SAMJ Vol 107, No 10 (2017) by HMPG

OCTOBER 2017

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CME Contraceptive implants IN PRACTICE ‘Best buys’ for surgery Barriers to implementing NHI CASE REPORT Cytomegalovirus retinitis and HIV: Case reviews RESEARCH Survival of Kaposi’s sarcoma patients on ART Hepatitis B distribution in Namibia Outcomes in very-low-birth-weight neonates

1 Relieves pain

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*Nicolas Hall & Company, Benchmarking the World of OTC, DB6,2016. “Voltaren is the world best-selling non-prescription topical pain reliever” Reference: 1. Zacher J et al. 2008. Topical diclofenac and its role in pain and inflammation: an evidence based review. Current Medical Research & Opinion. Vol 24. No 4 (925-950). 20g & 50g

100g Voltaren® Emulgel®. Each 100g contains 1,16g diclofenac diethylammonium corresponding to 1g diclofenac sodium. Reg. no.: U/3.1/77. Botswana:

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Indicated for use in adults and adolescents older than 12 years. Safety in pregnancy and lactation has not been established. Consult your pharmacist/healthcare professional if needed. Applicant: GlaxoSmithKline Consumer Healthcare SA (Pty) Ltd, Company Reg. No. 2014/173930/07.39 Hawkins Avenue, Epping Industria 1, 7460. Tel. No. 0800 118 274. CHZAF/CHVOLT/0018/17

OCTOBER 2017 PRINT EDITION

FROM THE EDITOR 4

EDITOR Bridget Farham, BSc (Hons), PhD, MB ChB

Reversing disease B Farham

EDITORS EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon) JP de V van Niekerk, MD, FRCR

EDITOR’S CHOICE CORRESPONDENCE

An approach to anaemia diagnosis – concerns in primary care D O’Mahony, M Mntonintshi, A G Parrish

IZINDABA 10

HMPG

30 days in medicine B Farham

CEO AND PUBLISHER Hannah Kikaya Email: hannahk@hmpg.co.za

BOOK REVIEW Accident P Ashton

MANAGING EDITORS Claudia Naidu Naadia van der Bergh

CONTINUING MEDICAL EDUCATION 14

17 24

GUEST EDITORIAL Introduction of the contraceptive implant in South Africa: Successes, challenges and the way forward S Mullick, M F Chersich, Y Pillay, H Rees ARTICLES User perspectives on Implanon NXT in South Africa: A survey of 12 public-sector facilities D Pillay, M F Chersich, C Morroni, M Pleaner, O A Adeagbo, N Naidoo, S Mullick, H Rees Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of healthcare workers O A Adeagbo, S Mullick, D Pillay, M F Chersich, C Morroni, N Naidoo, M Pleaner, H Rees Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts D Pillay, C Morroni, M Pleaner, O A Adeagbo, M F Chersich, N Naidoo, S Mullick, H Rees

IN PRACTICE 34

ISSUES IN PUBLIC HEALTH ‘Best buys’ for surgery in South Africa T Wilkinson, M Smith, A Kinghorn, K J Hofman HEALTHCARE DELIVERY Exploring the barriers to implementing National Health Insurance in South Africa: The people’s perspective R V Passchier Evaluating 5 years’ NIMART mentoring in South Africa’s HIV treatment programme: Successes, challenges and future needs M Jones, D Cameron CASE REPORT Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa R Hassan-Moosa, T Chinappa, L Jeena, L Visser, K Naidoo

Protection of the human research participant: A structured review L Roets

RESEARCH 55

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients* M Held, M Laubscher, L Workman, H J Zar, R Dunn

TECHNICAL EDITORS Emma Buchanan Kirsten Morreira Paula van der Bijl PRODUCTION MANAGER Emma Jane Couzens DTP AND DESIGN Clinton Griffin Travis Arendse CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za SALES MANAGER (CAPE TOWN) Azad Yusuf JOURNAL ADVERTISING Reneé Hinze Ladine van Heerden Makhadzi Mulaudzi Charmalin Comalie ONLINE SUPPORT Gertrude Fani

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October 2017, Print edition

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Deep-vein thrombosis in the era of high HIV and tuberculosis prevalence: A prospective review of its diagnosis and treatment in a quaternary centre* K E Hodkinson, J N Mahlangu

Male involvement in prevention of mother-to-child transmission of HIV in the context of partner testing in Goba town, Ethiopia: A facility-based cross-sectional study* M T Alemayehu, J Haidar

Survival of patients with Kaposi’s sarcoma in the South African antiretroviral treatment era: A retrospective cohort study* M M Sengayi, D Kielkowski, M Egger, L Dreosti, J Bohlius

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Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa* L Gibbs, L Tooke, M C Harrison

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Respiratory comorbidity in South African children with atopic dermatitis* C L Gray, M E Levin, G du Toit

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Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa* G Lamacraft, C Labuschagne, S Pretorius, M C Prinsloo, M D Smit, J-R Steyn

The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA.

Bibliometric trends of South African environmental health articles between 1998 and 2015: Making local research visible and retrievable* C Y Wright, F Dominick, Z Kunene, T Kapwata, R A Street *Abstract only, full article available online. CAREERS AND CLASSIFIEDS

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HIV-positive patients in the intensive care unit: A retrospective audit P Mkoko, R I Raine

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Distribution of hepatitis B virus infection in Namibia P Mhata, T W Rennie, L F Small, P M Nyarang’o, Z Chagla, C J Hunter

887

Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio: Adherence tools in patients referred for apparent treatment-resistant hypertension E S W Jones, M Lesosky, M Blockman, S Castel, E H Decloedt, S L U Schwager, E D Sturrock, L Wiesner, B L Rayner

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Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon L N Aminde, A Dzudie, A P Kengne, J Ndjebet, S Mapoh, X Kuelang, F Kamdem, B H Mbatchou Ngahane, M-S Doualla, K B Ngu, K Sliwa, F Thienemann

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Background photo: A patient eats his lunch at Brooklyn Chest Hospital in Cape Town | Damien Schumann Box photos: The 40 mm length contraceptive implant is the same size as a match | Melanie Pleaner, Wits Reproductive Health and HIV Institute, Johannesburg; Kaposi’s sarcoma | Greg Dyer; Premature baby in incubator | Daynia Ballot, Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg

October 2017, Print edition

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11883 Telfast launch ad A4 SAPJ.indd 1

2017/09/07 1:56 PM

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FROM THE EDITOR

Reversing disease ‘It was recognised early in the course of the global epidemic of type 2 diabetes that variation in the prevalence of the disease among populations could be explained largely by relative weight gain.’[1] This quote is from a 2013 article that reported the results of an evaluation of associations between population-wide loss and gain in weight with diabetes prevalence, incidence and mortality, as well as cardiovascular and cancer trends, in Cuba over a 30-year interval. The global epidemic of type 2 diabetes is generally thought to be a result of the increasing incidence of obesity among all populations. If weight gain causes type 2 diabetes in susceptible individuals, would weight loss reverse the disease? A recent analysis in the BMJ[2] would suggest that it can. Louise McCombie and her colleagues[2] from the University of Glasgow, Scotland, point out that type 2 diabetes is generally regarded as progressive and incurable. In the UK alone this disease now affects 5 - 10% of the population. The estimated national prevalence of type 2 diabetes in South Africa in 2012 was 9.5%,[3] so we are dealing with a similar problem. The current approach to treating this disease relies on frequent measurements of glycated haemoglobin (HbA1c) along with early introduction of drugs and some lifestyle recommendations, such as weight loss and exercise. While this approach has improved clinical outcomes to some extent, most patients still go on to develop vascular complications and their life expectancy is up to 6 years shorter than that of individuals without diabetes. However, overseas at least (and I know among some pioneering practitioners locally) diabetes management is beginning to focus on reversing the underlying disease mechanism rather than treating symptoms and the long- and short-term consequences of the pathology. Current clinical guidelines focus on lowering blood glucose and HbA1c, generally using antidiabetic drugs. There are 488 drugs (excluding insulins) currently licensed worldwide to treat type 2 diabetes, with 70 generic compounds. All these lower HbA1c and blood glucose significantly – but diabetics continue to suffer the consequences of the disease, become sick and die prematurely. To date, there have been no trials looking at the combination of drugs given along with optimal diet and lifestyle advice for weight control. On the other hand, consistent evidence shows that weight loss is associated with extended life expectancy for people with diabetes and that weight loss of around 15 kg often produces total biochemical remission of type 2 diabetes, restoring beta-cell function.[4] We now know that one of the main reasons for the pathology is the accumulation of ectopic fat in the liver and pancreas that impairs

organ function, and that reversing this accumulation reverses the disease. McCombie et al.[2] suggest that a simple approach to classifying remission as two normal tests (either blood glucose or HbA1c) at least 2 months apart and regular annual follow-up should be sufficient to diagnose ‘remission’. However, although we are now starting to accept the idea that a diagnosis of diabetes need not be for life, few patients are achieving the weight loss required for remission. In Scotland, for example, results that included every patient in Scotland with diabetes showed that <0.1% of those with type 2 diabetes were coded as being in remission in March 2017. McCombie et al.[2] suggest that the main reason for this is that neither patients nor their doctors are focusing on trying to achieve remission. Indeed, they may be unaware that this can be achieved. There is wide doubt that people can sustain weight loss, despite evidence of structured approaches that have recorded rapid initial weight loss and then maintenance of weight loss of 12 - 15 kg for >12 months.[5] For many, realising that losing weight will lose them the diagnosis of diabetes will be enough motivation to find a lifestyle and diet that allows them to do this. All doctors need to start looking at type 2 diabetes as a potentially reversible disease, so that their patients can be encouraged to do the same. Bridget Farham Editor ugqirha@iafrica.com 1. Franco M, Bilal U, Orduñez P, et al. Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980 - 2010: Repeated cross sectional surveys and ecological comparison of secular trends. BMJ 2013:346:f1515. https://doi.org/10.1136/bmj.f1515 2. McCombie L, Leslie W, Taylor R, Kennon B, Sattar N, Lean MEJ. Beating type 2 diabetes into remission. BMJ 2017:358:j4030. https://doi.org/10.1136/bmj.j4030 3. SEMDSA Type 2 Diabetes Expert Committee. SEMDSA 2017 guidelines for the management of type 2 diabetes mellitus. J Endocr Metab Diabetes S Afr 2017;22(1, Suppl 1):S1-S196. https://www.semdsa. org.za/images/647-4385-1-PB.pdf (accessed 18 September 2017). 4. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011;54(10):2506-2514. https://doi.org/10.1007/s00125-011-2204-7 5. Stevens S, Hollingsworth KG, Al-Mrabeh A, et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: Pathophysiological changes in responders and nonresponders. Diabetes Care 2016;39(5):808-815. https://doi.org/10.2337/dc15-1942

S Afr Med J 2017;107(10):807. DOI:10.7196/SAMJ.2017.v107i10.12877

October 2017, Print edition

Plasmoquine,

for the treatment of rheumatoid arthritis Rheumatoid arthritis is a chronic condition mainly caused by inflammation in the joints of the hand, wrist, elbows, shoulders, hips, knees and feet. These conditions are usually on both sides of the body.

New packaging coming soon

Medchem Pharmaceuticals CC Reg. No. Z/20.2.6/127

EDITOR’S CHOICE

CME: Contraceptive implants

In 2014, the contraceptive implant was introduced into public sector facilities in South Africa (SA). Several thousand healthcare workers were trained, and demand was generated for the method, achieving high uptake. Use of the implant has since declined, but currently accounts for ~7% of all contraceptive use – a not insignificant achievement for a ‘new’ method. In this edition of CME, the authors take stock of the early years of implant provision in SA. The articles, based on research in 2016, capture women’s motivations for using the implant and their perspectives towards the method, healthcare providers’ competencies and experiences with service provision, and the quality of the systems used for monitoring implant provision. Insights may be generalisable to family planning services more broadly, but are also relevant to the introduction of other new technologies, especially those related to HIV.

Short-term outcomes of inborn v. outborn very-low-birth-weight neonates

The Groote Schuur Hospital (GSH) neonatal nursery provides level 3 care for the Metro West Health District in the Western Cape Province of SA. Worldwide, very-low-birth-weight (VLBW) neonates delivered in level 3 neonatal units have better outcomes than those transported from other facilities. Gibbs et al.[1] set out to identify the characteristics and outcomes of VLBW neonates at GSH in a retrospective cohort study, with an emphasis on differences between inborns and outborns. VLBW neonates admitted to the GSH neonatal nursery between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford Network database and reviewed. Of 1 032 neonates enrolled, 906 (87.8%) were delivered at GSH and 126 (12.2%) were outborn. Access to antenatal care, antenatal steroids and inborn status were statistically significant predictors of mortality and survival without morbidity. The mothers of inborn patients were more likely than those of outborn patients to have received antenatal care (89.1% v. 57.9%; p<0.0001) and antenatal steroids (64.2% v. 15.2%; p<0.0001). Inborns required less ventilatory support (16.2% v. 57.9%; p<0.0001) and surfactant administration than outborns (25.3% v. 65.1%; p<0.0001), and developed less late infection (8.8% v. 23.4%; p<0.0001), severe intraventricular haemorrhage (3.7% v. 13.9%; p<0.0001) and chronic lung disease (5.3% v. 13.4%; p=0.003). The incidence of necrotising enterocolitis was similar in the two groups (5.9% v. 8.7%; p=0.227). The mortality rate was 18.4% for inborns and 33.3% for outborns (p<0.0001). Mortality declined as birth weight increased. Of the survivors, 85.0% of inborns and 70.2% of outborns did not develop serious morbidity (p=0.003). VLBW neonates delivered at GSH had better outcomes than their outborn counterparts. Perinatal regionalisation is beneficial to patients, with antenatal care, timeous transfer in utero and antenatal steroids contributing to excellent outcomes.

Bibliometric trends of SA environmental health articles between 1998 and 2015: Making local research visible and retrievable

SA has to grapple with multiple burdens of disease for which environmental factors have a role to play in both causation and prevention. Wright et al.[2] describe a bibliometric review of environmental health indexed literature for SA over an 18-year period. The article provides an overview of the nature of SA-based published environmental health indexed research, aiming to identify

search challenges, frequently researched topics, and gaps and opportunities for future research. The Web of Science, PubMed and Science Direct were used to search for original, peer-reviewed and review articles with the inclusion criteria ‘environmental health’ and ‘South Africa’ available online and published between 1998 and 2015, inclusively. A total of 230 journal articles were included in the bibliometric analysis. The highest number of articles (n=54) was published in 2015. The majority of the first authors were affiliated with SA institutions (n=160, 69.5%). For the articles where funding was explicitly declared (n=148), the three most frequently occurring agencies that funded the published research were the National Research Foundation in SA (n=17), the South African Medical Research Council (n=13) and the Water Research Commission (n=9). There was little inter-annual/ environmental health category variation over time owing to the relatively small sample size. The largest number of retrieved journal articles was in the area of environmental pollution control (n=76), followed by environmental health lifestyle and behaviour-related topics (n=42) and then water monitoring (n=26). Despite the research needed to solve large environmental health challenges in SA, environmental health was only used as a keyword in the title, author keywords or abstract for 230 SA-based studies over an 18-year period. This makes it extremely difficult for environmental health research to be located and used to inform the profession as well as the research agenda. Several issues that environmental health practitioners are typically tasked to implement and monitor are not indexed as environmental health topics. The need for authors to use ‘environmental health’ as a keyword is emphasised, particularly if research is to inform decision-making and policy support, as well as guide future research in the country.

Survival of patients with Kaposi’s sarcoma in the SA antiretroviral treatment era

When SA implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi’s sarcoma (KS) patients shifted from symptomatic palliation to potential cure. The study by Sengayi et al.[3] evaluates survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA, using a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012. Kaplan-Meier survival functions were used to estimate 1- and 2-year survival, and Cox regression models to identify changes over time and prognostic factors. The study included 357 AIDS-KS patients, almost all of whom were black Africans (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37 (interquartile range 30 - 43) years, and the median baseline CD4 count was 242 (130 - 403) cells/ µL. Most patients received ART (n=332, 93.0%) before or after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%) with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95% CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR 2.88, 95% CI 1.36 - 6.09) predicted mortality. The results show that large national ART roll-out programmes can successfully reduce KS-related mortality at the individual patient level. If ART coverage is extended, KS-associated morbidity and mortality are likely to drop.

October 2017, Print edition

EDITOR’S CHOICE

Male involvement in prevention of mother-to-child transmission of HIV in the context of partner testing in Goba town, Ethiopia

Antenatal care (ANC) is an entry point for prevention of mother-tochild transmission (PMTCT), particularly when a man accompanies his spouse for voluntary counselling and testing (VCT), even though this seldom happens in Ethiopia. In the study by Alemayehu and Haidar,[4] the role of male partners in improving PMTCT/ANC, which is essential to prevent HIV/ AIDS transmission in Ethiopia, is examined. The study focused on identifying barriers for the low involvement in PMTCT/ANC among male partners whose spouses received ANC. A total of 422 male partners in Goba town, Oromia regional state, Ethiopia, were recruited in September - October 2014 and enrolled by a systematic sampling method. A facility-based cross-sectional study and two focus group discussions (FGDs) were conducted. Binary logistic regression and odds ratios were calculated to ascertain sociodemographic and other important information compared with the outcome variable and PMTCT/ANC, while the findings of the FGDs were grouped according to the emerging themes and analysed manually by means of a thematic approach. The percentage of male partners (22.7%) accompanying their spouses for HIV testing and counselling at antenatal clinics improved three-fold when an invitation letter was introduced as a new initiative to increase male participation. Individuals in the age group 15 -

29 years (adjusted odds ratio (AOR) 5.4, 95% confidence interval (CI) 1.66 - 17.85), and duration of marriage <5 years (AOR 5.6, 95% CI 1.83 - 17.30), were more likely to be tested than their referent groups. Men without a higher education (AOR 0.1, 95% CI 0.02 0.50) and who disagreed with legal enforcement (AOR 0.1, 95% CI 0.07 - 0.32) were less likely to be tested, while those who did not notify their partners (AOR 8.4, 95% CI 1.92 - 37.12) were more likely to use the service. Being busy, proxy testing, fears of testing HIV-positive, neglecting the importance of VCT, and inadequate knowledge about the PMTCT/ANC programme were other barriers that came to the fore in the FGDs. Identified barriers need to be addressed, and practices such as using invitation letters to increase the uptake of the service by male partners need to be instituted. BF 1. Gibbs L, Tooke L, Harrison MV. Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa. S Afr Med J 2017;107(10):900-903. https://doi.org/10.7196/SAMJ.2017.v107i10.12463 2. Wright CY, F Dominick F, Kunene Z, Kapwata T, Street RA. Bibliometric trends of South African environmental health articles between 1998 and 2015: Making local research visible and retrievable. S Afr Med J 2017;107(10):915-924. https://doi.org/10.7196/SAMJ.2017.v107i10.12429 3. Sengayi MM, Kielkowski D, Egger M, Dreosti L, Bohlius J. Survival of patients with Kaposi’s sarcoma in the South African antiretroviral treatment era: A retrospective cohort study. S Afr Med J 2017;107(10):871-876. https://doi.org/10.7196/SAMJ.2017.v107i10.12362 4. Alemayehu MT, Haidar J. Male involvement in prevention of mother-to-child transmission of HIV in the context of partner testing in Goba town, Ethiopia: A facility-based cross-sectional study. S Afr Med J 2017;107(10):864-870. https://doi.org/10.7196/SAMJ.2017.v107i10.11371

Conﬁdence Through Clinical and Real World Experience1-3 #1 Scripted Non-VKA Oral Anticoagulant by Cardiologists* Millions of Patients Treated Worldwide Across Multiple Indications4 REFERENCES: 1. Patel M.R., Mahaffey K.W., Garg J. et al. Rivaroxaban versus warfarin in non-valvular atrial fi brillation. N Engl J Med. 2011;365(10):883–91. 2. Tamayo S., Peacock W.F., Patel M.R., et al. Characterizing major bleeding in patients with nonvalvular atrial fi brillation: A pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol. 2015;38(2):63–8. 3. Camm A.J., Amarenco P., Haas S. et al. XANTUS: A Real-World, Prospective, Observational Study. 4. Calculation based on IMS Health MIDAS, Database: Monthly Sales January 2017. S4 Xarelto 15: Each film-coated tablet contains rivaroxaban 15 mg. Reg. No: 46/8.2/0111; Namibia NS2 : 12/8.2/0006; S2 Botswana: BOT1302296; Zimbabwe: PP10 Reg. 2017/10.2/5363 S4 Xarelto 20: Each film-coated tablet contains rivaroxaban 20 mg. Reg. No: 46/8.2/0112;Namibia NS2 : 12/8.2/0007; S2 Botswana: BOT1302297; Zimbabwe: PP10 Reg. 2017/10.2/5364 PHARMACOLOGICAL CLASSIFICATION: A.8.2 Anticoagulants. INDICATIONS: (1) Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (SPAF); (2) Treatment of deep vein thrombosis (DVT) and for the prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE); (3) Treatment of pulmonary embolism (PE) and for the prevention of recurrent pulmonary embolism (PE) and deep vein thrombosis (DVT). For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority (MCC). HCR: Bayer (Pty) Ltd, Co. Reg. No.: 1968/011192/07, 27 Wrench Road, Isando, 1609. Tel: 011 921 5044 Fax: 011 921 5041. L.ZA.MKT.GM 06.2017.1808 © Bayer June 2017 *Impact RX Data 2016 NOAC: Non Vitamin K Oral Anticoagulant

