.e6564]

ARTICLE

An approach to the young hypertensive patient P Mangena,1 MB ChB, FCP (SA); S Saban,2 MB ChB, MFamMed, FCFP (SA); K E Hlabyago,3 BSc (Education), MSc, MB ChB, MMed (Family Medicine); B Rayner,1 MB ChB, MMed, FCP (SA), PhD Division of Nephrology and Hypertension, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, South Africa Private Practice, and Division of Family Medicine, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 Department of Family Medicine, Dr George Mukhari Academic Hospital and Sefako Makgatho Health Sciences University, Pretoria, South Africa 1 2

Corresponding author: P Mangena (mngphe002@myuct.ac.za)

Hypertension is the leading cause of death worldwide. Globally and locally there has been an increase in hypertension in children, adolescents and young adults <40 years of age. In South Africa, the first decade of the millennium saw a doubling of the prevalence rate among adolescents and young adults aged 15 - 24 years. This increase suggests that an explosion of cerebrovascular disease, cardiovascular disease and chronic kidney disease can be expected in the forthcoming decades. A large part of the increased prevalence can be attributed to lifestyle factors such as diet and physical inactivity, which lead to overweight and obesity. The majority (>90%) of young patients will have essential or primary hypertension, while only a minority (<10%) will have secondary hypertension. We do not recommend an extensive workup for all newly diagnosed young hypertensives, as has been the practice in the past. We propose a rational approach that comprises a history to identify risk factors, an examination that establishes the presence of target-organ damage and identifies clues suggesting secondary hypertension, and a limited set of basic investigations. More specialised tests should be performed only where there is a clinical suspicion that a secondary cause for hypertension exists. There have been no randomised clinical trials on the treatment of hypertension in young patients. Expert opinion advises an initial emphasis on lifestyle modification. This can comprise a diet with reduced salt and refined carbohydrate intake, an exercise programme and management of substance abuse issues. Failure of lifestyle measures or the presence of target-organ damage should prompt the clinician to initiate pharmacotherapy. We recommend referral to a specialist practitioner in cases of resistant hypertension, where there is severe target-organ damage and when a secondary cause is suspected.

S Afr Med J 2016;106(1):36-38. DOI:10.7196/SAMJ.2016.v106i1.10329

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Hypertension is a major cause of mortality and morbidity globally. It is estimated that >1 billion persons worldwide suffer from hyper­tension.[1] In the 2010 Global Burden of Disease study[2] 9 million deaths were attributed to hypertension, making it the leading cause of death worldwide.

The rate of hypertension has risen over the past few decades to reach epidemic proportions among the young[3] (defined in this article primarily as adolescents and adults <30 years of age). There is a paucity of data on the best way to treat younger patients, and most recommendations are extrapolated from evidence in older patients.[4] This rapid rise is of concern, as it portends an explosion of cardio­ vascular disease, cerebrovascular disease and chronic kidney disease in the coming years. Furthermore, due to the traditional approach that extensively investigated young hypertensives in search of a secondary cause, there are high healthcare costs associated with this epidemic.

This article provides a brief overview of hypertension in South African (SA) adolescents and young adults. Specific reference is made to diagnostic criteria, treatment considerations and referral options.

Epidemiology

Hypertension is defined as a persistent elevation of office blood pressure >140/90 mmHg. Approximately a third of the adult SA population is hypertensive.[5] Among adolescents and young adults (15 - 24 years old) the incidence is ~10%.[5] Worryingly, there has been a startling increase, with the prevalence approximately doubling in this age group within a decade.[3] The reasons include the ‘risk transition’, which is characterised by urbanisation, a change in diet and lower levels of physical activity.[6] There are few data on the long-term outcomes of hypertension in the young. However, the available evidence shows that young people with hypertension have similar target-organ damage as older hypertensives, such as left ventricular hypertrophy (LVH), microalbuminuria and carotid intimal thickness. These are associated with adverse cardiovascular outcomes.[7,8]

Pathophysiology

The causes of hypertension in the young can be divided into primary and secondary.

Primary hypertension

Primary hypertension (also called essential hypertension) has no specific cause, although genetic and environmental factors play an important role.[9] More than 90% of young people with hypertension have primary hypertension.[7,10] It is often associated with a family history of hypertension and frequently accompanied by obesity or the metabolic syndrome. International population surveys show an increase in obesity in children and adolescents, which parallels an increase in the prevalence of hypertension in the same age groups.[11] Hypertensive children and adolescents go on to become hypertensive adults – a phenomenon known as ‘BP tracking’.[12] Novel mechanisms implicated in the pathogenesis include low birth weight (the Barker-Brenner hypothesis)[13] and hyperuricaemia.[14,15] Low-birth-weight and/or small-for-gestational-age infants have a lower nephron number at birth (the so-called ‘nephron endowment’), which induces physiological changes that lead to hypertension and chronic kidney disease later in life.[13] Hyperuricaemia as a cause for hypertension in adolescents is an intriguing concept. Experimental data indicate that hyperuricaemia invokes renal changes that drive hypertension. This ‘hyperuricaemic hypertension’ has in small studies been shown to be reversible with urate-lowering therapy, at least in

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the early stages, i.e. soon after diagnosis. (There is not yet enough evidence to recommend routine use of urate-lowering therapy in young patients.[14,15])

Secondary hypertension

This form of hypertension affects approximately 10% of young hypertensives.[7] The probability of secondary hypertension is inverse­ ly proportional to the age of the patient (i.e. higher in a school-going child, but lower in a young adult).[7] The importance of identifying secondary hypertension lies in the potential for cure with appropriate treatment.

The causes of secondary hypertension can be further divided as follows: • renal parenchymal disease (e.g. glomerulonephritis) • renovascular disease (e.g. renal artery stenosis) • mineralocorticoid-mediated hypertension (e.g. primary hyper­ aldosteronism) • catecholamine-mediated hypertension (e.g. phaeochromocytomas) • medication (e.g. the oral contraceptive pill) • abuse of cocaine or amphetamines[16] • coarctation of the aorta • rarer causes.

Clinical features

Most young patients are asymptomatic and diagnosed during screening or when presenting with an unrelated condition. It is therefore imperative that opportunistic screening should take place at every opportunity. A minority present with a hypertensive emergency (such as heart failure, renal failure or malignant hypertension).

The history should enquire about whether a raised blood pressure has been recorded previously and the circumstances in which the hypertension was first noted; diabetes mellitus and premature cardiovascular disease; use of medication (especially oral contraceptives); use of alcohol and tobacco products; and abuse of illicit drugs, especially methamphetamines (commonly known as ‘tik’), which is associated with severe hypertension and chronic kidney disease.[17] Blood pressure should be recorded using an approved and calibrated electronic device or mercury sphygmomanometer. Raised blood pressure should be confirmed with multiple readings, and consideration should be given to performing out-of-office blood pressure measurement (such as home blood pressure or 24-hour ambulatory blood pressure monitoring) to exclude ‘white coat’ hypertension.[4] The examination is focused on establishing if there is target-organ damage or whether there are features that suggest a secondary cause.

The presence of target-organ damage should prompt the institution of pharmacotherapy and closer follow-up.[4] The clinician should look for: • an elevated body mass index (BMI) and increased waist circum­ ference • features of insulin resistance (e.g. acanthosis nigricans) • urinary dipsticks to detect primary renal disease (e.g. glomerulo­ nephritis) or renal damage • a pressure overloaded apex in keeping with LVH • fundoscopy to check for retinal hypertensive changes.

Features that point to a secondary cause include: • pulse discrepancies (this may suggest a vasculopathy, such as Takayasu’s arteritis) • radiofemoral delay (this suggests coarctation of the aorta) • abdominal bruits (these are suggestive of renal artery stenosis)

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• flushing, sweating and tachycardia (this may be a clue to the presence of a phaeochromocytoma) • acne, striae, moon facies (these suggest Cushing’s syndrome) • positive dipsticks for blood and/or protein.

Investigations

We recommend that young hypertensives are not routinely investi­ gated for secondary causes, given the scale of the epidemic and that the majority of patients have primary hypertension. Baseline tests that should be routinely performed include:[4] • serum potassium (hypokalaemia may suggest primary hyper­aldos­ teronism) • serum creatinine and determination of estimated glomerular fil­ tration rate • urine microalbumin-to-creatinine ratio • fasting blood glucose and lipogram • 12-lead electrocardiogram (ECG). The clinician should note that the ECG is not validated for diagnosis of LVH in individuals <30 years, and should be interpreted with caution.[16] • Where resources allow, an echocardiogram to evaluate for LVH may be performed, which is the gold standard for diagnosis.

Specific tests for a secondary cause should only be performed if there is a clinical suspicion. These include: • plasma renin and aldosterone for suspected primary hyper­ aldosteronism • urinary catecholamines for suspected phaeochromocytoma • renal sonography for suspected renal disease • computed tomography angiography of the renal vessels for suspected renal artery stenosis • urine screening for amphetamines and cocaine.

Therapy

Therapy for young hypertensives has not been defined by randomised clinical trials and is based on expert opinion. In all instances the main focus should be on instituting lifestyle changes.[4] All patients should be encouraged to lose weight by eliminating refined carbohydrate from their diet, reducing saturated fat intake and undertaking an exercise programme or joining an organised sports programme. Fresh fruit and vegetables in the diet should be encouraged and salt intake must be reduced. Avoidance of junk food is strongly recommended.

Alcohol use needs to be moderated and all tobacco product use discontinued. If substance abuse is detected, the patient should be referred for appropriate treatment.

The role of pharmacotherapy has not been established in young people. It should be considered in the following situations: after failure of lifestyle therapy, in patients with target-organ damage or secondary causes, and in cases of severe hypertension.

Few data are available on the choice of antihypertensive agents.

It is recommended that medication should be similar to that used in adults, as recommended by the South African Hypertension Society Practice Guideline on the management of hypertension.[18] The three front-line classes of antihypertensive agents are thiazide or thiazide-like diuretics, calcium channel blockers, and either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin

38

receptor blocker. However, it is recommended to reserve the use of diuretics in cases of more severe hypertension or where there is a compelling indication, such as fluid overload, to avoid the long-term metabolic consequences of diuretics, especially the predisposition to diabetes mellitus.[4]

When to refer

It is no longer recommended that all young hypertensives be referred for specialist evaluation, especially if they are >25 years of age.

Referral should be considered in the following circumstances: • blood pressure >180/110 mmHg • the presence of target-organ damage or complications of hyper­ tension (e.g. heart failure and renal impairment) • resistant hypertension • suspected secondary causes.

Conclusion

Hypertension in young people has doubled during the past 10 years and has necessitated a re-evaluation of our approach to their evaluation, investigation and treatment. There is an urgent need to address lifestyle issues that are driving this epidemic. It is also no longer recommended that all young hypertensives undergo extensive investigation or referral to a specialist. Practical recommendations regarding the investigation and treatment of young hypertensives are presented.

References 1. Alwan A. Global Status Report on Noncommunicable Diseases 2010. Geneva: World Health Organization, 2011.

2. Lim S, Vos T, Flaxman A, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990 - 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2224-2260.

3. Bradshaw D, Steyn K, Levitt N, Nojilana B. Non-communicable Diseases: A Race Against Time. Cape Town: Medical Research Council South Africa, 2011.

4. Falkner B, Daniels S. Summary of the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Hypertension 2004;44(4):387-388.

5. Shisana O, Labadarios D, Rehle T, et al. South African National Health and Nutrition Examination Survey (SANHANES-1): 2014. Cape Town: HSRC Press, 2014.

6. Reddy S, Resnicow K, James S, et al. Rapid increases in overweight and obesity among South African adolescents: Comparison of data from the South African National Youth Risk Behaviour Survey in 2002 and 2008. Am J Public Health 2012;102(2):262-268. [http://dx.doi.org/10.2105/AJPH.2011.300222] 7. Assadi F. The growing epidemic of hypertension among children and adolescents: A challenging road ahead. Pediatr Cardiol 2012;33(7):1013-1020. [http://dx.doi.org/10.1007/s00246-012-0333-5] 8. Drukteinis J, Roman M, Fabsitz R, et al. Cardiac and systemic hemodynamic characteristics of hypertension and prehypertension in adolescents and young adults: The Strong Heart Study.

Circulation 2006;115(2):221-227.

9. Weber M, Schiffrin E, White W, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. A Statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens 2014;32(1):3-15.

10. Flynn JT. Hypertension in children. In: Kaplan N, ed. Kaplan’s Clinical Hypertension. 9th ed.

Philadelphia: Lippincott Williams and Wilkins, 2006.

11. Din-Dzietham R, Liu Y, Bielo M, Shamsa F. High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation 2007;116(13):1488-1496.

12. Tirosh A, Afek A, Rudich A, et al. Progression of normotensive adolescents to hypertensive adults: A study of 26 980 teenagers. Hypertension 2010;56(2):203-209. [http://dx.doi.org/10.1161/ HYPERTENSIONAHA.109.146415] 13. Luyckx V, Brenner B. Birth weight, malnutrition and kidney-associated outcomes – a global concern.

Nat Rev Nephrol 2015;11(3):135-149. [http://dx.doi.org/10.1038/nrneph.2014.251] 14. Feig D, Soletsky B, Johnson R. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 2008;300(8):924. [http://dx.doi.org/10.1001/jama.300.8.924] 15. Gaffo A, Jacobs D, Sijtsma F, Lewis C, Mikuls T, Saag K. Serum urate association with hypertension in young adults: Analysis from the Coronary Artery Risk Development in Young Adults cohort. Ann Rheum Dis 2012;72(8):1321-1327. [http://dx.doi.org/10.1136/annrheumdis-2012-201916] 16. Hancock E, Deal B, Mirvis D, Okin P, Kligfield P, Gettes L. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram: Part V: Electrocardiogram Changes Associated With Cardiac Chamber Hypertrophy. Circulation 2009;119(10):e251-e261.

17. Jones E, Rayner B. Hypertension, end-stage renal disease and mesangiocapillary glomerulonephritis in methamphetamine users. S Afr Med J 2015;105(3):199-201. [http://dx.doi.org/10.7196/samj.8731] 18. Seedat Y, Rayner B, Veriava Y. South African hypertension practice guideline 2014: Review article.

Cardiovasc J Afr 2014;25(6):288-294. [http://dx.doi.org/10.5830/CVJA-2014-062]

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ARTICLE

An approach to the diagnosis and management of valvular heart disease B J Cupido,1 FCP (SA), Cert Cardiology (SA); F Peters,2 FCP (SA), Cert Cardiology (SA); N A B Ntusi,1 FCP (SA), DPhil Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa 2 Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand and Baragwanath Hospital, Johannesburg, South Africa 1

Corresponding author: B J Cupido (bj.cupido@uct.ac.za)

Valvular heart disease poses a common yet difficult problem in everyday clinical practice. A thorough clinical evaluation with basic common investigations such as an electrocardiogram (ECG) and a chest radiograph (CXR) remains the cornerstone of diagnosis. Echocardiography and more invasive testing, if needed, are usually performed at specialist level to confirm the diagnosis, assess severity and assist in definitive decision-making.

The causes and clinical, ECG and CXR features of the common valve lesions are described. Patients with symptomatic valve lesions should be referred for specialist assessment. In most cases, medical therapy serves as a bridge to definitive mechanical or surgical therapy.

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The diagnosis of valvular heart disease is a difficult problem in everyday clinical practice. There is a wide spectrum of presentation – in some cases murmurs are found incidentally and in others, patients present very late with dire haemodynamic consequences of neglected valve lesions that may preclude them from definitive surgery. This review serves as a guide to the primary care clinician in the diagnosis and management of valve disease.

With the decline in rheumatic heart disease and the ageing population in the developed world, there has been a change in the disease patterns of valve lesions over the last few decades. Western populations are experiencing greater numbers of degenerative valve disease. In the developing world, however, rheumatic heart disease remains an important cause of valve pathology. Sliwa et al.,[1] in the Heart of Soweto Study, showed an incidence of new cases of rheumatic heart disease of 23.5/100 000 cases per annum.

Clinical evaluation (history and examination) remains the corner­ stone of screening for valve pathology. An electrocardiogram (ECG) and a chest radiograph (CXR) are seen as important adjuncts to clinical evaluation and may provide important diagnostic clues to confirming pathology.

Echocardiography with colour flow and Doppler (not focusassessed transthoracic echocardiography (FATE) scans) plays a pivo­ tal role in confirming the diagnosis, and assessing the severity of the valve lesions and concomitant pulmonary hypertension, other valve lesions and haemodynamic consequences.

Invasive testing with cardiac catheterisation is reserved for patients in whom there is a discrepancy between clinical findings and echocardiography.

Mitral stenosis

Mitral stenosis (MS) is almost exclusively caused by chronic rheumatic heart disease. The rheumatic process leads to inflammation, resulting in commissural fusion, thickening and fibrosis of both the leaflets and subvalvular apparatus. Fewer than half of patients with MS recollect an episode of acute rheumatic fever. Other rare causes of mitral

39

valve (MV) obstruction include congenital MS, degenerative mitral annular calcification, atrial myxomas, large thrombus or vegetations, systemic lupus erythematosus (SLE) and carcinoid syndrome.

A normal MV area is 4 - 6 cm2. During diastole, the MV opens to allow the unobstructed flow of blood into the left ventricle. With MS, there is obstruction to ventricular inflow; the resultant pressure gradient causes an increase in left atrial (LA) pressure. Pulmonary oedema usually occurs secondary to this rise in pressure.

Any condition that increases heart rate, including sepsis, thyroid disease, anaemia, atrial fibrillation (AF) and pregnancy, may precipi­ tate symptoms.

Clinical features and special investigation findings are described in Table 1.[2] Patients with mild disease and symptoms may require diuretic therapy and sodium restriction to reduce congestion. Beta-blockers are often prescribed, the rationale being that reducing the heart rate increases diastolic filling time, reduces the gradient and improves effort tolerance. It is generally used in patients with Class II - III symptoms. There is no evidence for its prognostic benefit or use in multivalve disease.[2] Verapamil may also be used for heart rate control, but should not be administered concomitantly with beta-blockers. There is no benefit from the use of angiotensin-converting enzyme (ACE) inhibitors. Digoxin may be used for heart rate control in patients with AF, but is otherwise contraindicated.

Anticoagulation with vitamin K antagonists (warfarin) is advised in patients with previous embolic events, clot in the LA or AF (regardless of the presence of LA clot). Aspirin is not used, as its benefit in stroke prevention is low, with a similar bleeding risk to warfarin. The CHADS or CHADS-VASc score should not be applied to patients with MV disease and AF, as the stroke risk is already high; these patients should be anticoagulated. The new oral anticoagulants have not been tested in this setting and should not be used.

For patients with moderate to severe disease or for those with an episode of acute pulmonary oedema, definitive surgical treatment should be considered and they should be referred for evaluation.

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Table 1. Clinical and special investigation features of mitral stenosis Mitral stenosis

Table 2. Clinical and special investigation features of mitral regurgitation Mitral regurgitation

History Exertional dyspnoea Orthopnoea Paroxysmal nocturnal dyspnoea Acute frank pulmonary oedema Haemoptysis Embolism: 20 - 25%, especially cerebral Chest discomfort Hoarseness: Ortner’s syndrome

History Heart failure symptoms (dyspnoea, paroxysmal nocturnal dyspnoea, orthopnoea) Leg swelling Physical findings Displaced, volume-loaded apex beat Soft S1 Pan-systolic murmur at apex, radiating to axilla Third heart sound

Physical findings Normal character, small volume pulse in severe MS Irregularly irregular pulse: atrial fibrillation JVP may be elevated: prominent cv wave if concomitant significant TR Undisplaced, tapping apex beat Loud first heart sound Loud pulmonary component of S2 if pulmonary hypertension Opening snap after S2, if pliable valve The closer to S2, the more severe the MS Low-pitched mid-diastolic murmur Best heard at the apex Longer murmur = more severe MS If patient is in sinus rhythm, presystolic accentuation of the murmur may be audible Pulmonary crepitations at lung bases Other associated valve lesions: mitral regurgitation, tricuspid disease, aortic disease

Special investigations ECG Usually unremarkable The presence of abnormal QRS complexes eludes to underlying myocardial pathology rather than primary isolated mitral valve pathology CXR Cardiomegaly Upper-lobe blood diversion/interstitial oedema

Special investigations ECG Usually unremarkable In sinus rhythm, LA enlargement: broad P wave in lead II or a predominantly negative deflection in lead V1 In AF, no comment on LA size can be made CXR Normal-sized heart (ventricle) Upper-lobe blood diversion/interstitial oedema Enlarged LA seen by: Straight left heart border Splaying on the coryna Double shadow on the right heart silhouette JVP = jugular venous pressure; TR = tricuspid regurgitation; MS = mitral stenosis; LA = left atrial; AF = atrial fibrillation.

Percutaneous balloon mitral valvuloplasty has superseded surgical valvotomy (closed and open) for patients with pliable valves.[3] This is also the treatment of choice for pregnant MS patients with pliable valves and poor response to medical therapy. Those with calcified, non-pliable valves or significant concomitant mitral regurgitation (MR) are referred for valve replacement surgery.

Mitral regurgitation

MR may be classified depending on the clinical presentation (acute or chronic) or leaflet pathology (functional versus organic).

Acute MR is a medical emergency presenting with acute pulmonary oedema and hypotension and is usually caused by endocarditis, myocardial infarction with papillary muscle rupture or spontaneous rupture of the chordae. Afterload reduction with intravenous nitrates or nitroprusside and early surgical intervention is usually required.

40

The clinical and investigational features of chronic MR are summarised in Table 2. Signs of severity include clinical features of heart failure, pulmonary hypertension, a loud murmur grade ≥3/6 and presence of a third heart sound in the absence of heart failure.

Functional MR is characterised by normal leaflets and is secondary to a dilated and dysfunctional left ventricle. Echocardiography is required to accurately confirm this diagnosis and may differentiate ischaemic from non-ischaemic causes. Functional MR requires optimisation of heart failure therapy, whereas moderate or severe ischaemic MR may require surgery with possible coronary revascularisation.

Organic MR refers to primary leaflet abnormality resulting in MR. The cause is most often rheumatic in South African (SA) patients, whereas degenerative or myxomatous disease is most common in the developed world. Other causes include fibro-elastic disease, congenital (isolated cleft or atrioventricular (AV) canal defect), Mar­fan syndrome and endocarditis.

Medical therapy has been shown not to be of benefit in MR. Indications for surgery include symptoms, development of AF, pulmonary hypertension, end-systolic diameter >40 mm and ejection fraction <60% on echocardiography. Surgical options include MV replacement or repair, which may mandate earlier surgery, provided a successful durable repair can be obtained.

Aortic stenosis

Aortic stenosis (AS) is the most common valve lesion in western countries and mainly a disease of the elderly. Common causes of AS include: • degenerative trileaflet AS • degenerative bicuspid AS • rheumatic heart disease – there would usually be concomitant MV • disease • other (rare): congenital AS, Paget’s disease, end-stage kidney disease, chronic inflammatory diseases.

Haemodynamically significant obstruction usually occurs when the valve area is <1 cm2. Left ventricular hypertrophy develops in response to the progressive obstruction. Risk factors for degenerative AS are similar to those for atherosclerosis, i.e. hypertension, diabetes, dyslipidaemia and smoking.

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Table 3. Clinical and special investigation features of aortic stenosis Aortic stenosis

Table 4. Clinical and special investigation features of aortic regurgitation Aortic regurgitation

History Exertional dyspnoea Angina Syncope Physical findings Small-volume, slow-rising pulses Narrow pulse pressure JVP normal, unless heart failure or MV disease Pressure-loaded undisplaced apex beat Soft or single second heart sound Crescendo-decrescendo ejection systolic murmur at base of the heart Radiated to carotids Longer murmur = more severe High-pitched widely radiating murmur: Gallavardin effect – can be mistaken for MR Systolic click in bicuspid valve may be heard Special investigations ECG Left ventricular hypertrophy CXR Normal-sized heart (ventricle) Aortic calcification Post-stenotic dilatation: especially in bicuspid valves

Patients are asymptomatic for many years. Once symptoms occur, however, there is a rapid decline in life expectancy.[4] Clinical features of AS are shown in Table 3.

There is no place for medical management of patients with symp­ tomatic AS. It is a mechanical obstruction for which the definitive treatment is aortic valve replacement. These patients should therefore all be referred promptly for assessment for valve replacement surgery,[5] which prolongs and improves quality of life, even in octogenarians.[6] For those in whom the risk of surgery is too high, transcatheter aortic valve replacement is currently a possibility.[7]

Aortic regurgitation

Aortic regurgitation may occur as a result of leaflet pathology or secondary to aortic root pathology. Acute regurgitation is poorly tolerated and constitutes a medical and surgical emergency. It is commonly caused by infective endocarditis or aortic root dissection.

Chronic regurgitation is well tolerated and patients are often asymptomatic for many years. Common causes of primary valve lesions are rheumatic heart disease, infective endocarditis, congenital bicuspid valves, and rheumatoid arthritis. Conditions primarily affecting the root, and hence causing regurgitation, are Marfan’s syndrome, syphilis, sero-negative spondyloarthritides, aortic dis­ section and osteogenesis imperfecta.

The clinical features are summarised in Table 4. Symptomatic aortic regurgitation requires referral for the assessment for aortic valve replacement. There is no place for medical therapy outside of it being a bridge to surgery or in those too ill for surgery.[2,8-10]

Tricuspid valve disease

Tricuspid stenosis (TS) is rare and usually rheumatic in origin.[11] Most patients with rheumatic tricuspid valve (TV) disease present with tricuspid regurgitation (TR) or a combination of TR and TS. Isolated

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History Long asymptomatic period Dyspnoea Orthopnoea Paroxysmal nocturnal dyspnoea Nocturnal angina Physical findings Collapsing pulses Wide pulse pressure (difference between systolic and diastolic is >50% of the systolic pressure) Duroziez sign Heart failure signs: elevated JVP, leg swelling, crepitations at lung bases Volume-loaded, displaced apex Early diastolic murmur at base of heart Best heard with patient sitting forward, in end-expiration Longer murmur = more severe A systolic murmur (due to increased flow or concomitant AS) An Austin-Flint murmur (late diastolic apical murmur) Special investigations ECG No specific diagnostic changes Occasionally in severe AR-left ventricular hypertrophy, and left axis deviation may be seen CXR Cardiomegaly Pulmonary congestion

rheumatic TS is uncommon, but usually accompanies MV disease.

Less common and unusual causes of obstruction to right atrial (RA) emptying include congenital tricuspid atresia, RA tumours, carcinoid syndrome, endomyocardial fibrosis, TV vegetations, pacemaker leads or extracardiac tumours.[11] TS is found at autopsy in 15% of patients with rheumatic heart disease, but is of clinical significance in <5%.

As is the case with MS, TS is more common in women. The RA is usually dilated in TS. Clinical and special investigation findings in TS are presented in Table 5.

The most common cause of TR is a dilated right ventricle (RV) and TV annulus (‘functional TR’).[12] Functional TR may follow on pulmonary hypertension and its causes, RV obstruction (e.g. pulmonary stenosis) or intrinsic RV abnormality (e.g. RV infarction). Rheumatic TR is rare.

Non-rheumatic, valvular causes of TR include infective endocarditis, Ebstein anomaly, TV prolapse, carcinoid syndrome, trauma, papillary muscle dysfunction, and connective tissue disease. The clinical and imaging features of TR are listed in Table 5.[11-13]

Prosthetic valves

There are two types of prosthetic valves: mechanical valves and bioprosthetic (tissue) valves. The major differences between the two relate to risk of thromboembolism (higher with mechanical valves) and structural deterioration (higher with bioprostheses).[14] Mechanical valves are classified into three groups: bileaflet, tilting disc and ballcage. Bileaflet mechanical valves are most commonly implanted.

Patients with mechanical valves require long-term anticoagulation.

The risk of thromboembolism is about 6 times higher without anticoagulants, and the risk of de novo valve thrombosis is also

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Table 5. Clinical and special investigation features of tricuspid valve disease Tricuspid stenosis

Tricuspid regurgitation

History Progressive fatigue, oedema, anorexia Minimal orthopnoea and paroxysmal nocturnal dyspnoea Pulmonary oedema and haemoptysis are rare

History Well tolerated in absence of pulmonary hypertension, often asymptomatic Right heart failure (swollen abdomen, swelling of legs and painful, congestive enlargement of liver) Throbbing pulsations in the neck (from elevated JVP) and eyeballs

Physical findings Diastolic rumble at lower left sternal border, increasing in intensity with inspiration Often confused with mitral stenosis Neck vein distention, with prominent a waves Absent right ventricular lift/heave Hepatic pulsation Ascites, peripheral oedema Associated murmurs of mitral and aortic valve disease

Physical findings Weight loss, cachexia, cyanosis and jaundice AF is common Elevated JVP with prominent cv waves Venous systolic thrill and murmur in neck Tender hepatomegaly S3 gallop originating from RV Loud P2 and parasternal heave if pulmonary hypertension present Pansystolic murmur of TR

Special investigations ECG Tall right atrial P waves and no RV hypertrophy CXR Dilated RA without enlarged pulmonary artery segment

Special investigations ECG Usually nonspecific; incomplete RBBB, Q waves in V1, AF are common CXR Marked cardiomegaly

higher. Warfarin is the anticoagulant of choice and the international normalised ratio should be between 2.5 and 3.5. Antiplatelet agents such as aspirin do not provide adequate protection and are not recommended without the use of anticoagulants.

Bioprostheses were developed to overcome the challenges of long-term anticoagulation and increased risk of thromboembolism associated with mechanical valves. A stented tissue valve consists of three tissue leaflets mounted on a ring with semi-rigid stents that facilitate implantation. Because stents add to obstruction and increase stress on the leaflets, stentless tissue valves were developed for the aortic position and are particularly useful for patients with small aortic roots. More recently, a transcatheter bioprosthesis has been developed, which can be implanted via a catheter at the aortic valve position.[15] Homograft aortic valves are harvested from cadavers, sterilised with antibiotics and cryopreserved at −196° for long periods before implantation. Pulmonary autografts (Ross procedure) involve removal of a patient’s native pulmonary valve and reimplantation to replace the diseased aortic valve.[15]

Conclusion

The clinical evaluation remains essential in establishing a diagnosis in patients presenting with heart failure due to valvular heart disease. Awaiting results of special investigations should not hinder timeous referral. Those with symptomatic valvular heart disease should be referred promptly for specialist evaluation with a view to definitive surgical correction.

42

References 1. Sliwa K, Carrington M, Mayosi BM, Zigiriadis E, Mvungi R, Stewart S. Incidence and characteristics of newly diagnosed RHD in urban African adults: Insights from the Heart of Soweto Study. Eur Heart J 2010;31:719-727. [http://dx.doi.org/10.1093/eurheartj/ehp530] 2. Braunwald E. Valvular heart disease. In: Braunwald EB, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 5th ed. Philadelphia, PA: W B Saunders, 1997:1007-1076.

3. Fawzy ME, Shoukri M, Buraiki J, et al. Seventeen years’ clinical and echocardiographic follow-up of mitral balloon valvuloplasty in 520 patients, and predictors of long term outcome. J Heart Valve Dis 2007; 16:454-460.

4. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation 2010;121:151-156. [http://dx.doi.org/10.1161/CIRCULATIONAHA.109.894170] 5. Rahimtoola SH. Indications for surgery in aortic valve disease. In: Yusuf S, Cairns JA, Camm AJ, eds.

Evidence Based Cardiology. London: BMJ Books, 1998:811-832.

6. Chukwuemeka A, Borger MA, Ivanov J, Armstrong S, Feindel CM, David TE. Valve surgery in octogenarians: A safe option with good medium-term results. J Heart Valve Dis 2006;15:191-196.

7. Leon MB, Smith CR, Mack M, et al. PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:15971607. [http://dx.doi.org/10.1056/NEJMoa1008232] 8. Vehanian A, Ottavio A, Andreotti F, et al. Guidelines on the management of valvular heart disease. Eur Heart J 2012;33:2451-2496. [http://dx.doi.org/10.1093/eurheartj/ehs109] 9. Nishimura R, Otto C, Bono RO, et al. 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease – a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(22):e57-e185. [http:// dx.doi.org/10.1016/j.jacc.2014.02.536] 10. Cupido B, Commerford PJ. Valvular heart disease. In: Rosendorff C, ed. Essential Cardiology. 3rd ed.

New York: Springer, 2013.

11. Bruce CJ, Connolly HM. Right-sided valve disease deserves a little more respect. Circulation 2009;119(20):2726-2734. [http://dx.doi.org/10.1161/CIRCULATIONAHA.108.776021] 12. Rogers JH, Bolling SF. The tricuspid valve: Current perspective and evolving management of tricuspid regurgitation. Circulation 2009;119(20):2718-2725. [http://dx.doi.org/10.1161/ CIRCULATIONAHA.108.842773] 13. Forfia PR, Wiegers SE. In: Otto CM, ed. The Clinical Practice of Echocardiography. Philadelphia, PA: Saunders/Elsevier, 2007:848-876.

14. Pibarot P, Dumesnil JG. Prosthetic heart valves: Selection of the optimal prosthesis and long-term management.

Circulation 2009;119(7):1034-1048. [http://dx.doi.org/10.1161/ CIRCULATIONAHA.108.778886] 15. O’Gara PT, Bonow RO, Otto CM. In: Otto CM, Bonow RO, eds. Valvular Heart Disease: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: Saunders/Elsevier, 2009:383-398.

January 2016, Vol. 106, No. 1

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ISSUES IN MEDICINE

Red meat, processed meat and cancer in South Africa D C Stefan Cristina Stefan, MD, MMed, FCP, CMO, MSc, PhD, is a paediatric oncologist and cancer epidemiologist. As the first woman president-elect of the African Organization for Research and Training in Cancer, she is deeply involved in African and global cancer activities. She is vice-president of the South African Medical Research Council.

Corresponding author: D C Stefan (cristina.stefan@mrc.ac.za)

Epidemiological studies around the world were analysed recently by the International Agency for Research on Cancer, demonstrating a positive correlation between consumption of red meat and processed meat and colorectal cancer. In South Africa (SA) there is a great variation in the incidence of this type of cancer between various ethnic groups, related to diet and other risk factors. Strengthening the SA cancer registry and co-ordinated research on diet and cancer are required to provide specific answers for our population.

S Afr Med J 2016;106(1):43. DOI:10.7196/SAMJ.2016.v106i1.10400

The most recent South African (SA) cancer registry analysis, from 2010,[1] shows that colorectal cancer is in seventh position for males, with a total number of 1 291 new cases, after basal cell carcinoma, pros­tate cancer, squamous cell carcinoma of the skin, primary site unknown, Kaposi’s sarcoma and lung carcinoma. The same cancer is in sixth position for females, with a total number of 1 129 new cases, after breast cancer, cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin and primary site unknown. The lifetime (0 - 74 years) risk of developing colorectal cancer is 1/114 for males and 1/182 for females in SA. There is a considerable variation in the incidence of diagnosed colorectal cancers in the different ethnic groups, possibly as a result of dietary differences, among other factors that need to be considered.

Among SA Asian males colorectal cancer was the second most common histologically confirmed cancer in 2010, accounting for 13.62% of total cancers (just after prostate cancer). It was also the second most common cancer among Asian females, accounting for 7.39% of total cancers, just after breast cancer. However, histologically confirmed colorectal cancer accounted for only 3.84% of total cancers (after adjustments) in the black male population, and for only 2.54% in black females, much lower than in the other groups. White females had a higher percentage of new histologically diagnosed colorectal cancers in 2010 than white males (5.17% v.

4.83% of all malignancies).

The incidence of pancreatic cancer in the SA population is low or not reported, and that of cancer of the prostate differs significantly among the various population groups.

A considerable amount of research indicates that consumption of red meat is associated with an increased risk of cancer. The Inter­ national Agency for Research on Cancer (IARC) will shortly publish a monograph on the epidemiological studies addressing the correlation between red meat consumption and cancer in humans.[2] Lancet Oncology of 26 October 2015 presented the IARC-analysed data on the association of red meat consumption with colorectal cancer.[3] A large section of the data originates in 14 cohort studies, done over 20 years. Positive associations were seen with high v. low consumption of red meat in half of those studies, including a cohort from ten European countries covering a wide range of meat consumption, and other large cohorts from Sweden and Australia.

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According to the IARC, studies around the world found ‘sufficient evidence in humans that the consumption of processed meat causes colorectal cancer’. The international organisation defines processed meat as any type of meat that is salted, cured, fermented or smoked to enhance its flavour or preserve it. Processed meat generally contains pork or beef, but may also contain poultry. In addition, the working group from the same agency concluded that there is limited evidence in human beings for the carcinogenicity of the consumption of unprocessed red meat, which was mainly associated with colon cancer but also with pancreatic and prostate cancer.

Since no data from Africa were included, it is important to assess the situation in SA. While the IARC data on the carcinogenic risk of red meat are strong, their application to the SA context requires careful consideration. SA is a country with a diverse population in which genetic factors, diet, cultural traditions, lifestyle and exercise contribute to various extents to the differences reported. The wide difference between the highest and the lowest income brackets may also have a substantial influence on the incidence of colorectal, prostate, pancreatic and the other types of cancers in question, because of its impact on food consumption patterns, In the quest for understanding the risk factors for cancer in our country, the need for an updated and comprehensive cancer registry cannot be sufficiently emphasised. Nevertheless, co-ordinated research into the epidemiology, risk factors (including dietary constituents) and prevention of cancer should be the key factor in establishing the national cancer control strategy.

Until more evidence based on research into local conditions is available, the IARC findings, which support ‘recommendations to limit intake of meat’, particularly in processed forms, should be considered in the context of promoting a healthy, balanced diet consisting mainly of vegetables and fruit, with limited sugar and alcohol consumption, as well as encouraging physical activity.

1. National Institute for Occupational Health. Cancer in South Africa, 2010. National Cancer Registry. http://www.nioh.ac.za/assets/files/NCR_Final_2010_tables(1).pdf (accessed 26 November 2015).

2. International Agency for Research on Cancer. Press release No. 240. IARC monographs evaluate consumption of red meat and processed meat. https://www.iarc.fr/en/media-centre/pr/2015/pdfs/ pr240_E.pdf (accessed 26 November 2015).

3. Bouvard V, Loomis D, Guyton KZ, et al. Carcinogenicity of consumption or red and processed meat.

Lancet Oncol 2015;16(15):1599-1600. [http://dx.doi.org/10.1016/S1470-2045(15)00444-1]

Accepted 27 November 2015.

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CLINICAL ALERT

Severe porphyric neuropathy – importance of screening for porphyria in Guillain-Barré syndrome C-M Schutte, C H van der Meyden, L van Niekerk, M Kakaza, R van Coller, V Ueckermann, N M Oosthuizen Clara Schutte is Professor and Head of the Department of Neurology in the School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa. Kees van der Meyden is Emeritus Professor and at the time of writing was working part-time in the Department, in which Linette van Niekerk is a senior registrar and Mandisa Kakaza is Professor and senior consultant. Riaan van Coller is a neurologist in private practice in Pretoria who has session appointments in the Department. Veronica Ueckermann is a physician in charge of the intensive care unit in the Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, and Nicky Oosthuizen is a senior pathologist in the Department of Chemical Pathology, University of Pretoria.

Corresponding author: C-M Schutte (cschutte@medic.up.ac.za)

The hepatic porphyrias are a group of rare metabolic disorders, each of which is associated with a specific enzymatic alteration in the haem biosynthesis pathway. In South Africa (SA), a high incidence of variegate porphyria (VP) is seen as a result of a founder effect, but acute intermittent porphyria (AIP) is also encountered. The development of acute neurovisceral attacks is related to environmental factors, including medications, hormones and diet. A possible manifestation of a severe attack is rapidly progressing quadriparesis, which may mimic GuillainBarré syndrome. We present four such cases, highlighting that acute porphyria should be considered in the differential diagnosis of GuillainBarré syndrome. Three patients presented to Steve Biko Academic Hospital, Pretoria, SA, with progressive quadriparesis, and one to a private hospital with acute abdominal pain followed by rapidly progressive quadriparesis. Two patients had started antiretroviral therapy before the development of symptoms, and one had started antituberculosis therapy. All patients had marked weakness with depressed reflexes, and showed varying degrees of confusion. An initial diagnosis of Guillain-Barré syndrome led to administration of intravenous immunoglobulins in two patients. On testing for porphyria, it was found that two patients had AIP and two VP. Electrophysiological investigations revealed severe mainly motor axonal neuropathy in all. Two patients deteriorated to the point of requiring mechanical ventilation, and one of them died due to complications of critical illness. Haemin was administered to three patients, but the process of obtaining this medication was slow, which delayed the recommended early administration. The surviving patients showed minimal recovery and remained severely disabled.

Porphyric neuropathy should always be considered as a differential diagnosis in a patient with an acute neuropathy, especially in SA. Absence of abdominal pain does not exclude the possibility of porphyria, and attacks may be precipitated by antiretroviral and antituberculosis medication.

The outcome of our patients was not favourable; specifically, obtaining haemin was a challenge in the state hospital setting.

S Afr Med J 2016;106(1):44-47. DOI:10.7196/SAMJ.2016.v106i1.10118

The porphyrias are a group of inherited metabolic disorders that are associated with a specific enzymatic abnormality in the haem biosynthesis pathway. Porphyrias are traditionally classified as hepatic or erythropoietic according to the site of accumulation of haem precursors, but classifications reflecting the clinical presentation, such as acute and cutaneous, may be more practical.[1] The acute porphyrias that are inherited in an autosomal dominant pattern include acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria, while acute porphyria due to d-aminolaevulinic acid (ALA) dehydratase deficiency is an autosomal recessively inherited condition.

AIP is estimated to occur in one in 75 000 people in Europe, except in Sweden, where the condition is seen in one in 1 000 owing to a founder effect.[1,2] Similarly, VP is estimated to occur in one of 150 000 people in Europe, but the prevalence in SA is much higher, estimated at 3/1 000 in the white population as a result of a founder mutation that was introduced from the Netherlands in 1688.[3] An acute porphyric attack may be precipitated by several factors, including starvation, certain medications and hormonal fluctuations. The typical attack begins with severe abdominal pain and autonomic hyperactivity, followed by psychiatric disturbances and possibly neuropathy. Whereas most patients recover well from acute porphyric attacks, neurological complications may develop; these include electrolyte disturbances and seizures, confusional states, autonomic dysfunction and severe quadriparesis.[1]

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We describe the clinical presentation and outcome of four patients with acute porphyria who presented to a neurology unit in Pretoria, South Africa (SA), during one year, emphasising that the presentation of acute porphyric neuropathy may be similar to that of GuillainBarré syndrome and occur in the absence of acute abdominal pain.

The occurrence of AIP in the black population is highlighted and some clinically relevant points regarding treatment are detailed.

Three patients presented to Steve Biko Academic Hospital with progressive quadriparesis, and one to a private hospital with acute abdominal pain followed by rapidly progressive quadriparesis. Two patients had started antiretroviral therapy before the development of symptoms, and one had started antituberculosis therapy. All had marked weakness with depressed reflexes, and showed varying degrees of confusion in the ward.

An initial diagnosis of Guillain-Barré syndrome led to the administration of intravenous immunoglobulins in two patients.

On testing for porphyria, it was found that two patients had AIP and two VP. Electrophysiological investigations revealed features of a severe mainly motor axonal neuropathy in all (Table 1). Two patients deteriorated to the point of requiring mechanical ventilation, and one of them died due to complications of critical illness. Haemin was administered to three patients, but the process of obtaining this medication was slow, proving a challenge in the state hospital setting, so the recommended early administration was delayed. As a result, the surviving patients showed minimal recovery and remained severely disabled.

January 2016, Vol. 106, No. 1

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Case reports Case 1

A 42-year-old black woman presented with an acute onset of pro­ gressive quadriparesis that had developed over 4 days. She was HIV-positive and antiretroviral therapy had been initiated 4 weeks previously; at around that time, she had also had a flu-like illness. In addition to the weakness, she experienced paraesthesiae and numbness over the extremities. In the ward, she was intermittently confused. On examination, she showed facial weakness and a global power of grade 2/5 with areflexia and loss of sensation of the ‘bathing suit’ type. A diagnosis of possible Guillain-Barré syndrome was made and she was treated with intravenous immunoglobulins (IVIG). It was also noted that her urine was a dark brown colour, and porphyria screening was requested. Her condition deteriorated in the ward and she required intubation and ventilation in the intensive care unit. The urinary porphobilinogen (PBG) level was 378 µmol/L (reference value <9), the faecal porphyrins were marginally elevated at 374 nmol/g dry weight (reference value <200) and the plasma emission spectrum was maximal at 619 nm. A final diagnosis of AIP was made. Lumbar puncture showed high cerebrospinal fluid (CSF) protein levels and serum biochemical investigations revealed hyponatraemia (126 mmol/L, reference range 136 - 145). Electromyography (EMG) demonstrated low compound muscle action potential (CMAP) amplitudes in all four

limbs, as well as reduced sensory nerve action potentials. Unfortunately it was impossible to obtain haemin for this patient. She developed a pulmonary embolism, received intensive physiotherapy and was eventually extubated. The weakness improved marginally, but she remained severely weak and was still bedridden after 2 months.