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CORRESPONDENCE

An approach to anaemia diagnosis – concerns in primary care

To the Editor: The approach to the diagnosis of anaemia[1] is a welcome addition to management of a common problem. A more nuanced approach may be warranted in primary care, where iron deficiency anaemia (IDA)[2] and anaemia of chronic disease (ACD) are common.[3,4] Iron administration is potentially deleterious in ACD associated with HIV[5] and tuberculosis (TB).[6]

Morphological v. biochemical approach

The diagnostic algorithm[1] reflects a contemporary morphological approach to anaemia utilising the reticulocyte response and mean corpuscular volume (MCV) as the starting point for evaluation.[7] Additionally, Alli et al.[1] propose that a blood film be done on all patients, but provide no evidence to support the diagnostic yield of this approach. In their algorithm for investigation of anaemia in HIV infection in southern Africa, Van den Berg et al.[8] do not advocate a blood film as routine. Nairz et al.[9] suggest that a blood film would be indicated primarily to diagnose conditions where there is an increased reticulocyte production index (RPI) or macrocytosis with a low RPI. Limiting the performance of smears would ensure that it is done when it is most useful, and reduce costs and laboratory workload. Assessment of red cell distribution width (RDW) was not discussed, but RDW can assist with diagnosis, generally being raised in IDA, vitamin B12 and folate deficiency and bone marrow disorders and normal in liver disease and alcohol use.[10] A second approach to anaemia is the use of biochemical tests as a starting point.[11,12] Reasons for this approach include the high prevalence of IDA and ACD, and the findings that up to 40% of patients with IDA can have a normal MCV,[13] that patients with dimorphic anaemia from combined nutritional deficiencies can also have a normal MCV, and that clinically important vitamin B12 deficiency can cause anaemia with a normal MCV.[14,15] A third approach is to combine biochemical testing (ferritin, vitamin B12 and folate) with morphological red blood cell indices for all patients.[8] There is no clarity on which approach is best in primary care. The third approach may be preferred in South Africa (SA), where nutrient deficiencies are common in females of reproductive age, e.g. a 15% prevalence of iron deficiency,[2] a 1.9% prevalence of folate deficiency and an 8.8% prevalence of vitamin B12 deficiency.[16]

Currently, National Health Laboratory Service (NHLS) reports give a normal range of ferritin of 13 - 150 µg/L for adult women and 30 400 µg/L for adult men. If clinicians use the lower limit of ferritin to exclude IDA in patients with or without inflammation, many patients with IDA will be untreated. It would assist generalists to have NHLS report ranges with narrative guidance. Newer tests such as soluble transferrin receptor (sTfR), sTfR/ log ferritin ratio, hepcidin, percentage of hypochromic red blood cells (%HRC) and reticulocyte haemoglobin content (CHr) can distinguish ACD from IDA, and can identify combined ACD and IDA.[9,12] sTfR is performed in the NHLS. %HRC and CHr are automatically calculated during full blood count analysis by some automated analysers available in the NHLS, but laboratory information systems may not be configured to extract the results. Guidelines should be available on the use of these tests in the public health sector.

TB as a cause of anaemia in patients with HIV

TB is the most common cause of moderate or severe anaemia in patients with HIV.[15,24] Current National Department of Health guidelines[25] recommend ruling out TB in patients with severe anaemia (haemoglobin concentration <8 g/dL[26]) and HIV infection and no clear cause, but do not specify which investigations to do. Extrapulmonary TB is as common as pulmonary TB in these patients,[27] so in addition to a chest radiograph and sputum Xpert MTB/RIF assay, it is important to consider an ultrasound scan of the abdomen, pericardium and lower chest.[28] In a recent series of 50 patients with severe anaemia and HIV infection in Mthatha, SA, 86% had clinical and/or bacteriologically confirmed and previously undiagnosed TB.[29] More research is needed into the prevalence and causes of anaemia in primary care in SA as well as performance characteristics of tests for anaemia, to inform a context-specific evidence-based diagnostic approach to this condition. D O’Mahony, M Mntonintshi Department of Family Medicine and Rural Health, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa donomahony@gmail.com

A G Parrish Department of Internal Medicine, Faculty of Health Sciences, Walter Sisulu University, Mthatha, and Cecilia Makiwane Hospital, East London, South Africa

Diagnosis of iron deficiency anaemia

In the absence of inflammation, ferritin is the most sensitive, specific and cost-effective test for iron deficiency[17,18] and can be used alone for confirmation.[19] However, while a ferritin level of ≤15 µg/L is very specific for iron deficiency, iron deficiency can only be ruled out when the ferritin level is >100 µg/L.[17] In adults with a ferritin level of 35 - 44 µg/L, the positive likelihood ratio for iron deficiency is 1.83. [20] It may be appropriate to rule out unsuspected inflammation by measurement of C-reactive protein.[21]

Diagnosis of anaemia of chronic disease

The diagnosis is currently one of exclusion.[17] As ferritin levels increase with inflammation, it can be difficult to differentiate between IDA and ACD, particularly when they coexist.[18] The ferritin level for ruling out iron deficiency depends on the disease. In heart failure, iron deficiency can be diagnosed if the ferritin level is <100 µg/L, or <300 µg/L with transferrin saturation (TSAT) <20%.[22] In chronic kidney disease, iron deficiency can be diagnosed if ferritin is <100 µg/L, or <200 µg/L with TSAT <20%.[23]

1. Alli N, Vaughan J, Patel M. Anaemia: Approach to diagnosis. S Afr Med J 2017;107(1):23-27. https:// doi.org/10.7196/SAMJ.2017.v107i1.12148 2. Shisana O, Labadarios D, Rehle T, et al. South African National Health and Nutrition Examination Survey (SANHANES-1). Cape Town: HSRC Press, 2013. 3. Walsh CM, Hattingh Z, Veldman FJ, et al. Iron status and anaemia of chronic disease in HIV-infected African women in Mangaung, Bloemfontein. S Afr Fam Pract 2010;52(1):55-59. https://doi.org/10.10 80/20786204.2010.10873936 4. Van Staden AM, Weich DJ. Retrospective analysis of the prevalence and causes of anaemia in hospitalised elderly patients. S Afr Fam Pract 2015;57(5):297-299. https://doi.org/10.1080/20786190 .2015.1071538 5. Gordeuk VR, Delanghe JR, Langlois MR, et al. Iron status and the outcome of HIV infection: An overview. J Clin Virol 2001;20(3):111-115. https://doi.org/10.1016/S1386-6532(00)00134-7 6. Boelaert JR, Vandecasteele SJ, Appelberg R, et al. The effect of the host’s iron status on tuberculosis. J Infect Dis 2007;195(12):1745-1753. https://doi.org/10.1086/518040 7. Means R, Glader B. Anemia: General considerations. In: Greer JP, Arber DA, Glader B, et al., eds. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia: Lippincott, Williams & Wilkins, 2014. 8. Van den Berg K, van Hasselt J, Bloch E, et al. A review of the use of blood and blood products in HIVinfected patients. S Afr J HIV Med 2012;13(2):87-104. https://doi.org/10.4102/SAJHIVMED.v13i2.146 9. Nairz M, Theurl I, Wolf D, et al. Iron deficiency or anemia of inflammation? Wien Med Wochenschr 2016;166(13-14):411-423. https://doi.org/10.1007/s10354-016-0505-7 10. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clinic Proc 2005;80(7):923-936. https://doi.org/10.4065/80.7.923 11. Goodnough LT, Shander A. In reply. Anesthesiology 2013;118(1):223-224. https://doi.org/10.1097/ ALN.0b013e318276c2c8 12. Kerkhoff AD, Meintjes G, Opie J, et al. Anaemia in patients with HIV-associated TB: Relative contributions of anaemia of chronic disease and iron deficiency. Int J Tuberc Lung Dis 2016;20(2):193-201. https://doi.org/10.5588/ijtld.15.0558

October 2017, Print edition

CORRESPONDENCE

13. Bermejo F, Garcia-Lopez S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol 2009;15(37):4638-4643. https://doi.org/10.3748/ wjg.15.4638 14. Carmel R. Pernicious anemia: The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking. Arch Intern Med 1988;148(8):1712-1714. https://doi.org/10.1001/ archinte.1988.00380080016007 15. Lewis DK, Whitty CJM, Walsh AL, et al. Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence. Trans R Soc Trop Med Hyg 2005;99(8):561-567. https://doi.org/10.1016/j.trstmh.2005.01.002 16. Modjadji S, Alberts M, Mamabolo R. Folate and iron status of South African non-pregnant rural women of childbearing age, before and after fortification of foods. S Afr J Clin Nutr 2007;20(3):89-93. https://doi.org/10.1080/16070658.2007.11734132 17. DeLoughery TG. Microcytic anemia. N Engl J Med 2014;371(14):1324-1331. https://doi.org/10.1056/ NEJMra1215361 18. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;372(19):1832-1843. https://doi. org/10.1056/NEJMra1401038 19. Short MW, Domagalski JE. Iron deficiency anemia: Evaluation and management. Am Fam Physician 2013;87(2):98-104. 20. Guyatt GH, Oxman AD, Ali M, et al. Laboratory diagnosis of iron-deficiency anemia. J Gen Intern Med 1992;7(2):145-153. 21. Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis 2015;9(3):211-222. https://doi.org/10.1093/ecco-jcc/jju009 22. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361(25):2436-2448 https://doi.org/10.1056/NEJMoa0908355

23. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: A randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014;29(11):2075-2084. https://doi.org/10.1093/ndt/gfu201 24. Kerkhoff AD, Wood R, Cobelens FG, et al. The predictive value of current haemoglobin levels for incident tuberculosis and/or mortality during long-term antiretroviral therapy in South Africa: AÂ cohort study. BMC Med 2015;13(1):70. https://doi.org/10.1186/s12916-015-0320-9 25. National Department of Health, South Africa. National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV (PMTCT) and the Management of HIV in Children, Adolescents and Adults. Pretoria: NDoH, 2015. 26. World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and mineral nutrition information system. WHO/NMH/NHD/MNM/11.1. Geneva: WHO, 2011. 27. Sharma S, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316-353. 28. Heller T, Wallrauch C, Goblirsch S, et al. Focused assessment with sonography for HIV-associated tuberculosis (FASH): A short protocol and a pictorial review. Crit Ultrasound J 2012;4(1):21. https:// doi.org/10.1186/2036-7902-4-21 29. Mntonintshi M, Oâ&#x20AC;&#x2122;Mahony D, Mabunda S, et al. Undiagnosed tuberculosis in patients with HIV infection who present with severe anaemia at a district hospital. Afr J Prim Health Care Fam Med 2017;9(1):e1-e6. https://doi.org/10.4102/phcfm.v9i1.1406

S Afr Med J 2017;107(10):808-809. DOI:10.7196/SAMJ.2017.v107i10.12809

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30 days in medicine Lower risk of rheumatoid arthritis with oral contraceptive pill

A large Swedish study has found that women who take the oral contraceptive pill are at reduced risk of developing rheumatoid arthritis. Taking the oral contraceptive pill for ≥7 years was linked to the lowest risk of the disease – a 19% reduction. The study was led by the Karolinska Institute, Stockholm, Sweden, and enrolled 5 578 women with rheumatoid arthritis and 4 129 agematched controls. Any link between breastfeeding among women who had given birth to at least one child was also studied. Researchers looked for anti-citrullinated protein antibodies (ACPAs), which are a blood marker for rheumatoid arthritis. Results showed that any use of the contraceptive pill was linked to a reduced risk of developing ACPA-positive rheumatoid arthritis. A lower risk of developing rheumatoid arthritis that was noticed in women who had breastfed was not significant. Orellana C, Saevarsdottir S, Klareskog L, et al. Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: Results from the Swedish EIRA study. Ann Rheum Dis 2017 (epub 17 August 2017). https://doi.org/10.1136/annrheumdis-2017-211620

Still large numbers of children under 5 dying of tuberculosis

Nearly 200 000 children aged <5 years died from tuberculosis (TB) in 2015, most in sub-Saharan Africa, a study published in Lancet Global Health has shown. Researchers from the University of Sheffield, UK, using mathematical modelling to show death rates from TB in under-5s for the first time, found that 239 000 children aged ≤14 died of TB in 2015 and 80% of these were aged <5. This high number of deaths implies that TB should rank as a major cause of death in children aged <5 years worldwide. In fact, the number of deaths is likely to be higher, because some deaths from pneumonia, meningitis or AIDS may be caused by TB. The data also showed that 17% of children who died of TB were HIV-positive. More than 90% of the deaths were in children who were not receiving TB treatment, meaning that more needs to be done to identify children at risk of disease, diagnose their condition and treat them correctly. Dodd PJ, Yuen CM, Sismanidis C, Seddon JA, Jenkins HE. The global burden of tuberculosis mortality in children: A mathematical modelling study. Lancet Glob Health 2017;358:e898-e906. https://doi. org/10.1016/S2214-109X(17)30289-9

Alternative cancer treatment linked to greater risk of death

Johnson SB, Park HS, Gross CP, Yu JB. Use of alternative medicine for cancer and its impact on survival. J Natl Cancer Inst 2017 (epub 10 August 2017). https://doi.org/10.1093/jnci/djx145

‘Five a day’ may be more than we need

The recent PURE (Prospective Urban Rural Epidemiology) study suggests that, while high fruit and vegetable consumption is associated with a lower risk of non-cardiovascular and total mortality, the maximum benefits appear at three to four servings a day. The study followed 135 335 individuals without cardiovascular disease from 613 communities in 18 low-, middle- and high-income countries in North America and Europe, South America, the Middle East, south Asia, China and southeast Asia and Africa between 2003 and 2013. Country-specific food questionnaires were collected, along with information on smoking and other lifestyle factors. Overall, 3.9 servings of fruit, vegetables and legumes were eaten daily, and there was no decrease in cardiovascular or other disease with higher daily consumption. Fruit consumption was specifically associated with a lower risk of all-cause mortality, legumes with a lower risk of cardiovascular mortality, and raw vegetables with a lower risk of total mortality. The number of servings associated with maximum benefits are equivalent to 375 - 500 g/day. Miller V, Mente A, Dehghan M, et al. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): A prospective cohort study. Lancet 2017 (epub 29 August 2017). https://doi. org/10.1016/S0140-6736(17)32253-5

The sole use of alternative medicine therapies by patients with cancer results in more than twice the risk of death from the disease compared with death rates associated with conventional cancer treatment. A study published in JNCI: Journal of the National Cancer Institute and carried out by Skyper B Johnson and colleagues from the Yale

School of Medicine identified 281 patients from the US National Cancer Database from 2004 to 2013 with breast, prostate, lung or colorectal cancer who chose alternative medicine therapy as their only anticancer treatment. Patients with metastatic disease were not included. The survival rates of patients who chose alternative medicine were compared with those of 560 matched patients who underwent conventional cancer treatment, defined as chemotherapy, radiotherapy, surgery or hormone therapy. Alternative medicine was defined as treatment coded in the database as ‘other or unproven: cancer treatments administered by nonmedical personnel’. The median follow-up was 66 months. The risk varied by type of cancer, the worst outcomes being among those who chose alternative therapy to treat breast cancer, followed by colorectal and lung cancer. Prostate cancer appeared not to be affected, possibly because of the long natural history of the disease and the short median follow-up period.

B Farham Editor ugqirha@iafrica.com

October 2017, Print edition

Tax benefits

of retirement annuities and

Tax-Free Savings Accounts

By Roenica Tyson, Investment Product Manager at Glacier by Sanlam Findings from the Sanlam A Survey show that many retirees’ income – even in the affluent market – is not keeping pace with inflation, leading to a reduction in the buying power of their post-retirement incomes. This points to the necessity of supplementing the savings you have in your employer’s pension and/or provident fund.

A retirement annuity, or RA, is an ideal vehicle for this purpose. Investors can receive tax benefits by investing up to 27.5% of the higher of their taxable income or remuneration into retirement savings products (RAs, pension and/or provident funds). The tax-deductible amount is capped at R350 000 per year. Re-investing the tax saving can significantly increase the final value of your investment. In addition, while saving in an RA, you don’t pay tax on any interest or dividends, and no capital gains tax is applicable on the growth in the investment. Depending on the investment platform, investors can select from a wide choice of underlying investments in their RA, including risk-profiled investment funds, local or foreign funds, actively managed or passive index-tracking funds, single manager or multi-manager funds, as well as an individual share portfolio or exchange traded funds. The maximum exposure to asset classes, however, is governed by Regulation 28 of the Pension Funds Act. Current limits include a 75% maximum exposure to equities, 25% to property and 25% to offshore investments, although an extra 5% can be invested in Africa. Investors have until the end of February each year to take advantage of the tax benefits for that particular tax year, by adding a lump sum to their RAs.

Tax-Free Savings Accounts – a vital part of any investment portfolio The benefits of Tax-Free Savings Accounts (TFSAs) are well-known by now – no tax on interest or dividends received, and no capital gains tax or tax on funds withdrawn. Making a TFSA work for you to your best advantage, and within the context of your overall investment portfolio, requires some consideration and professional financial advice in this regard is invaluable. It will take investors 15 years to reach the maximum lifetime contribution limit of R500 000 to their TFSA. While you can access the money at any time, any amount withdrawn will be regarded as a further contribution (towards your lifetime contribution limit) when re-invested in the TFSA. Given this negative impact of withdrawals on your contribution limit, your TFSA should be viewed as more of a long-term investment; there are other investment vehicles more suited to short-term savings or emergency funds.

Other important considerations involve weighing up contributions into a TFSA versus a regular investment plan, as well as into a TFSA versus a retirement annuity.

TFSA vs Investment Plan If an investor is currently investing, for example, R5 500 a month into a discretionary savings plan, it will make financial sense to split the investment, i.e. invest R2 750 into the discretionary savings plan and R2 750 into a tax-free savings plan in order to utilise the tax benefits of the TFSA.

TFSA vs Retirement Annuity Weighing up contributions to a retirement annuity (RA) versus a tax-free savings account is a slightly more complex decision. Together with your adviser, you need to look at the advantages and disadvantages from a tax perspective. While for both options the growth within the product is free of dividends tax, income tax on interest and capital gains tax, only contributions into an RA are tax-deductible. The TFSA will, however, offer more flexibility in terms of access to money, whereas RA funds can only be accessed from age 55 upwards. Lump sum withdrawals from RAs are only tax free up to certain limits, while there is no tax when withdrawing from a TFSA. However, it needn’t necessarily be an ‘either/or’ choice. Using the two in combination can deliver superior results.

Investing on behalf of your children Parents can also open tax-free savings plans for their children, i.e. a family of four, with two children, can save up to R132 000 tax free (in the 2017 tax year). This is an ideal way to save for a child’s education and can also help to cultivate a savings ethic from a young age. Note that when investing on behalf of your children or transferring an investment to them, donations tax of 20% of the amount donated is payable. Investors, however, have an annual donations tax exemption of R100 000. Investors are encouraged to consult with a qualified financial adviser to ensure their investment portfolio is in line with their personal circumstances and risk profile.

To find out about our unique solutions for professionals, contact Sanlam on 0860 118 888 or send an e-mail to prof@sanlam.co.za and we will call you.

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Supplementing your retirement savings with a retirement annuity

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2017/09/21 10:13 AM

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BOOK REVIEW

Accident

By Dawn Garisch. Cape Town: Modjaji Books, 2017. ISBN: 978-1928215-33-2 Dawn Garisch lives in the Cape Peninsula, and is a prize-winning writer of poetry, novels and non-fiction. She is also a general medical practitioner.