Case 2

A 34-year-old black man was admitted with progressive quadri­ paresis that had developed over 3 - 4 weeks. He had had a respiratory tract infection before the onset of symptoms and had possibly received antibiotics. He also complained about a cold sensation in his limbs, as well as hoarseness and a soft voice. On examination, he appeared confused and had a bovine cough (later confirmed to be due to left-sided vocal cord paralysis), power of grade 0/5 in the arms proximally and 3/5 distally, and weakness in the legs of 4/5 proximally and 5/5 distally. The deep tendon reflexes were absent and glove-and-stocking-type sensory loss was evident. The patient was initially treated with IVIG for possible Guillain-Barré syndrome.

However, investigations for porphyria revealed a urinary PBG level of >100 µmol/L, total urinary porphyrins of 2 236 nmol/L (reference value <300 nmol/L), faecal porphyrins of 333 nmol/g dry weight, and a plasma peak at 619 nm on emission spectrofluorimetry. A diagnosis of AIP was made, and it was discovered that the patient’s sister had

Table 1. Motor nerve conduction studies of patients Median nerve

Ulnar nerve

Peroneal nerve

DL (ms)

Amp (mV)

NCV (m/s)

DL (ms)

Amp (mV)

NCV (m/s)

Right distal

4.1

1.08

51.2

3.0

2.21

64.7

Right proximal

8.2

0.860

7.65

1.89

Left distal

3.55

2.12

Left proximal

7.75

1.36

Right distal

3.5

3.6

Right proximal

8.2

3.6

Left distal

3.2

3.0

Left proximal

8.0

2.9

Right distal

5.1

3.3

3.3

3.7

Right proximal

10.4

0.470

10.3

2.4

Patient

DL (ms)

Amp (mV)

NCV (m/s)

4.6

1.46

41.5

12.85

1.3

Tibial nerve DL (ms)

Amp (mV)

NCV (m/s)

4.3

4.57

47

12.5

3.63

Patient 1

50

2.75

2.25

6.0

1.48

2.8

3.2

9.5

2.7

2.5

5.8

9.4

4.5

72.3

8.85

0.072

14.5

0.06

64.6

4.3

4.17

12.2

5.47

48.1

Patient 2 46.8 54.2

40.9 48.2

4.3

3.2

13.5

2.9

4.4

2.3

13.8

1.6

5.8

1.5

16

1.2

38.6 37.2

7.8

11.2

19.2

10.6

3.7

9.7

14.2

8.0

4.7

7.5

16.8

4.6

35.6 40

Patient 3 (baseline) 43.1

38.1

31.4

Left distal Left proximal Patient 3 (after 2 mo) Right distal

Absent

Right proximal

Absent

Left distal

4.9

0.101

Left proximal

10.35

0.079

3.1

0.100

42.2

Absent

Absent 6.2

0.021

Patient 4 Right distal

33.8

Right proximal

2.5

3.3

11.2

2.3

Left distal Left proximal DL = distal latency; Amp = amplitude; NCV = nerve conduction velocity; ms = milliseconds; mV = millivolts; m/s = metres per second.

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January 2016, Vol. 106, No. 1

47.9

4.1

6.5

13.2

5.8

41.8

IN PRACTICE

also previously been diagnosed with this condition. The CSF protein level was within normal limits and hyponatraemia (128 mmol/L) was present. On EMG, the patient had low CMAP amplitudes and slowing of conduction velocity in motor and sensory nerves, while an electroencephalogram showed generalised slowing at 6 - 7 Hz. The patient received a course of haemin, which was only available 6 weeks after admission. He improved somewhat, but remained weak and quadriparetic with persistent hoarseness.

Case 3

A 69-year-old white woman presented with weakness, which had developed over a 10 - 14-day period, and complaints of numbness and paraesthesiae in the hands and feet. She was known to have VP and reported that her last acute porphyric attack some 30 years previously had been characterised by abdominal pain and an impaired level of consciousness. The current attack was probably precipitated by antituberculosis treatment that had been started for pulmonary tuberculosis. The patient’s weakness quickly progressed to respiratory failure, necessitating intubation and ventilation. On examination, she showed facial weakness and a global power of only grade 2/5 with 1+ reflexes in the upper limbs and absent reflexes in the lower limbs. The urinary PBG level was elevated at 201 µmol/L, total urinary porphyrins were 1 516 nmol/L and faecal porphyrins were markedly elevated at 5 736 nmol/g dry weight. The plasma emission spectrum revealed a peak at 625 nm, consistent with a diagnosis of VP. Molecular genetic analysis confirmed the presence of the R59W mutation. Severe hyponatraemia developed with the administration of glucose solutions, and although haemin was finally administered after 3 weeks, the patient’s clinical condition continued to deteriorate. She developed multiple complications related to critical care and ultimately died due to sepsis after 4 months in the intensive care unit.

Case 4

A 32-year-old white man presented with acute abdominal pain, con­ fusion and hallucinations, followed by rapidly progressive weakness of the arms more than the legs and generalised seizures. He had taken antiretroviral therapy for post-exposure prophylaxis before this admission. On examination, he was acutely delirious, with facial weakness, proximal weakness of grade 0/5 and distal weakness of 1/5 in the arms, and proximal weakness of 2/5 and distal weakness of 4/5 in the legs. The ankle reflexes were the only reflexes that were retained. The urine was a dark brown colour and porphyria investigations revealed a positive urinary PBG screening test, total urinary porphyrins of 1 429 nmol/L and markedly elevated faecal porphyrins. The plasma emission spectrum was maximal at 625 nm, in keeping with VP. The R59W mutation was also positive. Haemin was administered after 5 days, leading to amelioration of the delirium and seizures. Although the weakness in the legs improved somewhat, the arms remained severely weak even at follow-up 4 months later.

Discussion

AIP and VP form part of the acute hepatic porphyrias, which are associated with a range of extrahepatic, gastrointestinal and neurological and psychiatric manifestations.[4] During an acute attack, haem precursors accumulate in front of the deficient enzyme, which in AIP is porphobilinogen deaminase and in VP protoporphyrinogen oxidase. The excess porphyrin metabolites are then excreted in the urine and faeces according to a characteristic pattern. In AIP urinary ALA and PBG are markedly elevated, and in VP urinary ALA, PBG and coproporphyrinogen levels are high. Protoporphyrinogen is usually markedly elevated in the faeces in VP.[4] These patterns were also observed in our patients, and genetic confirmation was available in both of our patients with VP.

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Typical acute porphyria attacks begin with severe abdominal pain, which may sometimes lead to exploratory laparotomies; consti­ pation, nausea and vomiting may be associated symptoms. The pain is usually followed by psychiatric disturbances which include confusion, delirium, hallucinations, and frank psychosis.[4,5] Autonomic instability with tachycardia and elevated blood pressure may be present and generalised tonic-clonic or partial seizures commonly occur. Mental changes may progress to coma. Only one of our patients presented with this typical clinical picture of abdominal pain followed by psychiatric disturbances and convulsions; the others showed varying degrees of intermittent confusion in the ward, but did not report any abdominal pain preceding admission.

Our patients all presented with an acute onset of progressive quadriparesis. However, the peripheral neuropathy of porphyria is reported to develop typically after the onset of abdominal pain and psychiatric disturbances. Three of our patients did not give any history of acute abdominal pain. Porphyric neuropathy may develop within 3 - 75 days after the onset of abdominal pain,[6] and 80% of patients develop the neuropathy within 1 month. A study by Hift and Meissner[7] from SA reported that a sudden cessation of abdominal pain in an acute attack may actually constitute a warning of an incipient quadriparesis.

These authors considered presentation without pain as highly atypical, a view that may, as in our patients, lead to consideration of Guillain-Barré syndrome as a cause for the severe weakness. One study from the USA, however, did not find a single case of porphyria in 450 patients with Guillain-Barré syndrome who were screened for the condition. [8] Our cases emphasise that in SA specifically, clinicians should have a high index of suspicion not only for VP, which is well known to have a high incidence in the white population, but also for AIP in patients of all population groups presenting with a Guillain-Barré-like picture.

The typical electrophysiological findings in porphyric neuro­pathies show an axonal mainly motor neuropathy, with varying sensory involvement.[9,10] Previous reports have demonstrated that electro­ physiological improvement of the neuropathy can take many months.

In one patient report, not all nerve conduction studies had returned to normal even after a period of over 21 months.[11] All our patients had low CMAP amplitudes on the nerve conduction studies of motor nerves, and in one patient, electrophysiological deterioration after 2 months was documented, with absent responses of the ulnar and peroneal nerves that had previously been present. This was also the patient who did very poorly and died in the intensive care unit without regaining the ability to breathe autonomously. No specific reports were found that correlated CMAPs with prognosis in porphyric neuropathy, but studies in patients with Guillain-Barré syndrome have shown that a very low CMAP (<10% of normal) is associated with a poor outcome.[12] In our patient, a superimposed critical care neuropathy, as well as the severe hyponatraemia aggravated by the glucose solutions against which Hift and Meissner[7] have cautioned, may have contributed to the findings and poor outcome.

Information on the prognosis of porphyric neuropathy is limi­ ted. As mentioned, the degree of axonal damage probably pre­dicts the ultimate prognosis and recovery often takes many months with some patients remaining permanently quadriparetic.[4,13] In the SA study that reported on clinical features recorded during 112 acute porphyric attacks, three patients with quadriparesis improved with rehabilitation and eventually regained the ability to walk. In the same study, several other patients with pre-existing neuropathy deteriorated markedly at the onset of a new attack, but the weakness resolved rapidly after haemin administration.[7] One patient with AIP improved even after a long period of being bedridden when a course of haemin was given,[14] and other authors similarly report a favourable outcome after haemin administration.[15] Unfortunately, the administration of haemin was delayed in most of our patients owing to local unavailability of the drug, which may have worsened

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the outcome, since studies recommend early administration of haemin[7,16] to limit or reverse the toxic effects of haem precursors on the peripheral nerves.

Porphyric attacks can be precipitated by many factors, the most common being restricted caloric intake, alcohol, hormones and specific medications.[4] Interestingly, in two of our patients we believe that the attack was precipitated by antiretroviral medication – one patient was started on highly active antiretroviral therapy (HAART) before the onset of the symptoms, and the other took antiretroviral medication for post-exposure prophylaxis. In the first case, the patient received tenofovir, emtricitabine and efavirenz. Although not many reports linking acute porphyria with these medications are available, one recent report describes a patient with VP who developed an acute attack after receiving the same HAART.[17] Drugs that induce cytochrome P450 proteins (CYP), by causing haem depletion, lead to enhanced transcription of the rate-limiting enzyme of the haem biosynthetic pathway, 5-aminolaevulinate synthase.[17] Since antiretroviral drugs that induce CYP3A4 and 2C9 have the greatest porphyrinogenicity, it is likely that the efavirenz (a strong CYP3A4 inducer) in the abovementioned regimens precipitated the acute attacks.[17] Treating HIV infection in patients with porphyria is therefore challenging.

Conclusion

Our cases emphasise that acute and severe porphyric neuropathy can occur without preceding symptoms and that this condition should be considered in patients with a Guillain-Barré-like clinical presentation. It is important to note that attacks may be precipitated by antiretroviral therapy, and that in SA speci­ fically, care should be taken when prescribing HAART and antituberculosis drugs to patients with possible porphyria. The availability of haemin proved to be problematic in our setting,

and streamlining the process of obtaining this medication should be made a priority in public hospitals.

1. Puy H, Gouya L, Deybach J-C. Porphyrias. Lancet 2010;375(9718):924-937. [http://dx.doi.org/10.1016/ S0140-6736(09)61925-5] 2. Floderus Y, Shoolingin-Jordan PM, Harper P. Acute intermittent porphyria in Sweden: Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin Genet 2002;62(4):288-297. [http://dx.doi.org/10.1034/j.1399-0004.2002.620406.x] 3. Meissner PN, Dailey TA, Hift RJ, et al. A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet 1996;13(1):95-97. [http://dx.doi.org/10.1038/ng0596-95] 4. Albers JW, Fink JK. Porphyric neuropathy. Muscle Nerve 2004;30(4):410-422. [http://dx.doi. org/10.1002/mus.20137] 5. Nia S. Psychiatric signs and symptoms in treatable inborn errors of metabolism. J Neurol 2014;261(Suppl 2):S559-S568. [http://dx.doi.org/10.1007/s00415-014-7396-6] 6. Ridley A. Porphyric neuropathy. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R, eds. Peripheral Neuropathy. Philadelphia: Saunders, 1984:1704-1716.

7. Hift RJ, Meissner PN. An analysis of 112 acute porphyric attacks in Cape Town, South Africa: Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity. Medicine 2005;84(1):48-60. [http://dx.doi.org/10.1097/01.md.0000152454.56435.f3] 8. The Guillain-Barré Syndrome Study Group. Plasmapheresis and acute Guillain-Barré syndrome.

Neurology 1985;35(8):1096-1104.

9. Albers JW, Robertson WC Jr, Daube JR. Electrodiagnostic findings in acute porphyric neuropathy.

Muscle Nerve 1978;1(4):292-296. [http://dx.doi.org/10.1002/mus.880010405] 10. Flügel KA, Druschky KF. Electromyogram and nerve conduction in patients with acute intermittent porphyria. J Neurol 1977;214(4):267-279. [http://dx.doi.org/10.1007/BF00316572] 11. Kuo H-C, Lee M-J , Chuang W-L, Huang C-C. Acute intermittent porphyria with peripheral neuropathy: A follow-up study after hematin treatment. J Neurol Sci 2007;260(1-2):231-235. [http:// dx.doi.org/10.1159/000330683] 12. Miller RG, Peterson GW, Daube JR, Albers JW. Prognostic value of electrodiagnosis in Guillain-Barré syndrome. Muscle Nerve 1988;11(7):769-774. [http://dx.doi.org/10.1002/mus.880110714] 13. Wikberg A, Andersson C, Lithner F. Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria. J Intern Med 2000;248(1):27-32. [http://dx.doi.org/10.1046/j.1365-2796.2000.00697.x] 14. Albertyn CH, Sonderup M, Bryer A, Corrigall A, Meissner P, Heckmann M. Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man. S Afr Med J 2014;104(4):283-285. [http://dx.doi.org/10.7196/SAMJ.7785] 15. Muthane UB, Vengamma B, Bharathi KC, Mamatha P. Porphyric neuropathy: Prevention of progression using haeme-arginate. J Intern Med 1993;234(6):611-613. [http://dx.doi.org/10.1111/j.1365-2796.1993.tb01022.x] 16. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005;142(6):439-450. [http://dx.doi.org/10.7326/0003-4819142-6-200503150-00010] 17. Pavitt CW, Rampling T, Byrne R, Tyebally S, Reid T, Nelson M. Acute porphyria precipitated by efavirenz. AIDS 2015;29(8):981-982. [http://dx.doi.org/10.1097/QAD.0000000000000615]

Accepted 29 September 2015.

HEALTHCARE DELIVERY

Comparison of two text message (mHealth) campaigns for the Deaf: Contracted out v. conducted in-house D Hacking, Y K Lau, H J Haricharan, M Heap At the time of this study, Damian Hacking (MPH), Yan Kwan Lau (MPH), Hanne Jensen Haricharan (MA) and Marion Heap (PhD) were all working in the Health and Human Rights Programme, as part of the School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. Marion’s research focuses on overcoming barriers to accessing health services by the Deaf community. Use of health technologies is one approach to overcoming these barriers, which is being investigated as part of ongoing research by second-language English speakers and the Deaf community.

Corresponding author: D Hacking (damianuct@gmail.com)

Cell phone-based health information (mobile health or mHealth) campaigns are an emerging technology. This evaluation focused on the aspect of cost of two health information campaigns, one on hypertension and one on pregnancy. Researchers could either contract out the technical components of the campaigns or attempt to run the campaigns themselves, in-house. The in-house campaigns cost an estimated ZAR13 548.72 v. the private provider quotes which ranged from ZAR27 542.97 to ZAR34 227.59. Running the campaigns in-house was more labour intensive and required more technical expertise, but had a reduced delivery failure rate (9.2% in-house v. 30.0% private provider). Running small to medium SMS (text message) campaigns for evaluative purposes proved advantageous over contracting out to private providers. Larger-scale evaluations and full-scale roll-out will require the services of private providers, but it is still essential that researchers actively engage with and monitor the technical aspects of these campaigns.

S Afr Med J 2016;106(1):47-49. DOI:10.7196/SAMJ.2016.v106i1.9640

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South Africa (SA) is in­creas­ ingly adopting mo­ bile health or mHealth inter­ ventions[1] (the practice of medicine and public health with the use of mobile devices to enable communication between healthcare workers and patients), with cell phone-based campaigns increasingly seen as a means to bridge health information gaps.[2] This is due in part to the high prevalence of cell phone ownership, even in resource-poor settings.[3] South Africans often have more than one mobile phone subscription, with a ratio of 147 cell phone subscriptions per 100 people.[4] As yet, however, there are relatively few comprehensive evaluations of these health information campaigns, especially of their cost.[5] We report an evaluation of the cost of two campaigns in which the costs of outsourcing short message service (SMS, i.e. text message) campaigns to a service provider were compared with conducting them in-house. We comment on the advantages and disadvantages of both methods, including some of the technical challenges encountered in the process of carrying out in-house and outsourced SMS campaign evaluations.

SMS campaigns

Two SMS health information campaigns, one on hypertension and one on pregnancy (University of Cape Town Health Sciences Faculty Human Research Ethics Committee ethics reference numbers 043/2011 and 044/2011, respectively), were carried out in resource-poor settings in Cape Town, SA (2011 - 2013), among hearing clinic attenders at two public health facilities.[6,7] The data capturing and storage of the baseline and exit questionnaires used to assess the effectiveness of these campaigns, as well as the management of the SMS campaigns, including opt-outs during the campaigns, were contracted out to a private provider.

Following this, two similar campaigns were carried out among signing deaf people (the Deaf) at similar socioeconomic but nonclinical sites.[8,9] For the Deaf SMS campaigns, those aspects that had previously been contracted out were dealt with in-house.

In both the hearing and Deaf campaigns the administration of the questionnaires and collection of all data was performed by in-house fieldworkers.

To capture baseline and exit data and store data for the Deaf SMS (in-house) campaigns, a Google Apps for Education subscription was purchased, and each fieldworker was given their own account. Google Forms was used to create baseline and exit questionnaires, which were accessed from General Packet Radio Service (GPRS)-enabled phones. Data

were automatically uploaded onto a Google spreadsheet via form submission, and the entire database was exported for further analysis and construction of SMS mailing lists. For sending out of the SMSs, bulk SMSs were purchased from a mobile network service provider in SA. The online interface allowed for bulk SMSs to be scheduled on a calendar, for specific days and times. SMSs were directly imported from an SMS mailing list spreadsheet, and were scheduled on the calendar on a per-week basis, with individuals who opted out exiting the program at the end of the week. Each week a researcher ensured that bulk SMSs were set up, removed any opt-outs and tracked delivery failures for follow-up. Opt-outs were determined by asking participants to send two free ‘please call me’ SMSs to a dedicated cell phone in short succession in order to minimise costs to the user (‘please call me’ SMSs are a free service that allows mobile users to send a predetermined text message asking the recipient to call the senders number, and are available on all networks in SA).

Comparison between outsourced and in-house

The costs of running the in-house SMS campaigns, including human resources, were calculated at the end of the campaigns and compared with quotes received from private providers prior to initiation of the campaigns, adjusted for any changes in the campaigns (e.g. number of SMSs quoted for v. actual number of SMSs sent). In total the Deaf SMS campaigns cost an estimated ZAR13 548.72 to run (costs for 2014). Quotes for equivalent campaigns ranged from ZAR27 542.97 to ZAR34 227.59. Costs are divided into four sections, outlined in Table 1. In addition to these cost savings, 30.0% of all SMSs reported delivery failure to the participants

by the private provider. In-house SMSs, on the other hand, had a delivery failure rate of 9.2% (10.4% in the pregnancy campaign and 8.5% in the hypertension campaign).

There is some uncertainty surrounding the exact cost of the in-house campaigns, as the researchers who oversaw the training component were not hired specifically for this role, and so a cost of their time devoted to the campaigns was estimated. However, even if their costs were tripled, in-house would still be notably cheaper than the two private contractors. As such, completing the SMS campaigns in-house had considerable savings. Furthermore, if the lower delivery failure rate were to be factored into the cost of the SMS by looking at a cost per successful SMS sent, the savings would be even greater.

A considerable amount of management was required to set up the software and hardware for data capturing and recruitment.

The Google interface was user friendly and allowed the creation of a questionnaire that could be accessed via the cell phones of the fieldworkers. The main advantage of this technique was that Google Forms had a high cross-compatibility with many phones, as long as they had basic internet access (Google Forms cannot capture data offline). The data were also kept in Google Cloud storage, which has the advantage of reducing the chance of data loss and increasing data accessibility, but could potentially have confidentiality issues if the security of the database was compromised.

However, Google is one of the more secure cloud services, and after consultation with information technology experts, it was felt that this would not pose a significantly greater risk than conventional cabinet file storage.

In addition, Google provides very useful security features, allowing administrators to

Table 1. Breakdown of costs for the Deaf SMS campaigns (in-house v. private contractor quotes)* In-house

Private contractor 1

Private contractor 2

Cost per SMS

32c

20c

50c

Total SMSs sent

10 121

10 121

10 121

Total SMS cost

ZAR3 238.72

ZAR2 024.20

ZAR5 060.50

Administration fees

ZAR5 160.00

ZAR28 000.00

ZAR13 200.00

Training fees

~ZAR5 000.00

ZAR2 800.00

Software fees

~ZAR150.00‡

ZAR300

†

Total (excl. VAT)

ZAR30 024.20

ZAR24 160.50

VAT

ZAR4 203.39

ZAR3 382.47

ZAR34 227.59

ZAR27 542.97

Total (incl. VAT)

ZAR13 548.72

Costs are broken down into cost of SMSs sent, administration fees, training fees and software fees. Private contractor quotes were broken down into these sections as well as we were able. † Training fees included setting up of the service in this case. Three research assistants were involved in this process. It is hard to disentangle the exact cost of these three researchers; however, one was paid on an hourly basis, which was used in conjunction with an estimate of relative contribution of the three researchers to arrive at this final figure. ‡ Software fees were Google subscription fees (EUR10.00). These are charged per year. Our campaigns only lasted 3 months, but the minimum subscription is for 1 year. *

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delete data remotely off a phone in the case of loss or theft of the phone and to vary the degree of data access per user.

Researchers were required to administer the in-house SMS campaigns continuously. Because mailing lists for SMSs could not be edited once scheduled, the SMSs were scheduled on a weekly basis to allow for any opt-outs. This required continuous administration and entry of the bulk SMSs. However, the same amount of work would still be required at the beginning to set up all bulk SMSs, and continuous administration would still be required to remove optouts. The researchers managing the campaigns had a vested interest in ensuring their success, and so were likely to micromanage them more efficiently and detect any problems that arose. Furthermore, researchers needed proficiency in cloud computing and mobile technologies. Our experience has been that this is not as daunting a task as it may seem at first. A baseline level of knowledge is required, but with enough training even modestly computer-literate researchers could engage with the campaigns. Furthermore, both Google and bulk SMS service providers provided effective and prompt troubleshooting services when needed.

While the use of a private provider obviated the need for both the setup and ongoing administration of the SMS campaigns, intense communication and monitoring of the private provider was still required. Data capturing of the in-house results was time intensive, as the Google system does not allow for automatic coding of responses, whereas the previously used private provider does. However, the coding from the private provider was not perfect and needed to be adjusted prior to analysis, so was not infallible either. Lastly, the in-house campaigns had a three times lower delivery failure rate than the private provider. This significantly improved the reliability of the results and therefore the strength of the conclusions.

Conclusion

In conclusion, we would strongly recomm­end that any group wishing to evaluate a small- to medium-scale mHealth project should consider doing it themselves using the readily available services. Not only is it cheaper, but it also allows for greater control over the campaigns, accountability and autonomy, which results in a better-run campaigns and more reliable research results. Larger-scale projects would probably need to be assigned to a private provider, but a degree of diligence is required to ensure that the services provided are correctly delivered and monitored.

1. Leon N, Schneider H. mHealth4CBS in SA. 2012. http://www.mrc.ac.za/healthsystems/MHealth4CBSReview. pdf (accessed 1 November 2014).

2. World Health Organization. mHealth: New Horizons for Health Through 414 Mobile Technologies. Geneva: WHO, 2011. http://www.who.int/goe/publications/goe_mhealth_web.pdf (accessed 1 November 2014).

3. Betjeman TJ, Soghoian SE, Foran MP. mHealth in sub-Saharan Africa. Int J Telemed Appl 2013;Jan:482324. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3867872&tool=pmcentr ez&rendertype=abstract (accessed 1 August 2014).

4. World Bank. 2013. http://data.worldbank.org/indicator/IT.CEL.SETS.P2 (accessed 26 August 2014).

5. Vodopivec-Jamsek V, de Jongh T, Gurol-Urganci I, Atun R, Car J. Mobile phone messaging for preventive health care. Cochrane Database Syst Rev 2012, Issue 12. Art. No.: CD007457. [http://dx.doi. org/10.1002/14651858.CD007457.pub2] 6. Lau YK, Cassidy T, Hacking D, Brittain K, Haricharan HJ, Heap M. Antenatal health promotion via short message service at a midwife obstetrics unit in South Africa: A mixed methods study. BMC Pregnancy Childbirth 2014;14(1):284. [http://dx.doi.org/10.1186/1471-2393-14-284] 7. Lau YK, Brittain K, Hacking D, Cassidy A, Haricharan HJ, Heap M. An evaluation of a short message service (SMS) hypertension health promotion at a community health centre (CHC) in Cape Town: A cautionary tale. Proceedings of the Public Health Association of South Africa Conference, Cape Town, 24 September 2013. https://www.phasa.org.za/ (accessed 20 November 2015).

8. Haricharan HJ, Heap M, Cassidy A, Lau YK, Hacking D. Bridging the language divide? Health promotion via short message system (SMS) advancing access to health information for Deaf and hearing adults in Cape Town. Presented at the Academy of Science of South Africa Symposium on Science and Society in Africa, Stellenbosch, South Africa, 18 September 2014. http://www.sayas.org. za/ (accessed 20 November 2015).

9. Haricharan HJ, Heap M, Lau YK, Hacking D. ‘So it’s like a learning curve’: Health promotion via short message system (SMS) advancing access to health information for signing Deaf adults in Cape Town?

Presented at the Research Day, School of Public Health and Family Medicine, University of Cape Town, 25 September2014.

Accepted 2 November 2015.

HEALTHCARE DELIVERY

Taking kangaroo mother care forward in South Africa: The role of district clinical specialist teams U Feucht, E van Rooyen, R Skhosana, A-M Bergh Ute Feucht is the paediatrician on the Tshwane District Clinical Specialist Team, Tshwane District Health Services, South Africa, and an adjunct professor in the Department of Paediatrics, Faculty of Health Sciences, University of Pretoria and Kalafong Hospital, Pretoria, South Africa. Elise van Rooyen is a medical officer in the Department of Paediatrics, Kalafong Hospital, and a lecturer in the Department of Paediatrics, University of Pretoria. Rinah Skhosana is the paediatric nurse on the Tshwane District Clinical Specialist Team. Anne-Marie Bergh is a senior researcher at the MRC Unit for Maternal and Infant Health Care Strategies, Faculty of Health Sciences, University of Pretoria.

Corresponding author: U Feucht (ute.feucht@up.ac.za)

The global agenda for improved neonatal care includes the scale-up of kangaroo mother care (KMC) services. The establishment of district clinical specialist teams (DCSTs) in South Africa (SA) provides an excellent opportunity to enhance neonatal care at district level and ensure translation of policies, including the requirement for KMC implementation, into everyday clinical practice. Tshwane District in Gauteng Province, SA, has been experiencing an increasing strain on obstetric and neonatal services at central, tertiary and regional hospitals in recent years as a result of growing population numbers and rapid up-referral of patients, with limited down-referral of low-risk patients to district-level services. We describe a successful multidisciplinary quality improvement initiative under the leadership of the Tshwane DCST, in conjunction with experienced local KMC implementers, aimed at expanding the district’s KMC services. The project subsequently served as a platform for improvement of other areas of neonatal care by means of a systematic approach.

S Afr Med J 2016;106(1):49-51. DOI:10.7196/SAMJ.2016.v106i1.10149

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Low birth weight (LBW) and prematurity are significant contributors to neonatal mortality and have become major barriers in reaching child mortality targets.[1] Kangaroo mother care (KMC) is a high-impact, lowtech, cost-effective intervention to reduce neonatal mortality and morbidity.[2] It has proven advantages in terms of infant feeding and weight gain and reduced infection risks, as well as improved maternal physical and psychological health, with an accompanying reduction in health institution utilisation.[3-7] The KMC components include securing infants skin-to-skin to their mothers’ chests in an upright position by means of a cloth or wrap, exclusive breastfeeding, early hospital discharge and adequate support of the mother-infant pair by health workers and family members.[8] The current global implementation and research agenda for improved newborn care includes accelerated KMC scale-up.[2,9] KMC has also become part of South African (SA) health policy through initiatives such as the Tshwane Declaration[10] and the Campaign on Accelerated Reduction of Maternal and Child Mortality in Africa. [11] The primary healthcare re-engineering process currently under way in SA is an excellent opportunity to enhance neonatal care and ensure translation of these policies into practice.[12] The district clinical specialist teams (DCSTs), comprising senior medical and nursing personnel in the fields of primary, maternal, paediatric and emergency care, form one of the pillars of this health system improvement initiative.[13,14] Their roles include training, supportive supervision, clinical governance and helping to establish the necessary linkages between hospital-based neonatal units, primary healthcare facilities, district-based health programme staff and communitybased organisations, all of which can potentially greatly enhance the neonatal care continuum. DCSTs are not facility based and are therefore not constrained by systems boundaries between the different levels of healthcare, which enables the members to move between the various health facilities in order to facilitate care networks, with an anticipated impact at health systems level.

This article describes a quality improve­ment process undertaken in the Tshwane District, Gauteng Province, in which strengthening of KMC was used as an entry point for the improvement of neonatal care under the supervision of the DCST. The district, which covers the northern part of Gauteng and has an urban and rural population of about three million people, has undergone major changes in the past 15 years with new boundary demarcations adding two district hospitals to the health facilities requiring oversight.[15] Currently there are two central, one tertiary, one regional and four district hospitals. The Tshwane DCST was established in 2012 and has a full complement of staff that includes three specialists, two medical officers and three professional nurses with advanced training.

Making KMC work in practice

Initial KMC training and implementation initiatives in Gauteng[16] had limited impact at scale as various factors hindered full KMC implementation in all hospitals. By 2013 Tshwane District had 45 KMC beds at tertiary institutions, 5 beds at the regional hospital and only 20 KMC beds for down-referrals at district hospital level. The district’s expanding population, with a resultant increase in deliveries, was placing a strain on obstetric and neonatal services at the large hospitals. The growing neonatal bed shortages were compounded by rapid up-referral of patients from district hospitals to higher levels of care, with very few patients reversely down-referred to district hospitals. The DCST, in conjunction with experienced local KMC implementers, identified this gap and jointly embarked on a quality improvement initiative from 2013 to 2015 to facilitate KMC scale-up.

The activities included three workshops and one walk-through visit to each hospital to provide support and assess the level of facility-based KMC implementation.

50

Training workshops with a multi­disciplinary team from each hospi­ tal were held in November 2013 and April 2014 and were attended by doctors, nurses, dieticians and other allied health workers.

Additional attendees were members of the health system support structures, namely the Tshwane District Maternal, Newborn, Child and Women’s Health (MNCWH) and Nutrition subdirectorate. The Tshwane DCST members provided workshop support and were upskilled simultaneously. Each workshop comprised two main components: feedback on each hospital’s KMC implementation process (including achievements and challenges), and training sessions. Struggling hospitals were encouraged to conduct benchmark visits to hospitals with well-established KMC units and to identify local champions to initiate KMC implementation with the support of the DCST. In July 2014, every hospital was visited by a team consisting of the DCST, experienced local KMC implementers and other members from the Tshwane District office. The walk-through visits also provided an in-service training opportunity for capacity building through supportive supervision. A standard progress monitoring tool was used for evaluating KMC implementation in each hospital.[16,17] A follow-up workshop was then held in May 2015 to ensure continued feedback from facilities on their KMC implementation progress and to discuss further topics related to the improvement of KMC practice and services.

Lessons learned: The role of DCSTs in KMC implementation

The project-type approach to advancing a specific aspect of neonatal care – in this case KMC implementation – was an excellent vehicle for implementing health systems improvements. Ongoing monitoring and evaluation of neonatal healthcare was already in place, but a focused intervention was required to strengthen KMC services at all hospitals through a team-orientated approach, with subsequent expansion

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to other neonatal care issues. This quality improvement initiative was introduced without additional funding, which demonstrates how resources can be mobilised to effect change. The process was furthermore enabled by national and provincial priority setting, with existing policies and guidelines strengthening the DCST’s ability to encourage all hospitals to participate, with the necessary support of the hospital management.

Empowerment of staff in the participating hospitals was achieved through workshops and on-site visits, with accompanying mentoring through a non-hierarchical approach. The equal empowering relationships helped promote ownership at hospital and district level, with mutual benchmarking visits leading to a high degree of transfer of learning.

Insights that emerged from the process included: • The importance of the non-separation of mother-infant pairs to encourage bonding and give babies a ‘voice’ through their mothers • The empowerment of mothers to take responsibility for the care for their LBW and preterm babies under medical and nursing supervision, with a focus on ‘special-needs groups’ with social or medical risk factors • The need for onsite protocols and guidelines • The integration of KMC with other maternal and child health programmes at facility level (e.g. family planning, HIV prevention and immunisation services), with the KMC environment providing the time and space for services to be delivered to these high-risk populations • The need to provide KMC wraps to ensure continued KMC practice after discharge.

Successful KMC implementation requires partnerships between neonatal and obstetric care workers, family physicians and primary healthcare nurses, illustrating the importance of a multidisciplinary team approach to effect change, with team members from different disciplines complementing each other. Collaboration between tertiary and district hospitals was additionally enabled. The workshops provided an egalitarian platform for dealing with weaknesses in the system in a relatively formal way, with discussions around particular index patients leading to further discussion on systems improvements.

The partnerships stretched beyond the DCST and included MNCWH and Nutrition staff members, as well as other clinical and management experts working at health institutions within the district boundaries. This provided the potential for the combination of clinical expertise, mentoring and health systems improvements.

Within any given DCST the required expertise to address particular clinical issues may not be available, but project implementation may benefit greatly from the inclusion of local experts. KMC units in the Tshwane hospitals additionally strengthened their collaboration with the in-facility allied health workers.

51

The permanent presence of the DCST in the district ensures contin­uous supportive supervision, thereby enabling accountability, mentoring and follow-up with encouragement of the onsite staff members beyond a once-off project. Relationships of trust and local ownership were identified as the basic characteristics of supportive supervision in a context in which home-grown solutions can be promoted successfully. Local initiative with the development of protocols and guidelines was supported, but the DCST also had sufficient authority to implement and monitor the use of protocols and guidelines in hospitals showing slow progress.

The chosen team approach, together with appropriate supportive supervision, had the potential ability to influence or effect change.

Improvements included appropriate medical care for late preterm infants, correct use of a breastmilk fortifier, and improved breast­feeding by mothers after hospital discharge. Infrastructural con­straints were highlighted with an emphasis on the provision of a thermoneutral environment in all areas designated for neonatal care. While the project was being implemented the number of KMC beds in the district hospitals increased from 20 to 39, thereby almost doubling the KMC capacity.

Additionally, improved cross-referrals were observed between hospitals in terms of specialised neonatal follow-up services. Staff morale and enthusiasm visibly improved in the period during which the workshops and support visits were held, and the DCST members had the authority to work with clinicians and facility management in order to address local KMC barriers that appeared insurmountable at times.

Conclusion

Mortality and morbidity in preterm and LBW infants can be reduced through healthcare interventions for the mother-infant pair before and during pregnancy and after birth.[18] The service provision of the relevant healthcare focus areas needs to be institutionalised and not individually driven, in order to reduce fluctuation in service delivery with staff mobility.

At the same time the maintenance of the neonatal care continuum relies on teamwork between the different care providers. The KMC implementation project described here was successful in improving KMC services in the Tshwane district, and it served as a platform from which to improve other areas of neonatal care by using a systematic approach.

Acknowledgements. The support of the members of the Tshwane DCST and MNCWH and Nutrition subdirectorate is acknowledged with thanks. Managers and clinical staff at the hospitals are thanked for their collaboration.

1. Howson C, Kinney M, McDougall L, Lawn J, on behalf of the Born Too Soon Preterm Birth Action Group. Born too soon: Preterm birth matters. Reprod Health 2013;10(Suppl):S1. http://www.reproductive-health-journal.com/ content/10/S1/S1 (accessed 29 September 2015).

2. World Health Organization. Every Newborn: An Action Plan to End Preventable Deaths. Geneva: WHO, 2014.

3. Conde-Agudelo A, Diaz-Rossello J. Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database Syst Rev 2011, Issue 3. Art. No.: CD002771. [http://dx.doi.org/10.1002/14651858.

CD002771.pub2] 4. Lawn JE, Mwansa-Kambafwile J, Horta BL, Barros FC, Cousens S. ‘Kangaroo mother care’ to prevent neonatal deaths due to preterm birth complications. Int J Epidemiol. 2010;39(Suppl 1):i144-i154. [http://dx.doi.org/10.1093/ije/dyq031] 5. Ludington-Hoe SM, Morgan K, Abouelfettoh A. A clinical guideline for implementation of kangaroo care with premature infants of 30 or more weeks’ postmenstrual age. Adv Neonatal Care 2008;8(3 Suppl):S3-S23. [http://dx.doi. org/10.1097/01.ANC.0000324330.25734.b6] 6. Affonso D, Bosque E, Wahlberg V, Brady J. Reconciliation and healing for mothers through skin-to-skin contact provided in an American tertiary level intensive care nursery. Neonatal Netw 1993;12(3):25-32.

7. De Alencar A, Arraes L, de Albuquerque E, Alves J. Effect of kangaroo mother care on postpartum depression. J Trop Pediatr 2009;55(1):36-38. [http://dx.doi.org/10.1093/tropej/fmn083] 8. Ruiz JG, Charpak N, et al. Evidence-based Clinical Practice Guidelines for an Optimal Use of the Kangaroo Mother Method in Preterm and/or Low Birthweight Infants at Birth. Bogotá: Fundación Canguro and Department of Clinical Epidemiology and Biostatistics, School of Medicine, Pontificia Universidad Javeriana, 2007.

9. Engmann C, Wall S, Darmstadt G, Valsangkar B, Claeson M, on behalf of the participants of the Istanbul KMC Acceleration Meeting. Consensus on kangaroo mother care acceleration. Lancet 2013;382(9907):e26-e27. [http:// dx.doi.org/10.1016/S0140-6736(13)62293-X] 10. The Tshwane declaration of support for breastfeeding in South Africa. S Afr J Clin Nutr 2011;24(4):214.

11. Department of Health, Republic of South Africa. South Africa’s national strategic plan for a campaign on accelerated reduction of maternal and child mortality in Africa (CARMMA) 2012. http://www.hst.org.za/sites/default/files/ carmma.pdf (accessed 30 June 2014).

12. Naidoo S. The South African national health insurance: A revolution in health-care delivery! J Public Health 2012;34(1):149-510. [http://dx.doi.org/10.1093/pubmed/fds008] 13. Ministerial Task Team. District Clinical Specialist Teams in South Africa. Ministerial Task Team Report to the Honourable Minister of Health, Dr Aaron Motsoaledi. 2012. http://www.rmchsa.org/wp-content/resources/ resources_by_type/DistrictLevelResources/MinisterialTTReport_DCSTInSouthAfrica.pdf (accessed 13 February 2013).

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14. Connell L. A Clinical Governance Handbook for District Clinical Specialist Teams. Durban: Health Systems Trust, 2014.

15. Ganief A, Thorpe J. City of Tshwane General and Regional Overview. Cape Town: Parliament of the Republic of South Africa, 2013. http://www.parliament.gov.za/content/Tshwane_General_and_Regions_Report_2013.pdf (accessed 10 September 2015).

16. Bergh A-M, van Rooyen E, Pattinson RC. ‘On-site’ versus ‘off-site’ facilitation: A randomised trial of outreach strategies for scaling up kangaroo mother care. Hum Resour Health 2008;6:13. [http://dx.doi.org/10.1186/1478-4491-6-13]

17. Bergh A-M, Arsalo I, Malan A, Pattinson R, Patrick M, Phillips N. Measuring implementation progress in kangaroo mother care. Acta Paediatr 2005;94(8):1102-1108. [http://dx.doi. org/10.1080/08035250510028380] 18. World Health Organization. WHO Recommendations on Interventions to Improve Preterm Birth Outcomes.

Geneva: WHO, 2015.

Accepted 27 October 2015.

Freezing healthcare posts “counter-productive,” say doctors

The freezing of critical physician and nursing posts in at least five provinces is “dangerously short-sighted” and will hurt vulnerable patient populations, boost billion rand litigation costs and aggravate working conditions, the SA Medical Association warned yesterday.

Introduced as austerity measures in stark contrast to the mushrooming of middle and senior management placements in recent years, the freezing of these critical service delivery posts this December and January comes exactly when most doctors and nurses are seeking them. Chairman of SAMA, Dr Mzukisi Grootboom said this would result in lost opportunities and chronic staffing shortages for 2016 – with multiple negative knock-on effects.

“Although mention is made of a process whereby critical posts can be unfrozen and advertised, the reality is that this is a long bureaucratic procedure which may require approval from the premier’s office. Over the last few years we have seen a mushrooming of middle and senior management positions in the various provincial departments of health at district and provincial level, with a net decrease in service level posts at institution level,” Grootboom added. The provinces that have frozen the healthcare staff posts are; the North West, Eastern Cape, KwaZulu-Natal, Mpumalanga and Free State.

The SAMA chairperson said many provincial departments of health had received qualified audits by the auditor general, indicating irregular and fruitless expenditure as the primary cause for not achieving a clean audit. Many of their problems were caused by dismal supply chain management, a major contributor to their financial woes.

The SAMA believed that the freezing of critical posts would have a negative impact, not only on patient care, but on working conditions and adverse events in health care. Litigation against departments of health have shown an alarming upward spiralling trend over the last few years with national health minister, Dr Aaron Motsoaledi, calling a summit to deal with this in March and the biggest private sector risk underwriter, the Medical Protection Society, (MPS), appealing for legal reforms at a similar seminar held in November. Grootboom said this litigation trend was set to continue unless the root causes were effectively dealt with.

Training more doctors pointless if you can’t employ them

In addition, the recent drive by the National Health Department to increase the number of medical graduates seemed pointless “if conditions on the floor prevent recruitment and retention of staff.” Many qualified doctors and specialists were forced to seek employment in the well-resourced private sector or emigrate because of the lack of available posts in the public sector. In addition, the training of medical students was often compromised as the burden of service delivery commitments prevented the more experienced doctors from being available to teach and train them.

Grootboom said that when austerity measures were introduced the first posts to be targeted were the medical ones, because there were always medical vacancies in the public sector due to the mobility of doctors. All public healthcare institutions had workloads which needed to be serviced by a defined staffing level. “The freezing of medical officer, specialist and registrar posts is very short sighted and will only serve to further compromise the quality of care being rendered by the public healthcare service to the most vulnerable populations in South Africa,” he concluded.

Contact: Head of PR & Communications Dr Simonia Magardie Spokesperson Chairperson: SAMA Dr Mzukisi Grootboom 30 November 2015

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DIAGNOSIS

Diagnosis of iron deficiency anaemia in hospital patients: Use of the reticulocyte haemoglobin content to differentiate iron deficiency anaemia from anaemia of chronic disease E Schapkaitz, S Buldeo, J N Mahlangu Dr Elise Schapkaitz is a haematologist in the Charlotte Maxeke Johannesburg Academic Hospital National Health Laboratory Service (NHLS) Complex and the Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Dr Suvarna Buldeo is a clinical pathologist at the NHLS and the Department of Haematology, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. Prof. Johnny Mahlangu is Head of the School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Head of the Diagnostic Section and Quality Management in the Department of Molecular Medicine and Haematology, NHLS, and Director of the Bleeding Disorders Unit at Charlotte Maxeke Johannesburg Academic Hospital.

Corresponding author: E Schapkaitz (elise.schapkaitz@nhls.ac.za)

The diagnosis of iron deficiency anaemia in hospital patients with chronic infections and inflammation presents a challenge. Recently laboratory tests such as the reticulocyte haemoglobin content, which are independent of infection and inflammation, have become available for routine diagnostic use.