This book is set in the Cape Peninsula, and the main interaction happens between Carol, a general practitioner, and her son Max, a performance artist. Carol is an overconcerned, rather obsessional mother and doctor, who (like many in the profession) pays little heed to her own health. Max, in a very different way, also pays no heed to his own health (or safety) while attempting to bring an awareness of significant problems to his viewers’ attention. Dawn’s description of Carol’s Surgery will evoke a sense of familiarity in fellow practitioners. The title, Accident, refers, I assume, to five different episodes involving Max or Carol, and through the course of the book one becomes aware of, and sympathetic to, the very different (from each other) ways in which this mother and son live their lives. Problems that engross her do not seem significant to him, and she initially finds it difficult to value his take on life. Over the course of the book, this changes, but in unexpected ways. By its nature, performance art is transgressive and in your face, and it is this quality that makes one wince while reading the novel, but also, if one is open to it, reassess one’s own moral certitude. Why Max has chosen to live on the edge in terms of his

October 2017, Print edition

art becomes clearer late in the book, and no moral judgement is given by the author. This gives thinking readers the opportunity to react freely to the material. The book leaves a number of issues opaque, which enhances the engaged reader’s enjoyment and will generate discussion, such as around how the psychiatrist-in-training behaves, why Carol has never married and how the accident involving his friend affected Max’s choice of career. The author mostly leaves space for the reader’s imagination, and the way the story ends is both unexpected and powerful. Although surprising from what we have come to know of the characters, it is congruent with the changes that have been wrought in both Carol and Max through their consciously suffering in their various ways. This is a good read and one that will get you thinking about both art and medicine. It is also one that will touch readers emotionally, so, for the ending at least, have some tissues handy. Paul Ashton Psychiatrist and Jungian psychoanalyst in parttime private practice, Heidelberg,Western Cape, South Africa paulwashton@gmail.com

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

CME

GUEST EDITORIAL

Introduction of the contraceptive implant in South Africa: Successes, challenges and the way forward In 2014, the contraceptive implant was introduced into public sector facilities in South Africa (SA). Several thousand healthcare workers were trained, and demand was generated for the method, achieving high uptake. Use of the implant has since declined, but currently accounts for ~7% of all contraceptive use – a not insignificant achievement for a ‘new’ method.[1,2] In this edition of SAMJ, three articles[3-5] take stock of the early years of implant provision in SA. The articles, based on research in 2016, capture women’s motivations for using the implant and their perspectives towards the method; and healthcare providers’ competencies and experiences with service provision. Insights may be generalisable to family planning services more broadly, but are also relevant to the introduction of other new technologies, especially those related to HIV.

Counselling and choice

As the implant was a ‘new’ method in the public health sector, one would have expected providers to give women detailed information about the benefits, potential side-effects and steps to follow should problems arise. This was not always the case, as pointed out by Pillay et al.[3] in this issue of SAMJ. For example, only about half of the clients interviewed in Johannesburg and the North West Province recalled being warned about side-effects, the principal cause of implant discontinuation. Moreover, only about a quarter remembered being informed about the method’s remarkable contraceptive effectiveness, the attribute that takes centre-place in family-planning counselling in many other countries.[6,7] Models, leaflets and flip charts can be used to facilitate such discussions.[8] In many settings, information about contraceptive methods is simply presented verbally – from most to least effective, beginning with the implant.[6,7] Among women who experience heavy or prolonged bleeding while using the implant, the decision to continue the method seems contingent on the dynamics of their relationship with their partner and the level of sexual activity. These issues need to be foregrounded in counselling for this group of women.[9,10] Encouragingly, Pillay et al.[3] found that many women had negotiated implant insertion, and indeed removal, with their partners. Others chose clandestine use, allowing them to use the implant without knowledge of their partners. Providers could raise this as an option, but then must inform women to consider the possibility of conflict with their partner, even violence, should the device be discovered. Clearly, providers’ confidence and competence to deliver a new contraceptive are critical to its success, as discussed by Adeagbo et al.[4] in a study of nurses in this edition of SAMJ. They found that providers generally felt inadequately prepared to carry out counselling, offer follow-up support and undertake removals. They ascribed these gaps mostly to deficiencies in training and, in particular, to the use of ‘cascade’ training methods. Even though the study did not directly examine providers’ willingness to offer the implant and changes in attitudes over time, reluctance to provide the contraceptive appears to be growing in the public sector, as negative experiences with the implant accrue. The promotion of specific methods over others is often justifiable, especially when a method holds compelling advantages for certain groups. In many settings, the implant is considered as ‘first-line’ for women within 48 hours of childbirth or after an abortion, as well as

for adolescents and young women.[6,11-13] The study by Pillay et al.,[3] however, found no evidence that the youth were being targeted; only ~15% of participants were aged 18 - 24 years, the age group with the highest unmet need for contraception.[1,14] Targeted implant provision is needed and creative approaches are called for. One possibility is to integrate implant provision into She Conquers,[15] a national campaign recently launched to address high rates of HIV, teen pregnancy, gender violence and school attrition among adolescent girls and young women in SA. Care must be taken to ensure that targeting does not occur simply on the basis of socioeconomic class, though. There is some evidence that such profiling is already occurring, with the income and educational levels of women who use the implant being considerably higher than those of the average woman in SA. This raises the question of whether providers are encouraging implant use among women of higher socioeconomic status, but favouring injectable contraceptives when counselling poorer clients.[14,16]

Misconceptions and demand creation

It is worth considering why instances of side-effects and implant removals spurred negative attention and press in SA, even though these seem similar to incidence rates elsewhere. Much of this may be related to the care and support provided to women who complain of side-effects, who are often told to persevere or wait for symptoms to settle, rather than being actively managed.[17] Both the women and nurses interviewed noted gaps in services for women who experienced side-effects. Providers need to be better equipped to precounsel women about anticipating side-effects, particularly bleeding changes. The highly variable treatment of problematic or intolerable bleeding by providers is a direct reflection of the lack of a standardised, evidence-based guideline on the medical management of these symptoms. In other settings, providers follow a clinical algorithm, laying out the counselling, treatment options and follow-up strategies for side-effects.[18,19] Bleeding in conjunction with other side-effects is particularly problematic, and needs to be addressed proactively.[20,21] Women who tolerate a significant amount of discomfort and inconvenience on the basis of advice from providers, may become justifiably angry about the care received and antagonistic towards the method itself. Other women who learn of these experiences understandably form negative impressions of the implant.[22] Equally, the voices of satisfied clients, who comprise the large majority of women who insert the implant, must be allowed to shape the public discourse about the method.[23] Even though few women cited pamphlets, television or social media as direct sources of information about the implant, these media could play an important role in reinforcing the testimonies of women who are satisfied with the method, and in counteracting negative perceptions and rumours before these become entrenched. Demand-creation efforts around the time of introducing the implant in SA, successfully generated positive impressions of the method. These efforts need to be redoubled, drawing on lessons from these early years.

Programme monitoring

Having actionable data is especially important when a new contraceptive method is introduced. A method’s long-term success is often determined in these first years – indeed, delays in detecting

October 2017, Print edition

CME

and rectifying problems in the past have resulted in many other methods being discarded.[24] An article by Pillay et al.,[5] published in this edition of SAMJ, examines the data-monitoring systems used in facilities, noting considerable gaps. A range of tools were being used to record insertions, while data were seldom captured on removals, and pharmacovigilance data not at all. Providers had developed their own registers, while the National Department of Health tools had been used in some facilities, but not in others, or different versions of the same tool were being used. Consequently, the actual numbers of insertions, incidence of complications, rates of removal and reasons for removal are largely unknown. Encouragingly, since the evaluation, many of these gaps in monitoring are being actively addressed.

Conclusion

Action is needed to ensure that the considerable gains made in the introductory phase of the implant translate into sustained uptake of the method in the long run. The potential of the implant to make a major contribution to reducing unintended pregnancies in SA is beginning to be realised, but gains could be substantially extended. Although commendable efforts were made to train healthcare workers with regard to implant use when it was first introduced in 2014, refresher training is currently required. Key topics that have to be emphasised are counselling on the method’s effectiveness and side-effects, specific groups to target, management of side-effects and removal skills. Providers require clarity on implant use in women taking efavirenz. Even though levels of etonogestrel and therefore the contraceptive effectiveness of the implant are lowered in these women, they still have lower rates of pregnancy than women using other contraceptives, such as injectables.[25] Also, healthcare workers need to be reminded that the women they consult at clinics are those who have side-effects, and that the majority are highly satisfied with the method and do not return to the clinic. This predominance of visits for side-effects may well account for negative perceptions among providers towards the implant. It is worth investing in demand generation; the implant offers 3 years of highly effective protection against pregnancy, making it very cost effective. Targeting men is also important, given that many women consulted their partners prior to use and men held considerable influence over continuation. Data collected in one standardised tool, capturing a limited number of carefully selected variables, could guide improvements in the post-introductory phase. Robust monitoring data could trigger support for areas with low uptake, or training regarding management of side-effects in areas with high discontinuation rates. A sense of urgency is required to implement the recommended actions. The worst-case scenario – withdrawal of the implant from the method mix owing to dwindling uptake – is not as implausible as it might seem. Difficulties with new methods, when left unaddressed, often lead to their discontinuation.[24] Moreover, the possibility that depot medroxyprogesterone acetate will be withdrawn from the method mix owing to its association with HIV acquisition, provides a particularly compelling reason for shoring up the performance of implant provision.[15] Importantly, the findings in this series pose searching questions about the performance of the family-planning programme in general. It is time to consider the inclusion of contraception in the package of services available in the postpartum ward, HIV clinics and several other clinical settings. The traditional approach of restricting the provision of contraception to familyplanning clinics may well be responsible for the slow progress made in reducing unintended pregnancies in the country. Acknowledgements. We thank Fiona Scorgie for reviewing earlier drafts of the editorial.

S Mullick Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa smullick@wrhi.ac.za

M F Chersich Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Y Pillay National Department of Health, Pretoria, South Africa

H Rees Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1. National Department of Health, Statistics South Africa, South African Medical Research Council, and the DHS Program, Inner City Fund. South Africa Demographic and Health Survey 2016: Key Indicators. Pretoria: Stats SA, 2017. 2. Massyn N, Peer N, English R, et al. District Health Barometer 2015/16. Durban: Health Systems Trust, 2016. 3. Pillay D, Chersich MF, Morroni C, et al. User perspectives on Implanon NXT in South Africa: A survey of 12 public-sector facilities. S Afr Med J 2017;107(10):815-821. https://doi.org/10.7196/SAMJ.2017.v107i10.12833 4. Adeagbo OA, Mullick S, Pillay D, et al. Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of health workers. S Afr Med J 2017;107(10):822-826. https://doi.org/10.7196/ SAMJ.2017.v107i10.12821 5. Pillay D, Morroni C, Pleaner M, et al. Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts. S Afr Med J 2017;107(10):827-831. https://doi. org/10.7196/SAMJ.2017.v107i10.12822 6. Committee on Adolescence. Contraception for adolescents. Pediatrics 2014;134(4):e1244-e1256. https:// doi.org/10.1542/peds.2014-2299 7. Madden T, Mullersman JL, Omvig KJ, Secura GM, Peipert JF. Structured contraceptive counseling provided by the Contraceptive CHOICE Project. Contraception 2013;88(2):243-249. https://doi. org/10.1016/j.contraception.2012.07.015 8. Modesto W, Bahamondes MV, Silva dos Santos P, Fernandes A, Dal’Ava N, Bahamondes L. Exploratory study of the effect of lifestyle counselling on bone mineral density and body composition in users of the contraceptive depot-medroxyprogesterone acetate. Eur J Contracept Reprod Health Care 2014;19(4):244249. https://doi.org/10.3109/13625187.2014.924098 9. Minnis AM, Mavedzenge SN, Luecke E, Dehlendorf C. Provider counseling to young women seeking family planning services. Perspect Sexual Reprod Health 2014;46(4):223-231. https://doi. org/10.1363/46e1414 10. Rominski SD, Morhe ESK, Maya E, Manu A, Dalton VK. Comparing women’s contraceptive preferences with their choices in 5 urban family planning clinics in Ghana. Glob Health Sci Pract 2017;5(1):65-74. https://doi.org/10.9745/GHSP-D-16-00281 11. Sothornwit J, Werawatakul Y, Kaewrudee S, Lumbiganon P, Laopaiboon M. Immediate versus delayed postpartum insertion of contraceptive implant for contraception. Cochrane Database Syst Rev 2017;(4):CD011913. https://doi.org/10.1002/14651858.CD011913.pub2 12. Secura GM, Allsworth JE, Madden T, Mullersman JL, Peipert JF. The Contraceptive CHOICE Project: Reducing barriers to long-acting reversible contraception. Am J Obstet Gynecol 2010;203(2):e1-e7. https://doi.org/10.1016/j.ajog.2010.04.017 13. Hognert H, Kopp Kallner H, Cameron S, et al. Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion – a randomized controlled equivalence trial. Hum Reprod 2016;31(11):2484-2490. https://doi.org/10.1093/humrep/dew238 14. Chersich MF, Wabiri N, Risher K, et al. Contraception coverage and methods used among women in South Africa: A national household survey. S Afr Med J 2017;107(4):307-314. https://doi.org/10.7196/ SAMJ.2017.v107i4.12141

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15. She Conquers. http://sheconquerssa.co.za/ (accessed 7 September 2017). 16. Volscho T. Racism and disparities in women’s use of the Depo-Provera injection in the contemporary USA. Crit Sociol 2011;37(5):673-688. https://doi.org/10.1177/0896920510380948 17. Obijuru L, Bumpus S, Auinger P, Baldwin CD. Etonogestrel implants in adolescents: Experience, satisfaction, and continuation. J Adolesc Health 2016;58(3):284-289. https://doi.org/10.1016/j. jadohealth.2015.10.254 18. Faculty of Sexual and Reproductive Healthcare. Problematic Bleeding with Hormonal Contraception. UK: FSRH, 2015. 19. Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep 2016;65(4):1-66. https://doi.org/10.15585/mmwr.rr6504a1 20. Hoggart L, Newton VL. Young women’s experiences of side-effects from contraceptive implants: A challenge to bodily control. Reprod Health Matters 2013;21(41):196-204. https://doi.org/10.1016/s09688080(13)41688-9 21. Hoggart L, Newton VL, Dickson J. ‘I think it depends on the body, with mine it didn’t work’: Explaining young women’s contraceptive implant removal. Contraception 2013;88(5):636-640. https://doi. org/10.1016/j.contraception.2013.05.014

22. Inoue K, Kelly M, Barratt A, et al. Australian women’s attitudes towards and understandings of the subdermal contraceptive implant: A qualitative study of never-users. J Fam Plann Reprod Health Care 2017;43(2):128-134. https://doi.org/10.1136/jfprhc-2014-101132 23. Duvall S, Thurston S, Weinberger M, Nuccio O, Fuchs-Montgomery N. Scaling up delivery of contraceptive implants in sub-Saharan Africa: Operational experiences of Marie Stopes International. Glob Health: Sci Pract 2014;2(1):72-92. https://doi.org/10.9745/ghsp-d-13-00116 24. Pleaner M, Morroni C, Smit J, et al. Lessons learnt from the introduction of the contraceptive implant in South Africa. S Afr Med J 2017;107(11). (Accepted for publication.) https://doi.org/10.7196/SAMJ.2017. v107i11.12805 25. Patel RC, Morroni C, Scarsi KK, Sripipatana T, Kiarie J, Cohen CR. Concomitant contraceptive implant and efavirenz use in women living with HIV: Perspectives on current evidence and policy implications for family planning and HIV treatment guidelines. J Int AIDS Soc 2017;20(1):1-6. https:// doi.org/10.7448/IAS.20.1.21396

S Afr Med J 2017;107(10):812-814. DOI:10.7196/SAMJ.2017.v107i10.12849

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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User perspectives on Implanon NXT in South Africa: A survey of 12 public-sector facilities D Pillay,1 MPH; M F Chersich,1 MB BCh, PhD; C Morroni,1,2,3,4 MB ChB, DFSRH, DTM&H, MPH, MSc, PhD; M Pleaner,1 MEd; O A Adeagbo,1 MA, PhD; N Naidoo,1 MPH; S Mullick,1 MB ChB, MSc, MPH, PhD; H Rees,1 MB BChir, MA (Cantab), MRCGP, DCH, DRCOG Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Women’s Health Research Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 EGA Institute for Women’s Health and Institute for Global Health, University College London, UK 4 The Botswana-UPenn Partnership, Gaborone, Botswana 1 2

Corresponding author: D Pillay (dianthapillay@gmail.com) Background. Implanon NXT, a long-acting reversible contraceptive, was introduced in South Africa (SA) in early 2014, aiming to expand the method mix and increase its effectiveness. Initial uptake was high, but has since declined considerably. In these early years after the implant’s introduction, it is important to identify reasons for the decline, and remedy gaps in services. Objectives. To determine periods of use, reasons for the use and early removal of the implant Implanon NXT. Methods. In 2016, we recruited 152 women from six clinics in the City of Johannesburg, and six in North West Province, SA. A semistructured interview was administered to 91 women currently using the implant and 61 previous users. We examined user perspectives, factors influencing women’s experiences with the implant and reasons for discontinuation. Results. The participants’ mean age was 30 years, with only 15% aged <25. Implant uptake was motivated by convenience (less frequent visits required than for short-acting methods) and by favourable views of the method among friends, family and healthcare providers. Only about a quarter of women recalled being counselled pre-insertion about implant effectiveness, and half about side-effects pre-insertion. Among discontinuers, the median time to device removal was 8 months (interquartile range 6 - 12), and this was primarily as a result of sideeffects (90%), especially bleeding-pattern changes and headaches. Removals were most common among married and cohabiting women, often ascribed to the effects of bleeding on their sexual relationships. Rumours and misinformation contributed to some removals. Overall, women’s experiences with the implant were rated ‘good’ or ‘very good’ by 74% of those continuing use, many of whom reported not having experienced any side-effects or that these had diminished over time. Conclusion. Levels of acceptability among continuing users were high, mainly linked to the method’s convenience. While early favourable views drove uptake, negative perceptions, if unaddressed, may now undermine services. Deficiencies in counselling around effectiveness and side-effects may extend to contraceptive services more generally. Women require more intensive support when experiencing sideeffects, including effective systematic approaches to ameliorating bleeding and headaches. Implant services could specifically target young women and first-time contraceptive users. These actions together could reverse the persistent decline in implant use in SA. S Afr Med J 2017;107(10):815-821. DOI:10.7196/SAMJ.2017.v107i10.12833

Implanon NXT, a single-rod subdermal contraceptive implant, is one of the most effective contraceptive methods available.[1] As a longacting reversible contraceptive (LARC), it is not dependent on user adherence for effectiveness.[2] High levels of uptake and acceptability have been reported worldwide.[3,4] The implant was introduced into the South African (SA) national contraception programme in early 2014, aiming to expand the contraceptive method mix and increase access to LARCs.[5] In the Demographic and Health Survey 2016, about 4% of sexually active women in the country were using the implant.[6] As with the introduction of any new contraceptive method into a national programme, it is critical to evaluate the experiences and perspectives of users in the early years after its introduction.[7] This evaluation was especially pressing given mounting concerns in the media and among healthcare providers in SA around the performance of implant services and declines in uptake.[8] Using a mixed-methods approach, we conducted a survey of implant users in two districts of SA. This study, one component of a larger evaluation of the implant programme, sought to identify shortcomings in the current services, and the steps required to improve users’ experiences.

Methods

Participant recruitment

We selected 12 primary healthcare facilities providing contraceptive services: six in the City of Johannesburg, Gauteng Province, and six in North West Province. The methods used to select the facilities and the results of other components of the evaluation have been detailed elsewhere.[9,10] We extracted contact details of women aged >18 years who had had an implant inserted since 2014 (n=751). In total, 262 of these women agreed to be interviewed, with the remainder either not contactable (telephone number not recorded or invalid), or not willing to participate. Owing to difficulties in finding a mutually convenient time for interview, or because a woman did not attend a scheduled appointment, only 152 of these women were interviewed (20% of the potentially eligible 751). A fieldworker conducted semistructured interviews face-to-face between June and November 2016. The interviews were held at the facility where the woman had had the implant inserted (Gauteng n=93, North West n=59). The study was approved by the University of the Witwatersrand Human Research Ethics Committee (ref. no. M151147), and permission for the study was granted by the District Research

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Committee of the City of Johannesburg (ref. no. 2015-16/048), and provincial ethics committee of the North West Province Department of Health (ref. no. NW_2015RP29_838). All participants provided written informed consent, and were reimbursed ZAR50 (~USD4) for their transport expenses.

Study tools and data analysis

We collected data on women’s sociodemographic, reproductive and contraceptive history, motivations for implant use, partner negotiation around use, counselling received, duration of implant use and experiences with the method. Women were asked if they knew how the implant works to prevent pregnancy, and for how long the implant could be used. Those who had removed the implant were questioned about the timing of the removal, reasons for discontinuing the method and subsequent contraception use. Overall experiences of the implant were assessed using a 5-point Likert scale ranging from ‘very bad’ to ‘very good’, and by asking women whether they thought the implant was better or worse than a range of other contraceptive methods. Women were asked several open-ended questions, enabling them to narrate their experiences in their own words. For example, women were requested to explain the rating they had given when they had scored the implant on the Likert scale. Data collectors captured women’s free text responses on the questionnaire. In some instances, a categorical variable was derived by categorising the free-text responses based on common themes identified in the text. In our analysis, we sought to describe women’s experiences and to contrast the perspectives of women who had continued implant use (‘users’) with those who had removed it (‘removers’), drawing on a World Health Organization analytical framework.[11] To determine whether the characteristics and perspectives of users and removers differed, we used χ2 tests to compare categorical variables, and Student’s t-tests or Wilcoxon rank sum tests for continuous variables, as appropriate. We then examined the full text responses, and used them to contextualise and interpret the quantitative data. Participant quotes were selected to illustrate key findings.

Results

Users (n=91) had inserted the implant a median 24 months ago, while removers (n=61) had used the implant for a median 8 months, with 60% removing the implant less than a year after insertion. Only 33% (20/61) removed the implant at the same facility where it had been inserted. Sixteen percent (10/61) of removals were performed by a doctor in the private sector.

Sociodemographic characteristics and contraceptive history

The mean age of both groups was 30 years (Table 1), with 15% (23/152) between ages 18 and 25. About 80% were SA citizens, with the remainder mostly from neighbouring Zimbabwe (14%). Around 60% of the women were employed, two-thirds (66% user, 67% remover) had completed secondary schooling and a further quarter (29% user, 26% remover) had some form of tertiary qualification. Half of the women (74/148) said they did not know their HIV status, and this was similar in both groups. While many characteristics of users and removers were similar, some important differences were noted. Removers were much more likely to be currently sexually active than users (92% v. 80%; p=0.06). Compared with users, removers were more likely to live with their partners (22% v. 46%; p=0.002), and to be married (34% v. 22%; p=0.05). In both groups, for 13% of women, the implant was the first contraceptive method that they had used, aside from condoms. Previous use of an intrauterine device (IUD), another LARC,

was negligible among all women, and only 28% of healthcare providers mentioned this as an option for women post-removal, only two of whom took up the offer. At the time of interview, 77% of the removers were using another contraceptive, mainly depot medroxyprogesterone acetate (DMPA) (36%) or the oral pill (26%). Male condoms were being used by 38% of removers (23/61), half of whom were using condoms as their sole contraceptive (11/23).

Factors influencing implant uptake

The majority (55%) of participants had first heard about the implant by word of mouth from friends, family and other implant users (Table 2). One woman explained how a family member had influenced her decisionmaking: ‘I was interested on it when my younger sister told me about it.’ Friends had also helped assuage women’s fears about the method: ‘At first I was scared that they gonna put something in my arm, but my friend told me it was not painful, so I went for it.’ One 18-year old stated that her mother had made the decision: ‘I didn't decide to use it, my mom said I must use it, she accompanied me to the clinic’. About 90% each of users and removers said that they had themselves gone to the clinic to request that the implant be inserted, rather than the method being suggested to them by a provider during a routine visit. About a quarter of women (30% user, 25% remover) had, however, previously heard of the method from a provider, who in some instances appeared to have swayed women’s choices: ‘The nurses kept teaching us about it and recommending it, so that’s why I tried it.’ Of note is that only 7% (11/152) of women mentioned publicity materials at clinics or schools, or on the internet and television, as sources of information, although one participant did say that she had heard of the implant ‘from the television; Dr Motsoaledi [the minister of health] was explaining about it’. The primary motivation for choosing the implant was convenience, because the long duration of pregnancy protection meant that frequent clinic visits were not required and women would not have to remember daily pill-taking (46% of users and 67% of removers; p=0.03). Reducing the number of visits was especially important for some women. One, aged 24, stated that she used the implant ‘because of the duration that it stays, [I have] enough time to complete my studies’. Similarly, another mentioned that ‘I just started working at that time [when the implant was inserted], so I couldn't afford to get leave days [for attending the clinic]’. Overall, only 11% of users and 3% of removers mentioned contraceptive effectiveness as the main motivation for use (p=0.08). One of these, a 19-year-old HIV-positive woman, recounted that ‘My mom said I must use it as I was sexual active, she thought it will be a good solution to prevent pregnancy’. Another 33-year-old user also explained: ‘I decided on implant because I didn't want to have unwanted pregnancy and the previous injection did not treat me well.’ As this suggests, use of the implant in some instances had been driven by dissatisfaction with other methods. Another respondent said: ‘The nurse told me about the method ’cos I was complaining about the Pill and how it made me feel.’

Women’s knowledge about the implant

Almost all the women knew that the implant could be used for 3 years (99%). In the free-text responses it was clear that counselling had strongly emphasised the notion that the implant ‘needs to’ or ‘should’ be used for that length of time. Many women, however, wondered whether the method was suitable for shorter time periods, for example, if they desired contraception for only 6 months. Seemingly, little information had been provided to participants about the effectiveness of the implant in preventing pregnancy. Only 29% of users and 20% of removers recalled this being discussed

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Table 1. Demographic characteristics and contraception history, comparing women currently using the implant and those who have removed the device

Variables Province Gauteng North West Age (years), mean (SD) Born in South Africa Home language Setswana isiZulu isiXhosa English Other Employed Household income, ZAR (USD) Unknown <5 000 (357) 5 000 - 9 999 (357 - 714) 10 000 - 30 000 (714 - 2 142) Highest level of education completed Primary Secondary Post-school qualification Currently in sexual relationship Current relationship status* Married Stable partner Casual partners Single Lives with partner Other contraceptives ever used† DMPA NET-EN Oral pill Intrauterine device Male condoms Female condoms Female sterilisation

(p=0.19). Not surprisingly, therefore, some were concerned about the method’s efficacy: ‘I just want to know whether is there any chance to conceive if you were using implant.’ Conversely, a few women were worried about how long it would take for fertility to return after removal, if at all: ‘I just want to know if I will be able to conceive again.’ Only 34% of users and 23% of removers answered in the affirmative to the question: ‘Do you know how the implant works to prevent pregnancy?’ (p=0.12). When asked what additional information they require, women mostly wondered about how side-effects should be managed and why specific effects occur. One woman wanted to have a better understanding of the ‘body’s reaction to it [the implant]’, and another was concerned about whether ‘the side-effects [can] damage anything in my body’. Many women also wondered why only some had experienced side-effects and not others, with one asking: ‘Why do

Implant users (N=91), n (%) or mean (SD)

Implant removers (N=61), n (%) or mean (SD)

p-value

63 (69) 28 (31) 30 (6) 73 (81)

30 (49) 31 (51) 30 (6) 48 (79)

0.01 0.35 0.71

19 (20) 26 (29) 10 (11) 5 (5) 31 (34) 56 (62)

25 (41) 7 (11) 7 (11) 3 (5) 31 (19) 33 (54)

0.04 0.32

21 (26) 39 (48) 18 (22) 4 (5)

11 (19) 28 (49) 14 (25) 4 (7)

0.81

5 (6) 59 (66) 26 (29) 72 (80)

4 (7) 41 (67) 16 (26) 54 (92)

0.92 0.06

20 (22) 28 (31) 8 (9) 34 (38) 20 (22)

21 (34) 25 (41) 4 (7) 11 (18) 28 (46)

0.05 0.002

50 (55) 21 (23) 30 (33) 1 (1) 51 (56) 9 (10)

29 (48) 16 (26) 35 (57) 1 (2) 43 (70) 8 (13)

1 (1)

1 (2)

0.37 0.60 0.003 0.77 0.07 0.54 0.77

other people react badly and I haven't even had a single side-effect?’ Among both users and removers, only 57% of users and 52% of removers reported having been informed about side-effects of the implant at the time of insertion. Three women wanted more information about potential drug interactions with the implant, especially about the combined use of the implant and antiretroviral drugs. One woman wished to know where to go for removal, and another asked how this would actually be done.

Overall perspectives of women on the implant

When asked to rate their overall experience with the implant, 74% of current users classified their experience as having been ‘good’ or ‘very good’, and the large majority felt the implant was superior to other methods. For example, 68% of users felt the implant was superior to injectable contraception. By contrast, 69% of removers viewed their

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Table 2. Initiation of the implant, duration of use and overall experiences with the method, comparing women currently using the implant and those who have removed the device

Variable category Initial source of information about the implant

Discussed implant use with partner before insertion*

Request for implant Reasons method was initiated

Information provided at initiation‡

Knowledge level Duration used Implant considered a better method than other options

Rating of overall experience with the implant

Variable Friend Family member Other implant user Clients at facility Provider at facility School Pamphlets or posters at clinics Television Internet No, but knows it’s inserted No, does not know it’s inserted Yes, talked and agreed Yes, talked and did not agree User initiated Nurse initiated Saves time and fewer clinic visits† Longer duration of protection† For effective pregnancy prevention Better than other methods Recommended at facility Information from others Does not want more children Other Effectiveness of implant How long implant can be used for When to return for removal Safety Side-effects How to know implant is in place Preventing STIs Believes she knows how implant works Knows to remove implant after 3 years Months, median (IQR) Range Injectables Oral pill IUD Male condoms Female condoms Female sterilisation Very good Good Average Bad Very bad

Implant users (N=91), n (%) or median (IQR) 27 (30) 11 (12) 12 (13) 6 (7) 27 (30) 1 (1) 0 (0) 3 (3) 2 (2) 13 (16) 27 (34) 37 (47) 2 (3) 80 (90) 9 (10) 29 (32) 14 (16) 10 (11) 7 (8) 6 (7) 6 (7) 6 (7) 12 (13) 27 (29) 61 (67) 46 (51) 37 (41) 52 (57) 16 (18) 14 (15) 31 (34) 90 (99) 24 (12 - 28) 0.3 - 36 62 (68) 64 (70) 36 (40) 56 (63) 44 (49) 34 (38) 30 (33) 37 (41) 11 (12) 9 (10) 4 (4)

Implant removers (N=61), n (%) or median (IQR) 18 (30) 9 (15) 6 (10) 7 (11) 15 (25) 2 (3 ) 3 (5 ) 0 (0) 0 (0) 13 (24) 7 (13) 35 (64) 0 (0) 53 (91) 5 (9) 22 (37) 18 (30) 2 (3) 3 (5) 5 (8) 3 (5) 1 (2) 5 (8) 12 (20) 40 (66) 34 (56) 12 (20) 32 (52) 6 (10) 8 (13) 14 (23) 60 (100) 8 (6 - 12) 2 - 24 8 (13) 12 (20) 10 (17) 10 (16) 11 (19) 12 (20) 1 (2) 8 (13) 10 (16) 27 (44) 15 (25)

p-value 0.30 0.02 0.76 0.19 0.19 0.85 0.53 0.007 0.57 0.18 0.70 0.12 0.42 <0.001 <0.001 <0.001 0.002 <0.001 <0.001 0.017 <0.001

STIs = sexually transmitted infections; IQR = interquartile range; IUD = intrauterine device. *Among those who had a partner at the time. † Saves time, fewer clinic visits and longer duration of protection were considered indicators of method convenience. ‡ Multiple-response question.

experience with the method as having been ‘bad’ or ‘very bad’. Still, some 15% of removers felt their experience had been ‘good’, and a similar proportion believed that the implant was better than oral contraception and injectable methods.

In describing their experiences with the implant, users mainly commented on the method’s convenience, mirroring the motives that had underlain their initial decision to use it. A 25-year-old described this as: ‘I don’t have to worry about coming to the clinic to collect

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pills,’ with another saying ‘I don't have to stress about being in long queues waiting to get prevention pills, so I only come once and be stressfree for 3 years.’ The effectiveness of the implant was also praised by some, especially by one woman who had previously had an unintended pregnancy while using DMPA. Another, a 21-year-old, spoke of how the contraceptive had allayed her anxiety about pregnancy: ‘Since I've started using it I am not worried about getting pregnant.’ Some enthusiasts suggested the method was especially suitable for younger women, with one woman saying: ‘I think if they can go to school and introduce it for teenage pregnancy, because it takes time to expire and I haven’t experienced side-effects.’

Side-effects among users and removers

In free-text responses, many users stated categorically that they had not experienced any side-effects. One woman summed this up well: ‘For me, I haven't experienced any side-effect unlike before using Depo, this one it is very good to me,’ and another concurred: ‘I haven't had a problem, not even one, everything is just normal.’ Ten of the users, however, reported having had heavy bleeding, with one saying: ‘Although I experienced constantly bleeding, I would say it is not that bad.’ A similar number (13/91) of users ascribed headaches to implant use. One said, for example, ‘I would say it’s a good preventive method I have ever used, but I experience a headache on early days when I inserted it, but now I’m ok and I would like to continue using it’. These sentiments were echoed by another woman: ‘I sometimes bleed and experience bad headache, but it disappear at times and it doesn’t bother my health.’ When asked about reasons for discontinuation, the vast majority of removers cited intolerable side-effects (90%). Two-thirds of these related to changed bleeding patterns, which were described as follows: ‘I was bleeding a lot, non-stop,’ or ‘I was having periods every day’ and ‘the bleeding I had, it was uncontrollable for 3 months.’ As this quote and several others suggest, women found not only the duration of bleeding problematic, but also the amount: 31% of removers said they had experienced heavy bleeding. Approximately a third (13/37) of the women who had had the implant removed for heavy or prolonged bleeding had sought advice from healthcare providers, and been given oral contraception for bleeding control. Though the medication had controlled bleeding for brief periods of time in some women, none reported that it provided long-term symptom relief. A few indicated that considerable gaps between bleeding intervals were also problematic, with one saying: ‘I haven’t experienced something bad, except I don’t see my periods now.’ Headaches were given as the reason for 44% of the removals related to side-effects. These were described as ‘constant headaches’ and ‘headaches every day’. One woman said: ‘It was fine in the beginning, but then as the months went by it [the implant] started to cause me severe migraines.’ Weight gain, often linked to an increased appetite, accounted for 15% of removals, but weight loss was also mentioned by a few women. Some women had multiple side-effects, which occurred in various combinations, for example: ‘Since I inserted it, I always had bleeding and terrible headache,’ and ‘because of heavy bleeding [my] sexual desires drop, it makes me sick, nausea, headaches and I will never use it again.’ Others reported generalised or nonspecific complaints, such as ‘I was always sick and I felt tired every time,’ and another woman attributed human emotions to the device: ‘Because it [the implant] doesn’t like me’. Many side-effects were described as having diminished with time. One woman explained that ‘I was bleeding in the beginning after a month that I had inserted it, but then it stop and I have been fine ever since.’ For some, however, the occurrence of side-effects did not

recede, nor were they confined to the period shortly after insertion. For example, one woman who had used the device for 26 months reported that ‘At first it was fine, but now I’m experiencing headache, bleeding and I’m also gaining weight, so I want to remove it now,’ and another recounted that ‘At first 2 years using implant I had a good experience, but now I am bleeding a lot and I want to remove it’. Complications at the site of insertion were reported by four women (three users and one remover). This included ongoing pain in the arm (‘a painful elbow on the side where implant was inserted’) and a rash (‘[I] recently develop some rash near the implant’). One woman reported that ‘[My] arm was swollen, black and painful’. Lastly, three women had the implant removed as they wished to conceive, while one woman removed the implant after using it for 2 years as she had become pregnant while using it. She then had an elective abortion and had an IUD inserted thereafter.

Effects of rumours and provider attitudes

The attitudes of others, including partners, family and community members, towards the implant had shaped the way that women perceived the method and their decision about whether to continue its use. A quote from a remover illustrates this well: ‘I didn't think it [headaches almost every day] was a problem, until I heard other women who have inserted it complain about the same thing.’ In keeping with this theme, several doubts about the implant were apparent, mainly concerning the effectiveness of the method: ‘I would like to know why you get pregnant while on it? I heard some rumours,’ and ‘Is it true that you can fall pregnant while using it, because other sister told me that you can fall pregnant?’ Rumours that appear to exaggerate the frequency and severity of side-effects were also commonly reported: ‘Why does it affect people so badly? I heard there are lot of side-effects,’ and ‘So many people are complaining about side-effects, can’t the health people do something to make it better?’ One woman summed this up well: ‘[The] perception is that most, or the large majority of women experience side-effects, even women who had not had any side-effects had the perception that most women had them.’ Several women were worried about potential drug interactions with the implant, but lacked detailed information, as illustrated by the question: ‘Is it true that if you are on chronic treatment is not good to use implant?’ In fact, three women reported concerns about potential interactions with antiretroviral drugs, an HIV-positive woman saying: ‘And I didn't have any complications, except for later I was told that I could get pregnant when using the Implanon while on ARVs [antiretrovirals]. So I had to remove it.’ Another said: ‘Now as I’m going to start the ARVs programme the sister who is going to initiate me with it said I must remove the implant because of the sideeffect.’ Finally, it is possible that negative connotations associated with the method had already reduced access to the implant. One woman asked: ‘Why they are not inserting implant anymore at the clinic? They refer us to other facility, my sister wanted to insert it.’ Another woman reported difficulties in accessing removal services, saying that ‘I came to remove it, but they told me the nurse who was inserting it is not around … they refer me to [clinic X] and at [clinic X] they refused, they said I must go to a clinic where I inserted.’

The influence of male partners and sexual relationships

The influence of partners on implant insertion and removal varied considerably by partner type. Of those in a relationship, levels of partner consultation and agreement prior to insertion were higher among married (82%, 32/39) than unmarried women (42%, 40/95; p<0.001). Partner involvement was also higher among removers (64%) than users (47%; p=0.02). Interestingly, a third of users were

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using the method without the knowledge of their partner (33%, 27/81), while only 13% of removers had informed their partner of implant use (7/55; p=0.06). One user explained this practice: ‘My partner wants more children and he doesn’t want me to use preventive method, so I thought implant would be good to hide that I’m on contraceptive.’ A number of women recounted how the implant had affected their sexual relationships. This mostly related to prolonged bleeding, with one woman in a stable relationship saying: ‘Because I was bleeding almost every day, so I couldn’t have sex with him because it felt uncomfortable,’ and another noting that ‘We couldn’t have sex anymore because I was always bleeding.’ Partners held strong views on bleeding side-effects, with one woman with a stable partner saying: ‘He was starting to get irritated by the fact that I was always sick and obviously we couldn’t have sex on a regular basis.’ One woman even said: ‘It was okay, but then my boyfriend told me to go and remove it.’ A few women reported that the implant had negatively affected their libido, with one saying: ‘I had excessive bleeding, headaches and I didn’t feel my boyfriend sexually.’ Vaginal dryness was also noted: ‘My vagina was always dry so it was hard for me to sleep with my husband.’ Lastly, men appear to have also contributed to propagating misconceptions or rumours about the implant. One woman recalled that ‘he [her stable partner] told me that people are saying it stops women from having children and that one day I would [be like] those women that struggle to have children’.