S Afr Med J 2016;106(1):53-54. DOI:10.7196/SAMJ.2016.v106i1.9934

Iron deficiency is one of the most common nutritional problems in the world and the leading cause of anaemia in children and pregnant women.[1] In South Africa (SA), iron deficiency and anaemia constitute a significant disease burden owing to chronic helminth infections and a predominantly cereal-based diet.[2] Iron deficiency is treatable. Successful management of iron deficiency anaemia (IDA) requires accurate diagnosis followed by investigation of the underlying cause of iron loss and treatment with iron supplements. Accurate diagnosis demands differentiation of IDA from the anaemia of chronic disease (ACD), also referred to as anaemia of inflammation. In hospital patients, chronic infection(s) and inflammation often coexist with iron deficiency. In SA there is a high burden of chronic infections such as tuberculosis and HIV.[3] Anaemia has been reported in up to 95% of HIV patients, reflecting cytokine dysregulation, drug therapy, presence of infection, presence of malignancy and/or nutritional deficiencies.[4] The distinction between concomitant iron deficiency and ACD is often difficult. Characteristically ACD is a mild to moderate anaemia (haemoglobin concentration 8.0 - 9.5 g/dL), which is normocytic and normochromic. However, ACD may also be microcytic and/or hypochromic. It is then important to distinguish it from true IDA, so that appropriate supplementaion can be administered.

Laboratory investigations

Bone marrow (BM) biopsy and iron staining is considered the gold standard test for the diagnosis of iron deficiency. However, BM biopsy is an invasive procedure and is no longer considered the standard of care for assessment of iron stores.[5] In everyday clinical practice, IDA and ACD are traditionally differentiated by assessment of iron studies, which include serum iron, transferrin, transferrin saturation and ferritin (Table 1).[6] A low ferritin level is

53

highly sensitive for the diagnosis of IDA, but ferritin is also an acutephase reactant showing an increase in the presence of infection or inflammation when iron is sequestered in reticuloendothelial system macrophages. A normal ferritin level therefore does not exclude accompanying IDA.[7] This is evident by the reduced ferritin sensitivity of 46.4% at the clinically recommended cut-off of 30 Âľg/L in hospital patients.[3] More recently, automated analysers can perform tests that are reported to be independent of infection and inflammation. These include biochemical parameters, namely zinc protoporphyrin and soluble transferrin receptor, as well as haematological parameters, namely the percentage of hypochromic red blood cells, and reticulocyte parameters such as the reticulocyte haemoglobin content (CHr). The advantage of measuring the haemoglobin of the reticulocyte is that the reticulocyte has a shorter lifespan (1 - 2 days) than the red cell. CHr therefore provides an early indicator of iron deficiency.[8]

The reticulocyte haemoglobin content

The CHr is a measure of the product of the reticulocyte haemoglobin concentration and the mean cell volume. Several recent studies[8-11] have confirmed the diagnostic performance of the CHr, which is routinely available.

At the National Health Laboratory Service Haematology Lab­ oratory at Charlotte Maxeke Johannesburg Academic Hospital, SA, we performed a prospective study in 74 hospital patients in order to compare the accuracy of the CHr with that of standard haematological and biochemical tests for the diagnosis of IDA using the BM iron stain as the reference.[3] In this study, a CHr of >28 pg reliably distinguished IDA from ACD with a sensitivity of 75.86% and a specificity of 84.10%. CHr is therefore a good discriminator of IDA.

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IN PRACTICE

Table 1. Laboratory findings in, ACD and combined iron deficiency anaemia and anaemia of chronic disease (IDA and ACD)[3] Laboratory test

IDA

ACD

IDA and ACD

MCV

↓

↓ or normal

↓ or normal

MCH

↓

↓ or normal

↓ or normal

Bone marrow iron stores

↓

↑

↓ or normal

CHr (pg)

<28

≥28

<28

Hypochromic red blood cells (%)

>5

<5

>5

Iron

↓

↓

↓

Transferrin

↑

↓ or normal

↓

Transferrin saturation

↓

↓

↓

Ferritin

↓

↑

↓ or normal

sTfR

↑

Normal

Normal or ↑

sTfR-ferritin index

High (>2)

↓

High (>2)

Zinc proptoporphyrin

↑

Normal

Normal or ↑

CRP

Normal

↑

↑

Hepcidin

↓

↑

↑

Haematology

Biochemistry

MCV = mean cell volume; MCH = mean cell haemoglobin; sTfR = soluble transferrin receptor; CRP = C-reactive protein.

However, the diagnostic CHr cut-off values vary according to the study population and diagnostic inclusion criteria, emphasising the importance of determining the CHr cut-off for each specific patient population.

In a study by Karlsson,[10] a higher CHr cut-off of 30.5 pg, corresponding to a sensitivity of 93% and a specificity of 69%, was shown to be indicative of IDA in 54 elderly patients. Studies performed in elderly patients have reported a higher mean cell volume (MCV) and mean cell haemoglobin (MCH) in the IDA and ACD groups.[10,12] A study performed at Pelonomi Regional Hospital, SA, in 100 infants and children aged 6 months - 6 years showed that the optimal CHr cut-off for the diagnosis of iron deficiency was 29 pg. This corresponded to a sensitivity of 86% and a specificity of 50%, using a transferrin saturation of <25% as the diagnostic criterion for iron deficiency.[13] The CHr has been compared with stan­dard haematological and biochemical tests for the diagnosis of IDA. We found that the sensi­ tivity of the CHr was not superior to the MCH parameter or the transferrin saturation, which is similar to the results of two other studies performed in hospital patients in which the authors also concluded that the CHr does not perform better than standard tests for IDA. [10,12] Further studies are required in order to identify an improved marker of iron deficiency in hospital patients compared with standard biochemical and haematological tests.

The CHr test has several advantages. It is a simple and cost-effective test. The current diagnostic panel for IDA, which includes a full blood count (FBC), peripheral smear review and iron studies, costs approximately ZAR610.00. A test panel based on the haematological parameters of FBC and CHr (as part of the reticulocyte count) costs approximately ZAR220.00. The CHr can be performed on 1 - 1.5 mL of blood in a single EDTA tube and in children a finger prick would produce an adequate sample, eliminating the need for additional tubes for the biochemical parameters.

The CHr test does have some obvious current limitations for routine use in that it can only be measured by ADVIA haematology analysers (Siemens Diagnostics, USA), the availability of which is laboratory specific. However, more recently reticulocyte parameters (Ret-He and Ret-Y) on the Sysmex haematology analyser (Sysmex Corporation, Japan) have shown good agreement with the CHr.[12,14] Also, since the CHr is calculated from the reticulocyte MCV, patients with haemoglobinopathy associated with microcytosis will have a falsely low CHr, while patients with megaloblastic anaemia or macrocytic indices (MCV >100 fl), including some patients on antiretroviral therapy, will have a falsely elevated CHr.[15] For the clinician, it is important to interpret the CHr in the context of the patient’s other clinical and laboratory investigations including red

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January 2016, Vol. 106, No. 1

cell indices, vitamin B12, folate levels and findings on haemoglobin electrophoresis.

Conclusion

The diagnostic distinction between IDA, ACD and the combined state of IDA and ACD in hospital patients with chronic infections and inflammation can be diffi­cult with standard biochemical and haemato­ logical tests. Although the CHr test is not superior to standard tests for IDA, it is a simple and cost-effective alternative to biochemical and haematological parameters for the diagnosis of IDA in hospital patients.

It is recommended that in hospital patients with anaemia a C-reative protein (CRP), or other biochemical markers of inflammation, and a CHr be added to the initial FBC assessment. If the CRP is elevated, IDA can be diagnosed in patients with coexistent ACD in the presence of a CHr <28 pg and hypochromic red cell indices.

1. Stoltzfus RJ. Iron deficiency: Global prevalence and consequences. Food Nutr Bull 2003;24(4 Suppl):S99-S103.

2. Nojilana B, Norman R, Dhansay MA, Labadarios D, van Stuijvenberg ME, Bradshaw D. Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000.

S Afr Med J 2007;97(8):741-746.

3. Schapkaitz E, Mahlangu JN, Buldeo S. Evaluation of the reticulocyte haemoglobin content as a screening test for iron deficiency anaemia in hospital patients. Presented at the Laboratory Medicine Congress, Cape Town, South Africa, 28-31 July 2013. Poster presentation.

4. Belperio PS, Rhew DC. Prevalence and outcomes of anemia in individuals with human immunodeficiency virus: A systematic review of the literature. Am J Med 2004;116(Suppl 7A):27S-43S. [http://dx.doi.org/10.1016/j.amjmed.2003.12.010] 5. Barron BA, Hoyer JD, Tefferi A. A bone marrow report of absent stainable iron is not diagnostic of iron deficiency. Ann Hematol 2001;80(3):166-169. [http://dx.doi.org/10.1007/s002770000261] 6. Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 2002;48(7):1066-1076.

7. Munoz M, Garcia-Erce JA, Remacha AF. Disorders of iron metabolism. Part 1: Molecular basis of iron homoeostasis. J Clin Pathol 2011;64(4):281-286. [http://dx.doi.org/10.1136/jcp.2010.079046] 8. Mast AE, Blinder MA, Lu Q, Flax S, Dietzen DJ. Clinical utility of the reticulocyte hemoglobin content in the diagnosis of iron deficiency. Blood 2002;99(4):1489-1491. [http://dx.doi. org//10.1182/blood.V99.4.1489] 9. Ullrich C, Wu A, Armsby C, et al. Screening healthy infants for iron deficiency using reticulocyte hemoglobin content. JAMA 2005;294(8):924-930. [http://dx.doi.org/10.1001/jama.294.8.924] 10. Karlsson T. Comparative evaluation of the reticulocyte hemoglobin content assay when screening for iron deficiency in elderly anemic patients. Anemia 2011;2011:925907. [http://dx.doi. org/10.1155/2011/925907] 11. Brugnara C, Zurakowski D, DiCanzio J, Boyd T, Platt O. Reticulocyte hemoglobin content to diagnose iron deficiency in children. JAMA 1999;281(23):2225-2230. [http://dx.doi. org/10.1001/jama.281.23.2225] 12. Joosten E, Lioen P, Brusselmans C, Indevuyst C, Boeckx N. Is analysis of the reticulocyte haemoglobin equivalent a useful test for the diagnosis of iron deficiency anaemia in geriatric patients?

Eur J Intern Med 2013;24(1):636-6 [http://dx.doi.org/10.1016/j. ejim.2012.09.001] 13. Swart PDR, Rautenbach K, Raubenheimer JE. Reticulocyte haemoglobin content as a diagnostic tool for iron deficiency and iron-deficiency anaemia in ill infants and children. S Afr J Child Health 2014;8(1):23-27. [http://dx.doi.org/10.7196/SAJCH.645] 14. Brugnara C, Schiller B, Moran J. Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states. Clin Lab Haematol 2006;28(5):303-308. [http://dx.doi.org/10.1111/ j.1365-2257.2006.00812.x] 15. d’Onofrio G, Chirillo R, Zini G, Caenaro G, Tommasi M, Micciulli G. Simultaneous measurement of reticulocyte and red blood cell indices in healthy subjects and patients with microcytic and macrocytic anemia. Blood 1995;85(3):818-823.

Accepted 14 October 2015.

IN PRACTICE

CARDIOVASCULAR MEDICAL DEVICES

Focus areas of cardiovascular medical device research in South Africa C Chimhundu, K de Jager, T S Douglas Chipo Chimhundu is a research co-ordinator in the Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town (UCT), South Africa. She holds a master’s degree in biomedical engineering from UCT, and her research interests include medical image analysis and the analysis of medical device development trends. Kylie de Jager is a post-doctoral research fellow in the Division of Biomedical Engineering at UCT. She completed a PhD in medical physics and bioengineering at University College London, and her research interests include collaboration network analysis as relevant to medical device development, as well as investigating knee function through electromyography and biomechanics. Tania Douglas is a Professor of Biomedical Engineering and Deputy Dean for Research in the Faculty of Health Sciences at UCT. Her research is broadly concerned with the use of technology to improve health.

Corresponding author: T Douglas (tania@ieee.org)

We investigated the focus of cardiovascular medical device research in South Africa over the 15-year period 2000 - 2014. Information drawn from journal articles was used for the analysis, with attention to articles describing a contribution to the development of a cardiovascular medical device, or a new application of an existing device. The findings suggest that research has focused on diagnostic and monitoring as well as prosthetic cardiovascular medical devices, with specific emphasis on vascular and valvular heart diseases.

S Afr Med J 2016;106(1):55-56. DOI:10.7196/SAMJ.2016.v106i1.10166

Cardiovascular diseases (CVDs) are the leading cause of death worldwide[1] and the leading cause of noncommunicable disease morbidity and mortality in South Africa (SA).[2,3] The main drivers of the CVD burden in the country include urbanisation, increased tobacco use, poor diets associated with high cholesterol, and diabetes, as well as a general lack of physical activity leading to overweight/obesity. [2,4] CVD mortality in SA is primarily a result of myocardial infarction, stroke, congestive heart failure, cardiomyopathy and diseases related to high blood pressure.[3] CVD-related morbidity is often a consequence of angina, atherosclerosis, coronary artery disease, cardiomyopathy and rheumatic heart disease (RHD),[3,5] with RHD being especially prevalent in underprivileged children below the age of 15 years.[5] It is estimated that between 1997 and 2004, 33 people died per day in SA from myocardial infarction, 37 per day from heart failure and 60 per day from stroke,[3] while there were approximately 130 myocardial infarction and 240 stroke survivors each day over the same period.

Cardiovascular medical devices are tools that can be employed for the diagnosis, monitoring, surgical intervention, therapy or prosthetic treatment of cardiovascular conditions;[6] they can potentially impact on CVD morbidity and mortality. In 2007, the World Health Organization implemented the priority medical devices project[7] with the aim of redirecting resources towards combating high-burden diseases such as CVD by improving medical device access, quality, clinical relevance and use. The 2006 guidelines of the National Department of Health[2] also encouraged collaboration for more focused medical device development. Previous work[6] has shown that there has been a general increase in collaboration for cardiovascular medical device development in SA since 2000, as indicated by journal publications.

However, the focus of this published activity has not been explored.

Identification of cardiovascular medical device focus areas

We examined the focus of SA cardiovascular medical device research over the period 2000 - 2014. Journal articles discussing CVDs in the

55

SA context were collected using methods and criteria detailed in previous work.[6] The journal articles were accessed using PubMed and Web of Science. An article was included in the study if at least one of the authors had an SA affiliation, it had been published between 1 January 2000 and 31 December 2014, and it described a contribution to the development (and not just the clinical use) of a device or a new application of an existing device. A set of 122 articles satisfied these criteria.

Two approaches were used to identify the research focus areas of the journal articles. One approach classified each article based on the CVD, condition or structure addressed by the device. The second involved assigning a category to each article in a similar manner to the Code of Federal Regulations Title 21 of the US Food and Drug Administration,[8] namely diagnostic, monitoring, therapeutic, surgical or prosthetic device. Diagnostic devices and monitoring devices were combined into a single class, since medical devices that play a diagnostic role are also often used for monitoring purposes.

Prosthetic devices included any implantable device intended for correcting CVD conditions, while surgical devices were those intended for CVD surgical interventions. Finally, therapeutic devices were those that assist in the management of CVD.

Diseases and conditions addressed

Fig. 1 shows the types of disease, condition or cardiovascular struc­ ture addressed.

Valvular heart diseases were most commonly addressed and accounted for 18% of the articles. Examples include the development of a percutaneous aortic heart valve,[9] numerical simulation of the behaviour of aortic valves[10] and the application of finite element methods to improve stent design for a percutaneous heart valve.[11] Similar in proportion to valvular devices were devices for vascular diseases (17%), addressing conditions related to blood vessels. A large proportion of the devices (12%) were classified as ‘nonspecific’ as these either addressed several aspects of the cardiovascular system or did not clearly define the disease, structure or condition addressed.

January 2016, Vol. 106, No. 1

IN PRACTICE

Umbilical artery Doppler flow Tuberculous pericarditis Takayasu disease Myocardial ischaemia Left ventricular hypertrophy Long QT syndrome Left atrial enlargment Intracardiac structures Cardiac sarcoidosis Congenital heart disease ALCAPA* Acute chest pain Arteriovenous malformation Peripartum cardiomyopathy Thromboembolic ischaemic stroke Heart failure Coronary heart disease Cardiac arrest Arrhythmia Blood pressure Myocardial infarction

were represented in the publications, approximately three times more local than foreign authors were represented per organisation.

1 1 1 1 1 1 1 1 1 1 1 1 1

Conclusion

The focus of cardiovascular medical dev­ ice research in SA has been examined using journal articles published between 2000 and 2014. The findings suggest that diag­ nostic and monitoring cardiovascular devices as well as prosthetic devices receive more attention in SA than surgical and therapeutic devices. The main structures addressed are heart valves and blood vessels.

This is consistent with a high incidence of atherosclerosis, which is one of the major causes of cardiovascular morbidity in SA. The majority of the articles examined were led by authors with SA affiliations, confirm­ ing strong local capacity in cardiovascular medical device research.

2 3 3 4 4 6 7 10

Blood Nonspecific Vascular disease

12 15 21 22

Valvular heart diseases 0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Fig. 1. Diseases, conditions or structures addressed by cardiovascular medical device research in SA between 2000 and 2014. The number of articles is shown next to each bar. The x-axis gives the proportion of articles as a percentage of all relevant search results. (*ALCAPA = anomalous origin of the left coronary artery from the pulmonary artery.)

Myocardial infarction and high blood press­ ure, which are among the leading contri­­­butors to cardiovascular deaths in SA, accounted for 8% and 6% of the articles, respectively, while heart failure and thrombo­embolic ischaemic stroke each accounted for only 2%. None of the articles captured addressed rheumatic heart disease, which is a prevalent heart condition among children from low-income settings in SA.[3,5]

monitoring devices drawn from published articles include new applications for electro­ cardiograms, artery waveform analysers and phonocardiograms. These devi­ ces addressed vascular and valvular diseases.

Prosthetic devices included vein grafts and heart valves, related also to vascular and valvular diseases.

Clinical applications

From the 122 articles in this study, 298 authors were affiliated to 51 SA organisations, with an additional 166 authors affiliated to 97 foreign organisations. The affiliations of the first and last authors were determined for each publication, as it was assumed that if either of these authors had an SA affiliation, the research could be considered to be locally driven.

Approximately 89% of the articles had a first and/or last author affiliated with an SA organisation, suggesting that despite foreign organisations outnumbering local organisations, the research focus was still largely dictated by local organisations. In addition, although fewer local organisations

An alternative approach to understanding the focus of cardio­vascular medical device research entailed classifying the articles based on their clinical applications. Research on development of cardiovascular devices was more focused on devices intended for diagnosis, monitoring or prosthetic treatment than on therapeutic or surgical devices. Nearly half (48%) of the articles described the development of diagnostic and monitoring devices, and just over onethird (35%) discussed the development of prosthetic devices. Therapeutic and surgical devices jointly accounted for 17% of the articles. Examples of diagnostic and

Influence of foreign collaborators

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January 2016, Vol. 106, No. 1

1. World Health Organization. Fact sheet N°317: Cardiovascular diseases (CVDs). WHO Media Centre, 2015. http://www.who. int/mediacentre/factsheets/fs317/en/ (accessed 11 November 2015).

2. Maredza M, Hofman KJ, Tollman T. A hidden menace?

Cardiovascular disease in South Africa and the costs of an inadequate policy response. SA Heart 2011;8(1):48-57.

3. Steyn K, Fourie JM. Heart disease in South Africa. The Heart and Stroke Foundation of South Africa, 2007. http://www.mrc. ac.za/chronic/heartandstroke.pdf (accessed 11 November 2015).

4. Alberts M, Urdal P, Steyn K, et al. Prevalence of cardiovascular diseases and associated risk factors in a rural black population of South Africa. Eur J Cardiovasc Prev Rehabil 2005;12(4):347-354. [http://dx.doi.org/10.1097/01.hjr.0000174792.24188.8e] 5. Engel ME, Haileamlak A, Zühlke L, et al. Prevalence of rheumatic heart disease in 4720 asymptomatic scholars from South Africa and Ethiopia. Heart 2015;101(17):1389-1394. [http://dx.doi.org/10.1136/heartjnl-2015-307444] 6. Chimhundu C, de Jager K, Douglas T. Sectoral collaboration networks for cardiovascular medical device development in South Africa. Scientometrics 2015;105(3):1721-1741. [http:// dx.doi.org/10.1007/s11192-015-1743-y] 7. World Health Organization. Medical devices: Managing the mismatch – an outcome of the Priority Medical Devices project. 2010. http://whqlibdoc.who.int/publi­ cations/2010/9789241564045_eng.pdf (accessed 8 August 2014).

8. US Food and Drug Administration. CFR - Code of Federal Regulations Title 21--Food And Drugs Chapter I--Food And Drug Administration Department of Health And Human Services Subchapter H--Medical Devices, Part 870, Cardiovascular Devices. 2015. http://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=870 (accessed 11 November 2015).

9. Van Aswegen KHJ, Smuts AN, Scheffer C, Weich HSV, Doubell AF. Investigation of leaflet geometry in a percutaneous aortic valve with the use of fluid-structure interaction simulation. J Mech Med Biol 2012;12(1):1250003. [http://dx.doi.org/10.1142/ S0219519411004538] 10. Koch TM, Reddy BD, Zilla P, Franz T. Aortic valve leaflet mechanical properties facilitate diastolic valve function.

Comput Methods Biomech Biomed Engin 2009;13(2):225-234. [http://dx.doi.org/10.1080/10255840903120160] 11. Esterhuyse A, van der Westhuizen K, Doubell A, Weich H, Scheffer C, Dellimore K. Application of the finite element method in the fatigue life prediction of a stent for a percutaneous heart valve. J Mech Med Biol 2012;12(1):1250007. [http://dx.doi. org/10.1142/S021951941200448X]

Accepted 5 October 2015.

REVIEW

Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia J Wing,1,2 MB BCh, FCP (SA), MMed; D Jivan,1 MB BCh, FCP(SA), Cert Endocrinol Metab, MMed ivision of Endocrinology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, D Johannesburg, South Africa 2 Donald Gordon Medical Centre, Johannesburg, South Africa 1

Corresponding author: D Jivan (daksha.jivan@wits.ac.za)

Middle-income countries need a rational and cost-effective approach to optimise management of type 2 diabetes mellitus (T2DM). There is a paucity of data from such countries on the extent of hypoglycaemia and its consequences for their healthcare systems. This review provides the context for health policy change and evaluates available data on diabetes complications, focusing on hypoglycaemia in T2DM patients in non-Western countries. Suitable guidelines are suggested for these communities, which are in transition from poverty to affluence and in transition from an environment where infectious diseases predominate to one where non-communicable diseases are predominant.

S Afr Med J 2016;106(1):57-61. DOI:10.7196/SAMJ.2016.v106i1.10284

The management of type 2 diabetes mellitus (T2DM) has improved over the past decade, following the introduction of new antidiabetic agents that are able both to lower glucose levels effectively and not affect the patient’s cardiovascular risk profile adversely.[1] Some of these new therapeutic agents, the incretins, have been shown to lower traditional cardiovascular risk factors and also mitigate newly identified risk factors such as hypoglycaemia and weight gain, both of which often develop as adverse effects when tight glucose control is achieved.[2] The WHO Multinational Study of Vascular Disease in Diabetes showed that 52% of deaths in T2DM are attributed to cardiovascular disease.[3] Addressing both traditional and emerging cardiovascular risk factors by utilising a more composite glucose-lowering strategy may more readily achieve a comprehensive reduction in cardiovascular risk factors and a meaningful reduction in cardiovascular mortality.

While long-term prospective cardiovascular outcome studies determining cardiovascular safety and/or protection for many of the incretin agents are still awaited, there is growing evidence that these agents are likely to be more effective than traditional antidiabetic agents in reducing the many long-term and costly complications of T2DM. Importantly, incretin therapy is able to treat high and low glucose levels more physiologically and is therefore likely to address the current global unmet needs in diabetes care, especially that of composite glucose lowering.[4] In developing countries and regions, the dual burden of infectious diseases and T2DM has increased significantly among all social classes. In South Africa (SA) between 2000 and 2009, the prevalence of T2DM in the adult population over the age of 30 years doubled, accounting for more than two million cases in 2009.[5] In sub-Saharan Africa, the incidence of T2DM is expected to grow by more than 100% over the next decade. This will pose an unprecedented challenge to healthcare resources.[6] If not effectively treated, the epidemic of T2DM has the potential to be as disruptive as the HIV pandemic in lowering life expectancy and reversing previous healthcare gains in Africa.[5-7] This review focuses on the developments that have added to the available therapeutic armamentarium, and introduces data to support

57

early rigorous but safe intervention so that the progressive adverse microvascular and in particular macrovascular complications may be reduced. This strategy is reviewed and evaluated particularly in the context of middle-income countries as defined by the World Bank.[8] The epidemic of new cases of T2DM over the past two decades, particularly among younger patients, has resulted in a re-evaluation of clinical strategies to lower hyperglycaemia and reduce costly morbidity and mortality arising from poor glycaemic control. The first strategy involved a greater emphasis on using traditional agents (metformin, sulphonylureas and insulin) to intensify glucose control,[9] and the second the introduction of new antidiabetic agents to improve clinical care in order to address the shortcomings of traditional agents, enable the introduction of composite treatment, promote the long-term benefits of early and aggressive glucoselowering therapy, and thereby imprint and optimise metabolic legacy in the long term.

Intensive glucose control is limited by hypoglycaemia

Four major studies[9-13] have investigated the long-term benefits of intensive glucose control in T2DM as well as the adverse effects that can be expected from this approach (Table 1).

The landmark United Kingdom Prospective Diabetes Study (UKPDS) compared the effects of intensive blood glucose control using either sulphonylureas or insulin with conventional treatment on the risk of microvascular and macrovascular complications.[9] The aim of the intensive intervention was to target a fasting plasma glucose (FPG) level <6 mmol/L. The conventional therapy group was treated with diet and were only given drugs if there were hyperglycaemic symptoms or FPG rose >15 mmol/L. The intensive group’s overall risk of diabetes-related sequelae was reduced by 12% per annum, mainly driven by the 25% reduction in microvascular endpoints, including retinal photocoagulation. This was achieved at an increased risk of hypoglycaemia and greater weight gain than in the conventionally treated group (Table 2).

Cardiovascular events were not significantly reduced in the first 10 years of the study, but in the longer non-interventional

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Table 1. Intensive glucose control (IGC) in T2DM Study

Protocol design

Benefits of intensive/ conventional therapy

Complications

UKPDS

Newly diagnosed, intensive arms (insulin/ sulphonylureas and metformin) v. conventional therapy

12% reduction in diabetes-related endpoints 25% reduction – microvascular

Severe hypoglycaemia (2%/year) Weight gain 2.9 kg (mean)

UKPDS (follow-up)[10]

10-year follow-up, questionnairebased, noninterventional

13% reduction in allcause mortality 15% reduction in myocardial infarction

Not recorded

ACCORD[11]

10 000 patients with CV risk, 62 years, 20% black Median follow-up 3.5 years Targeting <6% in intensive arm Conventional –7.0 - 7.9%

None

Severe hypoglycaemia (10.5%) requiring medical assistance in intensive arm 16.2% requiring assistance in intensive arm Weight gain >10 kg in 28% of intensively treated patients

VADT[12]

1 791 patients 40% CV history Median follow-up 5.6 years Insulin prescribed if HbA1c not <6% in intensive arm, 9% in conventional arm

None

Severe hypoglycaemia 203/100 in patient-years in IGC: 52/100 in standard therapy Weight gain double in intensive arm v. conventional arm

ADVANCE[13]

11 140 patients, diabetes diagnosed at >30 years, average duration 8 years Median follow-up 5 years IGC targeted 4.4 - 6.1 mmol/L, conventional group 10 - 11 mmol/L

Reduced incidence of nephropathy

Severe hypoglycaemia 2.7% in IGC group v. 1.5% No weight gain

[9]

CV = cardiovascular.

Table 2. Principal findings from intensive glucose control (IGC) Early IGC induces a legacy effect of reduced microvascular and macrovascular events over subsequent years IGC using sulphonylureas (glibenclamide, glimepiride, gliclazide) or insulin increases severe hypoglycaemic events two- to fourfold over conventional therapy As the duration of type 2 diabetes increases, the rate of hypoglycaemic events increases Hypoglycaemia is associated with increased cardiovascular mortality

questionnaire-based follow-up for a further 10 years, cardiovascular risk reduc­ t ion reached significance (Fig. 1). [10] This

finding was subsequently termed the ‘legacy effect’ and has driven the clinical approach of early intensive treatment for

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T2DM, particularly in newly diagnosed younger individuals.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study[11] was con­ ducted in the USA and Canada and compared intensive glucose control with lower HbA1c levels (<6%) with conventional therapy targeting HbA1c levels of 7.0 - 7.9%. The study included 20% African American patients and was conducted over a period of 3.5 years.

The ACCORD study identified, for the first time, the potential harm of this intensive approach in patients with multiple cardiovascular risk factors, 35% of whom had experienced a cardiovascular event prior to entry into the study. This study was halted early after increased mortality was observed in the intensively treated group of patients.

Patients were treated with sulphonylureas, rosiglitazone and insulin, and a very small percentage (12.0%) with the first available incretin mimetic, exenatide. Rates of hypo­ glycaemia were very high, with 10.5% of patients in the intensive therapy group experiencing severe hypoglycaemia requiring medical assistance. This was a threefold increase over the standard therapy group (3.5%). Also weight gain was much higher in the intensively treated group, with 28% of patients gaining >10 kg. The absolute increase in cardiovascular mortality has been shown to be directly proportional to the frequency and severity of hypoglycaemia.[14,15] The Veterans Affairs Diabetes Trial (VADT),[12] a trial among male veterans with a mean age of 60 years and T2DM duration of 11.5 years, also treated patients with conventional agents (metformin, glimepiride, rosiglitazone and insulin) for a period of 5.6 years. There was no difference in the rate of progression of microvascular complications, development of macrovascular complications or death. There was, however, a dramatic increase in the rate of sudden death in the intensively treated group. Severe hypoglycaemia in the intensively treated group was fourfold higher than in the conventionally treated group (Table 3).

The Action in Diabetes and Vascular Dis­ ease-Preterax and the Diamicron modif­ ied release Controlled Evaluation (ADVANCE) [13] trial included more than 11 000 patients with T2DM diagnosed at age 30 years and older, with diabetes-related vascular disease or an additional vascular risk factor; they were observed for a mean follow-up period of 5 years. The average duration of diabetes was 8 years, lower than in VADT (11.5 years) and ACCORD (10 years). The risk of developing microvascular complications was reduced, mainly as a result of a reduction in nephropathy or worsening nephropathy. There was no impact on macrovascular events in either the

REVIEW

Intensive v. conventional treatment 1977 - 1991

Hypoglycaemia and antidiabetic treatment

10-year post-trial follow-up (non-interventional)

1997

(30 years)[3]

2007

Randomisation

9%*

(20 years) Trial end[5]

12%* 15%*

16%** 24%*

Microvascular disease

25%*

Myocardial infarction

Fig. 1. Legacy effect of UKPDS study.

[10]

Any diabetes-related endpoint

(*p<0.05, **p=0.052: intensive v. conventional treatment.)

Thrombosis • Increased platelet count • Increased coagulation • Factor VIII and fibrinogen • Increased platelet aggregation and activation Myocardial injury • Decreased MBFR • Increased oxygen demand, cardiac output, workload

Hypoglycaemia

Conduction disturbances • Increased QT interval and risk of sudden cardiac death • Increased catecholamines • Hypokalaemia

Endothelial dysfunction • Increased inflammation • Increased oxidative stress • Vasconstruction Fig. 2. Hypoglycaemia and the cardiovascular system.

Table 3. Comparison of severe hypoglycaemia (<2.8 mmol/L) in ACCORD, VADT and ADVANCE trials ACCORD[11] % of patients with events

VADT[12] Events per 100 patient-years

ADVANCE[13] % of patients with events

Conventional 5.0

Conventional 50

Conventional 1.5

Intensive 16.2

Intensive 200

Intensive 2.7

intensive or the conventional therapy arm.

Hypoglycaemia was twofold higher in the intensive group, but overall was less frequent than in either VADT or ACCORD. There was no weight gain in the intensive arm.

Severe hypoglycaemia, defined as a plasma glucose concentration of <2.8 mmol/L, was associated with a two- to threefold increase in

cardiovascular mortality.[16] Therapy did not include any incretin mimetics, but did include thiazolidinediones.

These intensive glucose control studies have shown that hypoglycaemia is an important factor in limiting the anticipated cardiovascular benefits that should accrue from tight glucose control (Table 2).

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An acute hypoglycaemic event induces insulin suppression followed by the release of counterregulatory hormones, glucagon and epinephrine (acutely) and growth hormone plus cortisol (chronically). The magnitude of the counterregulatory response is attenuated and delayed with increasing age (>60 years). The response in older individuals is also triggered at lower glucose levels than in the young healthy population.[17] The counter-regulatory response in T2DM occurs at a higher threshold of glucose than in type 1 DM, allowing some degree of protection against hypoglycaemia. However, when insulin is given to improve glucose control in T2DM, the counter-regulatory response resets to a lower glucose level. The development of hypoglycaemia-associated autonomic failure also occurs in T2DM,[18] and is accompanied by a further drop in the glucose level that triggers counter-regulation. This hypoglycaemic un­aware­ness can be partially reversed by avoid­ ing further hypoglycaemic events.[19] Initially, hypoglycaemia limits the achieve­ ment of target glucose control, and in particular limits attainment of longer-term cardiovascular benefit in terms of the legacy effect.

Hypoglycaemia and the cardiovascular system

Greater clarity is emerging with regard to the mechanisms under­ lying the dele­ terious effects of hypoglycaemia on the cardiovascular system, as illustrated in Fig. 2.

Hypoglycaemia and cardiac ischaemia

Studies using continuous glucose monitoring and simultaneous cardiac Holter monitoring have shown that hypoglycaemia in T2DM is more likely to be associated with cardiac ischaemia and angina symptoms than with hyperglycaemia.[20] Even prior to the development of coronary artery disease (CAD) in T2DM, myocardial blood flow (MBF) reserve is reduced as a result of microangiopathy, which is attributed to poor glycaemic con­trol.[21] The baseline MBF was shown to be comparable among T2DM patients with microvascular angina, T2DM patients with CAD and control subjects.

However, the MBF (not peak stress), measured during dipyridamole administration, was significantly lower in T2DM patients with microvascular angina than in patients with macrovascular disease.[22] It is therefore plausible that early control of glucose in T2DM can also limit the development of coronary microangiopathy; moreover, this control should be obtained without inducing hypoglycaemia.

REVIEW

Hypoglycaemia and cardiac arrhythmias

Hypoglycaemia is known to affect the electrocardiograph (ECG), resul­ ting in lengthening of the QT interval in both type 1 and type 2 DM.[23] While the exact mechanism is not accurately defined, investigations using continuous interstitial glucose and ambulatory ECG monitoring are improving the understanding of the roles of hypoglycaemia-induced sympathetic neural activation, hypoglycaemia and defective counterregulation. A recent evaluation in insulin-treated T2DM using this technique has shown a greater frequency of hypoglycaemia-induced bradycardia and atrial and ventricular ectopic counts during the night ascompared with the day, and compared with periods of euglycaemia.[24] Excessive compensatory vagal activation after the counter-regulatory phase may be responsible for the bradycardia and arrhythmias. QT prolongation only reached significance during the day in a 2014 study by Chow et al.[24] of diabetic patients at cardiovascular risk.

Recent research on patients with long-QT syndrome due to loss-offunction mutations in KCNZQ1 has shown that these patients also have hyperinsulinaemia and symptomatic hypoglycaemia, caused by altered potassium channels in cardiomyocytes and pancreatic beta cells.[25] This is the first identification of an extracardial phenotype in KCNZQ1 and long-QT syndrome patients. The episodes of syncope, ventricular tachyarrhythmias and cardiac arrest may also therefore be the result of hypoglycaemia and low potassium levels in these patients and not only a consequence of the genetically produced disturbance in conduction.

Hypoglycaemia and thrombosis

Acute hypoglycaemia alters platelet and clotting factors, producing a procoagulant and prothrombotic state. In a study by Dalsgaard-Nielsen et al.,[26] platelet counts were decreased significantly and activated partial thromboplastin time was also reduced during insulin-induced hypoglycaemia. Fibrinogen and factor VIII levels were substantially increased in the diabetes patients compared with healthy controls.

Overall, there was a two- to threefold increase in platelet aggregation and a 50% increase in factor VIII concentrations in the diabetic patients.

Hypoglycaemia and endothelial dysfunction

Endothelial dysfunction is the early predictor of atherosclerosis.[27] In diabetes, endothelial dysfunction is primarily caused by oxidative stress and increased formation of advanced glycation end-products.

Oxidative stress reduces nitrous oxide bioavailability with increased free radical superoxides promoting vascular smooth-muscle cell proliferation and inflammation. Endothelin-1, the most potent vasoconstrictor of blood vessels, has also been shown to increase following hypoglycaemia.[28] These vascular events, combined with an increase in high-sensitivity C-reactive protein and other inflammatory markers in diabetic patients experiencing hypoglycaemia,[29] create a favourable environment for the development of atherosclerosis.

These findings are particularly important to middle-income countries with their epidemiologically younger populations, typically higher rates of complications from T2DM and inadequate resources for costly hospitalisation following adverse cardiovascular and other vascular events. There is a need to establish normoglycaemia to induce the long-term benefit of metabolic legacy. This is more readily achieved if composite therapy is available.

Type 2 diabetes complications and hypoglycaemia in Africa and nonWestern developing countries

A substantially higher than expected diabetes prevalence was found among urban-dwelling black South Africans in a 2008/2009 community-based study conducted in predominantly black African

60

areas of Cape Town compared with a similar prevalence study undertaken two decades earlier.[30,31] The age-standardised prevalence was the highest reported in sub-Saharan Africa. Of particular importance is the finding that prevalence rose extremely sharply in people aged >45 years; 20 - 25% of people screened and found to be diabetic were in the younger economically active group aged 45 - 64 years. More than 50% of the diabetes cases identified were previously unknown to the participants. The high rates of impaired glucose tolerance and obesity will ensure a continuing and ever-increasing diabetes caseload for SA healthcare facilities.

Diabetes complications, including macrovascular sequelae, will be extensive in middle-income countries. In an evaluation of the nonfatal disease burden caused by T2DM in 2009 in SA, the years lost to disability (YLD) were modelled and estimated at 78Â 900.[5] These included 8 000 new cases of blindness, 2 000 new amputations, 7 000 strokes and 5 500 YLD attributable to ischaemic heart disease.

A systematic review of diabetes prevalence and its complications in North Africa (Morocco, Algeria, Tunisia, Libya, Egypt, Sudan, South Sudan and Western Sahara) also highlighted that undiagnosed diabetes is common. The prevalence of complications among known and treated diabetic patients ranged from 8% to 42% for retinopathy, 21% to 22% for albuminuria, 6.7% to 46.3% for nephropathy and 21.9% to 60% for neuropathy.[32] Data on the influence of hypoglycaemia on diabetes-related outcomes in middle-income countries are rare. There are no SA or African data.

A single traceable study was found on the influence of hypoglycaemia on total mortality and cardiovascular events in a non-Western, recently developed country, Taiwan, conducted using the Taiwan National Health Insurance medical records.[33] The study included 77 661 new cases of diabetes diagnosed between 1998 and 2009. From this database, 500 patients were identified with severe hypoglycaemic events, who were hospitalised, and 1 344 patients were treated for mild hypoglycaemia, on an outpatient basis. These patients were matched to a cohort of patients who did not experience hypoglycaemic events.

This real-world study showed that clinically driven hypoglycaemia increased adverse cardiovascular outcomes and hospitalisation approximately twofold. Adverse events occurred primarily in the first year that followed the hypoglycaemic event.

Strategies to prevent hypoglycaemia

Effective approaches to reduce hypoglycaemia include patient education, dietary and exercise modification, regular glucose monitoring by the patient and the use of safer glucose-lowering therapies by the clinician.[34]

Medication adjustment to minimise the impact of hypoglycaemia

The Working Group of the American Diabetes Association (ADA) and the Endocrine Society advise clinicians to substitute sulphonylureas with other classes of oral agents or with glucagon-like peptide 1 (GLP-1) analogues in patients experiencing hypoglycaemic events.

In cases of frequent and recurrent hypoglycaemia, which leads to hypoglycaemic unawareness, this strategy of using oral agents that cause limited hypoglycaemia is even more important.

Incretin-based therapies, such as the GLP-1 analogues and the dipeptidyl peptidose-4 (DPP-4) inhibitors carry an overall lower risk of hypoglycaemia than the sulphonylureas and insulin and are favoured agents to minimise the extent of hypoglycaemia while still ensuring that patients reach appropriate glucose control targets.[35] The incretins and DPP-4s appear in the Society for Endocrinology, Metabolism and Diabetes of South Africa management of diabetes guideline,[36] and while available in the private sector are not available in the state sector owing to their cost.

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REVIEW

Contemporary evidence-based guidelines for treatment of T2DM patients in middle-income countries and their impact on hypoglycaemic risk

Expert guidance for the management of T2DM has been issued by many professional international bodies; examples include the ADA/ European Association for the Study of Diabetes position state­ ment on individualised therapy[37] and the American Association of Clinical Endocrinologists guidelines.[38] While these developed-world guidelines provide useful guidance to best practice, developing nonWestern countries need to develop their own national guidelines as incorporation of local needs has been shown to make a substantial difference to standards of care.

A recent review of non-Western countries with identifiable national guidelines provides important insights on potential strategies for middle-income countries to avoid hypoglycaemia and improve outcomes in T2DM.[39] Overall, 33 non-Western countries have national guideline recommendations. Many are based on recent international guidelines but do not yet incorporate their individualised therapy approach.[39] With regard to oral antidiabetic agents, 34% of the 33 countries monitored did not provide for the preferential use of specific sulphonylureas as second-line agents, but rather made provision for the use of any second oral agent such as the thiazolidinediones, DPP-4 inhibitors or alpha-glucosidase inhibitors. Some 30% of nonWestern guidelines (12 of 33) also suggest the option of injectable GLP-1 receptor agonists as an alternative to insulin as second-line therapy.

The SA guidelines[40] appear to follow international best practice, but still place traditional agents (metformin, sulphonylureas and insulin) in a preferred therapeutic silo. The SA positioning of newer agents (those with a minimal risk of hypoglycaemic complications or weight gain) as part of an alternative approach has reduced clinicians’ ability to prescribe these agents, as their availability is restricted in the formularies of both public and private funders.

Conclusion

It is clear that hypoglycaemia is a potential independent cardio­ vascular risk factor in diabetes. It is also evident that good glycaemic control at the outset is important for metabolic imprinting.

Current guidelines are inappropriate for many middle-income countries in the setting of primary healthcare. This is reducing the opportunity for the least-resourced level of care to achieve tight glucose control and obtain a legacy effect, as there is only access to traditional, not-fit-for-purpose agents.

There is an urgent need to review primary healthcare policy in middle-resourced countries and provide a better selection of therapeutic agents so that tight control can be achieved without the complications of hypoglycaemia. A long-term health economic study is also needed to support the expansion of these policies in resourcepoor settings.

Acknowledgement. We acknowledge the assistance of Julia Aalbers in the compilation of this article.

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24. Chow E, Bernjak A, Williams S, et al. Risk of cardiac arrhythmias during hypoglycaemia in patients with type 2 diabetes and cardiovascular risk. Diabetes 2014;63(5):1738-1747. [http://dx.doi. org/10.2337/db13-0468] 25. Torekov SS, Iepsen E, Christiansen M. KCNQ1 long QT syndrome patients have hyperinsulinaemia and symptomatic hypoglycaemia. Diabetes 2014;63(4):1315-1325. [http://dx.doi.org/10.2337/db131454] 26. Dalsgaard-Nielsen J, Madsbad S, Hilsted J. Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects. Thromb Haemost 1982;47(3):254-258.

27. Mudau M, Genis A, Lochner A, Strijdom H. Endothelial dysfunction: The early predictor of atherosclerosis. Cardiovasc J Afr 2012;23(4):222-231. [http://dx.doi.org/10.5830/CVJA-2011-068] 28. Wright RJ, MacLeod KM, Perros P, et al. Plasma endothelin response to acute hypoglycaemia in adults with type 1 diabetes. Diabetic Med 2007;24(9):1039-1042. [http://dx.doi.org/10.1111/j.14645491.2007.02199.x] 29. Wright RJ, Newby DE, Striling D, et al. Effects of acute insulin-induced hypoglycaemia on indices of inflammation. Diabetes Care 2010;33(7):1591-1597. [http://dx.doi.org/doi: 10.2337/dc10-0013] 30. Peer N, Steyn K, Lombard C, et al. Rising diabetes prevalence among urban-dwelling black South Africans. PLoS One 2012;7(9):e43336. [http://dx.doi.org/10.1371/journal.pone.0043336] 31. Levitt NS, Katzenellenbogen JM, Bradshaw D, et al. The prevalence and identification of risk factors for NIDDM in urban Africans in Cape Town, South Africa. Diabetes Care 1993;16(4):601-607.