Discussion

This study, the first evaluation of the implant introduction in SA, provides important insights into why women chose the method, their experiences with it and their reasons for discontinuation. Examining differences in the characteristic of users and removers, and the reasons underpinning their very divergent experiences, provides useful insights for improving implant services, especially pre-insertion counselling and management of side-effects. The findings about side-effects may appear concerning, but are similar to studies of removers elsewhere,[12] as are the high levels of acceptability among users, who commonly make up about 80% of all those who insert the implant.[13-16] The motivations for implant use were strongly tied to the method’s convenience, such as its long action and lack of requirement for adherence by the user. Reductions in clinic visits were especially important for women working or studying. Interestingly, convenience was more commonly cited as the motive for use in removers than users. Perhaps, if convenience is overwhelming the primary motive rather than factors such as contraceptive effectiveness, then women more readily remove it once ‘inconvenient’ effects become apparent. Women with motives such as contraceptive effectiveness appear to be more resilient in tolerating difficulties encountered. Rumours, based on partially accurate information, appear to have accrued rapidly, despite many women being very satisfied with the method. Both users and removers recalled how they, other women and healthcare providers had held very favourable views towards the implant when it was first introduced, but that these opinions are being eroded by negative perceptions around side-effects and even of a lack of efficacy in preventing pregnancy. These perceptions may become entrenched within popular culture unless they are redressed soon. While interactions with providers are clearly important, the influence of family and community in shaping women’s attitudes to contraceptive methods should not be underestimated. These groups – who were commonly the initial, but also ongoing source of

information about the method – may promote a certain method, but can also rapidly undermine its use. It is promising that many women had negotiated implant use with their partners, the majority of whom apparently supported implant use, at least initially. Other women, however, had elected to use the device clandestinely. Men reportedly exerted influence over removals, especially where prolonged bleeding had affected sexual relations. The large majority (50/61, 82%) of removers had discontinued the implant within a year of insertion. As is consistent with studies elsewhere,[13,17] the principal reasons for implant removal were sideeffects, specifically intolerable bleeding for two-thirds of removers and headaches in almost a half. Users and removers often appeared to have similar side-effects. More nuanced qualitative data are needed to understand why some women elect to remove the implant, while it is retained by others with seemingly identical effects. Relationship status and sexual activity may explain this, at least in part. Removals were especially common among married or cohabiting women. In a long-term intimate relationship, the inconvenience of prolonged bleeding may be felt more than in a situation where a woman is single or in a casual relationship. This consideration, which has not been reported in several similar previous studies,[3,14] should perhaps be discussed with women prior to their selection of the implant. The topics covered in pre-insertion counselling appear to vary widely and require standardisation. Heightened emphasis on the considerable strengths of the implant may promote its uptake and continuation (only a quarter (29% users, and 29% removers) recalled being informed of the method’s remarkable effectiveness, for example. Aside from some reduction in effectiveness due to drug interactions with some drugs, the implant is as much as 180 times more effective than short-acting methods.[18] Even though efavirenz use reduces the effectiveness of the implant, by lowering levels of the active drug in Implanon (etonogestrel),[19,20] the implant still appears more effective in these patients than other contraceptive methods. Relative effectiveness – as well as the likelihood of side-effects – can be hard to convey in counselling.[21] Job aids may facilitate this, but some recommend simply discussing contraceptive options in order of effectiveness from highest (LARCs) to lowest.[22,23] This ‘LARC-first’ approach to counselling extends, in some settings, to LARCs being promoted explicitly as first-line contraception and other methods as second-tier.[23] In the absence of pre-insertion counselling preparing women for sideeffects, these may be particularly alarming, leading to implant removal in some who otherwise may have retained it. Support, both clinical and psychosocial, is required when side-effects occur.[24] This would include providing medication to mitigate abnormal bleeding and headaches. Although women only ‘need’ to return every 3 years, they should be encouraged to attend the clinic for assistance, reassurance and support as needed. Counsellors had strongly emphasised the notion that the device ‘needs to’ or ‘should’ be used for 3 years, rather than it ‘could’ be. Emphasis on the former may needlessly discourage uptake among women desiring protection for shorter periods. Providers require a clear policy on interactions between the implant and enzyme-inducing drugs, including certain ARVs.[20,25] In the presence of ambiguity, providers may understandably err on the side of caution, either by not offering implants to potentially eligible women, or through unnecessarily recommending implant removal.[20] The groups commonly targeted by implant programmes, such as young women, first-time contraceptive users and women immediately postpartum or post-abortion,[26,27] do not appear to have been specifically prioritised in SA. Only 15% of participants were aged 18 - 24, the group in SA in which almost a third have an unmet

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need for contraception, according to national surveys.[5,6] Low levels of HIV testing among the participants also reinforces long-standing calls for the integration of HIV and contraception services.[28] The study has several limitations. Owing largely to deficiencies in record-keeping, only 20% of potentially eligible women were enrolled. Also, there are some notable gaps in our data. For example, we did not enquire whether women had experienced difficulties with accessing implant removal. The inclusion of many open-ended questions, however, allowed us to explore the data in more detail than would have been possible with a quantitative approach alone. Lastly, the diversity of the study population is a strength of the study. Views were gathered of women from many clinics, across both a densely urbanised and a semi-rural district.

Conclusions

While favourable views towards the implant initially drove its uptake, negative perceptions may now risk undermining these gains. Media campaigns, including visual and social media and patient materials addressing rumours or misinformation about the method, are required to reshape the negative discourse around the method. Implant services need to focus on counselling regarding the method’s advantages, especially its high effectiveness and women’s rapid return to fertility after discontinuation, attributes seemingly not highlighted during counselling. But, equally importantly, much greater attention during pre-insertion counselling is needed to ensure that women are aware of potential side-effects, particularly bleeding changes, enabling potential users to make an informed decision about whether the implant is the right method for them. Standardised counselling tools could assist providers to explain the complexities around the relative effectiveness of contraceptives, and side-effects. Treatment protocols could guide providers on clinical care for women experiencing side-effects, especially bleeding and headaches. Moreover, more efforts are needed to promote the implant among young women, those employed or studying, as well as firsttime contraceptive users. All these actions together could reverse the persistent decline in implant use in SA. Acknowledgments. We thank the Department of Health for allowing us access to the health facilities, the anonymous reviewers of this article and the clinics that participated. We also would like to acknowledge the data collectors, Fortunate Gombela, Iris Sishi, Lindiwe Mbuyisa, Ntombenhle Twala, Siziwe Sidabuka and Tebogo Mokoena. Author contributions. DP was the project lead, and was responsible for the project design, implementation and write-up and was supported by CM, MP, OAA, NN and SM. MFC largely supported data analysis and write-up and HR is the senior author providing oversight and review. Funding. Funding was received from the United Nations Population Fund (UNFPA), which also provided technical assistance. Conflicts of interest. None.

1. Jacobstein R, Stanley H. Contraceptive implants: Providing better choice to meet growing family planning demand. Glob Health Sci Pract 2013;1(1):11-77. https://doi.org/10.9745/GHSP-D-12-00003 2. Blumenthal P, Voedisch A, Gemzell-Danielsson K. Strategies to prevent unintended pregnancy: Increasing use of long-acting reversible contraception. Hum Reprod Update 2011;17(1):121-137. https:// doi.org/10.1093/humupd/dmq026 3. Dickerson LM, Diaz VA, Jordon J, et al. Satisfaction, early removal, and side effects associated with longacting reversible contraception. Fam Med 2013;45(10):701-707. 4. Duvall S, Thurston S, Weinberger M, Nuccio O, Fuchs-Montgomery N. Scaling up delivery of contraceptive implants in sub-Saharan Africa: Operational experiences of Marie Stopes International. Glob Health Sci Pract 2014;2(1):72-92. https://doi.org/10.9745/GHSP-D-13-00116 5. Chersich MF, Wabiri N, Risher K, et al. Contraception coverage and methods used among women in South Africa: A national household survey. S Afr Medi J 2017;107(4):307-314. https://doi.org/10.7196/ SAMJ.2017.v107i4.12141 6. National Department of Health, Statistics South Africa (StatsSA), South African Medical Research Council, Inner City Fund. South Africa Demographic and Health Survey 2016: Key Indicators: StatsSA, 2017. http:// www.statssa.gov.za/publications/Report%2003-00-09/Report%2003-00-092016.pdf (accessed 15 September 2017). 7. World Health Organization. Expanding Family Planning Options: Contraceptive Introduction Reconsidered: A review and conceptual framework. Geneva: WHO, 1994. http://apps.who.int/iris/ bitstream/10665/58660/1/WHO_HRP_ITT_94.1.pdf (accessed 15 September 2017). 8. Lince-Deroche N, Pleaner M, Morroni C, et al. Achieving universal access to sexual and reproductive health services: The potential and pitfalls for contraceptive services in South Africa. S Afr Health Review 2016;2016(1):95-108. https://www.health-e.org.za/wp-content/uploads/2016/05/South-African-HealthReview-2016.pdf (accessed 15 September 2017). 9. Pillay D, Morroni C, Pleaner M, et al. Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts. S Afr Med J 2017;107(10):827-831. https://doi. org/10.7196/SAMJ.2017.v107i10.12822 10. Adeagbo OA, Mullick S, Pillay D, et al. Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of health workers. S Afr Med J 2017;107(10):822-826. https://doi.org/10.7196/ SAMJ.2017.v107i10.12821 11. Sundari Ravindran TK, Berer M, Cottingham J, World Health Organization. Beyond Acceptability: Users’ Perspectives on Contraception. London: Reproductive Health Matters, 1997. http://apps.who.int/iris/ bitstream/10665/42012/1/0953121003.pdf (accessed 15 September 2017). 12. Diedrich JT, Desai S, Zhao Q, Secura G, Madden T, Peipert JF. Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction. Am J Obstet Gynecol 2015;212(1):50.e1-e8.1. https://doi.org/10.1016/j.ajog.2014.07.025 13. Bahamondes L, Brache V, Meirik O, et al. A 3-year multicentre randomized controlled trial of etonogestreland levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls. Hum Reprod 2015;30(11):2527-2538. https://doi.org/10.1093/humrep/dev221 14. Abraham M, Zhao Q, Peipert JF. Young age, nulliparity, and continuation of long-acting reversible contraceptive methods. Obstet Gynecol 2015;126(4):823-829. https://doi.org/10.1097/AOG.0000000000001036 15. Casey PM, Long ME, Marnach ML, Bury JE. Bleeding related to etonogestrel subdermal implant in a US population. Contraception 2011;83(5):426-430. https://doi.org/10.1016/j.contraception.2010.09.012 16. O’Neil-Callahan M, Peipert JF, Zhao Q, Madden T, Secura G. Twenty-four-month continuation of reversible contraception. Obstet Gynecol 2013;122(5):1083-1091. https://doi.org/10.1097/AOG.0b013e3182a91f45 17. Mutihir JT, Nyango DD. One-year experience with Implanon sub-dermal implants in Jos, Nigeria. Niger J Clin Prac 2010;13(1):28-31. 18. Darney P, Patel A, Rosen K, Shapiro LS, Kaunitz AM. Safety and efficacy of a single-rod etonogestrel implant (Implanon): Results from 11 international clinical trials. Fertil Steril 2009;91(5):1646-1653. https://doi.org/10.1016/j.fertnstert.2008.02.140 19. Chappell CA, Lamorde M, Nakalema S, et al. Efavirenz decreases etonogestrel exposure: A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS 2017;31(14):1965-1972. https://doi.org/10.1097/qad.0000000000001591 20. Patel RC, Morroni C, Scarsi KK, Sripipatana T, Kiarie J, Cohen CR. Concomitant contraceptive implant and efavirenz use in women living with HIV: Perspectives on current evidence and policy implications for family planning and HIV treatment guidelines. J Int AIDS Soc 2017;20(1):1-6. https://doi.org/10.7448/IAS.20.1.21396 21. Lopez LM, Steiner M, Grimes DA, Hilgenberg D, Schulz KF. Strategies for communicating contraceptive effectiveness. Cochrane Database Syst Rev 2013(4):CD006964. https://doi.org/10.1002/14651858. CD006964.pub3 22. Secura GM, Madden T, McNicholas C, et al. Provision of no-cost, long-acting contraception and teenage pregnancy. New Engl J Medicine 2014;371(14):1316-1323. https://doi.org/10.1056/NEJMoa1400506 23. Ott MA, Sucato GS, Committee on Adolescence. Contraception for adolescents. Pediatrics 2014;134(4):e1257-e1281. https://doi.org/10.1542/peds.2014-2300 24. Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS. The effects of Implanon on menstrual bleeding patterns. Eur J Contracept Reprod Health Care 2008;13:Suppl 1:S13-S28. https://doi.org/10.1080/13625180801959931 25. Pyra M, Heffron R, Mugo NR, et al. Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AIDS 2015;29(17):2353-2359. https://doi.org/10.1097/QAD.0000000000000827 26. Bryant AG, Bauer AE, Stuart GS, et al. Etonogestrel-releasing contraceptive implant for postpartum adolescents: A randomized controlled trial. J Pediatr Adolesc Gynecol 2017;30(3):389-394. https://doi. org/10.1016/j.jpag.2016.08.003 27. Berlan E, Mizraji K, Bonny AE. Twelve-month discontinuation of etonogestrel implant in an outpatient pediatric setting. Contraception 2016;94(1):81-86. https://doi.org/10.1016/j.contraception.2016.02.030 28. Smit JA, Church K, Milford C, Harrison AD, Beksinska ME. Key informant perspectives on policy- and service-level challenges and opportunities for delivering integrated sexual and reproductive health and HIV care in South Africa. BMC Health Services Res 2012;12:48. https://doi.org/10.1186/1472-6963-12-48

Accepted 31 August 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of healthcare workers O A Adeagbo,1 MA, PhD; S Mullick,1 MB ChB, MSc, MPH, PhD; D Pillay,1 MPH; M F Chersich,1 MB BCh, PhD; C Morroni,1,2,3,4 MB ChB, DFSRH, DTM&H, MPH, MSc, PhD; N Naidoo,1 MPH; M Pleaner,1 MEd; H Rees,1 MB BChir, MA (Cantab), MRCGP,, DCH, DRCOG Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Women’s Health Research Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 EGA Institute for Women’s Health and Institute for Global Health, University College London, UK 4 The Botswana-UPenn Partnership, Gaborone, Botswana 1

Corresponding author: O A Adeagbo (oadeagbo@wrhi.ac.za) Background. The South African (SA) government introduced Implanon NXT, a long-acting subdermal contraceptive implant, in 2014 to expand contraceptive choice. Following an initial high uptake, its use declined considerably amid reports of early removals and frequent side-effects. We examine providers’ perceptions of training and attitudes towards Implanon NXT, as well as their views on the causes of early removals and the impact on the implant service. Objective. To assess healthcare providers’ perceptions and attitudes towards implant services in SA. Methods. In-depth interviews were conducted with eight nurses providing implant services in public facilities in Gauteng and North West Province. Emerging themes were identified, manually coded and thematically analysed following an interpretivism approach. Results. Nurses lacked confidence in providing implant services effectively, particularly removals, which they ascribed to the brief, cascade-type training received. Nurses generally held negative views towards the method. They also reported that side-effects are the most common reason for early removals – particularly irregular bleeding – and that men often do not support their partners who use the method. Lastly, it was found that providers require guidance on counselling regarding the method and standardised guidelines on the management of side-effects. Conclusion. Retraining and support of providers are needed to address competency gaps and negative attitudes towards the method. Assessment of providers’ readiness to perform removal procedures is also important. Finally, effective plans are necessary to improve implant continuation rates, especially among women whose partners are unsupportive. S Afr Med J 2017;107(10):822-826. DOI:10.7196/SAMJ.2017.v107i10.12821

The Sustainable Development Goals (SDGs), commissioned in 2015, include universal access to sexual and reproductive health, and make direct references to addressing the unmet contraceptive needs of women. [1] Similarly, Family Planning 2020 (FP2020) aims to make modern contraceptive methods accessible to an additional 120 million women by 2020.[2] These initiatives are particularly pressing in subSaharan Africa, where most women of reproductive age still have unmet contraceptive needs, despite considerable increases in contraception coverage over the past two decades.[3,4] In South Africa (SA), the 2016 Demographic and Health Survey (DHS) estimated that unmet needs for contraception were as high as 39% among married and sexually active unmarried women. Cognisant of these gaps in services, the SA government has committed to achieving the SDGs around family planning and the FP2020 goals, which align with the country’s laws and policies that support sexual and reproductive health and rights.[3] The 2001 National Contraceptive Policy Guidelines (updated in 2012), the National Health Act as well as the National Adolescent Sexual and Reproductive Health and Rights Framework Strategy (2014 - 2019) recognise the challenges and health needs of women and adolescents, particularly family planning needs.[3,5-8] Consistent with the 2012 Contraception Policy objectives, the National Department of Health (DoH) introduced Implanon NXT in 2014 to increase the range of contraceptive options for women, particularly long-acting methods.[9,10] Implanon NXT is a single-rod subdermal implant containing 68 mg of the progestin etonogestrel and

offers 3 years of highly effective pregnancy protection (<1 pregnancy per 100 women-years).[5] Before implant roll-out, preparations such as healthcare provider training, programmatic guidelines and manual development were put in place, and >6 000 healthcare providers trained across the country, mostly using a cascade training approach – training provided by healthcare workers who have attended a training.[3] Based on the DHS, almost 4% of women of reproductive age were using the implant by 2016, with injectables remaining the most common method, accounting for 25% of contraceptive coverage.[11] Concerns, however, have grown about a sharp decline in implant method uptake and rise in the number of women returning for early removal of the implant, mostly because of intolerable side-effects.[3] Implant side-effects received negative attention from the general populace (including healthcare workers and the media) in SA, which has brought into question the appropriateness and sustainability of the method in the country. Side-effects, especially bleeding, are also the main cause of early removal in other areas, although studies across a range of settings, including sub-Saharan Africa, indicate that between 80% and 85% of users continue the method 1 year after insertion,[12,13] including women 25 years of age.[14] A minority of studies reported continuation rates of 70%; again, mostly ascribed to changes in bleeding patterns.[15-17] Clearly, family planning providers are critical to the success or failure of contraceptive programmes, and play a crucial role in shaping how women perceive a contraceptive method. In Mali, for example, providers in community health centres served as positive

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agents of change, increasing access and quality of family planning services, particularly for the implant.[18] We, therefore, conducted a qualitative study of providers’ attitudes towards the implant and their perspectives on the factors that underlie early removals, as well as how these have influenced uptake of the method.

Methods

This article draws on data collected in a mixed-methods evaluation, which aimed to assess the effectiveness of Implanon NXT services in SA. The evaluation included primary healthcare (PHC) clinics, sampled from the City of Johannesburg (CoJ), Gauteng, (6 clinics) and Dr Kenneth Kaunda District (DKKD), North West Province (6 clinics). Participants consisted of family planning service providers (also referred to as nurses), who were purposively selected on the basis of having been directly involved in the provision of implant services. Of 13 professional nurses contacted across the 12 participating facilities, 8 agreed to be interviewed (3 were no longer working at the facility and 2 declined to participate). Five nurses in CoJ, who were drawn from four facilities, participated, and 3 nurses in DKKD, each representing one facility. Data were collected through face-toface in-depth interviews in May - November 2016. All participants were female, and their ages ranged between 29 and 60 years. The interview guide was piloted and revised before data collection commenced. Interview questions included enquiry about the implant and general family planning training the nurses had received, their perception of levels of removal and reasons for removal, their personal attitudes towards the implant, and perceptions of women’s experiences with regard to side-effects and their partners’ reaction to these. Interviews took place in the facility, at a location chosen by the participant. These were conducted in English by trained female field workers, although in a few instances interviewers translated some words from English to the local languages of participants for ease of comprehension. Conversations lasted 1 - 2 hours and were digitally recorded. Telephonic follow-up interviews were done with some of the providers (two each in both DKKD and CoJ) to further clarify aspects of the interviews. Interview transcripts were reviewed by the lead researcher (OAA) and another investigator (DP). Emerging themes were identified, categorised manually and analysed thematically following interpretive ideology.[19] The study was approved by the Human Research Committee of the University of the Witwatersrand, Johannesburg (ref. no. M151147) and permission for the study was granted by the DoH.

Key findings and discussion

This section presents the main themes emerging from the data. It begins with a discussion about the perceptions of providers towards the training they received, and then examines providers’ experiences with dealing with implant side-effects, counselling and management, and removal. The final sections explore providers’ attitudes towards the implant, as well as their perceptions of men’s involvement and influence in women’s decisions to begin and continue or discontinue the method.

‘We were only trained for 2 days’: Impact of insufficient training on service delivery

This theme examines the training that healthcare providers received on insertion and removal of the implant, as well as on counselling about the method and providing long-term support for women using the implant. The impact of gaps in training is also discussed and potential actions that might be taken by the DoH to address these. The following excerpts show individual interviewees’ perceptions of the training they received:

‘… We were only trained for 2 days … I feel like the training was not sufficient … I think I need intense trainings in order for me to deliver the service effectively.’ (Professional nurse H, DKKD) ‘We had some trainings and we were shown how to insert and remove the implant and each clinic was expected to do that … It was like a once-off thing … .’ (Professional nurse E, CoJ) ‘… I was trained by another professional nurse, I would really not call it a proper training honestly … I think I need to start afresh when it comes to the implant and receive training for months … .’ (Professional nurse A, DKKD) ‘My colleagues went for the theory part and I went for the practical training on insertion … I don’t think I have had sufficient training to do this … .’ (Professional nurse F, CoJ) Providers’ perceptions of having received inadequate training on Implanon NXT provision came out strongly across the interviews. In particular, they indicated that the training was too brief and covered only some components of the service, and that little or no refresher training and long-term support have been made available. Providers felt that the training was insufficient, given what they perceived to be the complexities of the method. According to nurse F, there were also considerable gaps in the training: ‘… If I remember correctly, I was only trained on the insertion … .’ Importantly, nurse A believed that having being trained by a colleague (the cascade training approach), who had been to only one training session, was insufficient to equip her to provide the method. From the nurses’ perspectives, inadequate training had directly affected the quality of the services they provided. This especially related to inadequate understanding of the method, limited training on how to counsel women about the method, as well as deficiencies in practical skills for implant removal. Perceived deficiencies in their knowledge and how to counsel, as well as their practical skills for implant provision, meant that nurses lacked confidence in their ability to provide quality services; one (nurse H) saying: ‘When clients came, I wasn’t sure of what I was doing’, and similarly, another (nurse F) simply said: ‘… I don’t know enough … .’ Despite a strong sense of deficiencies in their training, nurses continued to provide the service, with one (nurse A) noting: ‘… I try to counsel the client with the little knowledge that I have … .’ Nevertheless, gaps in knowledge and skills, and the providers’ own doubts in their competencies, may undermine the quality of services provided, as noted in the section below on implant removals. Consistent with this, several studies on implant services in a range of settings have shown that providers’ level of knowledge, especially around counselling, is a key determinant of the uptake of the implant and subsequent continuation.[9,15,18,20] Of note, a study across several sub-Saharan African countries showed the benefits of competency-based training on the implant, sideeffect management, and regular mandatory refresher courses and mentorship.[9] These efforts boosted the confidence of providers to remove implants; at follow-up, none of those trained had refused to do removals, an issue which had previously hampered the programme.[9] All the nurses expressed enthusiasm about the prospect of attending further training by qualified personnel. Opportunities for practical experience, where several insertions and removals are done under supervision, and for continued mentoring, appear to be particularly important, with nurse E saying: ‘It just needs some practice. The more you insert or remove, the more you’d be skilful … .’ Overall, more intensive training, grounded in effective training methodologies, could augment individual provider’s skills, empowering them to become increasingly confident and competent. Practically, this might entail: (i) reassessing the training curriculum,

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and evaluating and revising the training provided, with input from providers who previously completed training; (ii) providing refresher training (both theory and practical) on counselling, side-effect management, insertion and removal; (iii) using master trainers, rather than cascade training; and (iv) offering ongoing in-service mentorship and competency sign-off.