32. Bos M, Agyemang C. Prevalence and complications of diabetes mellitus in Northern Africa: A systemic review. BMC Public Health 2013;13:387. [http://dx.doi.org/10.1186/1471-2458-13-387] 33. Hsu PF, Sung SH, Cheng HM, et al. Association of clinical symptomatic hypoglycaemia with cardiovascular events and total mortality in type 2 diabetes. Diabetes Care 2013;36(4):894-900. [http:// dx.doi.org/10.2337/dc12-0916] 34. Seaquist ER, Anderson J, Childs B, et al. Hypoglycaemia and diabetes: A report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care; 2013;36(5):1384-1395. [http://dx.doi.org/10.2337/dc12-2480] 35. Noh RM, Graveling AJ, Frier BM. Medically minimising the impact of hypoglycaemia in type 2 diabetes: A review. Expert Opin Pharmacother 2011;12(14):2161-2175. [http://dx.doi.org/10.1517/1 4656566.2011.589835] 36. Society for Endocrinology, Metabolism and Diabetes of South Africa. SEMDSA guidelines for the diagnosis and management of type 2 diabetes mellitus for primary health care. South African Family Practice 2010;52(6):507-511. [http://dx.doi.org/10.1080/20786204.2010.10874035] 37. Inzucchi SE, Bergenstal RM, Buse JB. Management of hyperglycaemia in type 2 diabetes: A patientcentred approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35(6):1364-1379. [http://dx.doi. org/10.2337/dc12-0413] 38. Garber AF, Abrahamson MJ, Barzilay JL, et al. AACE comprehensive diabetes management algorithm 2013. Endocrinol Pract 2013;19(2):327-336. [http://dx.doi.org/10.4158/endp.19.2.a38267720403k242] 39. Home P, Haddad J, Latif ZA, et al. Comparison of national/regional diabetes guidelines for the management of blood glucose control in non-Western countries. Diabetes Ther 2013;4(1):91-102. [http://dx.doi.org/10.1007/s13300-013-0022-2] 40. The 2012 SEMDSA guideline for the management of type 2 diabetes (Revised). JEMDSA 2012;17(2):S1S95. http://www.jemdsa.co.za/index.php/JEMDSA/article/view/329 (accessed 25 November 2015).

Accepted 9 November 2015.

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RESEARCH

The impact of an electronic clinical decision support for pulmonary embolism imaging on the efficiency of computed tomography pulmonary angiography utilisation in a resource-limited setting C Murthy,1 MB ChB; R Davis,1 MB ChB, MMed (Rad D), FCRad (Diag) (SA); C F N Koegelenberg,2 MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulm (SA), PhD; E M Irusen,2 MB ChB, FCP (SA), PhD; R D Pitcher,1 MB ChB, FCRad (Diag) (SA) ivision of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, D Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa 2 Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa

1

Corresponding author: C Murthy (cmurthy05@gmail.com)

Background. Pulmonary embolism (PE) is associated with high morbidity and mortality. Effective intervention requires prompt diagnosis.

Computed tomography pulmonary angiography (CTPA) is sensitive and specific for PE and is the investigation of choice. Inappropriate CTPA utilisation results in unnecessary high radiation exposure and is costly. State-of-the-art electronic radiology workflow can provide clinical decision support (CDS) for specialised imaging requests, but there has been limited work on the clinical impact of CDS in PE, particularly in resource-constrained environments.

Objective. To determine the impact of an electronic CDS for PE on the efficiency of CTPA utilisation in a resource-limited setting.

Methods. In preparation, a PE diagnostic algorithm was distributed to hospital clinicians, explaining the combined role of the validated modified Wells score and the quantitative D-dimer test in defining the pre-test probability of PE. Thereafter, an automated, electronic CDS was introduced for all CTPA requests. Total CTPA referrals and the proportion positive for PE were assessed for three study phases: (i) prediagnostic algorithm; (ii) post-algorithm, pre-CDS; and (iii) post-CDS. Results. The proportion of CTPAs positive for PE after CDS implementation was almost double that prior to introduction of the diagnostic algorithm (phase 1 v. 3, 17.4% v. 30.7%; p=0.036), with a correspondingly significant decrease in the proportion of non-positive CTPAs (phases 1 v. 3, 82.6% v. 69.3%; p=0.015) During phases 2 and 3, no CTPAs were requested for patients with a modified Wells score of ≤4 and a documented negative D-dimer, indicating adherence to the algorithm.

Conclusion. Implementing an electronic CDS for PE significantly increased the efficiency of CTPA utilisation and significantly decreased the proportion of inappropriate scans.

S Afr Med J 2016;106(1):62-64. DOI:10.7196/SAMJ.2016.v106i1.9886

Pulmonary embolism (PE) is a common and poten­ tially fatal condition[1,2] with an annual incidence of 29 - 69 cases per 100 000 population[3-5] and a 15 - 30% mor­tality rate[6] if untreated. It is the most common preventable cause of death in hospital patients, accounting for 10% of all hospital deaths.[7] A 5-year retrospective autopsy study[8] implicated undiagnosed PE in 10% of cases.

The nonspecific and highly variable presentation of PE makes the clinical diagnosis challenging.[4] Only 25 - 30% of patients with PE-compatible symptoms have objective evidence of thrombo­ embolism.[4,9] Furthermore, PE symptoms may be masked by comorbidities.[10] Recent advances in multidetector computed tomography (MDCT) have decreased scan times and increased diagnostic accuracy. CT pulmonary angiography (CTPA) can now be completed in seconds, with 83% and 96% sensitivity and specificity for PE, respectively.[11] The accuracy of CTPA and its ability to provide alternative diagnoses, coupled with short scan times and widespread availability, have contributed to most clinicians having a low threshold for requesting the examination.[12] However, this low threshold has resulted in overutilisation, without a commensurate increase in PE diagnosis. [2,12] In a recent study only 10 - 15% of CTPAs performed in a large emergency unit were positive for PE.[12]

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The safe and effective management of suspected PE, utilising a diagnostic algorithm that combines a validated clinical decision rule, the D-dimer test and CTPA[10] has been documented in various studies in the past decade.[13-15] The combination of a low Wells score (≤4) and a negative D-dimer test has been shown to have a negative predictive value for PE of >99.5%, allowing patients with low clinical probability of PE to be spared CTPA and anticoagulants, while all other patients undergo definitive CTPA work-up.[13-15] Inappropriate utilisation of CTPA results in exposure to un­necessary high doses of ionising radiation and potential contrastrelated anaphylactic reactions and is costly, particularly in a resourcelimited setting.[10] The technical advances in diagnostic imaging over the past four decades have been paralleled by major developments in information technology. Filmless and paperless digital radiology departments, utilising electronic workflow, are now commonplace in wellresourced healthcare environments.[16] In addition, digital imaging and electronic workflow are increasingly being introduced into resource-limited settings, where they have particular benefit in supporting remote reporting via teleradiology.[17] Electronic work­ flow in radiology is driven by the radiology information system (RIS), which has a number of efficiency-enhancing features. These include the capacity for clinicians to request imaging studies electronically

January 2016, Vol. 106, No. 1

RESEARCH

and to be guided in real time by embedded, evidence-based imaging algorithms during the ‘order entry’ process. Decision-support systems for advanced imaging are being implemented with increased frequency, but evidence of their effectiveness in reducing inappropriate imaging utilisation is limited.

This is particularly true for resource-limited healthcare environments, where improved efficiency and cost-saving are pivotal.[18] We therefore aimed to determine the impact of an electronic clinical decision support (CDS) for PE on the efficient utilisation of CTPA in a resource-limited setting.

Methods

Research site

The study was conducted in a 1 386-bed public-sector tertiary-level teaching hospital in the Western Cape Province of South Africa.

The hospital performs approximately 180 000 radiological examinations annually and has a filmless, digital radiology department with an RIS-driven electronic workflow. Before December 2013, all imaging requests were submitted in hard copy, using standard request forms; thereafter all requests were generated electronically by way of the RIS. The study was approved by the institutional Health Research Ethics Committee and Hospital Management: Faculty of Medicine and Health Sciences of Stellenbosch University and Tygerberg Hospital, respectively.

Study design

The study was conducted in three phases.

Phase 1 (baseline observation). This was a retrospective analysis before December 2012, which served to secure a reasonable quantum of data to represent the baseline observation.

Phase 2 (preparatory – clinical guideline without prompting). In December 2012, by way of preparation, a PE diagnostic algorithm was distributed to all hospital clinicians, outlining the combined role of the validated modified Wells score (Table 1) and the quantitative D-dimer test in defining the pre-test probability of PE (Fig. 1).

Phase 3 (CDS). In December 2013, coin­ ciding with the implementation of electronic requests for diagnostic imaging, a CDS for PE was introduced, which appeared in real time whenever a CTPA was requested on the RIS. Clinicians were prompted to enter the Wells score and the D-dimer test result, thereby defining the pre-test probability of PE and hence the appropriateness of the CTPA request.

Results were stratified as positive or nonpositive for PE. Inclusion and exclusion criteria.

All requested CTPAs were approved by a radiology consultant prior to scanning. Con­ secutive CTPAs performed in the respective time periods were analysed, excluding patients who were pregnant, post partum or <18 years of age.

CTPA technical and diagnostic parameters

Examinations were performed on either a 6-slice or a 40-slice MDCT scanner, with transfer of axial acquisitions to a dedicated workstation (Intellispace Portal, Philips Healthcare, USA).

CTPA technique and diagnostic criteria for PE were constant across all study phases.

Examinations were initially interpreted by registrars in training as radiologists. The final report of the duty consultant radiologist served as the reference standard.

Statistical analysis

Data were collected on a customised Microsoft Excel spreadsheet and analysed in Statistica 12. Continuous data were analysed using means and standard deviations (SDs), with 95% confidence intervals (CIs). The proportion of positive and non-positive examinations during each of the three phases

was analysed using Pearson’s χ2 test. In cases where small frequencies were observed, exact methods tested the nature of the association.

A 5% significance level (p<0.05) was applied.

Results

Patients

A total of 603 CTPA examinations were performed across the three study phases; 424 patients (phase 1 n=149, phase 2 n=174, phase 3 n=101) were included in the analysis and, 179 were excluded (<18 years n=3, pregnant n=56, postpartum n=115, indications other than PE n=5) (Table 2). Patient demographics are presented in Table 3.

Shortness of breath was the most common symptom, present in 354 patients (83.5%); other symptoms were chest pain (n=130, 30.7%), limb swelling (n=53, 12.5%) and haemoptysis (n=27, 6.4%).

The mean (SD) Wells score was 4.77 (1.5).

During the prospective phases (2 and 3), no CTPAs were requested for patients with a modified Wells score ≤4 and a negative D-dimer test, indicating referring clinician adherence to the diagnostic guideline.

CTPA findings

The proportion of CTPAs positive for PE increased across the three phases (17.4% v. 22.4% v. 31.7%, respectively), with a corresponding decrease in the proportion of non-positive examinations over the same periods (82.6% v.

77.6% v. 69.3%, respectively) (Fig. 2).

Although the difference between phases 1 and 2 (17.4% v. 22.4%; p=0.267) and between phases 2 and 3 (22.4% v. 31.7%; p=0.128) was not significant, the trend was clear and the overall difference between phases 1 and 3 (17.4% v. 31.7%; p=0.014) was significant.

Diagnostic pathway: Suspected PE (non-pregnant patients)

History, physical examination, ECG, CXR and, selected cases, D-dimer Note: D-dimer ONLY if PE considered (based on history and examination), never as a ‘screening test’ or on inpatients

Table 1. Modified Wells score Previous PE or DVT

1.5

Calculate modified Wells score

Heart rate >100 bpm

1.5

Surgery or immobilisation within 4 weeks

1.5

Note: Emphasis on alternative diagnosis, particularly pneumonia and TB Treat patients with high probability expectantly (do not wait for CTPA)

Haemoptysis

1

Active cancer

1

Clinical signs of DVT

3

Alternative diagnois less likely than PE

3

Clinical probability PE unlikely

≤4

PE likely

>4

DVT = deep-vein thrombosis; bpm = beats per minute.

≤4

>4 Creatinine

Image D-dimer

Positive* >140 µmol/L

≤140 µmol/L

Negative (or inpatient*) Invesitigate for other pathology (can be discharged if stable)

VQ-scan or CTPA with renal support (refer nephrology if indicated)

CTPA*

Fig. 1. Pulmonary embolism diagnostic guideline. (ECG = electrocardiograph; CXR = chest X-ray; TB = tuberculosis; VQ-scan = ventilation-perfusion scan; *Only image if no other explanation can be found.)

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January 2016, Vol. 106, No. 1

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Discussion

emergency physicians, partly as a result of increased computer time, leading to selective use and decreased impact on overall yield, with ultimate removal of the PE from the computer order entry. Our substantial decrease in the proportion of inappropriate scans over time has considerable economic benefit, reflected in savings on consumables, and technician and radiologist time,[15] enhancing overall institutional cost-effectiveness and efficiency.

The success of the PE CDS bodes well for similar initiatives in a broad range of clinical settings, since numerous clinical algorithms are well suited to electronic prompting in radiology with a similar potential impact on clinical efficiency.

Strengths of our study were the two prospective study phases and the com­ prehensive availability of patient data on the RIS. A minor limitation was the lack of definitive diagnostic work-up, with either subtraction angiography or ventilationperfusion scanning, of the small proportion (6.3%) of patients with an equivocal CTPA. Lastly, this study had limited power in distinguishing between the three phases and had limited external validity.

Since ours was a derivation cohort, we recommend validation of the results in a larger, prospective cohort. However, this intervention demands rigorous com­ pliance and mindful application of the clinical decision rule. Hospital education programmes should include existing diagnostic guidelines, thereby encouraging its implementation by clinicians.

In this first study of its kind in a resourcelimited environment, we have shown that the phased implementation of a computerprompted pre-test probability scoring system for PE almost doubled the efficiency of CTPA and significantly decreased the number of inappropriate scans.

Both our 17.4% positive CTPA yield for PE in phase 1 and our 30.7% phase 3 yield are substantially higher than the pre-intervention (3 - 10%) and post-intervention (10 - 17%) ranges documented in recent similar studies[21-25] in well-resourced environments. Furthermore, our overall 82% increased CTPA yield from baseline (17.4% v. 30.7%) compares very favourably with recent studies. The emergency unit-based work of Prevedello et al.,[22] Drescher et al.[23] and Raja et al.[24] reported 37% (9.3 v. 12.6), 53% (8.3% v. 12.7%) and 69% (5.8% v. 9.8%) improvements after intervention, respectively.

Dunne et al.’s [21] study of hospitalised patients yielded a modest 16.3% overall improvement (10.4% v. 12.1%). Soo Hoo et al.[11] documented a striking 430% increased CTPA yield from a very low baseline (3.1% v. 16.5%) in a general radiology department.

Our results are testimony to our clinicians’ acceptance of, and adherence to, a simple PE diagnostic algorithm, reinforced by electronic CDS. Our experience differs from that documented by Drescher et al.,[23] who found that the CDS was poorly accepted by Table 2. Non-positive and positive results for the three time phases Positive, n (%)

Non-positive, n (%)

Total

Table 3. Patient demographics

Phase 1

26 (17.4)

123 (82.6)

149

Age (years), mean

48.2

Phase 2

39 (22.4)

135 (77.6)

174

Gender, male/female ratio

1:1.9

Phase 3

31 (30.7)

70 (69.3)

101

Inpatient, n (%)

213 (50.2)

Total

96

328

424

Outpatient, n (%)

211 (49.8)

90.0

82.6 77.6

80.0

69.3

70.0 60.0

%

50.0 Positive for PE

40.0 30.7 30.0 20.0

Non-positive

22.4 17.4

10.0 0.0 Phase 1

Phase 2

Phase 3

Phases

Fig. 2. Comparison of the proportion of positive and non-positive results for the three phases.

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January 2016, Vol. 106, No. 1

References 1. Soderberg M, Brohult J, Jorfeldt L, et al. The use of D-dimer testing and Wells score in patients with high probability for acute pulmonary embolism. J Eval Clin Pract 2009;15(1):129-133. [http:// dx.doi.org/10.1111/j.1365-2753.2008.00967.x] 2. Rohacek M, Buatsi J, Szucs-Farkas Z, et al. Ordering CT pulmonary angiography to exclude pulmonary embolism: Defense versus evidence in the emergency room. Intensive Care Med 2012;38(8):1345-1351. [http://dx.doi.org/10.1007/s00134-012-2595-z] 3. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population-based study. Arch Intern Med 1998;158(6):585-593.

4. Lee AY, Hirch J. Diagnosis and treatment of venous thromboembolism. Annu Rev Med 2002;53(1):15-33.

5. Lucignani G, Pistolesi M. Diagnosing pulmonary embolism: Clinical problem or methodological issue? Eur J Nucl Med Mol Imaging 2009;36(3):522-528.[http://dx.doi.org/10.1007/s00259-008-1059-8] 6. Heit JA, Silverstein MD, Mohr DN, et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost 2001;86(1):452-463.

7. Jacobson BF, Louw S, Mer M, et al. Venous thromboembolism: Prophylactic and therapeutic practice guideline. S Afr Med J 2013;103(4):260-267. [http://dx.doi.org/10.7196/SAMJ.6706] 8. Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: Are we detecting enough deep vein thrombosis? J Royal Soc Med 1989;82(4):203-205. [http://dx.doi. org/10.1177/014107688908200407] 9. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990;263(20):2753-2759.

10. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83(3):416-420.

11. Soo Hoo GW, Wu CC, Vazirani S, et al. Does a clinical decision rule using d-dimer level improve the yield of pulmonary CT angiography? AJR Am J Roentgenol 2011;196(5):1059-1064. [http:// dx.doi.org/10.2214/AJR.10.4200] 12. Shujaat A, Shapiro JM, Eden E. Utilization of CT pulmonary angiography in suspected pulmonary embolism in a major urban emergency department. Pulm Med 2013 (2013), Article ID 915213. [http://dx.doi.org/10.1155/2013/915213] 13. Writing group for the Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-Dimer testing and computed tomography.

JAMA 2006;295(2):172-179. [http://dx.doi. org/10.1001/jama.295.2.172] 14. Pasha SM, Klok FA, Snope JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-Dimer concentration: A meta-analysis.

Thromb Res 2010;125(4):e123-e127. [http://dx.doi.org/10.1016/j. thromres.2009.11.009] 15. Ong CW, Malipatil V, Lavercombe M, et al. Implementation of a clinical prediction tool for pulmonary embolism diagnosis in a tertiary teaching hospital reduces the number of computed tomography pulmonary angiograms performed. Intern Med J 2013;43(2):169-174. [http://dx.doi.org/10.1111/j.14455994.2012.02926.x] 16. Nance JW, Meenan C, Nagy P. The future of the radiology information system. AJR Am J Roentgenol 2013;200(5):1064-1070. [http://dx.doi.org/10.2214/ajr.12.10326] 17. Benjamin M, Aradi Y, Shreiber R. From shared data to sharing workflow: Merging PACS and teleradiology. Eur J Radiol 2010;73(1):3-9. [http://dx.doi.org/10.1016/j.ejrad.2009.10.014] 18. Blackmore CC, Mecklenburg RS, Kaplan GS. Effectiveness of clinical decision support in controlling inappropriate imaging.

J Am Coll Radiol 2011;8(1):19-25 [http://dx.doi.org/10.1016/j. jacr.2010.07.009] 19. Hedner C, Sundgren PC, Kelly AM. Associations between presence of relevant information in referrals to radiology and prevalence rates in patients with suspected pulmonary embolism.

J Acad Radiol 2013;20(9):1115-1121. [http://dx.doi.org/10.1016/j. acra.2013.05.010] 20. Mittadodla PS, Kumar S, Smith E, et al. CT pulmonary angiography: An over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism. J Community Hosp Intern Med Perspect 2013;3(1). [http://dx.doi.org/10.3402/jchimp.v3i1.20240] 21. Dunne RM, Ip IK, Abbett S, et al. Effect of evidence-based clinical decision support on the use and yield of CT pulmonary angiographic imaging in hospitalized patients. Radiology 2015;276(1):167-174. [http://dx.doi.org/10.1148/radiol.15141208] 22. Prevedello LM, Raja AS, Ip IK, et al. Does clinical decision support reduce unwarranted variation in yield of CT pulmonary angiogram?

Am J Med 2013;126(11):975-981. [http://dx.doi.org/10.1016/j. amjmed.2013.04.018] 23. Drescher FS, Chandrika S, Weir ID, et al. Effectiveness and acceptability of a computerized decision support system using modified Wells criteria for evaluation of suspected pulmonary embolism. Ann Emerg Med 2011;57(6):613-621. [http://dx.doi. org/10.1016/j.annemergmed.2010.09.018] 24. Raja AS, Ip IK, Prevedello LM, et al. Effect of computerized clinical decision support on the use and yield of CT pulmonary angiography in the emergency department. Radiology 2012;262(2):468-474. [http://dx.doi.org/10.1148/radiol.11110951]

Accepted 28 September 2015.

RESEARCH

The relationship between stunting and overweight among children from South Africa: Secondary analysis of the National Food Consumption Survey – Fortification Baseline I E A Symington,1 M (Diet); G J Gericke,2 M (Diet); J H Nel,3 DSc; D Labadarios,4 PhD, MB ChB epartment of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, D Johannesburg, South Africa 2 Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, South Africa 3 Department of Logistics, Faculty of Economic and Management Sciences, Stellenbosch University, Stellenbosch, South Africa 4 Population Health, Health Systems and Innovation, Human Sciences Research Council, Cape Town, South Africa 1

Corresponding author: E A Symington (syminea@unisa.ac.za)

Background. Globally, in children the prevalence of overweight and obesity is increasing, and this is associated with an increased risk of non-communicable diseases in adulthood. There is a need to examine the growing trends of overweight and obesity in children and their consequences in low- and middle-income countries.

Objectives. To describe the prevalence of, and determine the relationship between, stunting and overweight among children in two provinces of South Africa.

Methods. Secondary data analysis was conducted on anthropometric measurements of 36 - 119-month-old children from Gauteng and Mpumalanga provinces (N=519) participating in the South African National Food Consumption Survey – Fortification Baseline I (2005).

The International Obesity Task Force (IOTF) body mass index (BMI) reference percentiles were used to determine overweight and obesity.

The World Health Organization standards were used to derive z-scores.

Results. The prevalence of overweight was 12.0% (IOTF BMI ≥25 kg/m2), including 3.7% obesity (IOTF BMI ≥30 kg/m2). The predominantly urban Gauteng Province had a significantly higher prevalence of overweight children (14.1%) compared with Mpumalanga (6.3%) (p=0.0277). The prevalence of stunting was 17.0% (16.5% Gauteng, 18.2% Mpumalanga; p>0.05). There was a significant correlation (r=−0.32) between BMI and height-for-age z-scores (p<0.0001). In the obese group, 68.4% were stunted, while in the normal and underweight group only 13.6% were stunted.

Conclusions. Stunted children were more likely to be obese. Further research is necessary for clarity on the physiological mechanisms of this relationship. In the interim, prevention of stunting requires priority.

S Afr Med J 2016;106(1):65-69. DOI:10.7196/SAMJ.2016.v106i1.9839

Early nutrition has been identified as an impor­ tant contributing factor to long-term health.

Undernutrition, i.e. underweight, stunting, wasting and deficiencies of essential micronutrients, during this period has short-term consequences (i.e. increased risk of morbidity, mortality and disability) as well as long-term consequences (influencing adult size, intellectual ability, economic productivity, reproductive performance and metabolic and cardiovascular disease).[1] Stunting, specifically in the first 2 years of life, is associated with shorter adult height, lower achievements at school, reduced adult income, and decreased birth weight in offspring.[2] The other side of the malnutrition coin is the effect of overnutrition, which includes overweight and obesity. According to the Centers for Disease Control and Prevention,[3] the short-term health consequences of childhood obesity include an increased risk of cardiovascular disease (CVD), impaired glucose tolerance, insulin resistance, type 2 diabetes, respiratory morbidity, musculoskeletal discomfort, hepatic steatosis, gallstones and gastro-oesophageal reflux, as well as impaired psychological and social function. In the long term, obese children are at a substantially higher risk of becoming obese adults,[3] with the attendant higher risk of developing

65

non-communicable diseases (NCDs) in adulthood. A systematic review[4] highlighted the complexity of the relationship between childhood (including adolescent) body mass index (BMI) and adult disease risk, and concluded that: (i) obese children growing into obese adults were at higher risk of NCDs in their adult years; (ii) obese children growing into normal-weight adults were not at greater risk of CVD in adulthood; and (iii) interestingly, children at the bottom range of BMI who became obese adults seemed most susceptible to the risks associated with adult obesity, in particular hypertension. Similarly, children who experienced undernutrition in the first 2 years of life and who thereafter rapidly gained weight during childhood or adolescence had an increased risk of chronic disease related to nutrition.[2] It is therefore crucial to understand the relationship between early childhood undernutrition and obesity in the ensuing life stages to ultimately reduce the risk of chronic diseases. This article therefore aims to determine the prevalence of, and the relationship between, stunting and overweight among a specific group of children in South Africa (SA).

Methods

The second SA National Food Consumption Survey – Fortification Baseline I (NFCS-FB-I), conducted in 2005, provided the

January 2016, Vol. 106, No. 1

RESEARCH

opportunity for secondary data analysis. This analysis included data of two neighbouring provinces that are geographically the smallest provinces in the country. Ethics approval (Ref No. 2003/107/N) from Stellenbosch University was obtained, and each participant’s next of kin was informed of the purpose of the study to obtain informed consent.

Study design and subject selection

This cross-sectional national survey was descriptive in the quanti­ tative research paradigm. The data used for this secondary analysis were extracted from the original data set (non-weighted) of the NFCS-FB-I for Gauteng and Mpumalanga provinces. It should be borne in mind that the two provinces included are neither 100% urban nor 100% rural, as in any natural setting. The number of rural enumerator areas (EAs) was much lower (n=12) than the number of urban EAs (n=52), and therefore rural/urban conclusions cannot be drawn. The details of the sampling strategy can be found elsewhere.[5] The inclusion criteria used in this secondary analysis were as follows: all children aged 3 - 9 years (36 - 119.9 months of age) from Gauteng and Mpumalanga provinces; children from households with at least one woman of reproductive age (16 - 35 years); and complete data on gender, date of birth, and weight and height measurements of the child. This total extracted sample consisted of 64 EAs (n=41 urban formal, n=11 urban informal, n=8 tribal, n=4 rural formal).[5] The total number of children with informed consent and included in this secondary analysis was 561.

Data collection

Validated questionnaires for the collection of sociodemographic data were administered by trained fieldworkers. The sociodemographic factors investigated for this secondary analysis were for descriptive purposes.

Each child was anthropometrically assessed (weight and height) by a trained fieldworker using standardised and internationally described procedures. Each fieldworker was equipped with a portable electronic scale and a standard weight for calibration purposes (Precision Health Scale, model UC-321, A&D Company, Japan; maximum capacity 150 kg) as well as a stadiometer for carrying out the measurements. Each child was weighed (preferably with an empty bladder) with minimum clothing. The average of two readings was used. The standing height of the children was taken using a stadiometer (without shoes). Two readings were taken and the measurement was repeated if the readings varied by >0.5 cm.[5]

Data analysis

We derived BMI (weight divided by height squared), and z-scores for BMI-for-age (BAZ), weight-for-age (WAZ) and height-for-age (HAZ)

by using the World Health Organization (WHO) AnthroPlus software for the applicable ages (Department of Nutrition, WHO, Geneva).

For each child, a z-score (i.e. the number of standard deviations (SD) from the reference population median) was calculated for BAZ, WAZ and HAZ. If the WAZ was <−6 SD or >+5 SD, the HAZ <−6 SD or >+6 SD, or the BAZ <−5 SD or >+5 SD, the record was first verified for accuracy of data entry. Where an error had occurred on data entry, this was corrected; where no error could be detected, the indicator with such an extreme z-score was set to missing and therefore excluded from the analysis (according to WHO standards).

The number of records with such extreme z-scores was 42, of which 19 were for HAZ, 10 for BAZ, 2 for WAZ and 11 for both HAZ and WAZ, leaving 519 subjects’ data for analysis.

The International Obesity Task Force (IOTF) recommended age- and sex-specific cut-offs for BMI to determine overweight and obesity in children aged 2 - 18 years were used, which were based on adult BMI cut-offs at 25 kg/m2 and 30 kg/m2 for overweight and obesity, respectively.[6] In explanation of the data analysis, Table 1 indicates the anthropometric operational definitions for this secondary analysis.

The statistical analyses were done using SAS 9.1.3 (SAS Institute, USA). The PROC Survey Means, which is part of the SAS program, was used to calculate confidence intervals (CIs). Descriptive statistics and frequency distributions were calculated as appropriate for recorded sociodemographic data. The secondary analyses included the χ2 test, which is a test of independence and assesses whether two variables are independent of each other. It also included the Pearson’s correlation coefficient, used to establish the strength of linear relationships between variables. Statistical significance was set at a p-value of <0.05.

Results

Sociodemographic profile of the children

More than two-thirds of the 519 children were from Gauteng (72.5%). The study subjects lived mainly in urban settings (81.5% v. 18.5% rural), and Gauteng represented mainly urban respondents (96.0%). Mpumalanga, on the other hand, had a closer to equal representation of urban- and rural-dwelling subjects (43.4% urban v.

56.6% rural). Of the 519 children, 46.4% were male.

The total household income per month indicated that these children were mainly (75.1%) from poor families (household income ≤ZAR1 000 per month; ~USD157.50 per month in 2005). In the majority of cases (60.0%) the father or mother was the head of the household, and in 16.9% of cases the husband of the responding woman was the head of the household. The mother (42.9%) and other female adults (26.7%) were mainly responsible for deciding what types of food to buy for the household, while in 14.7% of cases

Table 1. Operational definitions for anthropometric classifications Anthropometric classification

WHO 2005/7 WAZ

WHO 2005/7 BAZ

IOTF cut-off points[6]

WHO 2005/7 HAZ

Underweight

<−2 SD

N/A

N/A

N/A

Normal weight

−2 - 1 SD

N/A

N/A

N/A

Overweight

1 - 2 SD

2 - 3 SD (<5 years)

BMI 25 - 29.9 kg/m2

N/A

BMI ≥30 kg/m2

N/A

N/A

<−2 SD

*

1 - 2 SD (5 - 19 years) Obese

≥2 SD

≥3 SD (<5 years) ≥2 SD (5 - 19 years)

Stunting

N/A

N/A

For the purpose of this study, BAZ <−2 SD were not reported since such values reflect wasting and not underweight per se. Underweight children were therefore defined as those with WAZ <−2 SD.

*

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Prevalence of overweight, obesity and stunting

Of the total group of children (N=519), 8.3% were overweight and 3.7% obese (IOTF cutoffs). For these two provinces, at least 1 in every 10 children (12.0%; 95% CI 8.9 - 15.0) was therefore overweight/obese (IOTF BMI ≥25 kg/m2) (Table 2). Gauteng had a significantly higher prevalence of overweight and obese children (14.1%) compared with Mpumalanga (6.3%) (p=0.0277) (p-values indicated in Table 3). Furthermore, Gauteng also had a significantly higher prevalence (4.8%) of obese children compared with Mpumalanga (0.7%).

Girls had a significantly higher prevalence of overweight and obesity (15.8%) compared with boys (7.4%) (p=0.0034). Stunting was

prevalent in 17.0% (95% CI 13.8 - 20.1) of the total group (Gauteng 16.5%, Mpumalanga 18.2%; p>0.05) (Table 2).

Stunted

100

Non-stunted

86.4

90 80

68.4

70

68.4

60 %

the father had this responsibility. A similar pattern was seen regarding the household member deciding how much money was spent on food procurement (42.9%, 21.8% and 16.3%, respectively). In 77.4% of cases, the mother was responsible for feeding or serving the food to the child. The majority of mothers had education up to grade 11 or 12 (48.8%) while 18.4% of mothers had primary or no education, and only 4.3% had tertiary education.

50 40

31.6

31.6

30 20

13.6

10 0

Normal & underweight

Overweight

Obese

Weight category

Fig 1. Relationship between stature and body weight in 3- to 9-year-old children from Gauteng and Mpumalanga (N=519) (p<0.0001).

Table 2. Weight and height status of the children by province and gender (N=519*) Province and gender GP

MP

Male

Female

All

Children, n

376

143

241

278

519

Underweight (WAZ <−2 SD), % (95% CI)

6.1 (3.7 - 8.6)

10.5 (3.9 - 17.1)

8.3 (5.1 - 11.5)

6.5 (3.3 - 9.7)

7.3 (4.8 - 9.9)

WAZ −2 - 1 SD

87.2 (83.5 - 91.0)

84.6 (79.0 - 90.2)

86.3 (81.7 - 90.9)

86.7 (82.6 - 90.8)

86.5 (83.4 - 89.6)

BAZ

75.8 (71.2 - 80.4)

77.6 (70.5 - 84.8)

77.2 (72.6 - 81.7)

75.5 (69.9 - 81.2)

76.3 (72.4 - 80.2)

Weight indicators

Normal weight, % (95% CI) †

Overweight, % (95% CI) WAZ 1 - 2 SD

4.8 (2.5 - 7.1)

4.9 (2.0 - 7.8)

4.6 (1.8 - 7.4)

5.0 (2.5 - 7.6)

4.8 (3.0 - 6.6)

BAZ†

13.0 (9.6 - 16.4)

9.8 (4.1 - 15.5)

11.6 (7.5 - 15.7)

12.6 (8.3 - 16.9)

12.1 (9.2 - 15.1)

IOTF BMI 25 - 29.99 kg/m2

9.3 (7.0 - 11.6)

5.6 (1.0 - 10.2)

6.6 (3.8 - 9.5)

9.7 (6.9 - 12.5)

8.3 (6.2 - 10.4)

WAZ ≥2 SD

1.9 (0.2 - 3.5)

0.0

0.8 (0.0 - 2.0)

1.8 (0.2 - 3.4)

1.4 (0.1 - 2.6)

BAZ

6.9 (4.2 - 9.6)

2.1 (0.0 - 4.5)

3.7 (1.2 - 6.3)

7.2 (4.2 - 10.2)

5.6 (3.5 - 7.7)

IOTF BMI ≥30 kg/m2

4.8 (2.4 - 7.2)

0.7 (0.0 - 2.1)

0.8 (0.0 - 2.0)

6.1 (3.3 - 9.0)

3.7 (1.9 - 5.5)

WAZ ≥1 SD

6.7 (3.6 - 9.7)

4.9 (2.0 - 7.8)

5.4 (2.5 - 8.3)

6.8 (3.7 - 10.0)

6.2 (3.8 - 8.5)

BAZ ≥1 SD

20.0 (15.4 - 24.5)

11.1 (6.2 - 17.6)

15.4 (10.8 - 19.9)

19.8 (14.5 - 25.0)

17.7 (14.0 - 21.4)

IOTF BMI ≥25 kg/m2

14.1 (10.3 - 17.8)

6.3 (1.8 - 10.8)

7.4 (4.3 - 10.6)

15.8 (11.4 - 20.2)

12.0 (8.9 - 15.0)

Obese, % (95% CI) †

Overweight and obese, % (95% CI)

Height indicators Stunted (HAZ <−2 SD), % (95% CI)

16.5 (13.0 - 20.0)

18.2 (11.6 - 24.7)

15.4 (11.0 - 19.7)

18.3 (13.6-23.1)

17.0 (13.8 - 20.1)

BMI <25 kg/m2

10.9 (7.9 - 14.0)

14.7 (9.8 - 19.6)

12.0 (8.2 - 15.8)

11.9 (8.1 - 15.6)

11.9 (9.3 -14.6)

BMI ≥25 kg/m2

5.6 (3.1 - 8.1)

3.5 (0.2 - 6.8)

3.3 (1.1 - 5.6)

6.5 (3.4 - 9.6)

5.0 (3.0 - 7.0)

GP = Gauteng Province; MP = Mpumalanga Province. *With quality assurance measures, 42 entries were excluded. † Refer to Table 1 for BAZ cut-off values per age group.

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With regard to body weight per se (WAZ criteria), there was an almost equal prevalence of the two extremes of weight status, namely 7.3% of children being underweight and 6.2% being overweight. However, when considering the children’s BMI, which includes height (BAZ criteria), more children were classified as being overweight and obese (17.7%) than when considering weight only (WAZ) criteria (6.2%). The disparity in the findings between the weight (WAZ) and BMI (BAZ) criteria was supported by the high prevalence of stunting (HAZ of <−2 SD 17.0%) among the total group of children. A statistically significant negative correlation (p<0.0001; Pearson correlation coefficient r −0.32) was found between IOTF BMI and HAZ. Of the obese children, 68.4% were stunted, while 31.6% of overweight children and only 13.6% of the normal and underweight children were stunted (Fig. 1). Almost a third of the stunted group of children were overweight/obese (BMI ≥25 kg/m2) (Table 2).

Discussion

There is a need to address the growing trend of overweight and obesity in children and its consequences by means of appropriate interventions, especially in low- and middle-income countries.[7] This study documented that in Gauteng and Mpumalanga provinces, SA, 12% of children were overweight/obese (IOTF BMI ≥25 kg/m2), which is somewhat lower than that reported at the national level for the entire 2005 survey (14%),[8] as well as for the1999 NFCS, in which 17.1% of children aged 1 - 9 years carried excessive weight.[7] No comparison could be made with the more recent South African National Health and Nutrition Examination Survey (SANHANES) conducted in 2012, which reported on an older group of children (aged 2 - 14 years).[9] The significance of these findings should be seen against the background that, in the settings of the present study, dietary patterns are lacking in variety and the foods most con­sumed were reported to be maize, sugar, tea, whole milk and brown bread.[10] Only one child from a household with at least one woman of reproductive age was the inclusion criterion for the national survey. It may be expected that children living in child- or elderly-headed households could have had worse nutritional status.

The global prevalence of overweight in developing countries was reported to be 6.1% for children 0 - 5 years of age.[11] Developing countries have shown a higher increase in prevalence relative to developed countries,[11] hence the concern regarding the results of overweight and obesity in the present analysis. In this study, urbanisation may be a major factor contributing to the overweight and obesity status, since children from Gauteng were more likely to be overweight than those from Mpumalanga. Generally in SA, urban children are more likely to be overweight.[9,12] SA has been shown to have an increasing urban population in which traditional diets are steadily being replaced by Western diets, characterised by decreases in fibre and increases in fat and added sugars. Recent work has confirmed dramatic increases in added sugars and sucrose-sweetened beverage consumption in both urban and rural areas of North West Province in SA.[13] However, in the midst of the overnutrition phenomenon, 17.0% of children in this secondary analysis were classified as stunted.

Although this is somewhat lower than the national data (21.5% in 1999 and 20.0% in 2005),[10,14] the figures are of concern. Chronic malnutrition and stunting, during early childhood[2] typically occur among children living in resource-limited settings (typically prior to urbanisation).[15] The current analysis indicated a significant association between BMI and HAZ (p<0.0001), which supports the literature from SA indicating that children who are short for their age have a

68

Table 3. Chi-square values for the different relationships tested (N=519) Factors tested

Provinces, p-values

Gender, p-values

WAZ ≥1 SD group

0.1415

0.6716

BAZ ≥1 SD group

0.0074*

0.2038

IOTF BMI ≥25 kg/m2 group

0.0277*

0.0034*

Stunted group

0.6462

0.3649

Stunted normal-weight group

0.2354

0.9546

Stunted overweight group

0.3298

0.1003

*Significant.

higher risk of being overweight.[8,12] The coexistence of stunting and overweight in a group of female children has been reported within a nutrition transition context.[15] Although Jinabhai et al.[16] did not confirm this association in 8 - 11-year-old SA children in 1994, this phenomenon has been studied in countries experiencing urbanisation and the nutrition transition, including SA, over a number of years.[12,17] In 2010, the coexistence of stunting and combined overweight and obesity in the same child (<5 years) was reported to be as high as 18% in a regional study in Mpumalanga. [17] Our study reported a lower prevalence of 3.5% in Mpumalanga, which may be explained by the age difference (<5 years and 3 - 9 years in the present study). However, it is noteworthy that this analysis revealed more stunted children (68.4%) in the obese group than in the normal-weight and underweight group (13.6%) (Fig. 1).

Possible mechanisms related to this predisposition are that stunted children have impaired fat oxidation and impaired regulation of energy intake.[12] This association, however, raises the interesting possibility that the clinical interpretation of BMI is different between those who are stunted and those who are of normal height.

Do the overweight stunted child and the overweight normal-height child have the same health risks? Although experiencing chronic undernutrition in early childhood and exposure to energy-dense diets (possibly with urbanisation) in later years could be argued as a cause of overweight, the broader social, environmental and dietary determinants of the association need to be better understood, as do the implication(s) of these findings in defining policy and appropriate interventions.

Conclusion

Of major concern in this study is the high prevalence of both overweight (12%) and stunting (17%) in the same cohort of mainly low socioeconomic groups of children. This study revealed a significant, negative association between BMI and HAZ, with more overweight children than normal-weight and underweight children being stunted. Even though the cause of overweight in these children cannot be determined by this cross-sectional set of data, the effects of an urbanised lifestyle within the nutrition transition could play a major role if children are less active and consume more convenience foods.

In the interest of public health, these results, in the context of other available data, should be considered as a high priority for the prevention of childhood obesity. Since malnutrition is preventable, policy and interventions should address inadequate early nutrition as well as high-energy, unbalanced nutrition during childhood and adolescence.

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Acknowledgements. The National Food Consumption Survey − Forti­ fication Baseline I (NFCS-FB-I) consortium is hereby acknowledged: the Medical Research Council and eight universities (Stellenbosch University, University of the Western Cape, University of KwaZulu-Natal, University of North-West, University of Pretoria, University of Limpopo, University of Cape Town, University of the Free State), and Statistics South Africa.

The financial support for the national survey was provided by the Global Alliance for Improved Nutrition provided through UNICEF, with financial inputs from the National Department of Health, the National Fortification Alliance and the Micronutrient Initiative.

References 1. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr 2003;133:1485S -1489S. 2. Victora CG, Adair L, Fall C, et al. Maternal and child undernutrition: Consequences for adult health and human capital. Lancet 2008;371(9609):340-357. [http://dx.doi.org/10.1016/S01406736(07)61692-4] 3. Centers for Disease Control and Prevention. Basics about Childhood Obesity. 2012. http://www.cdc. gov/obesity/childhood/basics.html (accessed 12 June 2015).

4. Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and risk of the adult metabolic syndrome: A systematic review. Int J Obes 2012;36(1):1-11. [http://dx.doi.org/ 10.1038/ijo.2011.186] 5. Labadarios D, Molefe D, Nel JH, Kotze TJvW. General methodology. In: Labadarios D, ed. The National Food Consumption Survey – Fortification Baseline I (NFCS-FB-I): The Knowledge, Attitude, Behaviour and Procurement Regarding Fortified Foods, a Measure of Hunger and the Anthropometric and Selected Micronutrient Status of Children Aged 1 - 9 Years. Pretoria: Directorate: Nutrition, Department of Health, 2007.

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6. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ 2000;320(7244):1240-1245. [http://dx.doi.org/10.1136/ bmj.320.7244.1240] 7. Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in lowincome and middle-income countries. Lancet 2013;382(9890):427-451. [http://dx.doi.org/10.1016/ S0140-6736(13)60937-X] 8. Kruger HS, Margetts BM, Vorster HH. Evidence for relatively greater subcutaneous fat deposition in stunted girls in the North West Province, South Africa, as compared with non-stunted girls. Nutrition 2004;20(6):564-569. [http://dx.doi.org/ 10.1016/j.nut.2004.03.002] 9. Shisana O, Labadarios D, Rehle T, et al. South African National Health and Nutrition Examination Survey (SANHANES-1). 2nd ed. Cape Town: HSRC Press, 2014:397.

10. Labadarios D, Steyn N, Maunder E, et al. The National Food Consumption Survey (NFCS): South Africa, 1999. Public Health Nutr 2007;8(5):533-543.

11. De Onis M, Blössner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr 2010;92(5):1257-1264. [http://dx.doi.org/10.3945/ajcn.2010.29786.1] 12. Steyn NP, Labadarios D, Maunder E, Nel J, Lombard C. Secondary anthropometric data analysis of the National Food Consumption Survey in South Africa: The double burden. Nutrition 2005;21(1):4-13. [http://dx.doi.org/10.1016/j.nut.2004.09.003] 13. Vorster HH, Kruger A, Wentzel-Viljoen E, Kruger HS, Margetts BM. Added sugar intake in South Africa: Findings from the Adult Prospective Urban and Rural Epidemiology cohort study. Am J Clin Nutr 2014;99(6):1479-1486. [http://dx.doi.org/10.3945/ajcn.113.069005] 14. Labadarios D, Swart R, Maunder E, et al. Executive summary of the National Food Consumption Survey Fortification Baseline I (NFCS-FB-I) South Africa, 2005. S Afr J Clin Nutr 2008;21(3 Suppl 2):245-300.