‘My concern is the side-effects’: Providers’ perceptions of how side-effects impact on uptake and removal of Implanon NXT

The views of the nurses on the impact of side-effects on uptake and early removals of Implanon NXT are articulated below: ‘… More women would use it, but my concern is the side-effects … The last time I inserted Implanon was last year … The main reason is the side-effects and more medical research has to be done so that we can introduce it again to the public … .’ (Professional nurse A, DKKD) ‘… The last time we inserted one [Implanon NXT] was in early 2015, and three months after we started doing removals. The news of side-effects is travelling fast because people talk … I have been threatened many times by clients because they want to get it removed immediately and we have had cases where clients are removing it themselves because of side-effects, especially bleeding … .’ (Professional nurse B, CoJ) ‘… [Implanon NXT] was recently introduced and in no time many women complained about it and would remove it immediately … Yes! Side-effects, such as excessive bleeding, cramps, headaches and dry mouth, are the reasons why clients are removing the implant … .’ (Professional nurse G, DKK) ‘… It [Implanon NXT] didn’t actually thrive well because of the adverse symptoms … ja [yes]! They don’t like the bleeding part … Initially we were told to give Ovral as we normally do when they bleed with Depo and others, but at the later stage we were told to give Ovral and Triphasil … The medications do not usually stop the bleeding; hence, you see clients coming here to fight for removals … People often come here to remove the implant and nobody wants to insert it because of the side-effects … .’ (Professional nurse E, CoJ) From the abovementioned quotes, it is clear that adequate preparation of women for potential side-effects and management thereof, including being able to confidently counsel women on which sideeffects are likely to be related to the implant or are coincidental, poses a considerable challenge to Implanon NXT provision and use in SA, with similar themes emerging from all nurses interviewed. As reported by providers, the main factor underlying removal of implants was intolerable side-effects, especially irregular bleeding. Changes in bleeding patterns, with almost all users experiencing some change and most experiencing light but unpredictable bleeding (~3/5), but some experiencing prolonged and/or heavy bleeding (~1/5), is a well-documented and expected side-effect of the implant. Thorough precounselling about this and discussion of the potential implications for users are essential to ensure that the implant is an appropriate method for the women who choose it. Even so, many users will need support and may choose to discontinue the method. Despite the changes in bleeding patterns and other side-effects, many studies have shown that, overall, Implanon NXT is highly acceptable, and most users view the method positively.[13,15,21,22] Providers highlighted their need for clear guidelines on how to deal with side-effects. A variety of medications had been given, similar to those prescribed to clients who have irregular bleeding with injectable and other contraceptive methods, but without a

standardised and evidence-based approach. Available evidence and guidelines elsewhere on side-effect management could be used to devise a standardised approach for SA. In summary, it is clear that providers in SA require additional tools on side-effect counselling and management to assist potential users in making informed contraceptive decisions, and supporting ongoing use of the implant when chosen. Extensive counselling and followup care by providers can raise continuation rates.[9] Clearly, women require detailed and evidenced-based counselling that encompasses the likely side-effects and other features of the method, their motivations and expectations of the method, as well as the meanings that they attribute to menstrual bleeding, and implications for their bleeding patterns. Equally, however, ongoing counselling and support for those experiencing side-effects are critical for optimising implant continuation rates.

‘We don’t know what we are damaging inside’: Providers’ experience of Implanon NXT removal

The preceding themes grappled with the nurses’ experiences of training and gaps in competence and confidence, as well as their perspectives on reasons for early removal. This theme explores the experiences of providers in managing implant removals. The following quotes shed light on the challenges encountered in this regard: ‘… Removals take forever [up to 2 hours] … it’s hard to remove those things [Implanon] … You worry about what you are damaging inside, because you are cutting with a blade and making a hole to get to the position of the implant in the flesh … .’ (Professional nurse B, CoJ) ‘… Insertion was quite easy, but removal was a problem in almost all the clinics because people are coming here from other clinics to remove. I don’t know why the nurses are sending those who want to remove away … Maybe they are scared, but it’s time consuming though … We sometimes struggle when removing the implant … .’ (Professional nurse E, CoJ) ‘… Sometimes the implant just disappears on the body and the doctor had to struggle to get it ... I prefer insertion to removal because removal takes a lot of time … .’ (Professional nurse C, CoJ) The above quotes reveal the significant concerns among providers about Implanon NXT removals, especially around the potential complications, the time required to perform the procedure and the consequent impact on their other services and duties. Nurses uniformly indicated that they lack confidence with regard to implant removal skills and do not feel sufficiently competent with the procedure. Some explained that clients can become aggressive if the removal process is prolonged. Providers clearly linked the challenges they are facing with implant removals to having received inadequate training. For some, this meant that they did not engage in implant removals, while others took the initiative to perform removals despite this. Both approaches – unwillingness to remove the implant when a client wanted to discontinue or feeling incompetent to do so – were considered to have negative implications for provider-client relationships and women’s trust in family planning services as a whole. One respondent also raised concerns about whether the surgical process of removal should be within the scope of a nurse’s duties: ‘… I think doctors should be removing the implant … .’ (Nurse B). Since Implanon NXT provides 3 years of protection against pregnancy before a replacement is required, ensuring there are effective services in place for removal is becoming ever more urgent.[9,23] To address this issue, one implant programme that operated across 15 countries chose

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to link women to specific clinics where providers had been selected and trained in removal and other aspects of follow-up care.[9] This approach had resolved many of the previous challenges with removals. Clearly, providers’ competence to perform removal procedures needs to be carefully assessed to ensure that they are able to remove the device timeously and safely, or to refer as necessary for difficult removals. Moreover, this task might extend beyond the scope of work of some nurses, so in some settings, removals may perhaps be reserved for specially trained nurses and doctors with the necessary expertise. Furthermore, adequate referral protocols are necessary, with clear criteria and pathways for difficult removals (e.g. impalpable, deep or inappropriately placed implants that may require special techniques or radiological investigation) that cannot be done by usual providers or in an outpatient clinic setting.

‘I wouldn’t recommend it to my daughter’: Providers’ perceptions of Implanon NXT

This theme engages with the perceptions and attitudes of family practice providers towards Implanon NXT, as they are at the interface of client decision-making with regard to the implant and other contraceptives and, as such, may play a crucial role in how women perceive the method. The following excerpts provide insights into the attitudes of the providers: ‘… I have a duty to inform the client of all the methods and the client must choose. She must make an informed decision based on what I explained to her without hiding it ... It has not been well received … The thing [Implanon NXT] that should be there for 3 years is being removed within a short space of time, especially during the first year of insertion … Given the state of financial problem that our country is in, I believe it’s not worth it … It has lots of problems that it has created socially and mentally … .’ (Professional nurse E, CoJ) ‘… To tell you the truth, lately, I hardly suggest Implanon unless a client wants it… .’ (Professional nurse H, DKKD) ‘… I wouldn’t go for it. I would stick to the known method – the pill or the injection. They’ve been around forever … It has its sideeffects, but when you deal with it, it’s sorted … For instance, when they take the injection, they bleed and I give them Ovral. It settles as the body adjusts to the method … I don’t think it’s [Implanon NXT] working, honestly, because of the removals we are doing and they [users] will tell you that they will never go for this method again ... .’ (Professional nurse B, DKKD) From the above, one can understand that nurses’ negative experiences and attitudes towards the implant could make it difficult for them to exercise their responsibility as professionals to provide women with balanced information about the advantages and disadvantages of the method. Although nurses appear to take this responsibility seriously, overtly or in more subtle ways, it is possible that their biases and beliefs about the implant will influence the information they give during counselling, as well as discussions they have with people in the community more broadly. A study in the USA found that family planning service providers attached strong personal beliefs to certain contraceptive methods (including the implant) and refused to suggest these to certain clients, as they believed that those methods were not appropriate for them.[24] Importantly, since the implant method requires users to return to clinics for discontinuation (unlike most other contraceptive methods), it could create an impression among providers that most users are unhappy with the method. Clearly, much work is needed to redress the perceptions and attitudes of family planning providers towards the implant, and to undo some of

the biases that have developed around the method. The nurses suggested that awareness and additional campaigns are required among healthcare providers and women.

‘Men don’t usually support women’: Ensuring male involvement in family planning services

This theme explores providers’ perceptions of men’s involvement in and influence over their partner’s use of the implant, as illustrated in the following quotes: ‘… No! There are no males that come here with the females, they all come alone. Some of them [women] often hide the implant from their partners … .’ (Professional nurse B, CoJ) ‘… I prefer women to talk to their partners before using the implant, because if it happens that a woman gets side-effects, at least a man is aware of what is going on … .’ (Professional nurse G, DKKD) ‘… Men usually don’t support women even when they come for oral pills or injectable, so it’s even worse when they find out their partners want the implant … .’ (Professional nurse H, DKKD) ‘… Men detest it [Implanon NXT], they don’t like it at all because of the bleeding … most people engage in relationships for sex more than love … For example, a woman who is having sexual relationships came here crying that her partner … they have three kids together … left because of continuous excessive bleeding. He said to her that he would look for a woman who is not always bleeding because he wanted to have sex.’ (Professional nurse E, CoJ) ‘It is important for male partners [of Implanon NXT users] to support their female partners because once a woman starts experiencing side-effects she will be open with her partner and they can both come to the clinic to find a solution … .’ (Professional nurse A, DKKD) It is evident that providers believed that men were often not supportive of their partners’ use of the implant, leading to women attempting to conceal its use or discontinue the method. Other studies have similarly noted that men’s knowledge and attitudes about contraceptive methods impact on women’s preferences,[25-28] and even that some men believe that they should take the final decision on contraception, while women take responsibility for usage.[29] While men generally seem to regard family planning clinics as a woman’s domain,[25,28,30,31] the majority of nurses interviewed believe that involving men in family planning services would enlighten them and make them more supportive of their partner’s contraceptive use. Men could thus play an important role in uptake and continuation of Implanon NXT, and in supporting women when they experience side-effects, e.g. irregular bleeding. As shown previously, couples who communicate about the use of family planning and family size are more likely to use a contraceptive method and achieve their reproductive objectives than those who do not.[25,31] Clearly, there is a need for novel strategies to raise men’s involvement in family planning services and foster a supportive attitude of men towards family planning.[25,32,33]

Study limitations and strengths

The small size restricted our ability to examine some aspects of our findings in detail, or to determine whether experiences of nurses were specific to some facilities or common to many. We included participants from seven clinics, which is a strength of the study, as it allowed us to draw on a range of experiences across sites. Moreover, this research is timely and important, given that the factors influencing the uptake and usage of Implanon NXT in SA have not

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been examined since its launch in 2014. This evidence comes at an important juncture for the service – i.e. the third stage of the World Health Organization framework on contraceptive introduction[34] – where it is critical to have detailed research analysis, followed by the development of appropriate strategies to maintain services and redress problems that have emerged to date.

Conclusion

This article, focusing on providers’ perspectives, adds to our understanding of current issues and challenges emanating from implant provision in SA, especially with regard to healthcare provider competence and attitudes towards the method. Overall, the findings of the study suggest that a concerted effort is needed to raise the competency of family planning providers, together with mass campaigns increasing the public’s awareness of the benefits of the implant, as well as its side-effects and how these might be mitigated. Importantly, providers require guidance on the counselling and clinical management of bleeding patterns and other side-effects common to Implanon NXT. Improving providers’ readiness to perform removal procedures, and the development of more structured removal services, is critical if quality, rights-based implant services are to be provided. To ensure the support of men, Implanon NXT awareness measures also need to target them; this possibly also applies to other contraceptive methods. In summary, the findings and recommendations of this study could inform a national effort to reinvigorate and improve implant services, which is urgently needed to secure the method’s long-term viability in SA. Most especially, retraining and support of healthcare providers are required to address competency and confidence challenges and negative attitudes. Acknowledgements. We thank the National Department of Health for allowing us access to the health facilities, the anonymous reviewers of this article, clinics that participated, and the nurses who gave their time to contribute to this study. We would also like to acknowledge the data collectors (Fortunate Gombela, Iris Sishi, Lindiwe Mbuyisa, Ntombenhle Twala, Siziwe Sidabuka and Tebogo Mokoena). Author contributions. OAA was responsible for the qualitative component of the study, write-up, and was supported by CM, MP, DP, NN, MFC and SM. HR, the senior author, provided oversight and review. Funding. Funding was received from the United Nations Population Fund (UNFPA), which also provided technical assistance. Conflicts of interest. None.

1. United Nations Department of Economic and Social Affairs. Sustainable Development Goals: Sustainable Development Knowledge Platform, 2015. Geneva: UNDESA, 2015. 2. Family Planning 2020. What we do. 2016. http://www.familyplanning2020.org/microsite/about-us (accessed 15 May 2017).

3. Lince-Deroche N, Pleaner M, Morroni C, et al. Achieving universal access to sexual and reproductive health services: The potential and pitfalls for contraceptive services in South Africa. S Afr Health Review 2016;2016(1):95-108. 4. Chersich M, Wabiri N, Risher K, et al. Contraception coverage and methods used among women in South Africa: A national household survey. S Afr Med J 2017;107(4):307-314. https://doi.org/10.7196/ SAMJ.2017.v107i4.12141 5. Patel M. Contraception: Everyone’s responsibility. S Afr Med J 2014;104(9):644. https://doi.org/10.7196/ SAMJ.8764 6. Department of Health. National Contraception Policy Guidelines. Pretoria: DoH, 2001. 7. Republic of South Africa. National Health Act No. 61 of 2003. 8. Department of Social Development. National Adolescent Sexual and Reproductive Health and Rights Framework Strategy 2014 - 2019. Pretoria: DSD, 2015. 9. Duvall S, Thurston S, Weinberger M, et al. Scaling up delivery of contraceptive implants in sub-Saharan Africa: Operational experiences of Marie Stopes International. Glob Health: Sci Pract 2014;2(1):72-92. https://doi.org/10.9745/GHSP-D-13-00116 10. Cleland JG, Ndugwa RP, Zulu EM. Family planning in sub-Saharan Africa: Progress or stagnation? Bull World Health Organ 2011;89(2):137-143. https://doi.org/10.2471/blt.10.077925 11. Department of Health, Statistics South Africa, South African Medical Research Council. South Africa Demographic and Health Survey 2016: Key Indicators. Pretoria: Stats SA, 2017. 12. Abraham M, Zhao Q, Peipert JF. Young age, nulliparity, and continuation of long-acting reversible contraceptive methods. Obstet Gynecol 2015;126(4):823-829. https://doi.org/10.1097/AOG.0000000000001036 13. Teunissen AM, Grimm B, Roumen FJ. Continuation rates of the subdermal contraceptive Implanon® and associated influencing factors. Eur J Contracept Reprod Health Care 2014;19(1):15-21. https://doi. org/10.3109/13625187.2013.862231 14. Diedrich JT, Klein DA, Peipert JF. Long-acting reversible contraception in adolescents: A systematic review and meta-analysis. Am J Obstet Gynecol 2017;216(4):e1-e64. https://doi.org/10.1016/j. ajog.2016.12.024 15. Weisberg E, Bateson D, McGeechan K, et al. A three-year comparative study of continuation rates, bleeding patterns and satisfaction in Australian women using a subdermal contraceptive implant or progestogen releasing-intrauterine system. Eur J Contracept Reprod Health Care 2014;19(1):5-14. https://doi.org/10.3109/13625187.2013.853034 16. Weisberg E, Fraser I. Australian women’s experience with Implanon. Austr Fam Phys 2005;34(8):694. 17. Harvey C, Seib C, Lucke J. Continuation rates and reasons for removal among Implanon® users accessing two family planning clinics in Queensland, Australia. Contraception 2009;80(6):527-532. https://doi. org/10.1016/j.contraception.2009.05.132 18. Gold J, Burke E, Cissé B, et al. Increasing access to family planning choices through public-sector social franchising: The experience of Marie Stopes International in Mali. Glob Health: Sci Pract 2017;5(2):286-298. https://doi.org/10.9745/GHSP-D-17-00011 19. Denzin NK, Lincoln YS. The Sage Handbook of Qualitative Research. UK: Sage, 2011. 20. Adams B. Subdermal implants: A recent addition to the choice of South African contraceptives. Prof Nurs Today 2015;19(2):32-34. 21. Blumenthal PD, Gemzell-Danielsson K, Marintcheva-Petrova M. Tolerability and clinical safety of Implanon®. Eur J Contracept Reprod Health Care 2008;13(Suppl 1):29-36. https://doi. org/10.1080/13625180801960012 22. Mansour D, Korver T, Marintcheva-Petrova M, et al. The effects of Implanon® on menstrual bleeding patterns. Eur J Contracept Reprod Health Care 2008;13(suppl 1):13-28. https://doi.org/10.1080/13625180801959931. 23. Jacobstein R, Stanley H. Contraceptive implants: Providing better choice to meet growing family planning demand. Glob Health: Sci Pract 2013;1(1):11-17. https://doi.org/10.9745/GHSP-D-12-00003 24. Akers AY, Gold MA, Borrero S, et al. Providers’ perspectives on challenges to contraceptive counseling in primary care settings. J Wom Health 2010;19(6):1163-1170. https://doi.org/10.1089/ jwh.2009.1735 25. Ijadunola MY, Abiona TC, Ijadunola KT, et al. Male involvement in family planning decision making in Ile-Ife, Osun State, Nigeria. Afr J Reprod Health 2010;14(4):43-50. 26. Mbizvo MT, Adamchak DJ. Family planning knowledge, attitudes, and practices of men in Zimbabwe. Stud Fam Plan 1991;22(1):31-38. https://doi.org/10.2307/1966517 27. Ezeh AC, Seroussi M, Raggers H. Men’s fertility contraceptive use and reproductive preferences. DHS Comparative Studies 1996;8(18):45. https://www.popline.org/node/297753 28. Oyediran KA, Ishola GP, Feyisetan BJ. Factors affecting ever-married men’s contraceptive knowledge and use in Nigeria. J Biosoc Sci 2002;34(4):497-510. https://doi.org/10.1017/S0021932002004972 29. Puri C, Balaiah D, Iyer K. Increased male responsibility and participation: A key to improving the reproductive health. ICMR Bull 1999;29(6):59. 30. Mason K, Lynam P. Not for women only: Child-spacing clubs for Malawian men. AVSC News 1992;30(4):4. 31. Khan M, Patel B. Male Involvement in Family Planning: A KABP Study of Agra District India. Final Report. New Delhi: Population Council, 1997. 32. Ogunjuyigbe PO. Spousal communication, changes in partner attitude and contraceptive use among the Yorubas of Southwest Nigeria. J Soc Sci 2002;6(1):59-64. 33. Lalla T. Male involvement in family planning: A review of the literature and selected program initiatives in Africa 1996. https://pdfs.semanticscholar.org/15a6/5e5df695118e7961c5c21012452df44bccb1.pdf (accessed 11 September 2017). 34. Spicehandler J, Simmons R. Expanding Family Planning Options: Contraceptive Introduction Reconsidered. A Review and Conceptual Framework. Geneva: World Health Organization, 1994.