15. Tathiah N, Moodley I, Mubaiwa V, Denny L, Taylor M. South Africa’s nutritional transition: Overweight, obesity, underweight and stunting in female primary school learners in rural KwaZuluNatal, South Africa. S Afr Med J 2013;103(10):718-723. [http://dx.doi.org/10.7196/SAMJ.6922] 16. Jinabhai CC, Taylor M, Sullivan KR. Implications of the prevalence of stunting, overweight and obesity amongst South African primary school children: A possible nutritional transition? Eur J Clin Nutr 2003;57(2):358-365. [http://dx.doi.org/10.1038/sj.ejcn.1601534] 17. Kimani-Murage EW, Kahn K, Pettifor JM, et al. The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children. BMC Public Health 2010;10:158. [http:// dx.doi.org/10.1186/1471-2458-10-158]

Accepted 16 July 2015.

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The socioeconomic and environmental health situation of international migrants in Johannesburg, South Africa A Mathee,1,2,3 PhD; N Naicker,1,3 MB BCh, FCPHM, MMed, PhD nvironment & Health Research Unit, South African Medical Research Council, Johannesburg, South Africa E Environment Health, Faculty of Health Sciences, University of Johannesburg, South Africa 3 School of Public Health Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1

2

Corresponding author: A Mathee (amathee@mrc.ac.za)

Background. Around the world, cities are dealing with growing numbers of international migrants (IMs). Many migrants are likely to have encountered exceptional challenges through the migration process, with implications for their health. Nevertheless, studies conducted in several developed countries point to a pattern of better health in migrant groups – the ‘healthy migrant’ effect. However, little is known about the health of migrants in poorly resourced destination countries, especially in African settings.

Objectives. To compare living conditions and environmental health status in IMs relative to South African (SA) households, both living in settings of poverty in Johannesburg, SA. Methods. Data were extracted from a long-term panel study underway in five neighbourhoods of Johannesburg. Cross-sectional studies, undertaken annually from 2006 to 2010, involved the annual administration of questionnaires to around 500 households to obtain information on living conditions and health.

Results. Most of the differences observed through univariate analyses in living conditions and health status between IM and SA households were explained by controlling for socioeconomic and neighbourhood factors.

Conclusion. This study revealed that SA respondents and IMs in settings of urban poverty in Johannesburg had remarkably similar health status, with little evidence of a ‘healthy migrant’ effect. Nevertheless the authors argue for vigilance and a finer understanding of the unique sociocultural dimensions of health in migrant communities in Johannesburg as they continue to transform the profile of urban health in SA and other African cities.

S Afr Med J 2016;106(1):70-75. DOI:10.7196/SAMJ.2016.v106i1.10215

International migrants (IMs) constitute a group of growing proportion and importance in cities around the world. Many migrants are likely to have encountered exceptional challenges through the migration process, which may have implications for their health in the short or longer term. For example, they may have needed to adapt to a foreign local culture and a new urban system and language, and may have experienced trauma in their country of origin.[1] Under certain circumstances, migrants may encounter poverty, marginalisation and exclusion, or even a hostile reception in their destination country. In 2008, for example, a wave of xenophobic violence swept across South Africa (SA), resulting in the deaths of 62 IMs, injury to 670, and the displacement of around 100 000.[2] Notwithstanding the recognised challenges associated with migration, studies conducted in several parts of the world point to a pattern of better health in migrant groups. While uncertainty continues to prevail in this regard, postulated explanations include the ‘healthy migrant’ effect (those who migrate are healthier than their counterparts who remain),[3] ‘salmon bias’ (migrants return to their home countries on retirement or becoming seriously ill),[4] and the ‘best of both worlds’ (the continuation or preservation of traditional behaviours favourable to health, family support and better access to healthcare).[5] For example, a study undertaken in the USA showed lower levels of psychiatric disorders in immigrants compared with locally born residents.[6] In Germany, it was shown that Eastern European immigrants had higher levels of ‘health satisfaction’ than their counterparts of local origin.[7] In further studies, migrant groups have been shown to have lower levels of mortality, chronic conditions

70

and mental ill health.[8] The health advantage in certain migrant groups has, however, been shown to decline over time.[7] The city of Johannesburg, SA, is characterised by high degrees of diversity and inequality, including diversity and inequality in respect of socioeconomic status, living conditions, culture and lifestyle. The observed inequalities are in part associated with the implementation over several decades of racially differentiated economic and development policies, resulting in SA currently having among the highest Gini coefficients (a measure of economic inequality) in the world. Despite the prevailing poverty and inequality, since the dissolution of apartheid SA, and Johannesburg in particular, has attracted large numbers of refugees and economic migrants from elsewhere on the African continent, further diversifying the city’s population and garnering the description of a cultural melting pot.[9] Despite the increasing size of the IM population in Johannesburg, few household-level studies have been conducted to gain a deeper understanding of the situation and health needs of this subgroup of the city’s population. The primary focus of most health-related studies conducted to date has been IMs’ access to, and treatment in, local health services.[10] In 2006, the World Health Organization (WHO) Collaborating Centre for Urban Health (a partnership of the South African Medical Research Council, the University of Johannesburg, the University of the Witwatersrand and the City of Johannesburg) initiated a study (the Health, Environment and Development (HEAD) study) of indicators of living conditions and health status in five sites of relative impoverishment in Johannesburg.

Three of the five study sites (Hillbrow, Bertrams and Hospital Hill) house significant proportions of IMs. In this article, HEAD study

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The data used in the preparation of this article were extracted from the Johannesburg-based HEAD study. The HEAD study is a long-term panel study involving the administration of prestructured questionnaires to respondents from households living in a predetermined set of dwellings in five relatively impoverished neighbourhoods: Hillbrow, Bertrams, River­lea Extension 1, Braamfischerville and Hospi­ tal Hill. At the start of the study in 2006, participating dwellings were randomly selected in the suburbs of Bertrams, Riverlea and Braamfischerville, conveniently sampled in Hospital Hill (an informal settlement for which no town planning maps were available), and systematically sampled in the high-rise suburb of Hillbrow (buildings, followed by floors and then apartments, were randomly selected). In each neighbourhood around 50% of dwellings were targeted for inclusion in the study. Data on, for example, socioeconomic status, place of birth, living conditions, health status, quality of life and perceptions of neighbourhood infrastructure and services were collected during August each year.

Data were collected from 2006 to 2010.

Respondents aged at least 18 years from the main or primary household on the dwelling site, from whom prior written informed consent had been obtained, were interviewed.

Households were defined as a group of people eating meals together. Interviews were conducted by environmental health students from the University of Johannesburg, who had been trained in interviewing techniques and fieldwork processes.

IMs were defined as having been born beyond SA borders. The status of the respondent (international migrant or SA native) was defined as the status of the household. To obtain an indicator of socioeconomic status, respondents were asked about ownership of a set of household commodities – such as a telephone, refri­ gerator, motor vehicle, microwave oven and satellite television – and the arithmetical mean was calculated. Data were analysed using the Stata version 9 statistical package.

Analyses were conducted in survey mode and weighted for area. Ethical clearance for the study was obtained from the University of the Witwatersrand Human Research Ethics Committee (Medical) (Ref. No. MO50451).

90

78.0

Household characteristics

Both SA and IM households comprised around four members. The average age of the heads of SA households was 39 years (range 18 - 76 years), while that for the heads of IM households was 35 (19 - 71) years. More IM (75%) than SA households (61%) were headed by men (p=0.0004).

Educational status was low in both groups, with 6% of the heads of IM households having a tertiary education compared with 76.7

78.0

74.0

70 60 50 40 30 18.4

20

26.0

23.3

22.0

22.0

10 0

2006

2007

2008

2009

2010

Year South African

International migrants

Fig. 1. Distribution of SA and IM households per year.

100 90 80 70 60 50 40 30 20 10 0

06 07 08 09 10 06 07 08 09 10 06 07 08 09 10 06 07 08 09 10 06 07 08 09 10 20 20 - 20 20 - 20 20 20 - 20 20 - 20 20 20 - 20 20 20 20 20 20 20 20 20 20 - 20 20 - 20 li l - ill - ill ill - ill ea - ea - lea ea - lea lle - lle - ille lle - lle - s - s - s - s - s - w - w - w w - w l H l H l H l H l H rl rl r rl r vi vi v vi vi am am am am am ro ro ro ro ro ta ta ta ta ta ve ve ive ve ive er er er er er tr tr tr tr tr llb llb llb llb llb pi spi spi spi spi Ri Ri R Ri R sch sch sch sch sch Ber Ber Ber Ber Ber Hi Hi Hi Hi Hi s fi fi fi fi fi Ho Ho Ho Ho Ho m m m m m aa aa aa aa aa Br Br Br Br Br Area and year

Results

Over the 5-year period of the study, the total proportion of respon­ dents who reported

81.6

80

Percentage

Methods

Bertrams, very few households in Riverlea and Braamfischerville were of international origin. Over the 5-year period of the study, the data showed that, on average, 41% of households in Hillbrow were of international origin, while the proportions for Bertrams and Hospital Hill were 20% and 10.0%, respectively. Given the very low numbers of IM households in Riverlea (2%) and Braamfischerville (1%) (Fig. 2), these sites were excluded from further analysis.

having been born outside SA remained relatively constant: 18.4%, 22.0%, 23.3%, 26.0% and 22.0%, respectively, for the years 2006 - 2010 (p=0.18, non-parametric (NP) test for trend) (Fig. 1). At the suburb level, there was also no significant change in the proportion of IM households in Hospital Hill and Bertrams over the 5 years (p=0.71 and p=0.28, χ2). In Hillbrow, however, the proportion of IM households increased from 30.0% in 2006 to 47.0% in 2010, a statistically significant increase (p=0.04).

The vast majority of IM households were Zimbabwean, with smaller proportions having migrated from a range of African countries including Malawi, Nigeria, Zambia, Ethiopia, Mali, Kenya, Somalia, Lesotho, Mozambique, Uganda, the Democratic Republic of the Congo, Ivory Coast, Rwanda and the Republic of the Congo.

IM households were not evenly distributed across the five HEAD study sites (p<0.01).

As shown in Fig. 2, relative to Hillbrow and

Percentage

data from these sites are used to describe the environmental health situation of IMs in relation to their SA counterparts.

South African

International migrants

Fig. 2. Distribution of IM households in the HEAD study, by area and year.

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4% in SA households (p=0.215). However, significantly more IM (53%) than SA (39%) household heads were employed on a fulltime basis (p=0.001) (Table 1).

Table 1. Demographic profile of the study households: SA v. IM Variable

Total

SA

IM

p-value 0.18 (NP trend over 5 year)

Households interviewed per year, n (%)

Indicators of socioeconomic status

Table 2 gives a breakdown by migration status of a range of indicators of socio­ economic and environmental health status in Hillbrow, Bertrams and Hospital Hill. As can be seen, from an economic perspective IM households appeared to be better off than their local counterparts. More IM relative to SA households earned relatively high incomes and fewer earned very low incomes. Over the study period, there was no statistically significant increase in IM or SA household incomes (NP trend: IM p=0.48, SA p=0.23 for low incomes and IM p=0.40, SA p=0.41 for high incomes).

On average IM households also owned more commodities (such as refrigerators, microwave ovens, dishwashing machines, motor vehicles, computers, telephones, etc.) than SA households (4.4 v. 3.9, respectively) (p=0.003). IMs spent more on, and lived in, housing of a higher standard. For example, a higher proportion of IM households lived in dwellings with indoor taps and used electricity for daily cooking. There was a lower level of concern among IM households over food insecurity, and a higher regard

2006

296

242 (81.8)

54 (18.2)

2007

223

174 (78.0)

49 (22.0)

2008

225

172 (76.4)

53 (23.6)

2009

177

131 (74.0)

46 (26.0)

2010

285

222 (77.9)

63 (22.1)

Hospital Hill

549

494 (89.9)

55 (10.0)

Bertrams

281

224 (79.7)

57 (20.3)

Hillbrow

376

223 (59.3)

153(40.7)

ge (years), mean A (range)

37.8 (18 - 76)

39 (18 - 76)

35 (19 - 71)

0.00

Tertiary education, n/N (%)

49/1 206 (4.1)

34/941 (3.6)

15/265 (5.7)

0.22

Full-time employment, n/N (%)

511/1 206 (42.4)

370/941 (39.3)

141/265 (53.2)

0.001

Gender male, n/N (%)

777

578/941 (61.4)

199/265 (75.1)

0.0004

Gender female, n/N (%)

426

362/941 (38.5)

64/265 (24.2)

Household members (N), mean

3.77

3.72

3.70

0.89

ength of residence L (years), mean (range)

9.06 (0.8 - 70)

10.02 (0.8 - 70)

5.81 (0.8 - 26)

0.000

Households per area, n (%) 0.00

Head of household

Table 2. Comparison of socioeconomic profile of SA v. IM households Total (N=1 206)

SA (N=941)

IM (N=265)

p-value

p-value after adjusting for area (CI)

Household income <ZAR1 000, n (%)

345 (28.6)

302 (32.1)

43 (16.2)

0.000

0.95 (0.64 -1.60)

Household income >ZAR5 000, n (%)

136 (11.3)

94 (9.9)

42 (15.8)

0.018

0.52 (0.73 -1.86)

Variable

Ownership of commodities, mean (range)

4.03 (0 - 10)

3.92

4.45

0.003

0.012 (0.023 - 0.003)

Monthly expenditure on rent, mean

ZAR700.11

ZAR718.26

ZAR1 273.61

0.000

0.84 (−0.00 -0.00)

Living in formal housing, n (%)

747 (61.9)

539 (57.3)

208 (78.5)

0.000

0.22 (0.45 -1.20)

Quality of housing: one or more major problem, n (%)

658 (54.5)

546 (58.0)

112 (42.3)

0.000

0.59 (0.66 - 1.25)

Daily cooking is undertaken using electricity, n (%)

744 (61.7)

529 (56.2)

215 (81.1)

0.000

0.385 (0.012 - 0.0366)

Water is accessed through an indoor tap, n (%)

636 (52.7)

434 (46.1)

202 (76.2)

0.000

0.72 (0.011 -0.039)

e worry whether our food will run out before W we get money to buy more

210 (17.4)

177 (18.8)

33 (12.4)

0.009

0.55 (0.731 -1.796)

e are often hungry, but we don’t eat because we can’t W afford food

214 (17.7)

175 (18.6)

39 (14.7)

0.084

0.05 (0.998 -2.285)

Food security, n (%)

Perceptions of services Healthcare, mean*

5.41

5.29

6.34

0.00

0.000 (0.007 -0.022)

Police services, mean*

4.55

4.43

5.52

0.00

0.013 (0.002 -0.017)

CI = confidence interval. *Health and police services were scored on a scale of 1 - 10. The mean of each score was calculated for analyses.

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for the health and police services in their neighbourhoods (Table 2). Only average commodity ownership (p=0.012) and the average perception of police (p=0.003) and health services (p=0.000) remained significantly different after controlling for area of residence.

As can be seen from Table 3, univariate analyses in respect of the total sample indicated that the prevalences of diseases of lifestyle (diabetes, hypertension, and stroke) were significantly higher in SA relative to IM households. SA households were also more likely to have a household member die (using a 1-year recall period) and to have children miss school because of illness. Multivariate analyses illustrated the importance of socioeconomic status and the areas or neighbourhoods in which households lived â&#x20AC;&#x201C; after controlling for these aspects, there were no statistically significant health differences between SA and IM households. The health status of SA and IM households neither improved nor declined over the study period.

Table 4 gives further evidence of the role of neighbourhood and socioeconomic status in comparisons of the health of local and migrant communities. It gives a comparative breakdown of the socio­ environmental characteristics of IM house­ holds in the informal settlement of Hospital Hill relative to those living in the inner-city neighbourhoods of Hillbrow and Bertrams, combined. As can be seen, there were significant differences between the two groups of IMs in respect of socioeconomic factors, environmental conditions and perceptions of local services. Similar differences were observed among SA citizens living in different neighbourhoods.

Discussion

Migration, national and international, is a phenomenon of growing importance for countries around the world, and may increase as the spectre of climate change unfolds.[11] While numerous studies of the health status of IMs have been undertaken in relatively wealthy recipient countries such as the USA and various European countries, there is a paucity of similar information available for African settings. This is especially the case for international, intra-African migration, for which there is a particular dearth of information. Our research seeks to address this gap, providing information on the environmental health situation of intra-African migrants living in three relatively impoverished neighbourhoods in Johannesburg.

Overall, as a proportion of the total study sample across five neighbourhoods, the IM population remained stable in the study settings over the study period. However, population changes could be observed at the neighbourhood level. For example, in the sample from the inner-city, high-rise residential area of Hillbrow, the proportion of IMs increased from 31% to 46% over the 5-year study period. Hillbrow has an established reputation as a magnet for new migrants to the city, both national and international. In contrast, the proportion of IM households in the study suburbs of Riverlea and Braamfischerville remained low and static throughout the study period. This clustering in particular neighbourhoods may indicate the value of social networks and cultural familiarity to IMs on arrival in their adoptive country.

Crude analyses of the socioenvironmental health status of the two groups indicated a number of differences between SA and IM households, including differences in respect of economic status, living conditions, food security and health status (chronic ill-health conditions, common mental disorders, school absenteeism and mortality levels).

However, multivariate analyses showed that differences in socioeconomic status and area of residence accounted for most of the variance observed. After socioeconomic status and area of residence were controlled for, the health of IMs was similar to that of SA households in respect of all parameters studied. The only differences that remained statistically significant were the higher level of ownership of household commodities and the higher regard among IMs for local health and police services. Instead, statistically significant differences in socioeconomic and living conditions were shown among IMs living in different Johannesburg neighbourhoods.

The absence of a higher level of health (this was the case in respect of indicators of chronic diseases, mental ill health, and communicable and acute ill health, as well as indicators of exposure to violence) in IMs (even though around 80% of respondents reported having lived in SA for less than 5 years) relative to locals in this study is unexpected. Studies undertaken in other parts of the world have often shown that migrants enjoy better health than nonmigrants,[3] albeit for a limited period.[7] In

Table 3. A comparison of household health: SA v. IM households Variable

Total n (%)

SA n (%)

IM n (%)

p-value

A member of the household has asthma

75 (6.2)

67 (7.1)

8 (3.0)

0.056

A member of the household has diabetes

56 (4.6)

52 (5.5)

4 (1.5)

0.00

A member of the household has hypertension

150 (12.4)

131 (13.9)

19 (7.2)

0.003

A member of the household has heart disease

42 (3.5)

35 (3.7)

7 (2.6)

0.638

A member of the household has a high cholesterol level

40 (3.3)

35 (3.7)

5 (1.9)

0.274

A member of the household has had a stroke

11 (0.9)

11 (1.2)

0

0.000

A member of the household has a psychiatric or mental illness*

17 (1.4)

15 (1.6)

2 (0.8)

0.62

SRQ >7

113 (9.4)

96 (10.2)

17 (6.4)

0.02

A member of the household has a disability

47 (3.9)

43 (4.6)

4 (1.5)

0.011

A member of the household is obese or very overweight

25 (2.1)

20 (2.1)

5 (1.9)

0.984

A member of the household has tuberculosis

39 (3.2)

31 (3.3)

8 (3.0)

0.854

A member of the household has HIV/AIDS

27 (2.2)

23 (2.4)

4 (1.5)

0.405

A child has missed one or more days of school in the past month due to illness

148 (12.3)

136 (14.5)

12 (4.5)

0.000

Someone in the household has had diarrhoea or vomiting in the past 2 weeks

71 (5.9)

60 (6.4)

11 (4.2)

0.441

A household member died during the past year

82 (6.8)

76 (8.1)

6 (2.3)

0.000

The household has been affected by violence (gunshot, rape, stabbing) in the past year

76 (6.3)

66 (7.0)

13 (4.9)

0.403

SRQ = self-reporting questionnaire. *WHO standardised common mental health disorder form.

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this study the vast majority of IMs originated from SA’s immediate northern neighbour, Zimbabwe. The relatively short distance between the countries, low cost of travel, porous national borders and relatively easy access to existing social networks at the destination may make the contemplation and act of migration possible for a relatively broad socioeconomic and health cross-section of Zimbabwean citizens (and other Africans), while the process of migration from African countries to locations such as the USA or European countries may be considerably more challenging in terms of cost, social support at the point of destination and stringent immigration policies. IntraAfrican migration may therefore not be as self-selecting of high levels of health as is the case in those migrating from Africa to destinations in developed countries, which may have contributed to the absence of or a narrower gap in health status (i.e. the absence of the healthy migrant effect) between migrants and locals in the destination country, such as shown in the current study.

Notwithstanding the lack of stark differences in health status between native and migrant communities observed in this study, vigilance and further research to gain a deeper understanding of the

unique health needs of migrant communities in SA is warranted, in part because IMs now constitute the majority population in certain neighbourhoods. In this study for example, IMs at times comprised up to 54% of the study sample in Hillbrow, and their health status and unique health needs are therefore of increasing importance in the SA urban health landscape. There are other compelling reasons for gaining a finer understanding of the health needs of IM populations; a recent study in Johannesburg of the prevalence of geophagia in pregnant women showed that around one-fifth of the sample were IMs, and that the level of geophagia in this group was twice as high as that among SA women (17% in women born in SA v. 32% in IMs).[12] Geophagia is associated with an increased risk of intestinal obstruction, lead exposure (both maternal and fetal) and anaemia, yet the current antenatal health screening tool in SA excludes a history of pica or geophagia. This and other aspects of the health system may need to change to respond more effectively to the health needs and status of SA urban populations as they are transformed by international, as well as national, migration in a longer-term process of urbanisation.

Table 4. Characteristics of IM households by area: Hospital Hill v. Hillbrow/Bertrams Variable

Total (N=265)

Hospital Hill (N=55)

Hillbrow/Bertrams (N=210)

p-value

Household income <ZAR1 000, n (%)

43 (16.2)

22 (40.0)

21 (10.0)

0.00

Household income >ZAR5 000, n (%)

168 (63.4)

38 (69.1)

130 (61.9)

0.008

Ownership of commodities (mean)

4.04

2.53

5.52

0.00

Mean monthly expenditure on rent

R1 146.73

R14.21

R1 419.69

0.000

Live in formal housing, n (%)

208 (78.5)

10 (18.2)

198 (94.3)

0.000

Cook with electricity, n (%)

215 (81.1)

13 (23.6)

202 (96.2)

0.000

Indoor tap, n (%)

202 (76.2)

0

202 (96.2)

0.000

Food security, n (%) We worry that our food will run out before we get money to buy more

33 (12.5)

20 (36.4)

13 (6.2)

0.000

We are often hungry, but we don’t eat because we can’t afford food

39 (14.7)

23 (41.8)

16 (7.6)

0.000

Healthcare*

6.23

5.25

6.49

0.002

Police services*

5.47

3.89

5.89

0.000

Perceptions of services, mean

Household health, n (%) A household member has asthma

8 (3.0)

0

8 (3.8)

0.14

A household member has diabetes

4 (1.5)

1 (1.8)

3 (1.4)

0.83

A household member has hypertension

19 (7.2)

7 (12.7)

12 (5.7)

0.07

A household member has heart disease

7 (2.6)

2 (3.6)

5 (2.4)

0.61

A household member has a high cholesterol level

5 (1.9)

2 (3.6)

3 (1.4)

0.28

A household member has a psychiatric or mental illness

2 (0.8)

1 (1.8)

1 (0.5)

0.31

The respondent has an SRQ score >7

17 (6.4)

4 (7.3)

13 (6.2)

0.79

A household member has a physical disability

4 (1.5)

3 (5.5)

1 (0.5)

0.01

A household member has tuberculosis

8 (3.0)

2 (3.6)

6 (2.9)

0.76

A household member has HIV/AIDS

4 (1.5)

1 (1.8)

3 (1.4)

0.83

A child has missed one or more days of school in the past month due to illness

12 (4.5)

2 (3.6)

10 (4.8)

0.57

Someone in the household has had diarrhoea or vomiting in the past 2 weeks

11 (4.2%)

1 (1.8)

10 (4.8)

0.17

A household member died during the past year

6 (2.3)

4 (7.3)

2 (0.1)

0.01

member of the household has been a victim of violence (gunshot, rape, A stabbing) in the past year

13 (4.9)

5 (9.1)

8 (3.9)

0.03

*Health and police services were scored on a scale of 1 - 10. The mean of each score was calculated for analyses.

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Study strengths and limitations

There is a particular paucity of data on international migration and health in Africa, and this study helps to fill that gap.

Xenophobic violence may have been responsible for low response rates in two of the study sites in some years, resulting in bias. Data were collected on a household rather than individual level, and as a result the study does not provide information on individual risk factors or consequences of migration. It is possible that health information may have been under-reported because respondents were not fully aware of the health histories of all household members.

This study is prone to the weaknesses generally associated with studies of a cross-sectional design. In this study households were regarded as IM households if the respondent had been born outside SA. Given that a degree of integration might have occurred, an IM respondent does not necessarily imply that the entire household comprised migrants. Hillbrow and Bertrams are unusual inner-city settings in Johannesburg, and the findings may not be representative of the situation of communities in other SA cities.

Conclusions

This study has revealed that on average, and taking account of differences in area and socioeconomic status, the living conditions and health status of SA and IM households are remarkably similar, showing little evidence of a healthy migrant effect. Despite this, the authors argue for increased research aimed at achieving a deeper understanding of the unique sociocultural dimensions of health in migrant communities as they continue to transform the profile of urban health in SA and African cities.

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Acknowledgements. The authors are grateful to the respondents for granting permission to be interviewed.

Funding. The study was funded by the South African Medical Research Council, the South African National Research Foundation and the University of Johannesburg.

References 1. Pernice R, Brook J. Relationship of migrant status (refugee or immigrant) to mental health. Int J Soc Psychiatry 1994;40(3):177-188.

2. Kapp C. South Africa failing people displaced by xenophobia riots. Lancet 2008;371(9629):1986-1987. [http://dx.doi.org/10.1016/S0140-6736(08)60852-1] 3. Khlat M, Darmon N. Is there a Mediterranean migrants mortality paradox in Europe? Int J Epidemiol 2003;32(6):1115-1118. [http://dx.doi.org/10.1093/ije/dyg308] 4. Abraído-Lanza A, Dohrenwend B, Ng-Mak D, et al. The Latino mortality paradox: A test of the ‘salmon bias’ and healthy migrant hypotheses. Am J Public Health 1999;89(10):1543-1548. [http://dx.doi. org/10.2105/AJPH.89.10.1543] 5. Powles J. The best of both worlds: Attempting to explain the persisting low mortality of Greek migrants to Australia. In: Caldwell J, Findley S, Caldwell P, et al., eds. What We Know about The Health Transition: The Cultural, Social and Behavioural Determinants of Health. Canberra: Health Transition Centre, 1990:584-594.

6. Breslau J, Aguilar-Gaxiola S, Borges G, et al. Risk for psychiatric disorder among immigrants and their US-born descendants: Evidence from the National Comorbidity Survey Replication. J Nerv Ment Dis 2007;195(3):189-195. [http://dx.doi.org/10.1097/01.nmd.0000243779.35541.c6] 7. Ronellenfitsch U, Razum O. Deteriorating health satisfaction among immigrants from Eastern Europe to Germany. Int J Equity Health 2004;3(1):4. [http://dx.doi.org/10.1186/1475-9276-3-4] 8. Lu Y. Test of the ‘healthy migrant hypothesis’: A longitudinal analysis of health selectivity of internal migration in Indonesia. Soc Sci Med 2008;67(8):1331-1339. [http://dx.doi.org/10.1016/j. socscimed.2008.06.017] 9. Van der Berg S. Inequality, poverty and prospects for redistribution. Development Southern Africa 2014;31(2):197-218. [http://dx.doi.org/10.1080/0376835X.2013.871196] 10. Vearey J. Migration, access to ART, and survivalist livelihood strategies in Johannesburg. African Journal of AIDS Research 2008;7(3):361-374. [http://dx.doi.org/10.2989/AJAR.2008.7.3.13.660] 11. Zimmerman C, Kiss L, Hossain M. Migration and health: A framework for 21st century policymaking. PLoS Med 2011;8(5):e1001034. [http://dx.doi.org/10.1371/journal.pmed.1001034] 12. Mathee A, Naicker N, Kootbodien T, et al. A cross-sectional analytical study of geophagia practices and blood metal concentrations in pregnant women in Johannesburg, South Africa. S Afr Med J 2014;104(8):568-573. [http://dx.doi.org/10.7196/SAMJ.7466]

Accepted 23 October 2015.

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South African medical schools: Current state of selection criteria and medical studentsâ&#x20AC;&#x2122; demographic profile L J van der Merwe,1 MB ChB, MMedSc, PhD; G J van Zyl,1 MB ChB, MFamMed, MBA, Dipl Community Health, Dipl Health Administration, PhD; A St Clair Gibson,1 MB ChB, PhD, MD; M Viljoen,1 BComm, MBA; J E Iputo,2 MB ChB, PhD; M Mammen,2 MSc, PhD, FAIMER; W Chitha,2 MB ChB, MPH Health Economics, AMDP; A M Perez,3 DBS, DHSM, MDent; N Hartman,3 BA, BSocSc Hons, MSocSc, PhD; S Fonn,4 MB BCh, FFCH, PhD; L Green-Thompson,4 MB BCh, FCA (SA); O A Ayo-Ysuf,5 BDS, MSc (Odont), DHSM, MPH, PhD; G C Botha,5 MA; D Manning,6 BSc Hons, MEd, PhD; S J Botha,7 BSc Hons, MSc, PhD; R Hift,7 MB ChB, MMed, PhD; P Retief,8 BA Hons, MA, DLitt; B B van Heerden,8 MB ChB, MSc, MMed; J Volmink,8 MB ChB, DCH, FRCP (Edin), MPH, DPhil aculty of Health Sciences, University of the Free State, Bloemfontein, South Africa F Faculty of Health Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa 3 Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa 4 Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Sefako Makgatho Health Sciences University, Ga-Rankuwa, Gauteng, South Africa 6 Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa 7 College of Health Sciences, University of KwaZulu-Natal, Howard College, Durban, South Africa 8 Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa 1 2

Corresponding author: L van der Merwe (merwelj@ufs.ac.za)

Background. Selection of medical students at South African (SA) medical schools must promote equitable and fair access to students from all population groups, while ensuring optimal student throughput and success, and training future healthcare practitioners who will fulfil the needs of the local society. In keeping with international practices, a variety of academic and non-academic measures are used to select applicants for medical training programmes in SA medical schools.

Objectives. To provide an overview of the selection procedures used by all eight medical schools in SA, and the student demographics (race and gender) at these medical schools, and to determine to what extent collective practices are achieving the goals of student diversity and inclusivity.

Methods. A retrospective, quantitative, descriptive study design was used. All eight medical schools in SA provided information regarding selection criteria, selection procedures, and student demographics (race and gender). Descriptive analysis of data was done by calculating frequencies and percentages of the variables measured.

Results. Medical schools in SA make use of academic and non-academic criteria in their selection processes. The latter include indices of socioeconomic disadvantage. Most undergraduate medical students in SA are black (38.7%), followed by white (33.0%), coloured (13.4%) and Indian/Asian (13.6%). The majority of students are female (62.2%). The number of black students is still proportionately lower than in the general population, while other groups are overrepresented.

Conclusion. Selection policies for undergraduate medical programmes aimed at redress should be continued and further refined, along with the provision of support to ensure student success.

S Afr Med J 2016;106(1):76-81. DOI:10.7196/SAMJ.2016.v106i1.9913

Selection procedures in most medical schools are necessary because substantially more applications are received than the number of places available.

Medical schools have a duty to ensure that students admitted to their programmes have the potential to successfully complete their studies and display competent and ethical behaviour in practice.[1] In South Africa (SA), there is also an imperative to ensure that adequate numbers of quality candidates are attracted and selected, not only to ensure their academic success, but also to provide future healthcare practitioners who are fit to practise in the local society, including rural and currently under-served areas in the country. Selection instruments must therefore be aligned with social accountability objectives, so that widening access is granted to those from a disadvantaged background and to ensure access across the entire demographic profile of SA. At a meeting of representatives of the South African Committee of Medical Deans, a decision was made to employ collective learning from current practices across medical schools in SA to point the way forward.

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A variety of indicators, tests, procedures and methods are used to select candidates for places in medical school, which include both academic proficiency and non-academic characteristics. Although it has been argued that certain core competencies important for future doctors should be considered in the selection process, this does not necessarily predict academic success,[2] nor does it assure that socially accountable practitioners are produced. At the same time, there is uncertainty as to whether the widely accepted view that academic success at high school is the best predictor of academic success at medical studies holds true.[3] Selection procedures at SA medical schools currently employ pooled data from academic performance tests indicating cognitive ability, comprising a combination of the National Senior Certificate (NSC) results in compulsory subjects and the National Benchmark Tests (NBT), and non-academic performance indicators. The latter include performance in extracurricular activities (leadership, sport, cultural, community engagement and service), measures of dis­advantage such as family income, schooling and rural origin, personal reports (biographical

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questionnaires) and interviews. Each medical school employs a particular combination of these admission criteria, but currently there is no uniformity in how they are applied across the medical schools.

A positive correlation between past academic achievement and future academic success has been demonstrated by previous research. [4] However, in a group of applicants with exceptional aca­ demic achievement in certain compulsory subjects at NSC level, it is not possible to predict among top achievers who is more or less likely to succeed. The NBT provides an additional method of differentiating cognitive ability by testing language, mathematical and reasoning ability. Internationally, tests such as the General Cognitive Ability test have been shown to have a significant relationship with future academic and career success.[1] In SA, data are lacking regarding the relationship between the NBT and success at medical school.

Non-academic tests are often used as additional measures to differentiate between applicants with exemplary cognitive ability, to ensure that candidates with desirable traits for future medical practice are not excluded by focusing solely on academic performance.

However, the reliability and validity of non-academic performance as selection criteria are debatable.[5] Scientific evidence of the predictive value of various selection criteria and processes is needed to guide future practice.

In SA, in an attempt to address historical inequalities with regard to access, medical schools attempt to select candidates reflecting the demographic profile of the country, and therefore aim to increase the number of black African and coloured students selected for medical training.[6] However, the demographic data regarding racial composition of student cohorts at individual medical schools may still not reflect that of the country at large. There are different demographic distributions in the geographical areas and provinces of SA, and the number of applicants who comply with minimum selection criteria in each of these areas may be insufficient to meet the required targets for transformation. All medical schools, however, are committed to transformation in their selection practices. The number of applicants who decline an offer of a place at a particular medical school because they have been accepted at another institution, poses difficulties for medical schools to increase the number of students in specific target groups. In addition to optimal selection processes, the throughput of selected candidates from first year to graduation needs to be monitored in order to reduce challenges experienced by students to complete their studies in the minimum time.

With 2014 marking the 20-year anniversary of democracy in SA, selection procedures continue moving towards methods of providing improved access to students from disadvantaged backgrounds.

However, defining disadvantage by race has become complicated by the fact that there is an emerging black middle class. Factors such as schooling and educational background (for example, quintile 1 and 2 schools[7]), rurality and socioeconomic circumstances have therefore been included as indicators of disadvantage. Further complexities exist, such as the emerging middle class and the fact that children of domestic workers, for example, often attend good schools in the area where their parents are employed. Students’ financial need,[8] the variable quality of primary and secondary schooling[9] and the importance of taking into account cultural differences in the selection process, are additional issues pointing to the need for a comprehensive re-evaluation of selection criteria.

Objectives

To provide information regarding the current selection criteria and medical student demographics at the eight SA medical schools, and to determine to what extent collective practices are achieving the goals of student diversity and inclusivity.

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Methods

A retrospective, quantitative, descriptive study design was followed.

All eight medical schools in SA, as listed in Table 1, participated in the study in 2014. Representatives from the South African Committee of Medical Deans at each institution provided information regarding selection criteria, selection procedures, and student demographics regarding race and gender.

Information on selection policies, criteria and procedures for 2014 included both academic and non-academic performance indicators used to select candidates for medical studies at SA medical schools.

Demographic variables included gender and race (black, coloured, Indian/Asian, white and ‘other’, where ‘other’ mainly referred to students from Southern African Development Community (SADC) countries) of students who were offered places at the respective medical schools, students who accepted these places, and the registered students’ demographic characteristics in 2014. Descriptive analysis of data was done by calculating frequencies and percentages of the variables measured.

Results

As shown in Table 1, all eight medical schools in SA participated in the study. All the medical schools offer a 6-year curriculum for the undergraduate medical degree, with the exception of the UFS, where a 5-year curriculum is followed. Extended programmes are available at UCT, UFS, SMU, SUN and UP, and a graduate entry programme at WITS. UCT has not yet introduced a graduate entry programme, although one or two students with degrees are offered places in second year. All the universities offer structured student support programmes.

In 2014, a total of approximately 1 900 places were available at these institutions for first-year medical students (UCT 220, UFS 140, UKZN 250, SMU 250, UP 300, SUN 290, WITS 250, WSU 120). These places included positions offered to students who have completed the NSC (matriculants/school leavers), as well as senior students, foreign students, dean’s/rector’s places, and students transferring from other medical schools, health sciences professions or degree programmes.

Each university, however, has its own rules regarding the admission of medical students.

Table 2 provides an overview of the NSC and NBT academic requirements and the weighting applied at each of the institutions for admission to their undergraduate medical programmes in 2014.

The demographic composition of selected applicants with regard to race and gender varies at different medical schools. All medical schools aim to include students from all races and both genders in their admissions, and make use of different criteria to achieve Table 1. SA medical schools and abbreviations (in alphabetical order) University

Abbreviation

Sefako Makgatho Health Sciences University*

SMU

Stellenbosch University

SUN

University of Cape Town

UCT

University of the Free State

UFS

University of KwaZulu-Natal

UKZN

University of Pretoria

UP

University of the Witwatersrand

WITS

Walter Sisulu University

WSU

*Formerly University of Limpopo Medunsa Campus.

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inclusivity in terms of black and coloured students, as well as those from disadvantaged backgrounds. At UCT, the Senate approves targets by population group for school leavers annually. No targets are set for gender, and students from rural areas may enter through special consideration with slightly lower cut-off points. At the UFS, which follows a parallel-medium language policy, the selection committee aims to select English and Afrikaans students in a ratio of 60:40, while the female/male ratio is 60:40 in order to ensure that minorities are represented. The ratio with regard to gender is maintained so that, for example, female students cannot be more than 60% of the selected applicants. A definite attempt is made to include candidates from disadvantaged backgrounds who demonstrate academic potential, while two points are allocated for rural origin.

At UKZN, 28% of students are selected from quintile 1 and 2 schools[7] without racial quotas, while 52% are selected on merit, with 69% of these places reserved for black students, 19% for Indian, 9% for coloured, 2% for white and 1% for other (Chinese) students.

The remaining 20% of the total number of students admitted are selected from students with prior tertiary education. At SMU, 20% of the 250 spaces available for first-year medical students are reserved for students from the foundation programme (i.e. the

extended curriculum programme). The remaining students are selected from matriculants and senior students transferring from other programmes. Of these, 78% of places are offered to black students, 11% to white, 8% to coloured and 3% to Indian students.

No allowance is made for gender or disadvantage.

At UP, targets are set for historically disadvantaged students, namely black and coloured, while at SUN male and female students are selected in the same ratio as the pool of qualifying applicants, and selection based on race is in accordance with enrolment planning of the university and its commitment to inclusivity and diversity. At WITS, selection is made in two racially defined groups, namely coloured/black and white/Indian, to achieve a representative demographic distribution.

Academic requirements include NSC results and compulsory subjects at specified levels of achievement (level 5 (>60%)). These subjects include Mathematics, Physical Science, Life Science and Language (English). NBTs are required by UCT (70:30), UFS (60:40), UP (60:40), SUN (45:30) and WITS (50:50), with varying weight attributed to these results (NSC:NBT ratios indicated in parentheses).

UKZN, SMU and WSU do not require students to write NBTs in their selection process.

Table 2. Academic (NSC and NBT) requirements for selection for undergraduate medical training at eight SA medical schools University

Academic (weight)

APS (minimum required based on NSC)

NCS compulsory subjects + minimum achievement level

NBT requirements

NSC:NBT

SMU

100%

30

Level 5 (60 - 69%) Maths, Physical Science, Life Science

Not required

NA

SUN

45% of selection factor (grade 11/ matric average)

Not applicable

Level 6 (70 - 79%) or higher Level 4 (50 - 59%) or higher Maths, Physical Science, Life Science

Intermediate or proficient Minimum 38% per component Weight: 30% of selection factor

45:30

UCT

NSC score out of 600 and NBT score out of 300 + (for Medicine) an optional personal report out of 100

450 (APS = NSC)

Level 5 (60 - 69%) Compulsory: English, Maths, Physical Science, plus next 3 best subjects excluding LO

Intermediate or proficient.

70:30

UFS

100 points (84.76%)

36

Level 5 (60 - 69%) Language, Maths, Physical Science, Life Science

Must pass each component and average 50% overall

60:40

UKZN

Aggregate of 4 compulsory subjects + 2 best subjects, excluding Maths 3 and LO

Not applicable

Level 5 (60 - 69%) English, Maths, Physical Science, Life Science Average 65%

Not required

NA

UP

100%

35 (excluding LO)

Level 5 (60 - 69%) Language, Maths, Physical Science or Life Science

AL 20%, QL 20%, Maths 60%

60:40

WITS

Composite index: NSC 40%, NBT 40%, BQÂ 20%

Not applicable

Level 5 (60 - 69%) English, Maths, Physical Science or Life Science, plus next 2 best subjects incl. LO

Required

50:50

WSU

Academic 50%; interview 50%

20 (4 subjects)

Level 5 (60 - 69%) English, Maths, Physical Science, Life Science

Not required

NA

APS = admission point score; LO = life orientation; AL = academic literacy; QL = quantitative literacy; Maths = mathematics; BQ = biographical questionnaire.

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Male 4 000

Female

Total

3 599

3 500 3 063 Students, n

3 000 2 500

2 289 1 930

2 000 1 500

1 310

1 264

1 244

1 000

818 577

426

500

1 133

687 64

59 123

0 Black

Coloured

Indian/Asian

Other

White

Fig. 1. Race and gender of undergraduate students at SA medical schools in 2014.

Census 2011 (N=51.5 m*)

UG medical students (N= 9 170†)

100

80

79.6

60 %

The non-academic requirements for selec­tion for medical training carry between 10% and 25% of the total weight during the selection process, and comprise the following: Extracurricular activities. These include leadership, community service, cultural and sporting achievements, of which UCT, UFS, UP, SUN and WITS include different components in the selection process.

Region of origin. Although UCT does not allocate extra points for region of origin, rural students may be admitted with lower cut-off points than the general pool of applicants. UFS offers an additional 2 points and SUN an additional 4 points for applicants of rural origin, while WSU tends to admit more of its students from rural Eastern Cape areas.

Advantage based on parents being alumni or staff members of the institution is given in the form of 2 additional points at UFS and SUN. Indices of disadvantage are specified at UCT to include redress for groups 1 and 2 (black and coloured students) who enter with lower points, redress for group 3 (Indian students) who enter with the same cut-off point as ‘Open’ students (who must meet requirements without dropping cut-off points), and redress for group 4 (Chinese) who may enter with points slightly lower than the Open group. At UP disadvantage is seen as historically based on race, while at SUN no disadvantage index is used as it is implicit in the selection process. At UKZN and SUN (for selection of students to the extended programme), schooling background (e.g. quintile 1 and 2 schools[7]) is taken into consideration. At SMU applicants from quin­ tile 1 and 2 schools are considered for the extended curriculum programme if they have not been selected directly into the medical programme on competitive basis.

Biographical questionnaires, personal reports or interviews. At UCT a personal report will be required from 2016 if students achieve at a high level with their NSC and NBT results. WITS has made use of a biographical questionnaire prior to admission for 2015. UFS conducted interviews in the past, while WSU currently uses interviews for selected students based on academic merit. The interview aims to assess students’ personal attributes.

Fig. 1 shows the student demographic profile with regard to race and gender of all undergraduate students in the medical training programmes offered at SA medical schools during 2014. Among 9 293 students, male students constitute 37.8% of the total group, with 62.2% female students. The

40

39.2 33.4

20 8.9

13.8

13.6

8.9

2.5 0 Black

Coloured

Asian

White

Fig. 2. Comparison of the racial distribution of the general SA population and undergraduate medical students attending SA medical schools in 2014. (UG = undergraduate; *51.5 million; †UG students enrolled at eight South African medical schools in 2014.)

majority of students are black (38.7%), followed by white (33.0%), coloured (13.4%), Indian/Asian (13.6%) and other (1.3%).