Accepted 23 August 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

CME

Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts D Pillay,1 MPH; C Morroni,1,2,3,4 MB ChB, DFSRH, DTM&H, MPH, MSc, PhD; M Pleaner,1 MEd; O A Adeagbo,1 MA, PhD; M F Chersich,1 MB BCh, PhD; N Naidoo,1 MPH; S Mullick,1 MB ChB, MSc, MPH, PhD; H Rees,1 MB BChir, MA (Cantab), MRCGP, DCH, DRCOG Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Women’s Health Research Unit, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 EGA Institute for Women’s Health and Institute for Global Health, University College London, UK 4 The Botswana-UPenn Partnership, Gaborone, Botswana 1 2

Corresponding author: D Pillay (dianthapillay@gmail.com) Background. Implanon NXT, a long-acting subdermal contraceptive implant, was introduced in South Africa (SA) in early 2014 as part of an expanded contraceptive method mix. After initial high levels of uptake, reports emerged of frequent early removals and declines in use. Monitoring of progress and challenges in implant service delivery could identify aspects of the programme that require strengthening. Objectives. To assess data management and record keeping within implant services at primary care facilities. Methods. We developed a checklist to assess the tools used for monitoring implant services and data reporting to district offices. The checklist was piloted in seven facilities. An additional six high-volume and six low-volume implant insertion clinics in the City of Johannesburg (CoJ), Gauteng Province, and the Dr Kenneth Kaunda District, North West Province, were selected for assessment. Results. All 12 facilities completed a Daily Head Count Register, which tallied the number of clients attending the clinic, but not information about implant use. A more detailed Tick Register recorded services that clinic attendees received, with nine documenting number of implant insertions and six implant removals. A more specific tool, an Insertion Checklist, collected data on insertion procedures and client characteristics, but was only used in CoJ (five of six facilities). Other registers, which were developed de novo by staff at individual facilities, captured more detailed information about insertions and removals, including reasons. Five of six low-volume insertion facilities used these registers, but only three of six high-volume facilities. No facilities used the form specifically developed by the National Department of Health for implant pharmacovigilance. Nine of 12 clinics reported data on numbers of insertions to the district office, six reported removals and none provided data on reasons for removals. Conclusion. For data to inform effective decision-making and quality improvement in implant services in SA, standardised reporting guidelines and data collection tools are needed, reinforced by staff training and quality assessment of data collection. Staff often took the initiative to fill gaps in reporting systems. Current systems are unable to accurately monitor uptake or discontinuation, or identify aspects of services requiring strengthening. Lack of pharmacovigilance data is especially concerning. Deficiencies noted in these monitoring systems may be common to family planning services more broadly, which warrants investigation. S Afr Med J 2017;107(10):827-831. DOI:10.7196/SAMJ.2017.v107i10.12822

In 2012, the National Department of Health (DoH) adopted the National Contraception and Fertility Planning Policy. The overarching goal of this policy was to expand the country’s contraceptive method mix by promoting long-acting reversible contraceptive (LARC) methods, such as the subdermal contraceptive implant.[1] The policy narrative states that injectable contraceptives account for half of contraceptive use nationally and for up to 90% in some areas,[1] and that this predominance of short-term methods has several drawbacks. Many women discontinue injectable methods, or return late for their next injection,[1,2] placing them at risk for unintended pregnancy. Introducing the Implanon NXT, a long-acting subdermal contraceptive implant, in the public sector in 2014, thus aimed to provide a more effective contraceptive alternative.[3] Contraceptive implants, such as Implanon NXT, which offers 3 years of protection against pregnancy, are highly effective and acceptable across multiple settings.[4,5] In the year after the launch of Implanon NXT, the DoH reported that ~800 000 implants had been inserted and that >6 000 healthcare providers had been trained with regard to implant provision (T Zulu. Updates on the implant roll-out in South Africa: National perspective

– unpublished paper presented at a meeting, Pretoria 2015). The DoH stated that by April 2015, according to their estimates, ~5 000 removals had been recorded and that this figure has been steadily rising over time. The DoH, however, was increasingly concerned following negative media reports on the implant and District Health Information System (DHIS) data showing a steady decline in uptake. Aside from a case report, where a woman in South Africa (SA) had the implant removed owing to bleeding irregularities 10 months after insertion, and unconfirmed estimates from the DoH, the actual number of and reasons for implant removals are unknown. These gaps in data signal weaknesses in monitoring systems in the family planning programme. When new contraceptive methods are introduced, there may be delays in incorporating indicators for use and safety within existing information systems.[7] The analysis of monitoring data from new methods, such as the implant in SA, therefore needs to be supplemented by the findings of periodic evaluations, and more rigorous, independent assessments of specific aspects of the services, such as the quality of the routine monitoring systems. We therefore examined the data management and record-keeping systems used

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Methods

Study setting

This study, conducted in late 2016, formed one component of a larger evaluation in which we assessed the quality of implant services in SA. We selected six facilities in the City of Johannesburg (CoJ), Gauteng Province, and six in the Dr Kenneth Kaunda District (DKKD), North West Province. Sites were chosen based on the number of implant insertions recorded in the DHIS for 2015. The sampling frame for selecting the study sites in CoJ consisted of 17 primary care facilities, with a total of 1 045 insertions in 2015; the sites in DKKD were chosen from 40 facilities, with a total of 727 insertions. In each district, three facilities with the highest and three with the lowest number of insertions were included. High-volume clinics had inserted as many as 305 devices in CoJ in 2015, while all three in DKKD had inserted ~60. In both districts, most of the low-volume clinics had performed fewer than five insertions. All the selected facilities had been providing the implant since February 2014.

Development and piloting of a checklist tool

We developed a study checklist to assess the presence and content of monitoring tools for recording and reporting data on the implant at primary care level. The tool was designed in consultation with a clinician, who had trained healthcare providers regarding the implant and was familiar with the services in SA and elsewhere. The checklist was then piloted in seven primary health facilities (three in CoJ and four in DKKD â&#x20AC;&#x201C; distinct from the study sites) in late 2015. Facilities for the pilot were also selected based on the number of insertions done (three high- and four low-volume clinics). The research team used the pilot checklist to review the tools used to monitor implant use and the mechanisms for reporting of data to district offices, and finalised the tool thereafter. The final study checklist documented the presence of the tools (captured as a binary variable: present or not), purpose of five data collection tools that had been identified during the pilot, and vari-

1. Data management and record keeping of implant services at facilities

ables collected in each (Table 1). The tool also assessed the reporting of statistics from facility to district level.

Audit of monitoring tools in the study sites

During site visits, using the study checklist, the study team reviewed the tools used for monitoring of implant services (any tool used from February 2014 onwards). In addition, family planning providers and clinic data capturers were asked about which data were reported to the district and the frequency of reporting. We present data using descriptive statistics for overall totals and for each district, and examine differences between high- and low-volume facilities.

Ethical approval

The study was approved by the University of the Witwatersrand Human Research Ethics Committee (ref. no. M151147).

Results

Data collection tools used for all facility attendees

All facilities have a Daily Reception Headcount Register, a standardised tool that was well established and maintained across all the facilities (Fig. 2). Although all clinics had a Primary Healthcare (PHC) Comprehensive Tick Register, different versions were being used in the two districts. The facilities in CoJ used the most updated version of the register, which included a section for recording both implant insertions and removals. DKKD facilities used an older version, which only records insertions. Overall, however, based on our observations, in only nine of the 12 facilities were data on insertions actually being captured in the PHC Comprehensive Tick Register, even though these registers included implant insertion fields in all clinics. Assessment of the Reception Headcount and PHC Tick registers during the pilot phase showed similar findings. Presence

Insertions recorded

Removals recorded

9 8 8

8 Facilities, n

to monitor implant insertions and removals in two districts of SA, focusing on their quality and standardisation across facilities. Identifying and addressing gaps in these systems will enable the DoH and other stakeholders to monitor whether the goals of implant services are being achieved, and to identify aspects of the services that require strengthening as per the process (Fig. 1). These findings may also inform decisions around the selection of indicators for the programme and the design of data collection tools.

6 5

trict to d is rted Repo

acov ig Form ilance

Inse rt Che ion cklis t

PHC T Regis ick ter

rtion /R Regis emoval ter

Phar m

3. Monitoring of performance and safety of implant services

Data collection tools

Fig. 1. A monitoring and evaluation framework for implant services in South Africa. (*Evaluation of monitoring systems reported here was one component of a larger evaluation of implant services.)

0 0 0

Inse

4. Evaluation of implant services, including monitoring systems*

0 0

2. Data reporting to district

Dail Hea y Recep dcou t nt R ion egis ter

5. Strengthening of services based on monitoring and evaluation data

Fig. 2. Data collection tools for capturing implant insertion and removal data, and reporting of data to district level at six facilities in the City of Johannesburg and six in Dr Kenneth Kaunda District. (PHC = primary healthcare.)

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Table 1. Purpose, description and variables collected in data collection tools identified in the pilot study Name of data collection tool identified in pilot* Daily Reception Headcount Register

Purpose of tool To register all clients accessing the facility

PHC Comprehensive Tick Register

To document visits to PHC services Can be used to trace clients who have had an implant inserted

Implant Insertion Checklist

To gather information on implant insertions and characteristics of implant users To provide concise instructions to health providers on how to insert an implant To capture detailed client information on insertion and removal, in addition to monitoring absolute numbers thereof

Implant Insertion and Removal Register

Active Surveillance Reporting Form for Subdermal Implants

Developed by DoH to track contraception use, medical history and adverse events related to implant use

Description of tool and variables collected Developed by DoH and nationally standardised. Documents the names, contact details and locator information of all clients attending PHC, including implant initiators, but does not specify reason for attendance Captures number of clients attending different services at a PHC. Includes client name and services that they receive. Contains a woman’s health section, capturing data on implant insertions and removals Absolute numbers of clients utilising services are tallied and reported as part of the District Health Information System Client contact details can be found by linking data with the Reception Headcount Register Developed by CoJ, to be completed for each implant insertion Contains date of insertion and client information, e.g. name, client file number, date of birth and contact details Captures reproductive history (i.e. parity, cervical cancer screening, breast cancer history and vaginal bleeding) Contains concise instructions on how to insert an implant

Register or book that records implant insertions and detailed data on reasons for removals. Data collected extends beyond that of the PHC Comprehensive Tick Sheet, which records only absolute numbers of clients. Tools developed de novo by individual facilities Registers either combine insertion and removal data, or separate registers are used for insertions and removals A nationally prescribed form for capturing pharmacovigilance data exclusively for the implant. Variables to be collected include anthropometric measures; concomitant medications for TB, HIV and epilepsy, and herbal products; laboratory results (pregnancy test, haemoglobin, CD4 cell count, HIV viral load); reproductive health history (parity, breastfeeding, contraception use and cervical cancer screening); content of implant counselling; insertion and removal date; reason for removal; and any adverse drug reactions

PHC = primary healthcare; DoH = Department of Health; CoJ = City of Johannesburg; TB = tuberculosis. *The five tools were identified at one or more of the pilot study sites. Variables collected in each tool are italicised.

Data collection tools used only for implant insertions and removals

The Implant Insertion Checklist had been created specifically for the CoJ and was present in all six facilities in the district, but only used in five of them. No facilities in DKKD were using this or a similar checklist. However, in eight facilities (four in CoJ, four in DKKD), facility-based nurses had, on their own initiative, developed an Insertion and Removal Register to capture detailed data on implant insertions and removals. These consisted of either A4 sheets of paper or A5 books. While all eight of these entered data on insertions, only six collected data on removals. These registers were also noted at several of the clinics visited during the pilot phase of the study. The ‘home-made’ Insertion and Removal registers collected considerably more detailed information on insertions and removals than the other registers. The variables collected varied across facilities, but included data on name of provider who did the insertion, date of expected return following insertion, date of removal, reason for removal and name of provider who removed the device. The tools also often contained data that could be used to identify aspects of the services that require further attention or investigation. For example, data in one removal register showed that the implant had been removed in 14 clients who had presented with a broken implant. In these cases, which occurred over the course

of a year, the broken devices had been discarded and the cases not communicated to the district or national level DoH. None of the 12 facilities was completing the Active Surveillance Reporting Form for Sub-Dermal Implant, and none of the staff was aware of the form’s existence. Similarly, none of the seven sites in the pilot study was using this form. Overall, 10 of the 12 facilities provided information to the district offices on the number of insertions done and nine reported removal numbers. No facilities reported the reasons for implant removals, or adverse events associated or potentially associated with the device.

Differences in monitoring of implant insertions and removals between high- and low-volume facilities

Recording of insertions in the PHC Comprehensive Tick Register was similar between high-volume (5/6) and low-volume (4/6) facilities (Fig. 3). Recording of removals in the PHC Comprehensive Tick Register was done in all three high-volume and three low-volume facilities in CoJ, and none in DKKD. However, more low-volume inserting facilities (5/6) were using implant insertion registers than high-volume inserting facilities (3/6). Half the high-volume and half the low-volume inserting facilities used the implant removal register. All the high-volume facilities reported insertion statistics to the district, compared with only four of the six low-volume facilities. More high-volume facilities (6/6) reported removal statistics to the

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High-volume insertion facilities

Low-volume insertion facilities 6

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Pha r

Rem Reg oval iste r

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Data collection tools

Fig. 3. Data collection tools for capturing of implant insertion and removal data, and reporting to district level in six high-volume and six low-volume clinics. (PHC = primary healthcare.)

district using the PHC Comprehensive Tick Register and removal register as source data compared with half of the low-volume facilities (3/6).

Discussion

The study shows major gaps in tools and standardisation of monitoring systems for implant services. Data are not systematically reported to district level, e.g. a quarter of facilities do not submit numbers of removals. Overall, gaps in data collection and reporting, even in high-volume clinics, mean that the current DHIS underestimates the actual utilisation of the implant and give little indication of the occurrence (and timing) of removals. The South Africa Family Planning programme is therefore unable to understand the true extent of and reasons for the decline in implant use. Importantly, more high- than low-inserting facilities were reporting both insertion and removal statistics to the district. Data are not available to guide the initiatives that are urgently needed to strengthen implant services in the country.[8] This is especially pressing given the importance of robust data for directing service delivery in the first years after the introduction of contraceptive methods.[9] Problems with new methods, if not corrected, often lead to withdrawal of methods from national programmes.[10] The World Health Organization (WHO) framework for the introduction of new contraceptive methods suggests a three-stage process, which starts with determining a need for the new method according to end-user needs (Stage 1), conducting service delivery and end-user research (Stage 2), and exploring implications of research for utilisation of the method (Stage 3).[9] As per Stage 1, the

DoH introduced the implant, recognising the need for an expanded method mix and methods that were not user dependent. This study addresses both Stage 2 (service-delivery research, monitoring in this instance) and Stage 3 (implications of assessment of monitoring for implant programmes). Poorly functioning monitoring systems hinder efforts of Stage 2 and compromise any efforts to strengthen services in Stage 3. The Policy Project suggests that a performance-monitoring system should not be developed in a vacuum, but rather constitute an integral part of the overall service delivery system that is capable of identifying problems and taking corrective actions.[7] Traditionally, too much emphasis has been placed on mere recording of new acceptors of contraception, without consideration of other pertinent information, such as method continuation and reasons for discontinuation,[7] as noted in this study. Additional data sources, such as a repeat of this evaluation, may be needed in a few years to assess improvements in monitoring systems and other gaps in programming.[11] Furthermore, there is a need for disaggregated data on implant insertions and removals, such as by age and whether women are new contraceptive users or method switchers. DHIS data are sourced from the PHC Tick Register, which as a monitoring tool is constrained by the limited data it gathers, which does not include age, for example. It is, however, encouraging that the PHC Tick Register has evolved over time, with later versions encompassing data on removals, although these were not yet being used in DKKD. Seemingly, deficiencies in the data collection tools were apparent to health providers, who themselves then developed data collection tools to capture pertinent information. This demonstrates considerable initiative and resourcefulness of nurses, and illustrates their awareness of the importance of data collection. Even though these data are useful for the purposes of fine-tuning services at individual facilities, standardising data collection and reporting across clinics could alter district and even national programming. Commodity use does not appear to be captured in the DHIS for the implant, which should show numbers of devices ordered and returned, analogous to how antiretroviral drugs are monitored. Antiretroviral stocks are monitored by the DoH at drug depots and facility level. Stock delivered to individual facilities is also captured, and stock ordering and returns are accounted for at drug depots. The Handbook of Indicators for Family Planning Program Evaluation,[12] developed through the Evaluation Project, suggests that to measure service delivery operations, commodities need to be monitored. They suggest tracking quantities of contraceptives procured annually, quantities in stock at central stores, amount distributed from central stores, and inventory levels and stock-outs at service-delivery points. These data could complement facility-level reporting, and together provide useful insights to inform the fine-tuning, reorientation and planning of service improvements. Of particular concern is that adverse events and other aspects of pharmacovigilance of the implant are not being collected. Removals, but also insertions, can have complications, which should be brought to the attention of district and provincial authorities. Even though complications are rare, a review of clinical studies of Implanon NXT showed that complications occur in ~1% of insertions.[13] These included deep insertions with fibrous adhesions, and non-palpable or broken implants.[13] The Active Surveillance Form for Sub-Dermal Implants has not been rolled out to the facilities, possibly as the number of data points it contains (24 variables) makes its completion onerous for health providers. If the purpose of this form is solely pharmacovigilance, fewer and more relevant indicators need to be selected and the form should be used.

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Study limitations

The study is limited by not having examined the quality and completeness of the data. Furthermore, the findings may not reflect the monitoring systems in the entire country, or of clinics that perform a moderate number of insertions. The generalisability of the findings are, however, enhanced by the inclusion of 19 sites (seven pilot study sites and 12 study sites) across two provinces, encompassing both urban and peri-urban locations. Also, sampling of both high- and low-volume clinics allowed for more detailed analysis of data systems.

Conclusion

This study is the first assessment of data management and reporting structures for monitoring the contraceptive implant in SA. The findings highlight aspects of the monitoring system that need to be strengthened to provide timely, actionable information to guide improvements in the country’s implant services. Our study underscores the need for standardised tools, and data collection and reporting guidelines. A single nationally standardised data collection tool could be developed, which consolidates and replaces the insertion checklist, insertion and removal registers, and pharmacovigilance forms. This could facilitate collection of data for a few carefully selected indicators of performance and obstacles to service delivery. Indicators need to be carefully considered and prioritised, so as to collect sufficiently detailed information, but without overburdening healthcare providers.[7] Clearly, data monitoring needs to extend beyond absolute counts of utilisation and discontinuation, which themselves are currently poorly collected. Other important data include client characteristics (especially age and most recent contraception), insertion and removal dates, reasons for removals, details of removal procedures (e.g. duration of the procedure and complications) and contraception choice after removal. As an immediate step, the reporting of data from the PHC Tick Register could be strengthened, and encompass insertions, removals and reasons for removal. Lastly, it is possible that deficiencies noted in this study are common to family planning services in SA in general, a concern that warrants further investigation.