Fig. 2 compares the racial distribution of undergraduate medical students in SA in 2014 with demographic findings of the National Census of 2011.[10] Although the majority of medical students at SA universities are black (approximately 39%), this group is still under-represented in relation to the national population, of which 80% of individuals are black.[10] Medical students from the other racial groups are over-represented in comparison with the national demographic profile. Slightly more than 33% of medical students in 2014 were white, while whites represent less than 10%

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of the total population. In 2014, nearly 15% of medical students were coloured, while the coloured population comprises less than 10% of the total population in the 2011 census. More than 10% of medical students were Indian/Asian, while Indians/ Asians represent less than 5% of the total population.[10] At all eight medical schools, large differences are prevalent in the number of offers made compared with offers accepted.

Students may receive more than one admission offer as they may have applied to more than one university. Therefore, the large cumulative number of offers made by the eight medical schools may be due to duplication. Large numbers of students

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Offers made in 2013 1 200

Offers accepted in 2013

1 062

1 000

Offers, n

800

804

761

600

486 378

400

304 154

200 0

217 15

Black

Coloured

Indian/Asian

6

Other/SADC

White

Fig. 3. Number of offers made and offers accepted in 2013 for admission for medical training in 2014 at all eight South African medical schools.

who are selected and do not take up the positions offered may therefore skew the representation of the different population groups eventually admitted at these institutions.

For 2014 admissions, only 67% of students accepted the offers made by medical schools.

Black students made up 49.4% of the total offers made to students, and 46.9% of those who accepted these offers. Only 62.4% of black students accepted the offers made.

White students comprised 27.3% of the offers made and 27.9% of the offers accepted. In this group, 61.8% accepted the offers made.

Coloured students comprised 11.6% of the offers made, and made up 9.5% of those who accepted offers at medical school. In this group, 49.3% accepted the offers made.

Of the offers made, 11.4% were to Indian/ Asian students, and of the offers accepted, 11.5% had been made to Asians. In this group, 61.2% accepted the offers made. Very low numbers of students in the group ‘other’ (including students from SADC countries) were offered places, and of these students only 40.0% (6/15) accepted the offers. There are no available data showing reasons for the difference between offers made and eventual admissions.

Fig. 3 represents the total number of offers made and accepted in 2013 for admission in 2014 at all eight medical schools.

At all institutions, with the exception of WSU, the number of students who take up positions offered to them was lower than the number of offers made. The largest number of offers made was to black and coloured students (53.3%), redressing previous disadvantage, followed by white (31.3%) and Indian/Asian (14.8%) students. When

looking at the number of students who accepted these offers, the majority (56.3%) were black and coloured students, followed by white (29.9%) and Asian/Indian students (13.4%).

Discussion

All eight medical schools in SA use academic and non-academic requirements in their selection processes, conforming to international practice.[1,5] In addition, these institutions aim to improve inclusivity among the students selected in order to meet the needs of the diverse socioeconomic and cultural populations that qualifying doctors will serve in future. For example, based on existing evidence,[11] targeting students from rural areas may enhance the number of rural practitioners. This approach is in line with the World Health Organization (WHO) guidelines stating that admission policies should be targeted to reflect student diversity in terms of socioeconomic, ethnic and geographic background.[12] We found that overall the demographic profile of selected students is beginning to reflect the diversity of the population groups in SA. Although the proportion of students in each population group varies between medical schools (probably reflecting the demographics of the province and region where the institution is situated), the percentage of students from historically disadvantaged racial groups (black and coloured students) has improved to a large degree when compared with pre-1994,[13] although less so since 1999.[6] The largest number of students enrolled for training as doctors at SA medical schools are the black and coloured groups (52.1%), followed by

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white (33.0%) and Indian/Asian students (13.6%). Black students remain under­ represented in medical schools compared with the national demographics in 2011,[10] while the minority groups are overrepresented.

In an attempt to address past inequality, at least 60% of offers made by medical schools are to black and coloured students. Of the students who accept offers, at least 60% are black and coloured.

The percentage of female students is higher than that of male students. Only the UFS sets a gender ratio of 60:40 female/male in order to ensure that the minority male gender among the applicants is represented.

Various indices of disadvantage (such as quintile 1 and 2 schools,[7] rural origin, disadvantaged population groups) have been suggested for inclusion, in order to address disadvantage effectively and to move beyond race as an indicator of disadvantage, especially when taking the emerging black middle class into account. However, more precise indicators of disadvantage may have to be developed for use in selection, or for deciding on students who may not fulfil the minimum academic requirements set in selection policies. Furthermore, culturally sensitive selection tools need to be explored in order to address issues related to cultural, socioeconomic and language diversity, which may affect students’ possible selection. For example, students from lower socioeconomic backgrounds may not have access to the wide array of cultural and sporting activities or leadership development compared with those from privileged backgrounds, placing them at a further disadvantage when these items are included in non-academic selection criteria. The erratic quality of secondary school education in SA[9] also leads to disadvantage, particularly for students whose schooling is affected by sociopolitical upheaval, poor teaching proficiency or lack of adequate learning resources. This is not limited to schools in rural areas or even historically black residential areas such as urban informal settlements.

In order to address socioeconomic dis­ advantage effectively, students from poor backgrounds must have greater access to bursaries and financial support for the duration of their studies. As stated by the WHO[12] in 2013: ‘It is clear that admission procedures by themselves will not overcome inequalities in healthcare systems. Where targeted admission policies are used, support mechanisms must be in place to ensure conditions in which students are able to complete programmes. … Currently many students who do not complete their courses

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do so for financial reasons, so disadvantaged students would need financial support.’[12]

Conclusion

The demographic profile of medical students selected at SA universities is moving closer to the population distribution of SA. However, the percentage of black students is still lower than that in the general population, while white, Indian/Asian and coloured students are overrepresented in relation to the general population.

Current policies target black and coloured students for selection into undergraduate medical programmes across all medical schools in SA. However, race-based selection policies may be inadequate for addressing historical inequalities. Indices of disadvantage such as origin in rural or underserved communities (possibly linked to poorer educational opportunities) and socioeconomic status should be considered to improve access. In compliance with international trends, both academic and non-academic indicators are used in the selection process. Stronger evidence is now needed to link throughput, academic success and possibly even future career paths to selection processes.

It is worth noting, however, that the quality and values of these graduates – irrespective of where they come from – are influenced by the training curriculum, quality of teaching and role models they are exposed to once they are enrolled in medical school.

Acknowledgements. We thank Dr Daleen Struwig, Faculty of Health Sciences, UFS, for technical and editorial preparation of the manuscript.

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References 1. Bore M, Munro D, Powis D. A comprehensive model for the selection of medical students. Med Teach 2009;31(12):1066-1072. [http://dx.doi.org/10.3109/01421590903095510] [PMID 19995169] 2. Koenig TW, Parrish SK, Terregino CA, Williams JP, Dunleavy DM, Volsch JM. Core personal competencies important to entering students’ success in medical school: What are they and how could they be assessed early in the admission process? Acad Med 2013;88(5):603-613. [http://dx.doi. org/10.1097/ACM.0b013e31828b3389] 3. Ross D, Loeffler K, Schipper S, Vandermeer B, Allan GM. Do scores on three commonly used measures of critical thinking correlate with academic success of health professions trainees? A systematic review and meta-analysis. Acad Med 2013;88(5):724-734. [http://dx.doi.org/10.1097/ ACM.0b013e31828b0823] [PMID 23524925] 4. Kuncel NR, Ones DS, Hezlett SA. A comprehensive meta-analysis of the predictive validity of the graduate record examinations: Implications for graduate student selection and performance. Psychol Bull 2001;127(1):162-181. [http://dx.doi.org/10.1037/0033-2909.127.1.162] 5. Benbassat J, Baumal R. Uncertainties in the selection of applicants for medical school. Adv Health Sci Educ 2007;12(4):509-521. [http://dx.doi.org/10.1007/s10459-007-9076-0] 6. Lehmann U, Andrews G, Sanders D. Change and Innovation at South African Medical Schools – An Investigation of Student Demographics, Student Support and Curriculum Innovation. Durban: Health Systems Trust, 2000. http://indicators.hst.org.za/uploads/files/medschools.pdf (accessed 22 June 2015).

7. Western Cape Government, Department of Education. Background to the national quintile system. Media release 14 October 2014. http://wced.pgwc.gov.za/comms/press/2013/74_14oct.html (accessed 30 June 2015).

8. Naidoo SS, van Wyk J, Higgins-Opitz SB, Moodley K. An evaluation of stress in medical students at a South African university. S Afr Fam Pract 2014;565(5):258-262. [http://dx.doi.org/10.1080/207861 90.2014.980157] 9. Spaull N. South Africa’s education crisis: The quality of education in South Africa 1994-2011. Report Commissioned by Centre for Development and Enterprise (CDE), October 2013. http://www. section27.org.za/wp-content/uploads/2013/10/Spaull-2013-CDE-report-South-Africas-EducationCrisis.pdf (accessed 30 June 2015).

10. Statistics South Africa. Census 2011. Statistical release (revised) P0301.4. www.statssa.gov.za/ publications/P03014/P030142011.pdf (accessed 28 July 2015).

11. Grobler L, Marais BJ, Mabunda SA, Marindi PN, Reuter H, Volmink J. Interventions for increasing the proportion of health professionals practising in rural and other underserved areas. Cochrane Database Syst Rev 2009, Issue 1. Art. No.: CD005314. [http://dx.doi.org/10.1002/14651858.CD005314.pub2] 12. World Health Organization. Transforming and scaling up health professionals’ education and training.

Geneva: WHO, 2013. http://apps.who.int/iris/bitstream/10665/93635/1/9789241506502_eng.pdf (accessed 30 June 2015).

13. Digby A. Black doctors and discrimination under South Africa’s apartheid regime. Med Hist 2013;57(2):269-290. [http://dx.doi.org/10.1017/mdh.2012.106]

Accepted 28 September 2015.

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Implementation of a new ‘community’ laboratory CD4 service in a rural health district in South Africa extends laboratory services and substantially improves local reporting turnaround time L M Coetzee,1,2 PhD; N Cassim,1,2 BTech, MPH; D K Glencross,1,2 MB BCh, MMed 1 2

ational Health Laboratory Service National Priority Programmes, Johannesburg, South Africa N Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Corresponding author: D K Glencross (debbie.glencross@nhls.ac.za)

Background. The CD4 integrated service delivery model (ITSDM) provides for reasonable access to pathology services across South Africa (SA) by offering three new service tiers that extend services into remote, under-serviced areas. ITSDM identified Pixley ka Seme as such an under-serviced district.

Objective. To address the poor service delivery in this area, a new ITSDM community (tier 3) laboratory was established in De Aar, SA. Laboratory performance and turnaround time (TAT) were monitored post implementation to assess the impact on local service delivery.

Methods. Using the National Health Laboratory Service Corporate Data Warehouse, CD4 data were extracted for the period April 2012 July 2013 (n=11 964). Total mean TAT (in hours) was calculated and pre-analytical and analytical components assessed. Ongoing testing volumes, as well as external quality assessment performance across ten trials, were used to indicate post-implementation success. Data were analysed using Stata 12.

Results. Prior to the implementation of CD4 testing at De Aar, the total mean TAT was 20.5 hours. This fell to 8.2 hours post implementation, predominantly as a result of a lower pre-analytical mean TAT reducing from a mean of 18.9 to 1.8 hours. The analytical testing TAT remained unchanged after implementation and monthly test volumes increased by up to 20%. External quality assessment indicated adequate performance. Although subjective, questionnaires sent to facilities reported improved service delivery.

Conclusion. Establishing CD4 testing in a remote community laboratory substantially reduces overall TAT. Additional community CD4 laboratories should be established in under-serviced areas, especially where laboratory infrastructure is already in place.

S Afr Med J 2016;106(1):82-87. DOI:10.7196/SAMJ.2016.v106i1.10081

Between April 2014 and March 2015, the South African National Health Laboratory Service (NHLS) CD4 network provided 3.9 million CD4 test results to referring health centres and clinics across South Africa (SA). Although there is an extensive network of ~260 national laboratories that provide general pathology services and 59 specialised labs that provide CD4 testing, gaps in service have been identified in remote districts (i.e. 14/53 districts).[1] An integrated tiered service delivery model (ITSDM)[1] consisting of six service tiers has been described in line with World Health Organization (WHO) recommendations,[2] which incorporates existing services and provides for extension of services into remote, under-serviced areas to address gaps in service delivery.

ITSDM tiers 4 and 5, at the higher end, are the backbone of existing CD4 services that currently provide high-volume testing in metro­ politan areas across SA; a harmonising sixth tier (tier 6) provides for external quality assessment, as well as network and training support.

Three new tiers of service are proposed in the ITSDM, to supplement tiers 4 and 5 and enable extended service delivery across the country into areas with service deficiencies. Firstly, tier 3/community laboratories can be established in an existing small general pathology laboratory, processing up to 150 samples per day using traditional or operatorindependent flow cytometry-based technologies (Beckman Coulter XL,[3] Beckman Coulter Aquios[4] and Becton Dickinson FACSCount (BDS, USA)[5]). Secondly, services are further extended with two pointof-care (POC) tiers into areas without reasonable access to a laboratory.

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The first POC tier/tier 2 is essentially a POC ‘hub’ or mini-laboratory that can provide services for up to ten referring community health/ primary health clinics (CHCs/PHCs) offering antiretroviral therapy within a radius of 50 km and be managed by a single technician (or recently a Health Professions Council of South Africa-approved cadre ‘phlebotomy technician’)[6] who will operate multiple POC technologies to provide a range of basic HIV and/or TB services.

These facilities can also be implemented into existing small NHLS laboratories and will process <50 but >10 samples per day, using CD4 technologies designed to be used at the POC, including FACSPresto (BDS, USA)[7] and Pima (Alere, SA). A mini-laboratory can also be set up in a designated area within an existing CHC. All are managed and overseen by the NHLS. The last ITSDM tier 1 provides similar services to tier 2 but will operate in remote, hard-to-reach sites as stand-alone facilities, providing services for the local clinic only. Attending nursing personnel or a phlebotomy technician could take responsibility for the CD4 testing. These extended tiers, which supplement the highvolume testing sites to provide full national service coverage, offer an optimised public health approach to balance overall programmatic costs,[8] while lowering and ensuring reliable turnaround time (TAT), irrespective of where the test request originates and in line with local HIV treatment algorithm requirements.[9] Pixley ka Seme, a remote district of SA and one of nine pilot sites for the introduction of National Health Insurance in SA, was identified through ITSDM planning as a district with poor access to CD4 testing. The existing De Aar laboratory in the district

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provides some basic pathology services across a service precinct of 103 410 km2 and eight municipalities. The local population of ~186 000 people attend multiple health facilities within a radius of up to 260 km, including ten local hospitals (hospital wards) and 34 PHC clinics. More than 70% of the population is under the age of 40 years, and the district has an HIV prevalence of 18.4% (2012 statistics).[10] A tier 3/community laboratory CD4 service was piloted at the existing De Aar NHLS laboratory to address the historically poor CD4 TAT and gaps in service. The impact of the newly implemented tier 3/community CD4 laboratory service in De Aar was assessed by reviewing the TAT before and after the implementation. Success of the implementation was measured through review of ongoing monthly CD4 test volumes and external quality assessment performance of the De Aar laboratory.

Methods

CD4 testing was implemented and training given at the De Aar laboratory in December 2012 using the Beckman Coulter Epics XLTM flow cytometry platform and the PanLeucogating method. [3] Using Corporate Data Warehouse (CDW), CD4 sample level data were extracted for the period April 2012 - July 2013 (N=11 964) for the wider Pixley ka Seme health area. This included pre-implementation data of CD4 workload referred to regional CD4 testing laboratories

for testing (Kimberly or Pelonomi) as well as data from the De Aar laboratory itself post implementation (sample volume data were extended to December 2014). The specimen data extract included the laboratory information system (LIS) episode number (which provided evidence of volumes of tests), province, health district and the health facility location name and code from which the sample was sent. Data that were collected with a listed LIS ‘tested date’ between 1 April and 30 November 2012 were categorised as ‘preimplementation’. Data collected after January 2013 were categorised as ‘post-implementation’. The reporting measures included CD4 monthly test volumes and mean TATs. To establish TAT, the following LIS date and time fields were used, including: (i) ‘registered date’, when samples are registered (order entry) at the referring hub or laboratory; (ii) ‘test registered date’ describing when samples are registered/received at the CD4 testing laboratory; (iii) ‘tested date’, when the CD4 Epics XLTM CD4 result data are downloaded into the LIS; and lastly, (iv) ‘reviewed date’, when a medical technologist authorises the CD4 results for printing (by SMS (text message)) at the original referring site. Using the LIS date and time fields, four distinct TAT measures were identified for this analysis: (i) ‘PRE-LAB TAT’ (pre-analytical component), test registered date minus registered date (interlaboratory or processing hub referral time); (ii) ‘IN-LAB TAT’, tested date minus test registered date (analytical processing

Fig. 1. Map of distribution of existing NHLS CD4 service (as pale yellow and pale orange circular service precincts) in relation to >4 000 referring PHC clinics (black dots), distributed across 53 defined districts in SA. A new community CD4 service (tier 3) was established in Pixley ka Seme (demarcated as a red circle), at the De Aar NHLS service laboratory in 2012, to address poor access to CD4 testing in this district identified through ITSDM planning. Insert: Map of the greater Pixley ka Seme district reveals existing referring health facilities serviced by the De Aar laboratory. Although the De Aar laboratory offered basic pathology testing, CD4 testing was referred to nearby centralised facilities including Kimberley (243 km away), Upington (433 km) and Bloemfontein/ Pelonomi (362 km) laboratories. Red circles are estimated existing precinct service coverage.

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time); (iii) ‘RVW-TAT’, reviewed date minus tested date (time to authorised results following analysis); and lastly (iv) ‘TOTAL-TAT’, reviewed date minus registered date. Anomalies, due to a computer internal data and time setting for the decentralised Disa*Lab LIS used previously, that were noted in the LIS date and time fields were excluded (e.g. a reviewed date in the year 1800 (1800/01/01 00:01).

This affected only 0.3% (36/11 964) of the total data set. All data were analysed using Microsoft Excel and Stata 12.

External quality assessment (EQA) performance of the De Aar laboratory on the NHLS CD4 Proficiency Testing (PT)/African Regional External Quality Assessment (AFREQAS) programme[11] was obtained from the De Aar laboratory from trial 19 (May 2013) through to trial 30. Each AFREQAS trial consists of two proficiency material samples, i.e. one normal (CD4 count >500 cells/µL) and one low (CD4 count <200 cells/µL) sample. Performance of the laboratory is measured against the consensus pooled mean result of each trial, and is regarded as adequate if the CD4 result reported by the laboratory falls within 2 standard deviations (SDs) of the consensus pooled trimmed-mean CD4 result.

Results

The geographical relationship of 44 referring health facilities and the De Aar laboratory in the Pixley ka Seme district to the preimplementation referral CD4 labs in the Free State (Pelonomi) or Kimberly (North West) is shown in Fig. 1. This figure also gives information about existing CD4 service coverage in SA, showing paucity of local services in the Pixley ka Seme district, in contrast

to the relatively well-serviced areas elsewhere in the country. Fig. 2 reveals the impact on TAT of longer (shorter) distances required to refer samples for testing elsewhere; the monthly mean TOTAL-TAT for Pixley ka Seme before implementation ranged from 12 to 38 hours (the majority of samples were referred from the De Aar laboratory to the Kimberley laboratory for testing). A marked difference in mean TOTAL-TAT was noted, reducing from a median of 20.45 hours before implementation to 8.17 hours after December 2012 (Fig. 2).

Following a 2-month settling-in period, by March 2013 (mean TOTAL-TAT of 16 hours was recorded), the TOTAL-TAT steadily decreased to a mean of 12 hours and stabilised at 5 hours or less by May 2013. This trend has continued beyond the TAT data extraction period (data not shown).

To assess what component of TAT contributed to TOTAL-TAT, the various components of TAT were assessed including PRE-LAB (pre-analytical), IN-LAB and RVW-TAT (both analytical), before (pre-) and after (post-) implementation (Fig. 2). The pre-analytical component of the TOTAL-TAT was noted to contribute the largest proportion of TOTAL-TAT in the pre-implementation time period.

During these pre-implementation months, April - November 2012, pre-analytical TAT showed marked daily variability (with a range of TAT from 4 hours in April 2012 extending to 45 hours in October 2012). After the De Aar CD4 lab was established, the mean PRE-LAB decreased from an average of 18.99 hours to 1.82 hours, reducing the mean monthly TOTAL-TAT substantially. By June 2013, the mean pre-analytical TAT had stabilised at ~2 hours. Evidence of an initial learning curve was revealed during the first 2 months, i.e. January

50

B

45 40

Turnaround time (hours)

35 30 25

New CD4 service implementation

A

Pre 18.99 6.82 0.95

Mean PRE-LAB TAT (hours) Mean IN-LAB TAT (hours) Mean RVW-TAT (hours)

Post 1.82 7.37 0.85

20 15 10 5 Apr-12 May-12 Jun-12

Jul-12 Aug-12 Sep-12 Oct-12

Nov-12 Jan-13 Feb-13 Mar-13 Apr-13 May-13 Jun-13 Jul-13

Pre-implementation

Post-implementation

Mean PRE-LAB TAT

4

8

23

35

16

15

45

8

3

3

5

0

1

1

Mean IN-LAB TAT

11

11

7

6

6

5

2

6

11

13

6

4

5

5

5

1.28

1.17

0.91

1.01

0.61

0.53

0.81

1.28

2.11

0.70

1.43

0.71

0.36

0.22

0.41

Mean RVW-TAT

1

Fig. 2. Breakdown of TOTAL-TAT in the pre-implementation (April - November 2012) and post-implementation phases (January - July 2013), into mean PRE-LAB TAT (blue), mean IN-LAB TAT (black) and mean RVW-TAT (grey). In the pre-implementation phase, the mean PRE-LAB TAT was 4 - 45 hours and the mean IN-LAB TAT 2 - 11 hours. In contrast, in the post-implementation period, the mean PRE-LAB TAT decreased to <6 hours but with no significant change in mean IN-LAB TAT at 4 - 13 hours (expected because of use of standardised testing protocols).

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and February 2013, where an IN-LAB TAT of 11 and 13 hours was noted respectively (highlighted in Fig. 2). However, the IN-LAB/ analytical TAT subsequently decreased to that expected of a typical CD4 laboratory processing time as staff became more familiar and integrated the new CD4 testing into their existing workflow (attributable to the adherence to the standardised NHLS CD4 testing procedures that are used irrespective of where testing is performed across the NHLS CD4 network). Further analysis of the TOTAL-TAT data revealed that before implementation of the De Aar CD4 site, 54% of CD4 samples were reported within a TOTAL-TAT of ≤12 hours.

After implementation however, 81% of samples had a TOTAL-TAT of ≤12 hours (Fig. 2). In a detailed subanalysis, CD4 sample results with a TOTAL-TAT between 13 and 24 hours decreased from 26% to 13%; those with a TOTAL-TAT >24 hours, decreased by 150%, from 19% to 6% of all samples tested. Overall, the percentage of samples with a ≤24 hours TOTAL-TAT increased from 81% before implementation to 94% post implementation.

Details of month-to-month variation of workload volume post implementation can be seen in Fig. 3, extending to December 2014.

Pre-implementation volumes were divided into ‘referred to and tested at Kimberley’ (mean of 571 samples/month) and ‘referred by De Aar and tested in Kimberley’ (mean 112 samples per month). After CD4 testing started at De Aar in December 2012, some samples were still referred through De Aar to be tested in Kimberley (~125 per month).

This was attributed to periods of downtime on the instrument (owing to long distances, reaction time of engineers to get instruments operational is prolonged) and/or availability of staff to operate the system. However, the majority of samples from the district are now tested at the De Aar laboratory (monthly mean of 358 samples). Some

samples are still referred directly to Kimberley at a mean rate of 287 per month and reflect NHLS business decisions to optimally refer testing from sites that lie far north in Pixley ka Seme to the nearest testing facility (in this instance Kimberley).

External quality assessment performance

During the post-implementation period of this study, ten trials (20 EQA samples) were tested by the De Aar laboratory. Across each trial, proficiency panel results (CD4 normal and CD4 low, as CD4 count and CD4% of lymphocytes (CD4%L)) were recorded within the required 2 SDI range (Fig. 4, shaded area; −2 - +2, with zero as the ideal target). There was an initial outlier EQA result on the normal CD4%L (intervention revealed a transcription error due to inexperience of staff filling in the EQAS submission form). The average SDI of the De Aar CD4 laboratory across all trials was −0.21, confirming that performance was well within the expected range.

However, SDI results from Trial 23 fell outside the expected range for both absolute count and CD4%L (intervention and corrective action revealed that new staff had been appointed without proper EQAS training). The laboratory has sustained acceptable performance on the scheme for the remaining reported trials (Fig. 4).

Discussion

CD4 testing has been used for establishing immune suppression and disease progression in HIV-positive patients, enabling identification of those patients who are eligible for antiretroviral therapy and/ or treatment for opportunistic infection. Current SA treatment guidelines[9] require that newly identified HIV-positive patients return to the clinic facility within 7 days of testing HIV-positive[12] to

Kimberley/De Aar for Pixley ka Seme district 1 000

RT De Aar R De Aar T Kimberley RT Kimberley

600

400

Implementation

CD4 samples per month, n

800

200

M

Ap r

il 2 01 ay 2 Ju 201 ne 2 2 Ju 012 l Au y 20 Se gu 12 pt s em t 20 Oc ber 12 2 t No obe 012 ve r 2 m 0 be 12 r2 01 De 2 ce m be r2 Ja n 0 Fe uar 12 br y 2 ua 01 ry 3 M 20 ar ch 13 Ap 201 ril 3 2 M 013 ay Ju 20 ne 13 2 Ju 013 l Au y 20 Se g 1 pt ust 3 em 2 0 b Oc er 13 No tob 201 ve er 3 m 20 b 1 Ja er 2 3 nu 01 3 Fe ar br y 2 ua 01 ry 4 M 20 ar ch 14 Ap 201 ril 4 2 M 014 ay Ju 20 ne 14 2 Ju 014 l Au y 20 Se g 1 pt ust 4 em 2 0 b Oc er 14 No tob 201 ve er 4 m 2 De be 014 ce r 2 m 0 be 14 r2 01 4

0

Year and month

Fig. 3. Total volumes of CD4 tests performed per month before (pre-) and after (post-) CD4 laboratory implementation at De Aar. Volumes of samples ‘referred to and tested at Kimberley’ (‘RT Kimberley’), are shown in contrast to samples ‘referred to and tested at De Aar’ (‘RT De Aar’). A small fraction of samples referred to De Aar for testing is still tested at Kimberley (‘R De Aar T Kimberley’/‘RT Kimberley’).

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receive the results of the required pathology work-up, including CD4 results outlined in the treatment guidelines. Since the commencement of the South African HIV/ AIDS Comprehensive Care, Management and Treatment programme, laboratorybased CD4 testing has been the mainstay of the CD4 services provided.[3,13] Locally, the NHLS provides access to the majority of these CD4 results within a 24-hour TAT to facilitate algorithm management.[1] In the rural areas of the Northern Cape Province, the closest tier 4/regional and tier 5/metro centralised laboratories are too far (up to 300 - 400 km) away to ensure reliable CD4 TATs.[1] Several service delivery options were con­ sidered for Pixley ka Seme area that would improve TAT, while taking into account the vast distances between facilities in the

district and proximity to the closest testing facilities. The first service option con­ sidered CD4 testing on a mobile unit,[14] with various scenarios proposed. These included a once-per-month service option (costing ZAR125.47/test), a fortnightly option (ZAR201.22/test/visit), a weekly option (ZAR352.73) as well as a daily service delivery option (ZAR1 564.75/test).[14] This approach was abandoned because of the prohibitively high, unaffordable cost per test required to maintain reasonable access to services on at least 4 days a week.

Implementation of widespread POC CD4 testing services in all 44 referring facilities was also considered as the second option, potentially providing immediate patient access to results and purporting the added advantage[13] of improving the number of patients enrolled into care. Aside from the

logistical and other problems of widespread POC technology implementation,[1] overall voluntary counselling and testing process compliance has been reportedly poor,[15] with specific areas of concern including specimen collection methodology and availability of equipment, e.g. gloves, etc., to perform the test (procurement challenges), poor or misuse of available consumables, poor adherence to stipulated incubation times before reading HIV rapid test results, lack of staff training and inconsistent or absent quality assurance practices.[15] This approach was also abandoned in the NHLS because of the substantively higher programmatic costs that could be incurred by implementing POC across multiple clinics; a CD4 test performed at the POC was shown to cost 5 - 7 times more than providing a CD4 test in a laboratory.[8]

%CD4: Normal

#CD4: Normal

#CD4: Low

%CD4: Low

Fig. 4. Performance on EQA after tier 3 CD4 service implementation at De Aar. Radial performance plots show laboratory performance on trials 19 through 30. A1 and A2 represent data from the normal CD4 count proficiency material while B1 and B2 depict results from low CD4 count EQA material. The acceptable range of â&#x2C6;&#x2019;2 - +2 SDI is shaded with a solid line indicating the ideal of zero. An initial outlier on trial 19 was shown to be a transcription error.

Another outlier was noted for trial 23 (both parameters). Intervention and corrective action ensured that future performance returned to expected.

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The third service delivery of providing a local small community laboratory was provided for in the ITSDM. This study confirms that the establishment of an ITSDM tier 3 laboratory in a remote, under-serviced area of SA with historically poor TAT can lead to a dramatic improvement of local service delivery. There was a notable reduction in the pre-analytical TAT after CD4 testing was started in the De Aar laboratory, from 18 hours when samples were referred in centrally for testing to the Kimberley laboratory, down to a mean of 1.82 hours post implementation. Although anecdotal, the responses from local clinics were favourable; a moderate increase in the number of CD4 tests requested post implementation (see Fig. 3) attested to this. Despite an initial hiccup of increased analytical/ IN-LAB TAT attributable to learning curve, IN-LAB TAT fell to expected levels as staff became better acquainted with NHLS standardised operating procedures. This is an encouraging aspect, and together with the satisfactory EQA review of the performance of the site, suggests that any small laboratory, with few staff members, is likely to cope well with an add-on tier 3 service. Although some CD4 testing was still referred to the larger metropolitan tier 4 lab at Kimberley after implementation, because referring clinic sites were in closer proximity to this centre (see Fig. 3), a moderately increased local workload (Fig. 3) was noted post implementation at De Aar. This is also an important outcome. If smaller laboratories are capable of an additional modest workload, without major implementation, overhead and staffing costs, this could potentially save the country millions of rands while extending the footprint of laboratory services. [1,8] Previous cost modelling work in Pixley ka Seme district[8] reveals that establishing this small tier 3 site may cost marginally more per CD4 test than a CD4 tested in a centralised larger laboratory (ZAR28.62/USD2.06 at exchange rate of ZAR13.90 per USD on 20 November 2015). This is, however, substantially cheaper than implementing widespread use of POC technology (44 tier 1 facilities) across the district’s 44 clinic sites, where it has been estimated that widespread CD4 provided at the POC could cost Pixley ka Seme in excess of ZAR4.5 million/USD325 700 (at ZAR449.25/USD32.32 per test) as opposed to an estimated ZAR1.03 million/USD74 000 needed to provide a tier 3 laboratory-based service offering the same number of tests per­formed, but at the De Aar facility. The additional benefit, as a trade-off for the small incremental cost, is that there are less local logistics costs incurred, as testing is performed on-site, coupled with better sample integrity and significantly improved local TAT – all of which has positive implications for better patient management.

Conclusion

The extended decentralised tier 3/community laboratory imple­ men­ tation at the De Aar laboratory in Pixley ka Seme offers a compromise between cost and accessibility, with a small incre­ mental cost (ZAR28.63/USD2.06)[8] but substantively lower TAT, while maintaining a quality of testing expected from a larger lab­ oratory. Owing to the success of the De Aar pilot site, additional implementation sites, also identified through ITSDM planning, have been proposed to improve and extend services elsewhere in underserviced districts using existing NHLS laboratories, including Aliwal North (Eastern Cape), Lephalale (Limpopo), St Patricks (Eastern Cape) and Vredenburg (Western Cape).

Study limitations

Owing to the absence of an end-to-end sample tracking system, it was not possible to report TAT for afferent (time from sample collection by the courier at the health facility to registration on

87

the LIS) and efferent (time from result authorisation to result delivery to the health facility) phases of the laboratory value chain.

Additionally, for interlaboratory referrals we were unable to identify whether delays were due to courier delays or to pre-analytical receiving office delays.

Acknowledgements. The authors thank Sue Candy and Manfred Tepper at the NHLS CDW for their assistance and support in extracting the test volume and turnaround time data. We would also like to thank the manager and staff of the De Aar laboratory, Janet Scholtz, the regional quality officer, for providing relevant EQA data. The authors thank the NHLS and National Priority Programme for ongoing support. DKG thanks the South African National Research Foundation for Incentive Funding for Rated Researchers.

This work was selected to represent the top 15% of local innovations, best practices and lessons learned that will help achieve HIV/AIDS UNAIDS proposed 90-90-90 targets in SA, presented at the UNAIDS/ USAIDS/ PEPFAR/HE2RO and National Department of Health collaborative showcase meeting entitled ‘Reaching 90-90-90 in South Africa: Innovations and Best Practices’, held at the South African HIV/AIDS meeting in Durban during June 2015.

Conflict of interest. DKG declares that the employer, the NHLS, is the sole owner of the patent held for the PanLeucogated CD4 method, currently licensed to Beckman Coulter International and receives royalties. Through open public tender, Beckman Coulter was awarded a service level agreement to provide CD4 testing services in the NHLS. All LIS sample-related CDW data were used with permission from the NHLS CEO, Dr Sagie Pillay.

References 1. Glencross DK, Coetzee LM, Cassim N. An integrated tiered service delivery model (ITSDM) based on local CD4 testing demands can improve turn-around times and save costs whilst ensuring accessible and scalable CD4 services across a national programme. PloS One 2014;9(12):e114727. [http://dx.doi. org/10.1371/journal.pone.0114727] 2. World Health Organization (WHO). Universal Coverage – Three Dimensions. Geneva: WHO, 2015. http://www.who.int/health_financing/strategy/dimensions/en/. (accessed 7 July 2015).

3. Glencross DK, Janossy G, Coetzee LM, et al. Large-scale affordable PanLeucogated CD4+ testing with proactive internal and external quality assessment: In support of the South African National Comprehensive Care, Treatment and Management Programme for HIV and AIDS. Cytometry Part B: Clinical Cytometry 2008;74(Suppl 1):S40-S51. [http://dx.doi.org/10.1002/cyto.b.20384] 4. Coulter B. Aquis CL: Beckman Coulter Life Sciences. 2015. http://www.Aquioscl.com (accessed 7 July 2015).

5. Biosciences B. BD FACSCount 2015. http://www.bdbiosciences.com/eu/instruments/clinical/cellanalyzers/bd-facscount/m/744703 (accessed 7 July 2015).

6. South African Qualifications Authority (SAQA). Further Education and Training Certificate: Phlebotomy Techniques 2015. http://allqs.saqa.org.za/showQualification.php?id=59345 (accessed 7 July 2015).

7. Biosciences B. BD FACSPresto 2015. http://www.bdbiosciences.com/eu/instruments/clinical/cellanalyzers/bd-facspresto/m/Cellanalyzersbdfacspresto (accessed 7 July 2015).

8. Cassim N, Coetzee LM, Schnippel K, Glencross DK. Estimating implementation and operational costs of an integrated tiered CD4 service including laboratory and point of care testing in a remote health district in South Africa. PloS One 2014;9(12):e115420. [http://dx.doi.org/10.1371/journal. pone.0115420] 9. National Department of Health. Revised Anti-Retroviral Treatment Guideline Update for Frontline Clinical Health Professionals. Pretoria: NDoH, 2013.

10. National Department of Health. The 2012 National Antenatal Sentinel HIV and Herpes simplex type 2 Prevalence Survey in South Africa. Pretoria: NDoH, 2013.

11. Glencross DK, Aggett HM, Stevens WS, Mandy F. African regional external quality assessment for CD4 T-cell enumeration: Development, outcomes, and performance of laboratories. Cytometry Part B: Clinical Cytometry 2008;74(Suppl 1):S69-S79. [http://dx.doi.org/10.1002/cyto.b.20397] 12. National Department of Health. National Consolidated Guidelines for the Prevention of Mother-toChild Transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults.

Pretoria: NDoH, 2015.

13. Faal M, Naidoo N, Glencross DK, Venter WD, Osih R. Providing immediate CD4 count results at HIV testing improves ART initiation. J Acquir Immune Defic Syndr 2011;58(3):e54-e59. [http://dx.doi. org/10.1097/QAI.0b013e3182303921] 14. Coetzee LM, Cassim N, Glencross DK, eds. A Cost Analysis of Mobile Laboratory CD4 Testing In a National Health Insurance (NHI) Pilot Site. First International Conference of the African Society for Laboratory Medicine (ASLM), Cape Town, South Africa, 1 - 7 December 2012.

15. Strategic Evaluation Advisory and Development Consulting (SEAD). Analysis of POCT/VCT Performed at South African Primary Health Care Clinics. Cape Town, 2011. http://www.sead.co.za/ downloads/POCT-clinics-2011.pdf (accessed 20 November 2015).

Accepted 2 November 2015.

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HLA typing: Conventional techniques v. next-generation sequencing J Mellet,1 BSc Hons, MSc; C M Gray,2,3 BSc Hons, MSc, PhD; M S Pepper,1 MB ChB, PhD, MD epartment of Immunology, Institute for Cellular and Molecular Medicine, and South African Medical Research Council Extramural Unit D for Stem Cell Research and Therapy, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa 2 Division of Immunology, Institute of Infectious Diseases and Molecular Medicine and Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa 3 Laboratory for Tissue Immunology, National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa 1

Corresponding author: M S Pepper (michael.pepper@up.ac.za)

Background. The large number of population-specific polymorphisms present in the HLA complex in the South African (SA) population reduces the probability of finding an adequate HLA-matched donor for individuals in need of an unrelated haematopoietic stem cell transplantation (HSCT). Next-generation sequencing (NGS) has numerous advantages compared with conventional typing techniques.

Objective. To evaluate whether NGS can provide any additional value over conventional techniques in the SA context for the purpose of HSCT and cord blood banking.

Methods. HLA genotyping was performed using NGS on 20 samples that had previously been HLA typed by conventional methods to evaluate whether NGS might provide any additional value over conventional HLA determination techniques.

Results. NGS of routinely sequenced loci and exons yielded accurate genotypes for 98.5% of the five loci of interest, compared with 98% when additional exons were included.

Conclusion. The study shows that the additional value of NGS over conventional techniques is limited, and unless done on a large scale to reduce cost may not be appropriate in SA at this stage in the context of HSCT and cord blood banking.

S Afr Med J 2016;106(1):88-91. DOI:10.7196/SAMJ.2016.v106i1.9571

The HLA complex, located on chromosome 6, comprises the most polymorphic genes in humans[1] and plays a pivotal role in matching for haematopoietic stem cell transplantation (HSCT).[2] Allele-level HLA matching between donors and recipients reduces the likelihood of rejection and graft-versus-host disease (GVHD).[3] The South African (SA) population is characterised by great genetic diversity and the presence of population-specific and uncommon alleles decreases the probability of finding an HLA-compatible donor.

The majority of individuals in a given population group possess common alleles, but several uncommon population-specific alleles are also present.[4] HLA typing was initially performed using serological techniques.

In the 1960s, this was the sole method of determining tissue types.

Even though this method is still performed in some laboratories today, there are numerous limitations. In the mid-1990s, DNA-based techniques became more popular and were used to complement serological techniques. Today most laboratories primarily use probe/ primer-based techniques, which assign genotypes on the basis of previously identified alleles. However, as a result of the everincreasing number of new alleles, genotyping has become challenging.

An accurate high-resolution HLA genotyping method is therefore a necessary tool for the matching of donors to patients in need of an unrelated HSCT. Inaccurate typing could lead to inadequate HLA matching between donors and recipients, which could ultimately increase the chances of graft rejection, GVHD and mortality.

The existing techniques have contributed significantly to our current knowledge of allelic diversity. At present, sequence-based typing (SBT) methods, in particular next-generation sequencing (NGS), provide the highest possible resolution. NGS platforms

88

were initially only used for genomic sequencing, but also showed potential for research and diagnostic purposes. Even though these newly developed techniques have already proved to be efficient in identifying novel alleles, the more conventional techniques are still preferred for routine procedures in many diagnostic laboratories.

Exons 2 and 3 for class I and exon 2 for class II are routinely sequenced because they constitute the peptide-binding region of the corresponding HLA molecules. Alleles that are identical across this region but differ in other exons are referred to as ambiguous alleles.

Sequencing of additional exons has been shown to reduce these ambiguities and produce better allele resolution, and could improve matching between unrelated donors and recipients for HSCTs.[5] The purpose of this study was to evaluate whether NGS can provide any additional value over conventional techniques in the SA context for the purpose of HSCT and cord blood banking.

Methods

Twenty DNA samples isolated from peripheral blood mononuclear cells were selected from the South African Bone Marrow Registry.

Each DNA sample had already been HLA genotyped by the Laboratory for Tissue Immunology at the time of commencement of the study. HLA typing was performed using low- and/or highresolution typing techniques. This study made use of the Life Sciences, Roche 454 NGS platform for genotyping of the samples. All laboratory procedures for this study were performed according to the HLA assay manual (Roche Applied Science GS GHLA Assay Manual, March 2011). The typing kit targets the most hypervariable regions of the MHC class I and class II genes. The GS GType HLA Primer sets (Roche Applied Science, Germany) were made available as two kits, medium resolution (MR) and high resolution (HR). Sequencing was

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performed by Inqaba Biotec on a GS Junior sequencer. The raw sequencing data were assembled and analysed using JSI SeqHLA 454 software (version 3.16.0) (JSI Medical Systems, Germany).

Ethical considerations

This study was conducted in the Department of Immunology at the University of Pretoria, SA. Ethical approval was granted in 2010 by the Faculty of Health Sciences Research Ethics Committee (Protocol No. 131/2010) for the project entitled ‘Feasibility study for a public cord blood stem cell bank in South Africa’, of which the current study formed part. The proposal for this study was submitted in November 2011, followed by ethical approval, which was granted by the Ethics Committee of the University of Pretoria (Protocol No. 219/2011).

Separate ethical approval was granted by the University of Cape Town (Protocol No. 523/2011) for the use of the 20 samples obtained from the Laboratory for Tissue Immunology, Groote Schuur Hospital, Cape Town.

Results

Samples 1 - 10 (Table 1) were previously typed by high resolution at class I and class II loci. Samples 11 - 20 (Table 2) were typed by low resolution at class I loci and by high resolution at class II loci. Genotypes obtained using these conventional techniques are shown in column 3, and the results obtained from the present study by NGS (Roche 454) of routinely sequenced exons and additional exons for the five loci of interest are shown in columns 4 and 5, respectively. Results from the conventional techniques are displayed at a two- to four-digit level of resolution, depending on the technique used. In cases where a conventional typing result was not identical to an allele in the ambiguity list obtained by NGS, a sample was said to be in disagreement.

Side-by-side comparison of the results obtained from conventional and NGS typing for samples 1 - 10 showed 99% and 98% concordance between conventional typing techniques and NGS for routinely sequenced exons and additional exons, respectively.

The results for samples 11 - 20 showed 98% concordance between conventional typing techniques and NGS for both routinely sequenced exons and additional exons. It was possible to assign accurate genotypes to 98.25% of the loci of interest for the 20 samples by NGS. The genotypic discordance between the conventional techniques and NGS typing of routinely sequenced exons was mainly due

Table 1. HLA genotyping results for samples 1 - 10 by conventional and 454 NGS techniques Ethnicity

Conventional techniques (SBT and SSP)

454 NGS (MR)

1

Mixed ancestry

02:01

03:01

02:01

03:01

02:01

03:01

2

Tanzanian

30:02

68:02

30:02

68:02

30:02

68:02

3

SA black

68:02

74:01

68:02

74:01

68:02

74:01

4

Mixed ancestry

02:01

66:01

02:01*

66:01*

02:135

69:02

5

SA black

02:01

29:02

02:01

29:02

02:01

29:02

6

Mixed ancestry

03:01

11:01

03:01

11:01

03:01

11:01

7

Kenyan

02:01

02:02

02:01

02:02

02:01

02:02

8

SA black

68:02

68:02

68:02

68:02

68:02

68:02

9

SA black

68:02

74:01

68:02

74:01

68:02

74:01

10

Mixed ancestry

30:01

43:01

30:01

43:01

30:01

43:01

ID

454 NGS (HR)

HLA-A

HLA-B 1

Mixed ancestry

07:02

08:01

07:02

08:01

07:02

08:01

2

Tanzanian

08:01

44:03

08:01

44:03

08:01

44:03

3

SA black

07:02

15:03

07:02

15:03

07:02

15:03

4

Mixed ancestry

13:02

35:02

13:02

35:02

13:02

35:02

5

SA black

45:01

45:07

45:01

45:01*

45:01

45:07

6

Mixed ancestry

07:02

07:06

07:02

07:06

07:02

07:06

7

Kenyan

45:01

51:01

45:01

51:01

45:01

51:01

8

SA black

15:10

57:02

15:10

57:02

15:10

57:02

9

SA black

15:03

15:10

15:03

15:10

15:03

15:10

10

Mixed ancestry

15:10

42:01

15:10

42:01

15:10

42:01

HLA-C 1

Mixed ancestry

07:01

07:02

07:01

07:02

07:01

07:02

2

Tanzanian

07:01

14:03

07:01

14:03

07:01

14:03

3

SA black

02:10

07:02

02:10

07:02

02:10

07:02

4

Mixed ancestry

04:01

06:02

04:01

06:02

04:01

06:02

5

SA black

06:02

16:01

06:02

16:01

06:02

16:01

6

Mixed ancestry

07:02

07:02

07:02

07:02

07:02

07:02

7

Kenyan

16:01

16:01

16:01

16:01

16:01

16:01

8

SA black

03:04

18:01

03:04

18:01

03:04

18:01

9

SA black

02:10

08:04

02:10

08:04

02:10

08:04

10

Mixed ancestry

04:01

17:01

04:01

17:01

04:01

17:01

HLA-DRB1 1

Mixed ancestry

01:01

03:01

01:01

03:01

01:01

03:01

2

Tanzanian

03:01

13:02

03:01

13:02

03:01

13:02

3

SA black

11:01

13:02

11:01

13:02

11:01

13:02

4

Mixed ancestry

07:01

11:04

07:01

11:04

07:01

11:04

5

SA black

11:02

13:01

11:02

13:01

11:02

13:01

6

Mixed ancestry

15:01

15:01

15:01

15:01

15:01

15:01

7

Kenyan

03:01

15:03

03:01

15:03

03:01

15:03

8

SA black

03:01

13:02

03:01

13:02

03:01

13:02

9

SA black

11:01

13:02

11:01

13:02

11:01

13:02

10

Mixed ancestry

03:02

04:01

03:02

04:01

03:02

04:01

Continued ...

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January 2016, Vol. 106, No. 1

RESEARCH

Table 1. (continued) HLA genotyping results for samples 1 - 10 by conventional and 454 NGS techniques ID

Ethnicity

Conventional techniques (SBT and SSP)

454 NGS (MR)

454 NGS (HR)

HLA-DQB1 1

Mixed ancestry

02:01

05:01

02:01

05:01

02:01

05:01

2

Tanzanian

02:01

06:04

02:01

06:04

02:01

06:04

3

SA black

03:19

06:09

03:19

06:09

03:19

06:09

4

Mixed ancestry

02:02

03:01

02:02

03:01

02:02

03:01

5

SA black

03:01

06:03

03:01

06:03

03:01

06:03

6

Mixed ancestry

05:02

06:02

05:02

06:02

05:02

06:02

7

Kenyan

02:01

06:02

02:01

06:02

02:01

06:02

8

SA black

02:01

06:09

02:01

06:09

02:01

06:09

9

SA black

06:02

06:09

06:02

06:09

06:02

06:09

10

Mixed ancestry

03:02

04:02

03:02

04:02

03:02

04:02

SSP = sequence-specific primers; bold font highlights the differences observed between conventional techniques and MR and HR. *Ambiguous typing result.

Table 2. HLA genotyping results for samples 11 - 20 by conventional and 454 NGS techniques ID

Ethnicity

Conventional techniques (Luminex and SSP)

454 NGS (MR)

454 NGS (HR)

HLA-A 11

SA black

29:XX

36:01

29:02

36:01

29:02

36:01

12

SA black

23:XX

43:XX

23:01

43:01

23:01

43:01

13

SA black

23:XX

66:XX

23:01

66:01

23:01

66:01

14

SA black

26:XX

80:XX

26:01

80:01

26:01

80:01

15

Mixed ancestry

02:XX

68:XX

02:03

68:02

02:03

68:02

16

SA black

23:XX

34:XX

23:01

34:02

23:01

34:02

17

SA black

24:XX

68:XX

24:02

68:01

24:02

68:01

18

Mixed ancestry

02:XX

29:XX

02:01

29:01

02:01

29:01

19

SA black

03:XX

34:XX

03:01

34:02

03:01

34:02

20

SA black

30:01

30:01

30:01

30:01

30:01

30:01

HLA-B 11

SA black

44:XX

53:XX

44:03

53:01

44:03

53:01

12

SA black

15:03

15:03

15:01

15:03

15:01

15:03

13

SA black

45:XX

58:XX

45:01

58:02

45:01

58:02

14

SA black

15:01

18:XX

15:01

18:01

15:01

18:01

15

Mixed ancestry

51:XX

53:XX

51:01

53:01

51:01

53:01

16

SA black

07:XX

44:XX

07:05

44:03

07:05

44:03

17

SA black

08:XX

58:XX

08:01

58:02

08:01

58:02

18

Mixed ancestry

40:XX

15:03

40:01

15:03

40:01

15:03

19

SA black

44:XX

44:XX

44:03

44:03

44:03

44:03

20

SA black

15:03

58:XX

15:03

58:01

15:03

58:01

HLA-C 11

SA black

04:XX

07:XX

04:01

07:01

04:01

07:01

12

SA black

04:XX

18:XX

04:01

18:02

04:01

18:02

13

SA black

06:XX

16:XX

06:02

16:01

06:02

16:01

Continued ...

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January 2016, Vol. 106, No. 1

to ambiguous typing results. Many alleles are identical across exons 2 and 3 of the HLA genes, since several polymorphisms are located outside the sequenced region.â&#x20AC;&#x160;[6] Discordance was observed for samples 4 (HLA-A in an individual of mixed ancestry), 5 (HLA-B in a black South African), 12 (HLA-B in a black South African) and 19 (HLA-DRB1 in a black South African).

Discussion

HLA genotyping is performed on a routine basis for various applications including HSCT. Mismatching between donors and recipients could lead to graft rejection and increased morbidity and mortality. Accurate HLA typing is therefore critical for successful engraftment. The limited number of studies that have targeted African populations and the high diversity of these individuals affect the degree of certainty with which a genotype is assigned. In many instances, genotypes are assigned based on the predominant frequencies of HLA genotypes in a given population. This could affect the assignment of rare alleles, especially in African populations, where many alleles have not yet been comprehensively described.

Numerous alleles are identical across exons 2 and 3 of the HLA genes,[6] which creates a challenge in accurately assigning HLA genotypes, leading to ambiguous typing results. The ambiguity observed in this cohort is greater when compared with the results of Holcomb et al.[7] The degree of ambiguity observed could be a result of the paucity of knowledge on polymorphisms at HLA loci present in black SA and African individuals in general. An alternative approach to resolving ambiguity would be to sequence the entire gene of interest,[8] which might be helpful in resolving this ambiguity.

However, polymorphisms outside the peptide-binding region may not affect the outcome of transplantation. According to a study by Pasi et al.,[9] several DRB1 alleles are identical across the peptide-binding region, but possess nucleotide changes outside the peptide-binding region that are unlikely to influence the outcome of transplantation.

The degree of resolution obtained for HLA typing has increased over the years with the emergence of various DNA-based typing techniques. Serological techniques are able to assess antigen expression but are unable to distinguish between crossreactive groups. Probe- and primerbased DNA typing methods are able to determine alleles based on known variants.

However, rare and undescribed variants cannot be identified by these techniques, which creates a challenge in accurately

RESEARCH

Table 2. (continued) HLA genotyping results for samples 11 - 20 by conventional and 454 NGS techniques Ethnicity

Conventional techniques (Luminex and SSP)

454 NGS (MR)

454 NGS (HR)

14

SA black

02:XX

04:XX

02:02

04:01

02:02

04:01

15

Mixed ancestry

04:XX

14:XX

04:01

14:02

04:01

14:02

ID

16

SA black

04:XX

07:XX

04:01

07:02

04:01

07:02

17

SA black

06:XX

07:XX

06:02

07:02

06:02

07:02

18

Mixed ancestry

03:XX

04:XX

03:04

04:01

03:04

04:01

19

SA black

02:XX

04:XX

02:02

04:01

02:02

04:01

20

SA black

02:XX

06:XX

02:10

06:02

02:10

06:02

11:01

11:01

11:01

11:01

11:01

11:01

HLA-DRB1 11

SA black

12

SA black

03:01

15:01

03:01

15:01

03:01

15:01

13

SA black

12:01

13:01

12:01

13:01

12:01

13:01

14

SA black

04:05

07:01

04:05

07:01

04:05

07:01

15

Mixed ancestry

01:02

14:04

01:02

14:04

01:02

14:04

16

SA black

03:01

13:01

03:01

13:01

03:01

13:01

17

SA black

12:01

13:01

12:01

13:01

12:01

13:01

18

Mixed ancestry

07:01

13:01

07:01

13:01

07:01

13:01

19

SA black

13:01

15:02

13:01

15:01

13:01

15:01

20

SA black

04:04

08:04

04:04

08:04

04:04

08:04

HLA-DQB1 11

SA black

06:02

06:02

06:02

06:02

06:02

06:02

12

SA black

03:01

06:02

03:01

06:02

03:01

06:02

13

SA black

03:01

06:02

03:01

06:02

03:01

06:02

14

SA black

02:02

03:02

02:02

03:02

02:02

03:02

15

Mixed ancestry

05:01

05:03

05:01

05:03

05:01

05:03

16

SA black

03:01

06:03

03:01

06:03

03:01

06:03

17

SA black

05:01

06:03

05:01

06:03

05:01

06:03

18

Mixed ancestry

02:02

06:03

02:02

02:02

02:02

02:02

19

SA black

06:02

06:03

06:02

06:03

06:02

06:03

20

SA black

03:19

04:02

03:19

04:02

03:19

04:02

XX = no high-resolution (four-digit level) data available; bold font highlights the differences observed between conventional techniques and MR and HR. *Ambiguous typing result.

assigning unknown HLA genotypes. The primer-based method has higher specificity and is able to genotype at an intermediate resolution. As more HLA alleles are discovered, both these techniques require updated primers and probes to account for the allelic diversity present in a given population. The degree of HLA variation found in African populations makes it challenging to assign genotypes typed at low to intermediate resolution. It is

therefore essential that a reliable minimal four-digit resolution typing method be used for correct assignment of HLA alleles and haplotypes, especially for HSCT. The question is whether SBT or NGS technologies enable better resolution of HLA ambiguities, especially in African populations. The data in this small sample set suggest that neither method has the advantage over the other, and that 454 NGS, despite generating large numbers of

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January 2016, Vol. 106, No. 1

shorter reads, does not provide a great enough increment in resolution to warrant implementation on a routine basis.

Conclusion

The equipment and reagents for NGS techniques are costly and not readily accessible to the majority of research and diagnostic institutions in developing countries such as SA. This study therefore indicates that the value of NGS over conventional techniques will only become significant in the context of HSCT and cord blood banking in SA when the number of samples increases to the point where NGS becomes more cost-effective than conventional techniques.[10] Acknowledgements. This research was funded by the South African Medical Research Council in terms of the MRC’s Flagship Award Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the National Research Foundation Internship Programme and the Institute for Cellular and Molecular Medicine of the University of Pretoria. We are grateful to Roche Diagnostics (SA and USA) for the technical support in the laboratory and data analysis.

References 1. A haplotype map of the human genome. Nature 2005;437(7063):1299-1320. [http://dx.doi.org/10.1038/nature04226 2. Fürst D, Müller C, Vucinic V, et al. High-resolution HLA matching in hematopoietic stem cell transplantation: A retrospective collaborative analysis. Blood 2013;122(18):32203229. [http://dx.doi.org/10.1182/blood-2013-02-482547] 3. Kanda Y, Kanda J, Atsuta Y, et al. Changes in the clinical impact of high-risk human leukocyte antigen allele mismatch combinations on the outcome of unrelated bone marrow transplantation. Biol Blood Marrow Transplant 2014;20(4):526535. [http://dx.doi.org/10.1016/j.bbmt.2014.01.003] 4. Paximadis M, Mathebula TY, Gentle NL, et al. Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population. Hum Immunol 2012;73(1):8092. [http://dx.doi.org/10.1016/j.humimm.2011.10.013] 5. Ehrenberg PK, Geretz A, Baldwin KM, et al. High-throughput multiplex HLA genotyping by next-generation sequencing using multi-locus individual tagging. BMC Genomics 2014;15(1):864. [http://dx.doi.org/10.1186/1471-2164-15-864] 6. Robinson J, Halliwell JA, Hayhurst JH, Flicek P, Parham P, Marsh SGE. The IPD and IMGT/HLA database: Allele variant databases. Nucleic Acids Res 2015;43(Database Issue):D423-D431. [http://dx.doi.org/10.1093/nar/gku1161] 7. Holcomb CL, Höglund B, Anderson MW, et al. A multi-site study using high-resolution HLA genotyping by next generation sequencing. Tissue Antigens 2011;77(3):206-217. [http://dx.doi. org/10.1111/j.1399-0039.2010.01606.x] 8. Erlich RL, Jia X, Anderson S, et al. Next-generation sequencing for HLA typing of class I loci. BMC Genomics 2011;12(1):42. [http://dx.doi.org/10.1186/1471-2164-12-42] 9. Pasi A, Crocchiolo R, Bontempelli M, et al. The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mis­ matches in unrelated hematopoietic SCT. Bone Marrow Transpl 2011;46(7):916-922. [http://dx.doi.org/10.1038/bmt.2010.246] 10. Gabriel C, Fürst D, Faé I, et al. HLA typing by next-generation sequencing – getting closer to reality. Tissue Antigens 2014;83(2):6575. [http://dx.doi.org/10.1111/tan.12298]

Accepted 13 October 2015.

RESEARCH

Time to fibrinolytics for acute myocardial infarction: Reasons for delays at Steve Biko Academic Hospital, Pretoria, South Africa R Meel, MB ChB, MMed (Int Med), Cert Cardiol (CMSA); R Gonçalves, MB ChB, MMed (Int Med), Cert Cardiol (CMSA) Department of Internal Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa, and Steve Biko Academic Hospital, Pretoria Corresponding author: R Meel (ruchikameel@gmail.com)

Background. Fibrinolytic therapy is a time-critical intervention proven to reduce mortality and morbidity in patients with ST-elevation myocardial infarction (STEMI). Limited data exist in South Africa (SA) regarding time to fibrinolytic therapy for STEMI patients and reasons for delayed therapy.

Objectives. To establish the proportion of STEMI patients receiving fibrinolytic agents at Steve Biko Academic Hospital (SBAH), Pretoria, SA, identify any delays to receiving fibrinolytic agents, and uncover reasons for those delays. The number of lives lost as a result of these delays was calculated.

Methods. This prospective, observational study included 100 consecutive patients presenting with a STEMI to SBAH. Using a researcheradministered questionnaire, the times from symptom onset to receipt of fibrinolytic therapy and the reasons for delays were documented.

The number of lives lost was then calculated.

Results. Only 37% of patients received fibrinolytic therapy and only 3% received the medication within 1 hour. The median total delay in receiving fibrinolytic therapy was 270 minutes (range 45 - 584). The median time delays from onset of symptoms to call for help, between calling for help and arriving at hospital, and from hospital arrival to fibrinolytic agent administration, were 35 minutes (5 - 1 185), 55 minutes (12.5 - 670) and 62.5 minutes (16.5 - 282), respectively. Numerous delays were identified at all stages, with patient and transport delays being most significant. Strikingly, an additional 32 patients per 1 000 treated could have been saved if a fibrinolytic agent had been administered within 1 hour.

Conclusions. This study highlights the important problem of delayed or non-administration of fibrinolytic therapy at a tertiary hospital.

The problems identified will contribute to the implementation of a robust STEMI management network in SA, similar to those in developed countries.

S Afr Med J 2016;106(1):92-96. DOI:10.7196/SAMJ.2016.v106i1.9801

ST-elevation myocardial infarction (STEMI) is most commonly caused by the total occlu­sion of [1] an epicardial coronary artery by a thrombus.

The cornerstone of STEMI management is early re­ v ascularisation, either by primary percutaneous coronary intervention or fibrinolytic therapy, in conjunction with other adjunctive pharmaceutical agents.[1] The most important determinant of outcome, irrespective of which form of revascularisation is selected, is the time from symptom onset to restoration of flow in the obstructed artery.[2] The ideal reperfusion strategy for STEMI is primary percutaneous coronary intervention (PCI), provided it is performed in an experienced centre within 90 minutes of the time of hospital arrival or arrival of the emergency medical services (EMS).[1] Fibrinolytic therapy should be administered as an alternative within 30 minutes, if primary PCI is unavailable or transport times exceed 60 minutes to the nearest centre capable of performing PCI.[1] Randomised controlled trials of fibrinolytic therapy have demonstrated the benefit of initiating fibrinolytic therapy as early as possible after the onset of angina.[3,4] A myocardial infarction may be aborted and mortality dramatically reduced if fibrinolytic therapy is administered within the first 2 hours, and particularly within the first hour.[2] Delays relating to patient factors, emergency service and transport factors, and in-hospital factors broadly account for the delays in provision of appropriate reperfusion therapy. Globally, numerous

92

studies have demonstrated that significant delays exist in the provision of any reperfusion strategy, including fibrinolytic therapy, to patients presenting with STEMI.[5-10] The largest time delay is attributed to delays by the patient in seeking medical attention. Further delays occur following the call for help and relate to delays in transportation, as well as in-hospital delays.

In South Africa (SA) only a few tertiary public centres and selected private hospitals, almost exclusively in urban areas, are capable of performing primary PCI. The cardiology department at Steve Biko Academic Hospital (SBAH), Pretoria, was unable to perform routine primary PCI at the time of the study. Fibrinolytic therapy therefore constituted the primary revascularisation modality for patients presenting with STEMI. Furthermore, based on observation, few if any patients receive prehospital fibrinolytic therapy in SA, and there are minimal published data regarding the time to provision of fibrinolytic therapy (either prehospital or in-hospital). We therefore embarked on this study to systematically document the aforementioned observations in a tertiary hospital.

Objectives and methods

This prospective, observational study was performed over a 14-month period between August 2008 and November 2009 at SBAH. The sample comprised 100 consecutive patients presenting to SBAH with STEMI. All patients with STEMI according to the new universal definition of myocardial infarction were included[11] unless

January 2016, Vol. 106, No. 1

RESEARCH

fibrinolytic therapy was contraindicated or primary PCI was performed. This study only addressed fibrinolytic therapy and not adjunctive agents such as aspirin. At the time of the study, SBAH was the only public tertiary referral hospital with a cardiology service for northern Gauteng and Mpumalanga provinces. Additionally, uninsured patients presenting to private hospitals were also referred to SBAH for further management. Patients at the time could not receive primary PCI or rescue PCI services, making timeous fibrinolytic administration essential.

Data in respect of demographics, timing of fibrinolytic therapy and reasons for delays in therapy were captured with the aid of a questionnaire. The questionnaire was personally administered by the first author during the hospital admission to reduce recall bias. Relevant information was also retrieved from the patients’ files, and via telephonic or personal interviews with the attending doctors where required. The total time delay between onset of symptoms and administration of fibrinolytic therapy was determined in minutes. Times were recorded to the nearest 5 minutes. A delay was defined as more than 60 minutes having elapsed from the time of symptom onset to the initiation of fibrinolytic therapy.[3] Only the data for patients receiving the medication within 12 hours of onset of symptoms were analysed for in-hospital delays. However, these patients were included to analyse the prehospital delays.

The total time delay was then divided into: (i) patient factors – time from onset of symptoms to call for help: (ii) prehospital factors – time from call for help to arrival of help, and time from arrival of help to arrival at the hospital; and (iii) in-hospital factors – door to assessment by a doctor, and time from assessment by a doctor to fibrinolytic therapy.

Potential reasons for delays were identified from the information obtained by the patient and patient record. Subsequently the impact of the delays in terms of loss of potential benefit (i.e. potential number of lives saved per thousand patients treated) was calculated from the above data.

Statistical analysis

All statistical analysis was performed using Matlab (version 7.1, MathWorks, USA). Categorical data were expressed as percentages. Continuous variables were expressed as means and standard deviations.

Non-parametric data were expressed as medians and interquartile ranges.

The loss of absolute benefit for the sample, as a mean, was also calculated utilising the data from Boersma et al.[2] The benefit of fibrinolytic therapy was 65, 37, 26 and 29 lives saved per 1 000 treated patients in the 0 - 1-, 1 - 2-, 2 - 3- and 3 - 6-hour intervals, respectively.[2] Based on the nonlinear regression equation f(x) = 19.4 − 0.6x + 29.3x-1, the loss of absolute benefit per 1 000 patients treated, expressed as a percentage, is L(x) = 100(1 – f(x)/f(1)).[2] The loss of benefit relative to the first hour, as a percentage, can then be calculated as a mean for the 1 - 12-hour period. This value can be used to calculate the potential number of lives that could have been saved per 1 000 patients treated for the 1 - 12-hour group, compared with the first hour (recalling that 65 lives were saved per 1 000 patients treated in the first hour).[2]

Ethics

Ethics approval was granted by the Faculty of Health Sciences Ethics Committee, University of Pretoria. The study was conducted in accor­­ dance with the Declaration of Helsinki.

Results

Baseline characteristics of the study patients are summarised in Table 1. The majority were white, male and had secondary level education. Seventy-three percent were employed. Fig. 1 outlines the referral course of the patients and the fibrinolytic therapy administration pattern. No patient received prehospital fibrinolytic therapy, and only 37% of eligible patients received fibrinolytic therapy at all. Thirty-nine patients appro­ priately did not receive the medication, because of delayed presentation (10 at the presenting hospital and 29 at SBAH). Only 3 patients received a fibrinolytic agent within 1 hour, 34 did so between 1 and 12 hours, and 63 either did not receive a fibrinolytic therapy at all or received it after 12 hours.

Table 2 summarises the mean treatment delays in minutes.

Prehospital delays

In respect of prehospital delays, the mean time from onset of symptoms to call for help was 35 minutes (range 5 - 1 185). Sixty patients called for help between 0 and 1 hour, 33 between 1 and 12 hours, and 7 after 12 hours. The last group were not candidates for fibrinolytic therapy.

The most common reason for delay (37%) was misinterpretation of symptoms as being non-cardiac in nature. Many patients (13%) adopted a wait-and-see approach, hoping that the symptoms would disappear spontaneously. Many of these patients

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January 2016, Vol. 106, No. 1

reported that they were not aware of the importance or availability of receiving rapid treatment. Some also tried self-medicating (4%). Patients who had had a previous heart attack (3%) were likely to accurately recognise their symptoms as being a possible myocardial infarction and seek help sooner.

Patient location did not influence helpseeking behaviour, except for patients who were driving. This latter group generally continued to their destination before seeking help.

Importantly, the vast majority (84%) of patients did not call for an ambulance at all, instead opting to use a private vehicle to reach the hospital, which was immediately available in 86% of cases.

The reasons cited for not calling an ambulance included ease of access and use of patients’ own transport, unfamiliarity with the emergency numbers, distrust of the emergency services (viewed as being slow, Table 1. Baseline characteristics Age (years), mean (range)

52 (30 - 84)

Gender male (%)

70

Race (%) Asian

9

Black

14

White

74

Coloured

3

Highest education level (%) None

2

Primary

8

Secondary

77

Tertiary

13

Employment (%) Employed

73

Unemployed

9

Pensioner

18

Table 2. Summary of treatment delays (minutes), mean (range) Onset of symptoms to call

35 (5 - 1 185)

Call to hospital

55 (12.5 - 670)

Call to arrival of help

5 (5 - 20)

rrival of help to A hospital

30 (10 - 435)

Door to fibrinolytic

62.5 (16.5 - 282)

Door to doctor

15 (0 - 654)

Doctor to fibrinolytic

30 (10 - 258)

Total delay

270 (45 - 584)

RESEARCH

In-hospital delays

inefficient and occasionally not responding at all), lack of understanding concerning the potential risks (e.g. ventricular fibrillation) associated with a myocardial infarction and the ability of paramedics to treat these problems, and lack of understanding of the availability of and need for early treatment.

When patients did call for an ambulance, its late arrival, either due to the EMS being overburdened or to the driver getting lost, further contributed to delays in many cases.

None of the patients who called for an ambulance received prehospital fibrinolytic therapy.

Ninety-one percent of patients who called for help accessed transport within 1 hour. The majority of patients (76%) arrived at the first hospital within 1 hour.

The most common reasons for delay were long distances travelled between the scene and the hospital, presenting to a general practitioner or clinic first (18%), and traffic delays. The majority (69%) of patients were driven to hospital in a private vehicle, while 14% drove themselves. Only 16% used an ambulance, and one patient walked to hospital.

A total of 38 patients were initially seen at primary or secondary level state hospitals, 20 at private hospitals and 42 at SBAH. The 58 patients who initially presented to other hospitals took a median of 8 hours (range 1 - 288) to be transferred to SBAH. The median time from onset of symptoms to first medical contact was 135 minutes (range 20 - 1 400) or 2.3 hours (range 0.3Â - 23.3). Only 34 patients arrived within 1 hour and 56 arrived between 1 and 12 hours after symptom onset. Ten of the patients were only seen 12 hours after the onset of symptoms and were therefore not candidates for fibrinolytic therapy; they were excluded from the in-hospital analysis of delays. Overlapping reasons for delays were noted for each of the components evaluated.

Of patients seen at referral hospitals, 32 (64%) were seen within 30 minutes. Only 4 out of a potential 50 patients (8%) received a fibrinolytic agent, all within 20 minutes of seeing a doctor. Three patients received fibrinolytic agents in the emergency room and one in an intensive care unit. Three

S TEMI 100 patients No patient received prehospital fibrinolytic therapy!

Prehospital Presenting hospital

Primary or secondary level state hospital

Fibrinolytic 21 patients

Private hospital

SBAH

20 patients

42 patients

38 patients

No fibrinolytic 21 patients

Fibrinolytic

No fibrinolytic

Fibrinolytic

No fibrinolytic

3 patients

25 patients

1 patient

19 patients

6 >12 hours 29 eligible

3 >12 hours 18 eligible

1 >12 hours 18 eligible

Referred to SBAH

Fibrinolytic 12 patients

No fibrinolytic 46 patients 29 >12 hours 13 eligible 4 had received a fibrinolytic

Fig. 1. Flow diagram of fibrinolytic administration patterns. Only 37% of patients received fibrinolytic therapy within 12 hours.

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January 2016, Vol. 106, No. 1

patients received streptokinase and one alteplase. Total delay from symptom onset to treatment was 45 minutes for 3 patients and 430 minutes for one patient. Generally, decisions on fibrinolytic administration were made by casualty officers following tele­phonic consultation with an internal medicine registrar rotating through cardiology.

The most common reasons for delays in seeing a doctor were inappropriate triage with no priority given to patients with chest pain, waiting in queues to open folders prior to being evaluated, understaffing of hospitals with busy emergency rooms, and underresourced hospitals (electrocardiograph (ECG) machines were occasionally not working in some hospitals).

The most common reasons for delays in receiving fibrinolytic therapy were mis­ diagnosis of STEMI (including delays waiting for cardiac enzymes despite STEMI being obvious on the ECG or due to misinterpretation of the ECG), denial of fibrinolytic therapy on financial grounds in patients presenting to private hospitals, lack of familiarity with treatment protocols and inappropriate decision-making among attending doctors, especially inexperienced doctors, fear of complications, lack of urgency in administering the agents, absence of fibrinolytic agents in the emergency room or hospital, and late patient presentation (after 12 hours).

At SBAH 66 patients (83%) were seen within 30 minutes. The reasons for delays in being assessed by a doctor were similar to those in the presenting hospitals. Only 58% of eligible patients received fibrinolytic agents within 12 hours. Twenty-seven patients received streptokinase while 5 received alteplase. Seven patients were given fibrinolytic therapy after 12 hours and were not included in the analysis.

At SBAH, after assessment by a doctor, 60% received a fibrinolytic agent within 1 hour of assessment, with 41% receiving the medication after more than 1 hour. Twentyfive patients received the fibrinolytic therapy in the emergency centre (EC), while 7 received it in the coronary care unit (CCU).

The median time delay between hospital arrival and arrival in the CCU was 420 minutes (range 10 - 2 960). The door-tofibrinolytic time was a median of 60 minutes for those receiving the medication in the EC compared with 85 minutes for those receiving the medication in the CCU. The common reasons for delays in receiving fibrinolytic therapy were again similar to the other hospitals. Additionally, delayed referral from the presenting hospital contributed significantly. The decision to administer a

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Discussion

The majority of patients in this study (67%) did not receive fibrino­lytic therapy at all.

Furthermore, the majority of those who did receive treatment received it late. A large number of eligible patients arrived at a facility capable of providing fibrinolytic therapy, but did not receive any treatment.

These missed opportunities are clearly resulting in excess mortality and morbidity, including heart failure, which would otherwise be preventable.

Total treatment delays and the components of prehospital and in-hospital treatment delays were all prolonged in comparison with the international literature. The largest cumulative delays were experienced as a result of predominantly prehospital factors.

With regard to patient factors, delayed time (>1 hour) from the onset of symptoms to call for help contributed significantly to delays in 40% of patients. The overriding reasons for these delays were lack of awareness of the symptoms of a myocardial infarction and how to respond appropriately and rapidly.

This knowledge emphasises the importance of public awareness campaigns, as part of creating a STEMI network approach.

Of concern was that only 16 patients called for an ambulance, none of whom received prehospital fibrinolytic therapy.

This represents an important opportunity for intervention by introducing paramedic training and certification to allow for prehospital fibrinolysis. Additionally, public awareness campaigns should focus on the risk of sudden death due to arrhythmias,

80 70

Loss of absolute benefit (%)

fibrinolytic was generally made by either the casualty officer or an internal medicine registrar rotating through cardiology.

(Owing to staff constraints, not all STEMI patients could be seen immediately by a registrar in internal medicine.)

Fig. 2 summarises the loss of absolute benefit as a percentage (i.e. the preventable 35-day mortality) for time delays beyond 1 hour but less than 12 hours. An analysis was performed to determine the loss of absolute benefit as a mean for the sample by utilising the data from Boersma et al.[2] The mean loss of benefit as a percentage, relative to the first hour, for the 1 - 12-hour period is 50.6%. This value was used to determine the additional number of lives that could have potentially been saved per 1 000 patients treated for the 1 - 12-hour group compared with the first hour. This value was 32/1 000.

An additional 32 patients per 1 000 treated could therefore have been saved if the treatment had been administered within the first hour.

60 50 40 30 20 10 0

1

2

3

4

5

6

7

8

9

10

11

12

Treatment delay (hours)

Fig. 2. Loss of absolute benefit (%) v. treatment delay (hours).

which may be reduced by appropriately trained first responders. Patient perception of an inefficient EMS was also of concern.

This may stem from the absence of a protocol-driven service, as well as poor resourcing, understaffing or poor training, although this requires further investigation.

Integration of the EMS, including all first responders such as firemen and police officers, into the STEMI network would be crucial to its success. Staffing the receiving hospitals with full-time qualified staff to receive an ECG and then advise on therapy should become the standard of care. Having a clear plan regarding where to transport a patient within a given geographical area and the route of transportation is key. The geographical and financial constraints in SA dictate that early fibrinolytic therapy, ideally prehospital, would be the most efficient revascularisation strategy.

In-hospital delays, although not accounting for the greatest proportion of the total delay, were important because of the fact that the median door-to-fibrinolytic time was more than double the current recommendation of 30 minutes. Large numbers of eligible patients were denied therapy despite arrival within 12 hours. Common themes emerged when reasons for these delays were explored.

These reflect practices that are contradictory to the current guidelines. The dominant problems were related to poor systems of care and staffing and, less commonly, lack of resources. Denying STEMI patients presenting to private hospitals fibrinolytic therapy cannot be justified at all, as this constitutes part of the emergency care of these patients as mandated by law. This again emphasises the need for protocol-driven care in the management of STEMI patients.

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The impact of having no system of care is clear. The ubiquitous lack of urgency on the part of staff, reflecting lack of know­ ledge, being over-worked or simply apathy, was disturbing. Inappropriate triage and registration delays were almost universal because of the lack of dedicated chest pain units. Furthermore, the first attending doctor who was appropriately able to administer a fibrinolytic agent generally did not do so. This should clearly be done at the hospital to which the patient presented first. Inappropriate diagnosis and lack of familiarity with fibrinolytic therapy and the management of the complications associated with its administration may explain this behaviour. Furthermore, the perception by many casualty officers that administering fibrinolytics is ‘not their responsibility’ should be addressed. In this regard, cardiology consultation was often sought in unambiguous cases, rather than initiating appropriate treatment. These deficiencies can clearly be improved by implementing a STEMI network of care that integrates chest pain units at receiving hospitals.

Other opportunities for improvement were identified. These include not ordering un­ needed tests unless the diagnosis was clearly in question, and improving ECG interpretation skills in general. The introduction of bedside echocardiography could rapidly help to classify equivocal cases. However, this was seldom performed because of skills and equipment deficiencies.

Interhospital transfer delays, while clearly problematic, could be mitigated if fibrino­ lytic agents were rapidly administered at the receiving hospital.

It is expected that public tertiary centres around SA may have a similar experience.

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Furthermore, based on personal observation, it is expected that many patients seen at the primary level of care are either missed or not appropriately referred at all. Owing to inappropriately constrained tertiary hospital capacity, patients are also frequently not accepted, although the exact numbers are difficult to estimate. Further research should be conducted in this regard.

Acknowledgements. We thank Dr Rita Sommers, Dr Shiraz Ellimdin, Dr Chris Mostert and Prof. James Ker (senior) for their valuable advice and for reviewing the manuscript. Furthermore, we appreciate the help provided by the staff of the coronary care unit at SBAH. Thanks also to Dr Duarte Gonçalves, PhD, for his assistance with the statistics.

References

Study limitations

This study represents the experience of a single tertiary centre.

Referral bias is clearly a concern. Additionally, patients presenting after 12 hours were included in the study although they had presented late for fibrinolytic therapy. This was done in order to demonstrate the ‘real-world experience’ in SA and account for the reasons behind these patient delays. Other limitations were recall bias on the part of the patient and occasional lack of documentation of the times of in-hospital events in the notes. The EMS scene time, door-toECG time and ECG-to-decision-to-give-fibrinolytic time were not routinely recorded in the available patient records.

Conclusion

Many patients failed to benefit from fibrinolytic therapy owing to a complete lack of fibrinolytic administration, delayed presentation and delayed therapy. This study highlights both the challenges and the opportunities that must be grasped in order to improve patient outcomes. Recognition of the seriousness and extent of this disease in the midst of numerous other healthcare priorities in SA is crucial. The authors encourage an urgent commitment to address these issues by all involved stakeholders. The implementation of a STEMI network, modified to local practice, is as possible as it is urgent.

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1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction. Circulation 2004;110(15):588-636. [http://dx.doi. org/10.1161/01.CIR.0000134791.68010.FA] 2. Boersma E, Mercado N, Poldermans D, et al. Acute myocardial infarction. Lancet 2003;361(9360):847858. [http://dx.doi.org/10.1016/S0140-6736(03)12712-2] 3. Gruppo Italiano per Io Studio della Streptochinasi nell Infarto miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;327(8478):397-402. [http://dx.doi.org/10.1016/S0140-6736(86)92368-8] 4. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: Collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;343(8893):311-322. [http:// dx.doi.org/10.1016/S0140-6736(94)91161-4] 5. Birkhead J. Trends in the provision of thrombolytic treatment between 1993 and 1997. Myocardial Infarction Audit Group. Heart 1999;82(4):438-442. [http://dx.doi.org/10.1136/hrt.82.4.438] 6. Doyle F, de la Harpe D, McGee H, et al. Nine-year comparison of presentation and management of acute coronary syndromes in Ireland: A national cross-sectional survey. BMC Cardiovasc Disord 2005;5(5):1-8. [http://dx.doi.org/10.1186/1471-2261-5-5] 7. Davies C, Christenson J, Campbell A, et al. Fibrinolytic therapy in acute myocardial infarction: Time to treatment in Canada. Can J Cardiol 2004;20(8):801-805.

8. Hirvonen T, Halinen M, Kala R, Olkinuora J. Delays in thrombolytic therapy for acute myocardial infarction in Finland: Results of a national thrombolytic therapy delay study. Finnish Hospitals’ Thrombolysis Survey Group. Eur Heart J 1998;19(6):885-892. [http://dx.doi.org/10.1053/euhj.1997.0866 885-892] 9. Gibson C, Pride Y, Frederick P, et al. Trends in reperfusion strategies, door-to-needle and door-toballoon times, and in-hospital mortality among patients with ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial from 1990 to 2006. Am Heart J 2008;156(6):1035-1044. [http://dx.doi.org/10.1016/j.ahj.2008.07.029] 10. Eagle K, Nallamothu B, Mehta R, et al. Trends in acute reperfusion therapy for ST-segment elevation myocardial infarction from 1999 to 2006: We are getting better but we have got a long way to go. Eur Heart J 2008;29(5):609-617. [http://dx.doi.org/10.1093/eurheartj/ehn069 609-617] 11. Thygesen K, Alpert J, White H, et al. Universal definition of myocardial infarction. Circulation 2007;116(22):2634-2653. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.187397]

Accepted 28 September 2015.

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Antenatal screening for hepatitis B virus in HIV-infected and uninfected pregnant women in the Tshwane district of South Africa Q Diale,1 MB ChB, FCOG; R Pattinson,1,2 MB ChB, FCOG, MD, FRCOG; R Chokoe,1 MB ChB, MMed (O&G); L Masenyetse,2 BSc Hons, MSc; S Mayaphi,3 MB ChB, FC Path (SA) Virol, MMed Path (Virol) aternal and Infant Health Care Strategies Unit, Department of Obstetrics and Gynaecology, School of Medicine, M Faculty of Health Sciences, University of Pretoria, South Africa 2 South African Medical Research Council, Gauteng, South Africa 3 Department of Medical Virology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa, and National Health Laboratory Service – Tshwane Academic Division, Pretoria 1

Corresponding author: Q Diale (qdiale@hotmail.com) Background. Despite enormous strides in preventing hepatitis B virus (HBV) infection, perinatal transmission still contributes significantly to HBV epidemiology worldwide; this could account for approximately 50% of chronically infected individuals.

Objective. To assess the need for HBV screening in antenatal clinics in the HIV/AIDS era.

Methods. This was a retrospective study conducted at the antenatal clinic of 1 Military Hospital, Tshwane, South Africa. Laboratory data for HBV, HIV and CD4 count were obtained and analysed for the period January 2008 - December 2013.

Results. A total of 2 513 patients’ results were retrieved and 2 368 patients were enrolled as both their HBV and HIV serology results were available. The mean age of participants was 29 years (range 14 - 46). HIV prevalence in this study was 20.5% (95% confidence interval (CI) 0.189 - 0.222). The median CD4 count in HIV-infected patients was 522 cells/μL (interquartile range 370 - 711). There was an overall HBV prevalence of 0.8% (95% CI 0.005 - 0.011). The hepatitis B surface antigen (HBsAg) prevalence was significantly higher (2.1%) among HIV co-infected compared with HIV-uninfected patients (0.4%) (p=0.0001). Hepatitis e antigen (HBeAg) positivity was 30% in the HIV co-infected compared with 37.6% in the HIV-uninfected individuals (p=0.7400).

Conclusion. This study showed a significantly higher HBV prevalence in HIV-infected compared with HIV-uninfected patients. The comparable HBeAg prevalence between the two groups indicates that both were at an increased risk of vertical transmission, therefore demonstrating a need for antenatal screening for HBV. Since antenatal screening is often not affordable in low-income countries, administration of HBV vaccine at birth is needed for prevention of vertical transmission.

S Afr Med J 2016;106(1):97-100. DOI:10.7196/SAMJ.2016.v106i1.9932

Hepatitis B virus (HBV) infection and its compli­ cations cause substantial medical and financial burdens to the healthcare system, and have become a major global public health concern.[1] A global estimate is that 240 million individuals are chronically infected with HBV.[2] South Africa (SA) had an estimated 10% prevalence of HBV in the prevaccination era, with a significant reduc­tion after the introduction of neonatal vaccination in 1995, as shown in recent studies.[3] The prevalence of chronic carriage of HBV in SA blacks is estimated to be 5 - 16% in rural males, 8 - 9% in urban males, 4 - 12% in rural females and 2.7 - 4% in urban females.[4] Despite enormous strides in preventing HBV infection, perinatal transmission continues to contribute significantly to HBV epi­ demiology worldwide and could account for approximately 50% of chronically infected individuals.[1] The horizontal route of transmission has been reported to be the predominant mode of HBV transmission in SA,[4,5] despite numerous African studies that have reported that perinatal vertical transmission occurs in 2 - 30% of infants born to HBV-infected mothers.[6-8] In the absence of immunoprophylaxis, perinatal transmission occurs in 10 - 20% of women who are seropositive for hepatitis B surface antigen (HBsAg) but seronegative for hepatitis e antigen (HBeAg), and up to 90% of perinatal transmission occurs in women who are seropositive for both HBsAg and HBeAg.[9] HBeAg is a surrogate marker of high HBV viral load, as it is positive during the

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high replicative phase of HBV.[9] The risk of progression of acute to chronic HBV infection is inversely proportional to the age at which the infection was acquired. HBV infection is associated with a partial immune tolerance in infected infants and therefore results in a 95% chance of chronicity, compared with 30% in children aged 1 - 5 years and <5% in adults.[10] Chronic hepatitis B sequelae include cirrhosis, hepatic carcinoma, glomerulonephritis and end-stage renal disease in children.[11] Risk factors known to predispose to perinatal transmission include maternal HBeAg positivity, HBsAg titre, detectable HBV DNA, acute hepatitis B acquired in pregnancy, a history of threatened preterm labour and specific allelic mutations in maternal HBV.[12] The risk of vertical transmission is higher during the intrapartum period (at or near the time of birth) and is reported to result from exposure of the neonate to maternal blood and secretions during delivery. Intrauterine transmission of HBV is rare, accounting for <5% of infants born to HbeAg- and HBsAg-positive mothers. It is understood to result from transplacental leakage of HBeAg-positive maternal blood during uterine contractions in pregnancy, and also from the disruption of placental membranes.[9,13] Antenatal screening and administration of the birth-dose HBV vaccine and immunoglobulins are known to be 95% effective in reducing vertical transmission of HBV.[11,14] In SA, universal maternal antenatal screening is not practised in the public sector. The HBV immunisation schedule in SA introduced in 1995 initiates HBV vaccination at 6 weeks of age, with subsequent doses at 10 and 14 weeks.

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Sub-Saharan Africa is also highly endemic for HIV/AIDS, which shares a common route of transmission with HBV.[15,16] Local studies have shown a higher HBV prevalence in HIV co-infected individuals compared with their HIV-uninfected counterparts.[17,18]

Objective

To assess the need for HBV screening in antenatal clinics in the era of HIV/AIDS.

Methods

This was a retrospective study conducted at the antenatal clinic of 1 Military Hospital in Tshwane, which offered universal hepatitis B antenatal screening and HIV testing to pat­ ients attending its antenatal clinic. During the study period (2008 - 2013), a total of 2 513 patients’ results were retrieved in the laboratory information system (LIS) for the antenatal clinic of 1 Military Hospital, Tshwane, SA. Of these patients, 2 368 were enrolled in this study as they had both HIV and HBV results. Those who did not have both results were excluded (Fig. 1). Laboratory data for the period of January 2008 to December 2013 were retrieved from the LIS and results for HBV (HBsAg, HBeAg), HIV and CD4 count were collected and analysed.

Axsym immunoassays (Abbott Diagnostics, Germany) were used for HBV and HIV serology, after which HIV confirmation was done on Vironostika HIV assay (bioMérieux, USA). Rapid HIV tests were also used for HIV diagnosis. Demographic data such as patient age were also retrieved. Ethical approval was received from the ethics committees of 1 Military Hospital and the University of Pretoria (6/2013).

(StataCorp, USA). A p-value of <0.05 was considered statistically significant.

Results

The mean age of the participants was 29 years (range 14 - 46). Twenty-seven patients’ results were in the under-18 years category, and none of them was HBsAg-positive (Table 1). HIV prevalence in the whole group was 20.5% (95% confidence interval (CI) 0.189 - 0.222). The median CD4 count was 522 cells/μL (interquartile range 370 711) in the HIV-infected women. There was an overall HBV prevalence of 0.8% (95% CI 0.005 - 0.011). The HBsAg prevalence

was significantly higher (2.1%) in the HIV co-infected as opposed to the HIVuninfected (0.4%) patients (p=0.0001) (Table 2). HBeAg positivity was 30.0% (3/10) in the HIV co-infected as opposed to 37.5% (3/8) in the HIV-uninfected women (p=0.7400) (Table 3).

Discussion

This study evaluated the value of screening for HBV in antenatal clinics in the era of HIV/AIDS. The HIV prevalence of 20.5% in this study is lower than the 2012 HIV prevalence estimate of 29.9% in Gauteng’s antenatal clinics.[19] The absence of HBsAg

N=2 513

HIV + HBV results

HIV results only

HBsAg results only

n=99

n=46

n=2 368

Excluded

Excluded

Enrolled

Data analysis

Descriptive statistics consisting of summary statistics (i.e. mean, range) for numerical data and frequencies for categorical data were used. Comparison between the groups was done using a two-sample t-test for propor­tions. The software used was Stata 13

Table 1. Age distribution of patients and HBsAg prevalence Age (years)

HBVpositive

HBVnegative

Total

≤18

0

27

27

19 - 24

3

558

561

25 - 29

3

690

693

30 - 34

7

592

599

≥35

5

483

488

Total

18

2 350

2 368

Fig. 1. Algorithm showing how patients were enrolled into this study. Only those who had both HIV and HBV results were enrolled.

Table 2. HBsAg prevalence among HIV-infected v. HIV-uninfected patients

HbsAg-positive, n (%) (95% CI)

HIV-infected (N=486)

HIV-uninfected (N=1 882)

10 (2.1) (0.008 - 0.034)

8 (0.4) (0.001 - 0.007)

p-value 0.0001

Table 3. HBeAg prevalence among HIV-infected v. HIV-uninfected patients HBeAg-positive, n (%) (95% CI)

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HIV-infected (N=10)

HIV-uninfected (N=8)

p-value

3 (30.0) (0.016 - 0.584)

3 (37.5) (0.395 - 0.710)

0.7400

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positivity in the under-18 age group in this study (Table 1) is suggestive of HBV prevention from vaccination, as these patients probably received HBV vaccination (introduced in SA in 1995) in childhood. It was not surprising to see that HBV prevalence was fivefold higher in HIV-infected as opposed to HIV-uninfected pregnant women (Table 2). This finding has been reported in other SA studies.[17,18] A study in pregnant women in KwaZulu-Natal (KZN) revealed a 7.4% HBV prevalence in HBV-HIV co-infected patients.[20] A study conducted on pregnant women delivering in a rural hospital in Malawi in 1998 reported that 8% of pregnant women had HBVHIV co-infection.[21] The low co-infection rate of 2.1% in this study could be due to higher CD4 counts (median 522 cells/μL) in this study group as opposed to the median of 328 in the KZN study and the fact that it was conducted in a low HBV prevalence area of SA (i.e. an urban setting in Gauteng Province).[17] Currently in SA, pregnant women are not screened for HBV in the public sector. This places the neonates of HBV-infected mothers at risk of acquiring HBV infection, as HBV vaccination is only started at 6 weeks of age. HIV-infected pregnant women are now treated for both HBV and HIV according to the new prevention of mother-to-child transmission (PMTCT) guidelines initiated in April 2013, which offer tenofovir, lamivudine (or amtricitabine) and efavirenz as the first line of treatment regardless of CD4 count.

Tenofovir, amtricitabine and lamivudine have activity against HBV and HIV, thereby reducing the chances of vertical transmission of both viruses.[12,22] Interestingly, the prevalence of HBeAg in this study was comparable in the HIV-infected (30.0%) and uninfected (37.5%) groups (p=0.7400) (Table 3). This finding indicates that without HBV treatment in pregnancy, or immunoprophylaxis to the exposed babies, both HIV-infected and HIV-uninfected mothers would be at the same risk of transmitting the virus to their neonates. However, HIV-infected mothers receive treatment for HBV during pregnancy, as highlighted above. It is therefore now the HIV-uninfected mothers who are at a much higher risk of transmitting HBV to their babies.

Without antenatal screening, these HBV-exposed babies would not be identified for post-exposure prophylaxis with HBV vaccine and immunoglobulins.

Omitting the birth dose of HBV vaccine results in an increased risk of HBV transmission to the neonate if the mother is HBsAgpositive.[23] The HBV vaccine is 70 - 95% effective in preventing perinatal infection when administered alone within 24 hours of birth.

HBV immunoglobulins provide passive immunisation to infants born to HBsAg-positive women. Administering the HBV vaccine in combination with one dose of hepatitis B immunoglobulin within 24 hours of birth provides 85 - 95% efficacy in preventing perinatal HBV infection.[23,24] One study showed that the risk of HBV infection for infants born to HBsAg-positive mothers increased significantly when the first dose of hepatitis B vaccine was received after 7 days (odds ratio 8.6) compared with those vaccinated on days 1 - 3 after birth.[8] The SA Expanded Programme on Immunisation (EPI) initiates HBV vaccination only at 6 weeks of life. Sub-Saharan African studies have shown a 10 - 20% breakthrough HBV infection rate in those who receive a 6-week dose compared with the birth-dose vaccination.[3,8] The practice of universal antenatal HBV screening ensures that all women with HBV infection receive optimal medical care through HBV treatment, regardless of their HIV status, and that their neonates receive the appropriate post-exposure prophylaxis.

However, in developing countries, antenatal screening may be costly and not feasible.[25] Some countries with an intermediate or low prevalence of chronic HBV infection or limited resources reduce costs by not screening pregnant women, but recommend starting

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HBV vaccination from birth without HBV immunoglobulins. This strategy is cost-saving but is of moderate efficacy compared with the high efficacy and higher cost of maternal screening plus passive and active immunisation of neonates.[9] A strategy of administering HBV vaccine at birth would be applicable in the SA setting, as there is no antenatal screening in the public sector.

A study published by Guidozzi et al.[26] in 1993, which found a low HBeAg prevalence of 4.6% in HBsAg-positive pregnant women, concluded that it would not be cost-effective to screen for HBV in pregnant urban SA women. However, this study may have underestimated the prevalence of HBV and HBeAg as it was conducted in predominantly white and urban-born black women, who are known to have low prevalence of HBV. The proportion of rural-born women, known to have a high prevalence of HBV,[4] was estimated at 10% in Guidozzi et al.’s study.

Our study has shown a high HBeAg prevalence of 30.0% and 37.5% in HIV-uninfected and infected individuals, respectively. Although the study was conducted in an urban setting, we do not know the birth origins of the study participants owing to the retrospective nature of this study. However, Gauteng is known to attract people from rural areas of SA to seek job opportunities. The current National Health Laboratory Service price for HBsAg is ZAR161.10. Screening for HBsAg in our cohort would therefore have cost the government ZAR381 484.80 to identify 18 HBV-infected patients. This amount could be spent on getting more than 69 000 doses of HBV vaccine, as the government used to buy the multidose HBV vaccine (with 10 doses) at ZAR54.93 (excluding tax) from the Biovac company before the introduction of hexavalent vaccine (containing HBV vaccine) at 6, 10 and 14 weeks (personal communication, Biovac staff, sales department, 20 November 2015). We therefore agree with Guidozzi et al.’s conclusion that it would not be cost-effective to screen for HBV in pregnant urban SA women. The HBV vaccine birth dose without immunoglobulins has an efficacy of at least 70% in preventing HBV infection.[23,24] Therefore, in the absence of HBV screening in the SA public sector, HBV vaccine alone given at birth as part of EPI would prevent at least 70% of infections in neonates.

Giving a birth dose of HBV vaccine to all neonates would serve as post-exposure prophylaxis to those exposed to HBV during pregnancy, while also fulfilling the role of pre-exposure prophylaxis for all neonates. Our data support the recommendation made by Spearman and Sonderup[27] that SA should implement a four-dose HBV vaccination schedule with just the addition of the birth-dose vaccine within 24 hours of delivery. This schedule would be slightly more costly but easier to implement as it does not disrupt the current HBV vaccination schedule.[27] A three-dose HBV vaccination schedule has also been proven to be effective in other parts of the world.[25]

Study limitations

The limitations of this study include a small sample size and the absence of HBV viral load. We were also not able to trace the records of babies born to HBsAg-positive mothers to determine whether they received post-exposure prophylaxis and their HBV status.

Conclusion

This study showed a significantly higher HBV prevalence in HIVinfected as opposed to HIV-uninfected women. The comparable HBeAg prevalence between the two groups indicates that both groups were at an increased risk of vertical transmission, therefore demonstrating a need for antenatal screening for HBV. Since antenatal HBV screening is often not affordable in low-income countries, there is a high demand for a birth dose of HBV vaccine for prevention

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of vertical transmission to the neonates. We therefore recommend that the SA National Department of Health review its current HBV vaccination schedule to include a birth dose of HBV vaccine to cater for neonates exposed to HBV during pregnancy, particularly those born to HIV-uninfected women and to HBV-HIV co-infected mothers who neither booked for antenatal care nor received PMTCT late in pregnancy.

References 1. Espoti SD, Shah D. Hepatitis B in pregnancy: Challenges and treatment. Gastroentrerol Clin North Am 2011;40(2):355-372. [http://dx.doi.org/10.1016/j.gtc.2011.03.005] 2. Ott JJ, Stevens GA, Groegerb J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30(12):2212-2219. [http://dx.doi.org/10.1016/j.vaccine.2011.12.116] 3. Burnett RJ, Kramvis A, Dochez C, Meheus A. An update after 16 years of hepatitis B vaccination in South Africa. Vaccine 2012;30(Suppl 3):C45-C51. [http://dx.doi.org/10.1016/j.vaccine.2012.02.021] 4. Kew MC. Hepatitis B virus infection: The burden of disease in South Africa. S Afr J Epidemiol Infect 2008;23(1):4-8.

5. Robson SC, Kirsch RE. National strategy for viral hepatitis: Recommendations and guidelines for management in South Africa. S Afr Med J 1991;80(4):347-358.

6. Vardas E, Mathai M, Blaauw D, McAnerney J, Coppin A, Sim J. Preimmunization epidemiology of hepatitis B virus infection in South African children. J Med Virol 1999;58(2):111-115. [http://dx.doi. org/10.1002/(SICI)1096-9071(199906)58:2<111::AID-JMV2>3.0.CO;2-B] 7. Sangare L, Sombie R, Combassere AW, et al. Antenatal transmission of hepatitis B virus in an area of HIV moderate prevalence, Burkina Faso. Bull Soc Pathol Exot 2009;102(4):226-229.

8. Howell J, Lemoine M, Thursz M. Prevention of materno-foetal transmission of hepatitis B in subSaharan Africa: The evidence, current practice and future challenges. J Viral Hepat 2014;21(6):381396. [http://dx.doi.org/10.1111/jvh.12263] 9. Chang M-h. Hepatitis B virus infection. Semin Fetal Neonatal Med 2007;12(3):160-167. [http://dx.doi. org/10.1016/j.siny.2007.01.013] 10. Ocama P, Opio CK, Lee WM. Hepatitis B virus infection: Current status. Am J Med 2005;118(12):1413. e15-1413.e22. [http://dx.doi.org/10.1016/j.amjmed.2005.06.021] 11. MacLean B, Hess R. Seroprevalance of hepatitis B surface antigen among pregnant women attending the Hospital for Women and Children in Koutiala, Mali. S Afr Med J 2012;102(1):47-49.

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12. Ho V, Ho W. Hepatitis B in pregnancy: Specific issues and considerations. J Antivir Antiretrovir 2012;4(1):3. [http://dx.doi.org/10.4172/jaa.1000046]Â 13. Jonas MM. Hepatitis B and pregnancy: An underestimated issue. Liver International 2009;29(suppl 1):133-139. [http://dx.doi.org/10.1111/j.1478-3231.2008.01933.x] 14. Shi Z, Li X, Ma L, Yang Y. Hepatitis B immunoglobulin injection pregnancy to interrupt hepatitis B virus mother-to-child transmission: A meta-analysis. Int J Infect Dis 2010;14(7):e622-e634. [http:// dx.doi.org/10.1016/j.ijid.2009.09.008] 15. World Health Organization. Hepatitis B. Fact sheet No. 204. July 2012. http://www.who.int/ mediacentre/factsheets/fs204/en/ (accessed 3 September 2014).

16. Thio C. Hepatitis B virus infection in HIV-infected persons. Curr Hepatol Rep 2004;3(1):91-97. [http:// dx.doi.org/10.1007/s11901-004-0015-8] 17. Mayaphi SH, Rossouw TM, Masemola DP, Olorunju SA, Mphahlele MJ, Martin DJ. HBV/HIV coinfection: The dynamics of HBV in South African patients with AIDS. S Afr Med J 2012;102(3):157-162.

18. Andersson MI, Maponga TG, Ijaz S, Theron G, Preiser W, Tedder RS. High HBV viral loads in HIVinfected pregnant women at a tertiary hospital. J Acquir Immune Defic Syndr 2012;60(1):4. [http:// dx.doi.org/10.1097/QAI.0b013e31825aeee7] 19. National Department of Health, South Africa. The 2012 National Antenatal Sentinel HIV & Herpes Simplex Type-2 Prevalence Survey. Pretoria: NDoH. www.doh.gov.za (accessed 16 September 2014).

20. Thumbiran NV, Moodley D, Parboosing R, Moodley P. Hepatitis B and HIV co-infection in pregnant women: Indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting.

S Afr Med J 2014;104(4):307-309. [http://dx.doi.org/10.7196/SAMJ.7299] 21. Ahmed SD, Cuevas LE, Brabin BJ, et al. Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women. J Infect 1998;37(3):248-251. [http://dx.doi.org/10.1016/S0163-4453(98)91983-1] 22. Chen HL, Lee CN, Chang CH, et al. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus. Hepatology 2015;62(2):375-386. [http://dx.doi. org/10.1002/hep.27837] 23. World Health Organization. Hepatitis B vaccines. Wkly Epidemiol Rec 2009;40(84):405-420. http:// www.who.int/wer/2009/wer8440.pdf (accessed 13 April 2015).

24. Centers for Disease Control and Prevention. Hepatitis B. http://www.cdc.gov/vaccines/pubs/ pinkbook/hepb.html (accessed 28 March 2015).

25. Van Herck K, van Damme P. Benefits of early hepatitis B immunization programs for newborns and infants. Pediatr Infect Dis J 2008;27(10):861-869. [http://dx.doi.org/10.1097/INF.0b013e318173966f] 26. Guidozzi F, Schoub BD, Johnson S, Song E. Should pregnant urban South African women be screened for hepatitis B? S Afr Med J 1993;83(2):103-105.

27. Spearman CWN, Sonderup MW. Preventing hepatitis B and hepatocellular carcinoma in South Africa: The case for a birth-dose vaccine. S Afr Med J 2014;104(9):610-612. [http://dx.doi.org/10.7196/ SAMJ.8607]

Accepted 21 September 2015.

January 2016, Vol. 106, No. 1

RESEARCH

Prevalence of anaemia in pregnancy in a regional health facility in South Africa K Tunkyi,1 MBBS, FCOG; J Moodley,1,2 MB ChB, FCOG, FRCOG, MD 1 2

epartment of Obstetrics and Gynaecology, Addington Hospital, Durban, South Africa D Women’s Health and HIV Research Group, Department of Obstetrics and Gynaecology, Nelson Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

Corresponding author: K Tunkyi (addington.gynae@kznhealth.za)

Background. Anaemia is a major global health problem affecting an estimated 42% of pregnant women worldwide. There is a paucity of South African (SA) data on anaemia in pregnancy, despite the fact that parasitic infections are endemic and the nutritional status of sections of the population is poor.

Objective. To determine the prevalence of anaemia among antenatal attendees in a regional hospital in Durban, SA. Methods. This was a cross-sectional prospective study in a regional health facility in an urban setting serving a population of low socioeconomic status. Venous blood samples to perform a full blood count were obtained from antenatal attendees at their first clinic visit.

Results. Two thousand pregnant women were studied; the mean (standard deviation) age and gestational age at booking was 27.6 (7.6) years and 21.7 (7.1) weeks, respectively. Eight hundred and fifty-four (42.7%) were anaemic (haemoglobin (Hb) levels <11 g/dL). The majority (81.4%) were mildly anaemic. There were five (0.6%) cases of severe anaemia (Hb <7 g/dL). The prevalence of anaemia was significantly higher in HIV-positive compared with HIV-negative pregnant women (71.3% v. 28.7%; p<0.0001). The common morphology was normochromic normocytic (n=588, 68.9%).

Conclusion. The prevalence of anaemia was 42.7%. In the majority (81.4%) the anaemia was mild and normocytic and normochromic (68.9%). Anaemia is a common problem among antenatal attendees in an SA urban population.

S Afr Med J 2016;106(1):101-104. DOI:10.7196/SAMJ.2016.v106i1.9860

Anaemia is a common condition globally and is associated with adverse events in pregnancy.[1-3] The World Health Organization (WHO) estimates that about 56% of pregnant women in low- and middleincome countries (LMICs) and 23% in high-income countries are anaemic. Most cases of anaemia in women are due to iron deficiency. Anaemia is associated with substantial health and economic cost implications in LMICs.[1-3] Iron deficiency in pregnancy is probably due to the fact that iron stores are inadequate and insufficient to meet the increased requirements in pregnancy. Iron-deficiency anaemia has been associated with an increased risk of stillbirths, low-birth-weight babies, intrauterine growth restriction, neonatal sepsis and maternal mortality.[4] The Saving Mothers Report (2010 - 2013)[5] found that 40% of maternal deaths in South Africa (SA) were associated with anaemia, despite the fact that micronutrients (prophylactic iron, folic acid and multivitamins) are provided routinely throughout pregnancy. It is plausible that the anaemia associated with maternal mortality may be due to poor adherence in taking prophylactic micronutrients and to the poor overall nutritional status of the population.

There is a paucity of data on anaemia among SA pregnant women, among whom there is high prevalence of HIV infection. HIV is asso­ ciated with a high prevalence of anaemia in sub-Saharan Africa.[6] A study in SA by Van Bogaert[7] found a prevalence of anaemia of 19.7% in a rural population. Prevalences reported from African countries indicate varying rates,[8-10] probably reflecting differing sizes of study populations, geographical area (rural or urban), rates of parasitic infestation and levels of education.

101

Objective

To determine the prevalence of anaemia at the first antenatal visit in a cohort of black SA women attending a regional hospital in an urban setting.

Methods

Ethical clearance and regulatory permission was obtained from the University of KwaZulu-Natal Biomedical Research Ethic Committee (BE 306/12) and from the Regional Hospital Administration. A crosssectional prospective study over a 2-year period (2012 - 2014) was performed in a regional hospital in Durban, SA, serving a population with largely low socioeconomic status. Written informed consent was obtained from consecutive women registering for antenatal care and the relevant demographic and clinical data were collected in a structured format. The standard practice at the study site was to perform a full blood count at the first antenatal visit and to repeat the investigation at between 34 and 36 weeks’ gestational age. All women regarded as low risk attended for prenatal care on four occasions at least during the pregnancy, while women who had ‘risk’ features were seen more frequently.

Anaemia was defined as a haemoglobin (Hb) concentration of <11 g/dL (WHO definition[1]). All women received prophylactic iron therapy (oral ferrous sulphate 200 mg) and folic acid 5 mg daily. If anaemia was present, therapeutic doses of iron (oral ferrous sulph­ ate 200 mg 3 times a day) and folate 5 mg daily were prescribed with instruction on appropriate nutritional intake. This management was standard clinical practice at the study site.

The Hb levels were arbitrarily divided into the following groups: (i) >11 g/dL; (ii) 10 - 10.9 g/dL (mild anaemia); (iii) 7 - 9.9 g/dL (mod­erate anaemia); and (iv) ≤7 g/dL (severe anaemia). Gestational

January 2016, Vol. 106, No. 1

RESEARCH

age was calculated taking into account the last menstrual period, an ultrasound dat­ ing scan and the symphysis-fundal height measurement.

N=2 000 patients enrolled

Statistical analysis

N=854 (42.7%) anaemia

Data were entered into a computer database using Microsoft Excel software and imported on SPSS (version 22) for analysis. A p-value of <0.05 was considered statistically significant.

Grades of anaemia

Types of anaemia

Mild (n=695; 81.4%) Moderate (n=154; 18.0%) Severe (n=5; 0.6%)

Hypochromic microcytic (n=12; 1.4%) Normochromic normocytic (n=558; 68.9%) Hypochromic normocytic (n=145; 17.0%) Normochromic microcytic (n=109; 12.8%)

Results

Fig. 1 shows the prevalence, grades and types of anaemia. Eight hundred and fifty-four (42.7%) were anaemic. The majority (81.4%) were mildly anaemic, whereas 18.0% were moderately anaemic. There were five (0.6%) cases of severe anaemia (Hb ≤7.0 g/dL).

The prevalence of anaemia at booking was significantly higher in HIV-positive than in HIV-negative pregnant women (609 (71.3%) v. 245 (28.7%); p<0.0001).

Table 1 shows the relevant clinical data; most women were young (mean (standard deviation (SD)) age 27.6 (7.6) years) and of low parity. The mean gestational age at the booking visit was 24 weeks.

Table 2 shows the demographic and obstet­ ric data of the anaemic antenatal attendees.

The data include HIV status of all participants.

Six hundred and nine of the 845 with anaemia were HIV-infected.

Table 3 shows the clinical characteristics and severity of anaemia; 124 (14.5%) anae­ mic patients were <19 years of age and 111 (13.0%) were aged >35 years. Six hundred and one primigravidas and 302 grand multiparas were included in the study. Anaemia was recorded in 197 primiparas and 111 grand multiparas, giving a prevalence of 32.7% and 36.8%, respectively.

Discussion

The prevalence of anaemia in pregnancy at the first antenatal visit in our study cohort of 2 000 pregnant women was 42.7%, a result that is consistent with prevalence rates of 40.0% in Kenya,[8] 38.2% in Ethiopia[9] and 47.4% in Tanzania.[10] Our sample size was large and confirms that anaemia is a common health problem in an SA setting.

There are several factors responsible for the high prevalence of anaemia in LMICs such as SA: socioeconomic deprivation, malnutrition, high incidences of malaria and HIV infection, hookworm infestation, high numbers of grand multiparas, late booking, and inadequate child spacing because of lack of family planning.

Recently there have been reports of differ­ ences in Hb levels based on racial groups. One of these studies found that mean Hb levels

HIV and anaemia

Negative (n=245; 28.7%) Positive (n=609; 71.3%)

Fig. 1. Prevalence, grades and types of anaemia in the study population.

Table 1. The clinical data of all participants at recruitment Total (N=2 000)

Anaemic (N=854)

Normal (N=1 146)

p-value

95% CI

Mean (SD)

27.6 (7.6)

24.7 (6.2)

30.2 (4 .2)

0.006

0.0153 - 0.0947

Range

19 - 45

19 - 28

25 - 45

≤19

356 (17.8)

124 (14.5)

232 (20.2)

0.001

0.0231 - 0.0909

20 - 24

377 (18.9)

133 (15.6)

244 (21.3)

0.001

0.0223 - 0.0917

25 - 30

670 (33.5)

295 (34.5)

375 (32.7)

0.3

−0.0238 - −0.0598

31 - 34

361 (18.1)

191 (22.4)

170 (14.8)

0.001

0.0419 - 0.1101

≥35

236 (11.8)

111 (13.0)

125 (10.9)

0.16

−0.0085 - 0.0485

0

601 (30.1)

197 (23.1)

404 (35.3)

0.001

0.0814 - 0.1626

1-4

1 097 (54.9)

546 (63.9)

551 (48.0)

0.001

0.1049 - 0.1931

≥5

302 (15.1)

111 (13.0)

191 (16.7)

0.03

0.0015 - 0.0645

Mean (SD)

24 (2.24)

21.7 (7.1)

26.4 (5.3)

0.01

0.0089 - 0.0851

Range

16 - 32

16 - 32

28 - 30

Positive

943 (42.2)

609 (71.3)

334 (29.1)

0.001

0.4267 - 0.5622

Negative

1 057 (52.8)

245 (28.7)

812 (70.9)

0.001

0.4431 - 0.6231

Variable Age (years)

Age groups, n (%)

Parity, n (%)

Gestational age (weeks, 1st visit)

HIV status, n (%)

were lower in non-Caucasian than Caucasian pregnant populations from 27 gestational weeks until term.[11] Further­more, lower Hb levels have been described for population groups such as African Americans (−1 g/dL),

102

January 2016, Vol. 106, No. 1

Vietnamese (−1 g/dL) and women in Green­ land (−1 g/dL).[12] Our patients were black South Africans of low socioeconomic status.

Variations in Hb concentrations obviously require the establishment of reference levels

RESEARCH

Table 2. Demographic and obstetric data of women with anaemia v. HIV status Variable

Total (N=854)

HIV +ve (N=609)

HIV –ve (N=245)

p-value

95% CI

Age (years), mean (range)

27.6 (14 - 45)

26.5 (14 -40)

27.4 (18 - 45)

0.3

−0.0566 - 0.0746

Parity, median (range)

2 (1 - 6)

1 (1 - 2)

2 (1 - 6)

0.2

−0.0067 - 0.0267

Gestation at booking (weeks), median (range)

22 (17 - 34)

22 (18 - 34)

22 (18 - 34)

1

−0.0614 - 0.0614

Table 3. Clinical data and severity of anaemia

Total (N=854)

Mild anaemia (Hb 10 - 10.9 g/dL) (N=695)

Moderate anaemia (Hb 7 - 9.9 g/dL) (N=154)

Severe anaemia (Hb <7 g/dL) (N=5)

p-value

95% CI

≤19

124 (14.5)

90 (12.9)

34 (22.1)

0 (0.0)

0.003

0.0304 - 0.1536

20 - 24

133 (15.6)

107 (15.4)

26 (16.9)

0 (0.0)

0.6

−0.0485 - 0.0785

25 - 30

295 (34.5)

259 (37.3)

36 (23.4)

0 (0.0)

0.001

0.0559 - 0.221

31 - 34

191 (22.4)

153 (22.0)

37 (24.0)

1 (20.0)

0.5

−0.0527 - 0.0927

≥35

111 (13.0)

86 (12.4)

21 (13.6)

4 (80.0)

0.6

−0.046 - 0.07

0

197 (23.1)

153 (22.0)

44 (28.6)

0 (0.0)

0.07

−0.0077 - 0.1397

1-4

546 (63.9)

496 (71.4)

49 (31.8)

1 (20.0)

0.001

0.3123 - 0.4797

≥5

111 (13.0)

46 (6.6)

61 (39.6)

4 (80.0)

0.001

0.2721 - 0.3879

Negative

245 (28.7)

189 (27.2)

54 (35.1)

2 (40)

0.5

-0.0519 - 0.0431

Positive

609 (71.3)

506 (72.8)

100 (64.9)

3 (60)

0.6

-0.0451 - 0.0532

Variables Age groups, n (%)

Parity, n (%)

HIV status, n (%)

for pregnant populations in SA. This may be logistically difficult, however, given the diversity of the population and the geographi­ cal nature of SA, with a sizeable population living at high altitudes. It has been reported that factors such as altitude of residence, genetics and nutrition have an impact on Hb levels. [8-10] While smoking behaviour also influences Hb concentrations, our study population is known to have low smoking rates (3.0% − unpublished departmental statistics).

In our study, the mean gestational age was 21 weeks. It is known that fluctuations in Hb levels occur by trimester as a result of mater­ nal and fetal physiological demands. It is therefore suggested that a 1.0 g/dL de­crease takes place between the first and third trimester of pregnancy, with Hb concentrations decreasing by a further 0.5 g/dL in the second tri­mester.[13] Although we defined anaemia according to WHO recomm­endations for practical reasons in our setting, we did not take into account trimester-adjusted Hb cutoff levels. As shown in Table 3, 34.7% had Hb levels of between 10 g/dL and 10.9 g/dL, while 8.0% had an Hb level <10 g/dL. Hb concentrations have also been reported to be affected by age. Jamaican girls between

the ages of 13 and 14 years have low Hb levels (−1.0 g/dL from normal).[13] In our study, 124 women who were aged <19 years had mild or moderate anaemia. Age-related anaemia in pregnancy in our setting needs further investigation.

HIV infection has been reported to be associated with anaemia, either independently or due to antiretroviral medica­ t­ ions such as zidovudine. A recent report by Nandlal et al.[14] states that anae­mia is a common finding in HIV-infected pregnant women.

In our study, a high prevalence of anaemia (71.3%) was observed in HIV-infected patients, 2.5 times higher than in those who were uninfected (Table 3). We did not investigate the prevalence of anaemia in the HIV-infected women.

Anaemia is reported to be strongly asso­ ciated with maternal mortality,[2,5] with severe anaemia also increasing the risk of perinatal mortality.[4] This association obviously needs more detailed investigation because anaemia in LMICs is underpinned by malaria, parasitic infections such as bilharzia, and poor nutrition.

Our study demonstrates that the common morphology of anaemia among pregnant

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January 2016, Vol. 106, No. 1

women was normochromic normocytic (in 68.9%), 1.4% having hypochromic micro­cytic anaemia. Although we did not do iron studies to establish iron status, it has been reported that only 50% of cases of anaemia in pregnant [14] women are responsive to oral iron.

There is a view that a uni­ versal approach of prophylactic iron therapy may neglect untreated diseases and universal therapeutic iron therapy may be inappropriate.[15] It should be noted that our study was conducted in a regional hospital and that the majority of pregnant women were urban residents. The prevalence of anaemia in the population as a whole could well have been underestimated. A large communitybased study needs to be done to determine the prevalence of anaemia in the general population.

Conclusion

The prevalence of anaemia at the first antenatal visit is high and a major health issue at the study site in Durban. There is a need to strengthen our healthcare system to ensure a definitive diagnosis so that appropriate counselling and treatment can be provided in early pregnancy.

RESEARCH

References 1. World Health Organization. Micronutrient deficiencies: Iron deficiency anaemia. 2008. http://www. who.int/nutrition/topics/ida/en/ (accessed 15 November 2015).

2. Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. Lancet 2011;378(9809):2123-2213. [http://dx.doi.org/10.1016/S01406736(10)62304-5] 3. De Benoist B, McLean E, Egli I, Cogwell M, eds. Worldwide Prevalence of Anaemia 1993-2005. WHO Global Database on Anaemia. Geneva: World Health Organization, 2008.

4. Bodeau-Livinec F, Briand V, Berger J, et al. Maternal anemia in Benin: Prevalence, risk factors, and association with low birth weight. Am J Trop Med Hyg 2011;85(3):414-420. [http://dx.doi.org/10.4269/ ajtmh.2011.10-0599] 5. National Committee for Confidential Enquiries into Maternal Deaths. Saving Mothers 2010-2013: Fourth Report of Confidential Enquiries into Maternal Deaths in South Africa. Pretoria: Department of Health, 2013.

6. Ouédraogo S, Koura GK, Accrombessi K, Bodeau-Livinec F, Massougbodji A, Cot M. Maternal anemia at first antenatal visit: Prevalence and risk factors in a malaria-endemic area in Benin. Am J Trop Med Hyg 2012;87(3):418-424. [http://dx.doi.org/10.4269/ajtmh.2012.11-0706] 7. Van Bogaert LJ. Anaemia and pregnancy outcomes in a South African rural population. J Obstet Gynecol 2006;25(7):617-619. [http://dx.doi.org/10.1080/01443610600902901] 8. Siteti MC, Namasaka SD, Ariya OP, Injete SD, Wanyonyi WA. Anaemia in pregnancy: Prevalence and possible risk factors in Kakamega County, Kenya. Sci J Pub Hlth 2014;2(3):216-222.

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9. Melku M, Addis Z, Meseret A, et al. Prevalence and predictors of maternal anemia during pregnancy in Gondar, Northwest Ethiopia: An institutional based cross-sectional study. Anemia 2014 (2014), Article ID 108593. [http://dx.doi.org/10.1155/2014/108593] 10. Msuya SE, Hussein TH, Uriyo J, et al. Anaemia among pregnant women in northern Tanzania: Prevalence, risk factors and effect on perinatal outcomes. Tanzan J Health Res 2011;13(1):33-39. [http://dx.doi.org/10.4314/thrb.v13i1.60881] 11. Harm SK, Yaser MH, Walters JH. Changes in haematological indices in Caucasian and non-Caucasian pregnant women in the United States. Kor J Hematol 2012;47(2):136-141. [http://dx.doi.org/10.5045/ kjh.2012.47.2.136] 12. Lynch S. Indicators of the iron status of populations: Red blood cell status parameters. In: Assessing Iron Status of Population: Report of Joint WHO/CDC Technical Consultation on the Assessment of Iron Status at a Population Level. WHO/Centers for Disease Control and Prevention. Geneva: WHO, 2004.

13. Nestle P. Adjusting Haemoglobin Values in Program Surveys. Washington, DC: INACG, 2002.

14. Nandlal V, Moodley D, Grobler A, et al. Anaemia in pregnancy is associated with advanced HIV disease. PLoS One 2015;9(9):e106103. [http://dx.doi.org/10.1371/journal.pone.0106103] 15. Steven GA, Finucane MM, De-Regi LM, et al. Global, regional and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant women for 19952011: A systematic analysis of population-representative data. Lancet Global Health 2013;1(1):e16-e25. [http://dx.doi.org/10.1016/S2214-109X(13)70001-9]

Accepted 2 November 2015.

January 2016, Vol. 106, No. 1

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CLINICAL PATHOLOGIST/CLINICAL MICROBIOLOGIST Klerksdorp/Potchefstroom/Welkom

We are a dynamic, cutting edge, purpose driven and values based Pathology and Diagnostic laboratory, caring for the health of patients, while offering support and expertise to medical professionals.

We are seeking appropriate individuals to assist us in our next phases of growth. We have an opportunity for a Clinical Pathologist to work at our Welkom branch and further vacancies for a Clinical Microbiologist/Clinical Pathologist to work at our Klerksdorp and Potchefstroom branch.

If you are a creative, dynamic and passionate professional who adopts a customercentric approach, is respectful and accountable and possesses a well-developed work ethic, while working with diverse groups of people and excelling within a multicultural environment then this opportunity could be what you are Looking for.

Requirements: - M. Med or FC Pathology (SA) - Current registration with the HPCSA as a Pathologist - Relevant working experience - High level of ethics and integrity Interested applicants who meet the criteria may email A CV to: lindyg@pathcare.co.za

Closing date for applications is Monday, 1st February 2016.

CAREERS & CLASSIFIEDS

… y a w o ll a G & s e i r f m Du t e cr se t p e k st e b ’s d n la Scot CONSULTANT PATHOLOGIST This post is based in Dumfries and Galloway Royal Infirmary, a district general hospital with a major reputation for delivering quality care as well as being at the forefront of innovative practice. The range of services provided by the hospital is, by virtue of its geographical location, considerably more wide and complex than many much larger traditional district general hospitals.

Applications are invited for a full-time post of Consultant Histopathologist.

This post is a replacement post. The successful candidate will join a team consisting of four Consultant Histopathologists.

The Department provides a wide range of clinical diagnostic and advisory services supported by scientific facilities in three inter-related disciplines: • Histopathology (approximately 15000 specimens per year) • Diagnostic Cytopathology (1000 requests per year) • Mortuary and Autopsy services (250 autopsies per year) In addition to routine diagnostic services expected for a district general hospital, Dumfries & Galloway is accredited, as a Cancer Unit, for the diagnosis and management of common cancers including Skin, Head & Neck, Breast, Colorectal & upper Gastrointestinal, Respiratory, Urological, Haematological, Gynaecological malignancies.

Dumfries is located in the South West of Scotland. Dumfries town boasts a brand new leisure centre with state of the art sporting and gym facilities. Dumfries and Galloway is a popular tourist resort for outdoor activities – walking, water sports and mountain biking.

Applicants must hold valid registration with the General Medical Council and have completed a period of training in Pathology that is recognised by the Royal College of Pathologists. They should be on, or eligible for, inclusion on the specialist register within six months of appointment.

For informal enquiries and arrangements to visit, please contact: Dr Stanford Mathe, Consultant Histopathologist and STL (email: smathe@nhs.net) or Dr Martin Connor, Clinical Director for Diagnostic Services (email: martinconnor@nhs.net).

Arrangements to visit the Department and the hospital can be made through Patsy Pattie, Project Lead for Medical Recruitment (tel: +44 1387 241790; email: patsy.pattie@nhs.net) Visit www.dumfriesmedicalrecruitment.co.uk or www.medicaljobs.scot.nhs.uk to download a Job Description and application form.

Please email completed application forms to: dg.applications@nhs.net Closing date: 15th January 2016.

Interview date: Early February 2016.

CONSULTANT – OBSTETRICS AND GYNAECOLOGY Mediclinic Middle East, a leading UAE private healthcare company and part of Mediclinic International, one of the 10 largest private hospital groups in the world, has a number of exciting opportunities for obstetrics and gynaecology consultants.

Requirements: • Certification of higher professional education, e.g. CCST, Board certification etc.

• Certification and experience in Maternal and Foetal Medicine is an advantage • Publication in peer reviewed journals desirable Candidates must be willing to relocate to the UAE within 3-6 months after a successful offer.

Please forward your CV to thembi.fula@mediclinic.ae

EXPERTISE YOU CAN TRUST. A MEDICLINIC INTERNATIONAL COMPANY www.mediclinic.ae

Salary: £76,761 to £103,490

CAREERS & CLASSIFIEDS

Guidance

Ospidéal Mhuire na Leanaí, Cromghlinn

Our Lady’s Children’s Hospital, Crumlin, Ireland

Be part of something amazing in Ireland’s largest Children’s Hospital...

Exciting Career Opportunities Our Lady’s Children’s Hospital is Ireland’s largest paediatric hospital and currently has 227 beds and cots in use. It provides evidence based quaternary, tertiary and secondary quality care to children and adolescents in a safe environment driven by knowledge through education and research for a range of specialties including childhood cancers and blood disorders, cardiac diseases, major burns, cystic fibrosis and rheumatology etc.

We are recruiting the following PAEDIATRIC posts commencing in JANUARY 2016, JULY 2016 and JANUARY 2017 for either six month or one year contracts at Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland:

1. FELLOW IN PAEDIATRIC ORTHOPAEDIC SURGERY 2. NON CONSULTANT HOSPITAL DOCTOR POSTS (SHO/Registrar/Fellow grade) in • Paediatric Medicine (all specialties) • Paediatric Surgery • Paediatric Orthopaedic Surgery • Paediatric Cardiothoracic Surgery • PICU • Anaesthesia • Child & Adolescent Psychiatry • Paediatric Emergency Medicine Successful candidates must register with the Medical Council of Ireland under ‘General Registration’ on www.medicalcouncil.ie To apply or for further details on any of the above posts please forward your CV to Email: brenda.mckenna@olchc.ie Closing date: Friday, 29th January 2016. www.olchc.ie

ASSOCIATE PRACTICE FOR SALEEVENDER MPUMALANGA Looking for an associate to buy practice. Medical Aid & Private fee structure Practice- Fully electronic clinical notes.

Fully dispensing practice.

No after-hours work. Hours: Monday-Friday 08:00-16:00 Alternative Saturdays 08:00-09:30. Finance options negotiable.

Contact 083 321 1072 / email: wtmedical@telkomsa.net

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The ESSENTIAL MEDICAL REFERENCE for every healthcare professional!

The convenient pocket-sized design enables you to fit it comfortably into your hospital bag or coat pocket, so it can always be at hand for ready reference. South African Medicines Formulary (SAMF), a joint initiative of the University of Cape Town’s Division of Clinical Pharmacology and the Health and Medical Publishing Group, publishers for the South African Medical Association, provides easy access to the latest, scientifically accurate information, including full drug profiles, clinical notes and special prescriber’s points. The thoroughly updated 12th edition of SAMF is your essential reference to the rational, cost-effective and safe use of medicines.

Please direct all order queries to: Diane Smith Tel: 012 481 2069 Health and Medical Publishing Group

Email: dianes@hmpg.co.za Tax invoice to be posted on dispatch of order

CPD

JANUARY 2016

The CPD programme for SAMJ is administered by Medical Practice Consulting.

CPD questionnaires must be completed online at www.mpconsulting.co.za.

True (A) or false (B): SAMJ Severe porphyric neuropathy – importance of screening for porphyria in Guillain-Barré syndrome 1. In patients presenting with a progressive quadriparesis, charac­ terised by marked weakness with exaggerated reflexes, porphyric neuropathy should always be considered.

Targeting composite treatment of type 2 diabetes in middleincome countries – the challenge of hyperglycaemia and hypoglycaemia 2. The WHO Multinational Study of Vascular Disease in Diabetes showed that 50% of the deaths in type 2 diabetes mellitus are attributed to CVD. 3. Intensive glucose control reduces the overall risk of diabetesrelated sequelae (e.g. diabetic retinopathy) but at an increased risk of hypoglycaemia and greater weight gain.

The relationship between stunting and overweight among children from South Africa (SA): Secondary analysis of the National Food Consumption Survey – Fortification Baseline I 4. Stunted children are more likely to be obese.

5. Health risks of childhood obesity include cardiovascular disease (CVD), type 2 diabetes, hepatic steatosis, gallstones, and gastrooesophageal reflux.

Time to fibrinolytics for acute myocardial infarction (AMI): Reasons for delays at Steve Biko Academic Hospital 6. The standard of care for AMI is to administer thrombolytic therapy as soon as possible to all patients without contraindications who present within 12 hours of symptom onset and have ST-segment elevation on the ECG or new-onset left bundle-branch block.

Antenatal screening for hepatitis B virus (HBV) in HIV-infected and uninfected pregnant women in Tshwane 7. In SA, there is a significantly higher HBV prevalence in HIVinfected compared with HIV-uninfected women.

8. Among pregnant women, the risk of perinatal transmission is 10 - 20% for women who are seropositive for hepatitis B surface antigen (HBsAg) but seronegative for hepatitis e antigen (HBeAg), but this rises to 90% for women who are seropositive for both HBsAg and HBeAg.

Prevalence of anaemia in pregnancy in a regional health facility in SA 9. The Saving Mothers Report (2010 - 2013) found that 40% of maternal deaths in SA were associated with anaemia, despite the fact that micronutrients (prophylactic iron, folic acid and multivitamins) are provided routinely throughout pregnancy.

10. The anaemia of pregnancy is typically macrocytic, reflecting folic acid deficiency owing to increased demand exerted by the growing fetus.

CME Heart failure in sub-Saharan Africa: A clinical approach 11. Non-ischaemic aetiologies are predominant in the epidemiology of heart failure in sub-Saharan Africa.

12. Left ventricular ejection fraction carries independent prognostic significance and is considered abnormal when <50%.

13. A normal electrocardiogram is a common finding in a patient presenting with heart failure.

Dyspnoea: Pathophysiology and a clinical approach 14. Dyspnoea is primarily of respiratory or cardiac origin, with almost 90% of all cases being due to asthma, heart failure, myocardial ischaemia, chronic obstructive pulmonary disease, pneumonia and psychogenic disorders.

15. ‘Red flags’ associated with dyspnoea include hypotension, rapid respiratory rate, altered mental status, hypoxia and unstable arrhythmia.

16. Chest pain during dyspnoea may be caused by cardiac, coronary or pleural disease.

An approach to the young hypertensive patient 17. Hypertensive children and adolescents go on to become hypertensive adults – a phenomenon known as ‘blood pressure tracking’.

18. The probability of secondary hypertension is inversely propor­ tional to the age of the patient, i.e. higher in a school-going child, but lower in a young adult.

An approach to the diagnosis and management of valvular heart disease 19. Mitral stenosis is almost exclusively caused by chronic rheumatic heart disease.

20. Aortic stenosis is the most common valve lesion in Western countries and is largely a disease of the elderly.

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Accreditation number: MDB015/038/01/2016

January 2016, Vol. 106, No. 1

INNOVATION IN DRY EYE THERAPY

1

NEW

Caring for the 3 layers between your eyes and the world1 Lipid deficiencies Aqueous tear-deficiencies Mucin deficiencies

References: 1. Liposic Product Monograph. Data on file, Bausch&Lomb Inc. Scheduling status: S0 Proprietary name and dosage form: Liposic Eye Gel. Composition: Each 1 g contains: 2 mg carbomer, triglycerides – medium chain, sorbitol, sodium hydroxide and purified water, Cetrimide 0,01 % m/m (preservative).

Pharmacological classification: A 15.4 Ophthalmic preparations - Other. Indications: Substitution of tear fluid for management of dry eye conditions such as symptomatic treatment of keratoconjunctivitis sicca. Registration number: 37/15.4/0224. © 2003 Bausch & Lomb Incorporated. ®/™ denote trademarks of Bausch & Lomb Incorporated. Applicant: SofLens (Pty) Ltd. Reg. No.: 1968/11787/07. Marketed by: Bausch & Lomb (SA) (Pty) Ltd. Reg. No.: 1996/003931/07. 15E Riley Road, Bedfordview, Gauteng, South Africa, 2008. Tel: +27 11 087 0000 www.bausch.co.za BL94/15