Acknowledgements. We thank the Department of Health for allowing us access to the health facilities, the anonymous reviewers of this article, clinics that participated, and Ntombizethu Dumakude for her contribution to tool development and the pilot study. We would also like to acknowledge the data collectors (Fortunate Gombela, Iris Sishi, Lindiwe Mbuyisa, Ntombenhle Twala, Siziwe Sidabuka and Tebogo Mokoena). Author contributions. DP: project leader and responsible for project design, implementation and write-up, and supported by CM, MP, OAA, NN, MFC, and SM. HR: senior author, providing oversight and review. Funding. Funding was received from the United Nations Population Fund (UNFPA), which also provided technical assistance. Conflicts of interest. None. 1. National Department of Health. National Contraception and Fertility Planning Policy and Service Delivery Guidelines: A Companion to the National Contraception Clinical Guidelines. Pretoria: DoH, 2012. 2. Baumgartner JN, Morroni C, Mlobeli RD, et al. Timeliness of contraceptive reinjections in South Africa and its relation to unintentional discontinuation. Int Fam Plan Perspect 2007;33(2):66-74. 3. Patel M. Contraception: Everyone’s responsibility. S Afr Med J 2014;104(9):644. https://doi.org/10.7196/ SAMJ.8764 4. Rowlands S, Searle S. Contraceptive implants. Curr Perspect 2014;5:73-84. https://doi.org/10.2147/ OAJC.S55968 5. Dickerson LM, Diaz VA, Jordon J, et al. Satisfaction, early removal, and side effects associated with long-acting reversible contraception. Fam Med 2013;45(10):701-707. 6. Adams B. Subdermal implants: A recent addition to the choice of South African contraceptives. Prof Nurs Today 2015;19(2):32-34. 7. United States Agency for International Development. The POLICY project – performance monitoring for family planning and reproductive health programs: An approach paper. Geneva: USAID, 1996. http://policyproject.com/pubs/workingpapers/wps-01.pdf (accessed 4 September 2017). 8. Adamchak SE, Okello FO, Kaboré I. Developing a system to monitor family planning and HIV service integration: Results from a pilot test of indicators. J Fam Plann Reprod Health Care 2016;42(1):24-29. https://doi.org/10.1136/jfprhc-2014-101047 9. Spicehandler JSR. Contraceptive Introduction Reconsidered: A Review and Conceptual Framework. Geneva: WHO, 1994. http://who.int/reproductivehealth/publications/family_planning/HRP_ITT_94_1/ en/ (accessed 4 September 2017). 10. Pleaner M, Morroni C, Smit J, et al. Lessons learnt from the introduction of the contraceptive implant in South Africa. S Afr Med J 2017;107(11). (Accepted for publication.) https://doi. org/10.7196/SAMJ.2017.v107i11.12805 11. Igras S, Sinai I, Mukabatsinda M, Ngabo F, Jennings V, Lundgren R. Systems approach to monitoring and evaluation guides scale up of the Standard Days Method of family planning in Rwanda. Glob Health Sci Pract 2014;2(2):234-244. https://doi.org/10.9745/GHSP-D-13-00165 12. Bertrand JTMR, Rutenberg N. Handbook of Indicators for Family Planning Program Evaluation. Geneva: USAID, 1994. 13. Evans R, Holman R, Lindsay E. Migration of Implanon®: Two case reports. J Fam Plan Reprod Health Care 2005;31(1):71-72. https://doi.org/10.1783/0000000052973068

Accepted 23 August 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

IN PRACTICE

ISSUES IN PUBLIC HEALTH

‘Best buys’ for surgery in South Africa T Wilkinson,1 MSc; M Smith,2 MB BCh, FCS; A Kinghorn,1 MB BCh, MSc; K J Hofman,1 MB BCh, FAAP ¹ PRICELESS SA, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ² Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: K J Hofman (karen.hofman@wits.ac.za)

Improving access to basic surgical interventions has great potential to improve the length and quality of life of many people in low- and middle-income countries (LMICs). However, research has shown that current access to surgical interventions is limited, and initiatives such as the Lancet Commission on Global Surgery 2030 advocate for improved access to basic surgical interventions for all. As the needs, health system context and available budgets in each country will be different, a critical component of effective local scale-up of surgical interventions will be to use tools and processes of health technology assessment (HTA). HTA has traditionally been used in high-income countries to make decisions about which medicines and devices should be available in a health system, but its central concepts, such as assessing clinical effectiveness, cost-effectiveness and feasibility, appraising all available evidence, and incorporating wider health systems objectives in decision-making, can be applied to decisons about how LMICs can best utilise basic surgical interventions from within available resources – in essence, to focus spending on the ‘best buys’. As South Africa (SA) moves towards National Health Insurance (NHI), HTA functions will be strengthened. There is potential for SA to lead the practice of application of HTA to decisions about how basic surgical interventions are chosen and implemented, contributing to the success and sustainability of NHI in SA and the health of people in LMICs worldwide. S Afr Med J 2017;107(10):832-835. DOI:10.7196/SAMJ.2017.v107i10.12414

A new era in surgery has emerged.[1] A discipline faced with multiple challenges in the universal health coverage environment is discovering how to integrate surgical care provision into the global health agenda. The traditional perception that surgery is less costeffective than other available interventions, such as medicines or public health interventions, is being challenged by new emerging evidence suggesting that surgery can represent good value for money. [2] Surgical care is not a pathology-based intervention, but rather a dynamic system that has a crucial role to play in managing the burden of disease, including communicable and noncommunicable diseases. Several recent developments have highlighted the crucial role of surgery in the health system. The 2015 World Health Assembly resolution 68.15 outlined the importance of ‘Strengthening emergency and essential surgery and anaesthesia care as a component of universal health coverage.’[3] In addition, the Lancet Commission on Global Surgery 2030 synthesised much of the evidence supporting the role of surgery and modelled a number of scenarios.[4] Key messages from these developments reflecting the role of surgery globally and the consequence of failure to address the unmet surgical need are: • 5 billion people cannot access safe surgery when needed • 33 million individuals face catastrophic expenditures paying for surgery and anaesthesia annually • Investing in surgery is affordable, saves lives, and promotes economic growth. In South Africa (SA), there is a need to develop a care package for the different levels of service delivery in the public health system, including a package for district hospitals. Developing these packages requires an understanding of the economic implications of intervention implementation. The content of these packages could then inform the development of a national surgical plan.

The success of an initiative focused on developing and implementing surgical care packages at different levels of care will be determined by many factors, including the ability of educational institutions to facilitate the skills transfer of appropriate competencies, and the availability of appropriate infrastructure and systems to allow the delivery of the different care packages. Surgical care is strongly linked to technology. There is a flood of new technologies and innovation in the surgical care environment, and determining the appropriate intervention for the right setting requires an evidence-based evaluation of the technologies. The spectrum of interventions that could be considered appropriate ranges from low-technology-driven procedures with a wide reach that can be offered to patients at primary care level, to high-end technologies that can only be performed at tertiary care level. So what surgical options should we offer? This question is at the heart of priority setting, which draws on the best traditions of evidence-based medicine, health economics and medical ethics, and can help us to identify what health interventions and technologies can and should be offered to people under a universal health coverage system in SA under the rubric of National Health Insurance (NHI). It is through the use of formal processes and methods that reasoned and defensible decisions can be made about investment and implementation of low- and high-cost surgical procedures. Priority setting allows us to identify the surgical ‘best buys’ for SA based on a review of available evidence and to support and ensure appropriate utilisation of resources. Best buys are packages of interventions, services and/or policies that could be implemented within a particular programme area given available resources and health-systems constraints. For example, the role of laparoscopic surgery in the management of appendicitis or hernia repairs needs to be determined in SA contexts. Utilising health technology assessment (HTA) and priority setting, we can achieve the best use of resources,

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and include the most cost-effective surgical interventions regardless of their level of complexity.

Priority setting, HTA and surgery

PRICELESS SA (Priority Cost Effective Lessons in Systems Strengthening, www.pricelesssa.ac.za) is a research-to-policy programme that uses SA data to demonstrate how scarce resources can be used to derive maximum impact on health. To demonstrate the potential benefits of priority setting, PRICELESS SA works to identify best buys, using HTA to ensure that limited resources are targeted towards interventions, policies and programmes that will offer the greatest health gain across the population. For example, by prioritising 15 maternal and child health interventions we identified as best buys, the lives of an additional 10 000 mothers and newborns per year in SA could be saved at a cost of USD7 per capita.[5] The principle of best buys and identifying cost-effective inter ventions can be applied across any programme area and setting, including surgery. Investigations of cost-effective surgical interventions relative to neglected tropical diseases across subSaharan Africa found that basic surgical services, emergency obstetric surgery, and surgical management of fractures, soft-tissue trauma and some cancers were relatively cost-effective compared with other prioritised interventions in the region.[6] Researchers have demonstrated that surgical management of acute appendicitis represents relatively good value for money in SA, at approximately USD1 700 per life-year saved.[7] Additional cost-effectiveness research is required, especially with regard to the availability and utilisation of elective surgical procedures as a treatment option, the availability of which is often linked with socioeconomic status (SES). For example, cataract surgery coverage in Cape Town was 68% in areas associated with the lowest SES compared with 100% in areas with the highest SES. This is one example of how priority setting could inform policy and planning decisions across the health system – by showing how to deploy scarce resources effectively to address avoidable blindness.[8] Although a consistent approach to establishing best buys and priority setting in surgery has not yet been established, progress towards NHI is likely to make this a reality. The White Paper on NHI released in 2015[9] and revised in 2017[10] indicated the important role HTA will play in the prioritisation, selection, distribution and management of medicines, devices and interventions. HTA will empower policy-makers to make the most efficient use of resources. The term HTA and associated concepts are used frequently in discussions about resource allocation improvement, so it is instructive to define it here. According to the International Society for Health Technology Assessment, HTA is a ‘field of scientific research to inform policy and clinical decision making on the introduction and use of health technologies … HTA is a multidisciplinary field that addresses the clinical, economic, organizational, social, legal, and ethical impacts of a health technology, considering its specific healthcare context as well as available alternatives’.[11] Importantly, technologies are defined broadly to mean pharmaceuticals, devices and procedures (including surgical procedures), as well as clinical, public health and service/organisational interventions. Put simply, HTA is the analysis of the costs and benefits of a health intervention, incorporating other relevant factors and then using the results of the analysis to make policy decisions. HTA is a useful tool to make an evidence-based case for surgery that might otherwise be perceived as too complex or expensive to implement – the same areas that are likely to represent the highest unmet need, and where we can get the biggest ‘bang for the buck’ from stretched health budgets. Importantly, HTA can be used to make the clinical, economic, social

and common-sense case for investment in high-impact surgical interventions that are good value for money. Priority-setting methods and processes can extend beyond an individual procedure to packages of care and service delivery platforms. For example, in some instances the most cost-effective way to provide highly specialised services may be to fund a smaller number of specialised hospitals providing limited ranges of procedures, but at a higher volume. However, over-specialisation of surgical staff in a context with limited human resources could lead to poorer overall outcomes and cost-effectiveness of services. SA policy and planning may need to consider alternative scenarios, for example by training clinical associates to perform a single procedure flawlessly, as is done in other middle-income settings.

Acknowledging unavoidable tradeoffs: Economists and surgeons

Priority setting, with its foundations in universal health coverage, takes a population-level approach. ‘Best buys’ defines ‘best’ as those interventions that can feasibly achieve the greatest health impact from available resources. Implicit in this approach is consideration of the opportunity cost: because budgets are fixed, the opportunity cost is the health gain that could be achieved elsewhere in the healthcare system had resources been used differently. All interventions involve resource use, whether it is time, money, or physical use of space. Priority setting is about weighing up these trade-offs and making an informed decision. While terms such ‘opportunity cost’ and ‘trade-off ’ are traditionally the parlance of economists, surgeons are likely to innately understand the concept. Surgical training prepares them to evaluate likely benefits and harms of a procedure, communicate this to the patient, and decide on a course of action. At a population level, surgical triage aims to arrange patient flows and prioritise treatment to maximise collective patient benefit from available resources, implicitly incorporating opportunity costs into service planning and decision-making. Priority setting is no different, except that instead of being applied to an individual patient or group of patients at a single place and time, it occurs continuously and at population level, across multiple delivery platforms and potential interventions. In addition to hard science about likely benefits, harms and costs, and their relative uncertainty, active priority setting also allows decisionmakers to take into account the wider social values and health system objectives that are an inherent factor in many medical and resource allocation decisions.

A NICE approach

The National Institute for Health and Care Excellence (NICE) in the UK is a priority-setting institution that uses HTA to advise the National Health Service (NHS) on the use of particular interventions and technologies. The pros and cons of a NICE-like approach in SA have been debated,[12-14] with principal consideration in the literature given to the implication of applying cost-effectiveness/HTA decision rules to access and eligibility decisions and the feasibility of applying the NICE structure and institutional arrangements to the SA context. This literature suggests that while SA will need to develop locally appropriate institutional arrangements, individual lessons and experiences from NICE can provide a comprehensive understanding of how priority setting could be applied to surgical interventions. For example, NICE guidance on gastro-oesophageal reflux disease (GORD) considered whether laparoscopic fundoplication should be routinely offered to patients suffering from reflux.[15] GORD patients are traditionally managed medically, but improvements in outcomes and safety of fundoplication techniques suggested that surgery might

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be a more appropriate intervention. The NICE evaluation used established processes and methodological frameworks to compare laparoscopic fundoplication with medical management. The surgical option represented comparatively high up-front costs and potential risks, but provided superior long-term health and cost outcomes for many patients. Part of the evidence-review process was consideration by a multidisciplinary committee that included lay membership, which is especially important when assessing patient perceptions and experience of surgery. In addition, the committee considered whether laparoscopic surgery could routinely and safely be offered to the population in an equitable way, or whether a recommendation for use would only favour those near major surgical centres. After evidence collation and economic modelling, laparoscopic fundoplication was found to represent a good investment option for the NHS and met patient safety and equity-of-access considerations. NICE recommends that it now be offered routinely when individual patient characteristics warrant surgical intervention. While management of reflux may not be a high priority in SA, the principles by which a robust and trusted priority-setting process might work are highly relevant to the proposed NHI environment.

HTA for surgery: Challenges

Traditionally, government institutions involved in explicit priority setting such as NICE in England, the Health Intervention and Technology Assessment Program in Thailand or the Pharmaceutical Management Agency of New Zealand started with assessments and decisions about pharmaceuticals. The reasons for this focus on pharmaceuticals vary, as the priority-setting journey is always unique, but a common factor is the tractability of the decision problem. HTA involves an assessment of the likely costs and effects of an intervention, and on a population level it is generally easier to isolate both the marginal spend and clinical effectiveness estimate of a pharmaceutical product compared with a surgical intervention. To apply HTA to surgery, we must ensure that we can accurately, reliably and consistently represent costs and effects of surgical interventions at population level. This will allow them to be considered on a level playing field with competing surgical interventions and other potential healthcare investments. Surgical skill and experience, in addition to health system organisation and referral structures, has a direct impact on costs and patient outcomes, just as the clinical effect of a course of medication will vary depending on the prescribing physician, the service environment and patient compliance. Surgical costs can, however, be vastly different between centres depending on surgical techniques, case mix, patient throughput volumes and financing arrangements for capital equipment. For example, annual surgical cost in India was USD5 000 per bed in a 60-bed charity hospital, USD800 per bed in a 400-bed, first-level public hospital, and USD2 000 per bed in a 655bed private teaching hospital; the high costs of the charitable hospital were attributed to expatriate staff and external funding.[16] This variation in costs and effects makes obtaining a central estimate and distribution challenging – a factor that can be overcome by improved data collection and management. Another challenge to HTA for surgery is the uneven nature of the inputs (costs) and outputs (patient health). For a patient receiving medical treatment for a chronic condition, the costs (e.g. one tablet per day) and clinical outcomes are relatively consistent and predictable. In contrast, with surgery the costs and risks are mostly incurred up front, with clinical benefit often extending for many years, particularly for life-saving interventions. Again, this calculation issue can be overcome through the use of analytical techniques that take into account short- and long-term effects

and costs. It is, however, important to acknowledge this analytical challenge and the potential unacceptability to policy-makers with limited budgets to prioritise surgical investments that may represent a large ‘pay now, benefit later’ offer. Using HTA to inform decisions on the use of surgical interventions and the appropriate level of care may also be challenging. In addition, once surgical services with their supporting infrastructure are in place, the estimates of the incremental cost-effectiveness of interventions will be affected (compared with facilities without this infrastructure), leading to inconsistent estimations of the cost-effectiveness of the interventions. These dilemmas require techniques to assess options for referral systems or different service delivery platforms, and for analyses that look more carefully at incremental and marginal costs rather than just average costs. While these approaches may add complexity to the analyses, the results enable more robust policy decisions on service availability and better resource use from primary to tertiary level, with better outcomes for patients.

Conclusion: Advancing priority setting for surgery

High-impact, low-cost surgical interventions may be a good use of limited health funds in SA. However, to make the case for the necessary investments, two key elements are required. Firstly, frameworks for accurately representing and analysing costs and clear outcomes for surgical interventions need to be developed. This is often seen as primarily an area for policy makers, but the surgical community must play its part in this process. The surgical community can contribute by conducting research to determine which surgical procedures account for better or worse balances between number of admissions, mortality, complications and costs on the one hand, and improvements in length and quality of life on the other. The second element that is required is the strengthening of priority-setting frameworks. This involves introducing processes and methods for analysing and deliberating the clinical and economic evidence, but also for more systematic consideration of social values such as the need to improve equity in access to health services. An important component of these processes will be to adopt a population-level perspective. This will ensure that opportunity costs of investments are understood and that optimal health outcomes are achieved from within available budgets. These frameworks would need to be applied across several programme areas and types of medical technology and intervention. However, it is certain that various surgical interventions would be considered good investments, strengthening the case for their implementation and ultimately improving the health of all South Africans.

Salient points

• There is a large unmet need for basic surgical interventions in many low- and middle-income countries. • Priority setting is a process by which decisions are made on health priorities based on evidence of potential benefit, risk, resource use and opportunity cost, in addition to consideration of values such as equity and fairness. • HTA is a mechanism to synthesise, present and appraise the evidence required for priority setting. • The case for high-impact, low-cost surgery in SA would be strengthened by an HTA approach, as well as establishment of an effective priority-setting system or agency.

Acknowledgements. The authors thank Agnes Erzse for final proofing and editing of the manuscript.

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Author contributions. KJH and TW made substantial contribution to conceptualisation and design of the article. All authors (TW, MS, AK, and KJH) contributed to the content, writing and editing of the article. All the authors commented on and approved the final version of the article. Funding. This article was produced by PRICELESS SA. The work received funding from the International Decision Support Initiative through a grant from the Bill and Melinda Gates Foundation (grant no. 740671). Conflicts of interest. None. 1. Mahoney C, Fleck F. Meeting the need for surgery. Bull World Health Organ 2016;94(3):163-164. https://doi.org/10.2471/BLT.16.020316 2. Prinja S, Nandi A, Horton S, Levin C, Laxminarayan R. Costs, effectiveness, and cost-effectiveness of selected surgical procedures and platforms. In: Disease Control Priorities, 3rd ed. (vol. 1): Essential Surgery. World Bank, 2015:317-338. https://doi.org/10.1596/978-1-4648-0346-8_ch18 3. World Health Assembly. Resolution A68/31: Strengthening emergency and essential surgical care and anaesthesia as a component of universal health coverage. 2015. http://apps.who.int/gb/ebwha/ pdf_files/WHA68/A68_31-en.pdf (accessed 16 February 2016). 4. Meara JG, Leather AJM, Hagander L, et al. Global Surgery 2030: Evidence and solutions for achieving health, welfare, and economic development. Lancet 2015;386(9993):569-624. http://dx.doi. org/10.1016/S0140-6736(15)60160-X 5. Chola L, Pillay Y, Barron P, Tugendhaft A, Kerber K, Hofman K. Cost and impact of scaling up interventions to save lives of mothers and children: Taking South Africa closer to MDGs 4 and 5. Glob Health Action 2015;8(1):27265. https://doi.org/10.3402/gha.v8.27265

6. Funk LM, Weiser TG, Berry WR, et al. Global operating theatre distribution and pulse oximetry supply: An estimation from reported data. Lancet 2010;376(9746):1055-1061. https://doi.org/10.1016/ S0140-6736(10)60392-3 7. Ozgediz D, Jamison D, Cherian M, McQueen K. The burden of surgical conditions and access to surgical care in low- and middle-income countries. Bull World Health Organ 2008;86(8):646-647. https://doi.org/10.2471/BLT.07.050435 8. Cockburn N, Steven D, Lecuona K, et al. Prevalence, causes and socio-economic determinants of vision loss in Cape Town, South Africa. PLoS One 2012;7(2):e30718. https://doi.org/10.1371/journal. pone.0030718 9. National Department of Health, South Africa. National Health Insurance for South Africa: Towards Universal Health Coverage, December 2015 (White Paper). Pretoria: NDoH, 2015. 10. National Department of Health, South Africa. National Health Insurance Policy: Towards Universal Health Coverage, June 2017 (White Paper). Pretoria: NDoH, 2017. 11. Health Technology Assessment international (HTAi). What is HTA? http://www.htai.org/htai/what-ishta.html (accessed 16 February 2017). 12. Kenyon CR, Boulle A, Ford N. When best practice is bad medicine: A new approach to rationing tertiary health services in South Africa. S Afr Med J 2008;98(5):350-355. 13. Parrish A, Blockman M. Clinical excellence and the NICEties of value-based priority setting. S Afr Med J 2008;98(10):758, 760-761. 14. Doherty J. Cost-effectiveness analysis for priority-setting in South Africa – what are the possibilities? S Afr Med J 2010;100(12):816-821. 15. National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults. September 2014. https://www.nice.org.uk/guidance/cg184 (accessed 16 February 2017). 16. Chatterjee S, Laxminarayan R. Costs of surgical procedures in Indian hospitals. BMJ Open 2013;3(6):e002844. https://doi.org/10.1136/bmjopen-2013-002844

Accepted 20 July 2017.

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This open-access article is distributed under CC-BY-NC 4.0.

Exploring the barriers to implementing National Health Insurance in South Africa: The people’s perspective R V Passchier, MB BCh, MSc

Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, South Africa; Department of Psychiatry, Steve Biko Academic Hospital, Pretoria, South Africa; and Bheki Mlangeni District Hospital, Soweto, South Africa Corresponding author: R V Passchier (ruthpasschier@gmail.com)

This article explores the challenges of implementing the proposed National Health Insurance for South Africa (SA), based on the six building blocks of the World Health Organization Health System Framework. In the context of the current SA health system, leadership, finance, workforce, technologies, information and service delivery are explored from the perspective of the people at ground level. Through considerations such as these, the universal health coverage goals of health equity, efficiency, responsiveness and financial risk protection, might be realised. S Afr Med J 2017;107(10):836-838. DOI:10.7196/SAMJ.2017.v107i10.12726

On 10 December 2015, the South African (SA) Department of Health proudly presented the nation with the White Paper for a National Health Insurance (NHI). The key features of NHI,[1] which are expected to be fully implemented by 2030, are: • universal access • mandatory prepayment of healthcare • comprehensive service • financial risk protection • single fund • strategic purchaser • single payer. However, a prerequisite for successful universal coverage, as defined by the World Health Organization (WHO), is a strong, efficient, well-

run health system that meets priority health needs through peoplecentred, integrated care.[2] With this in mind, challenges within the six building blocks of the WHO Health System Framework[3] (Fig. 1) will be explored in the SA context, from the perspective of the people who will become a part of the new health system.

Finance

The NHI will introduce a mandatory prepayment of healthcare costs, which is distinct from other modes of payment such as voluntary prepayment, out-of-pocket payments and tax.[1] Currently, primary healthcare is free in SA, and hospital-care costs are waived for vulnerable populations and those in the lowest income bracket. For the remainder of patients, hospital fees are relatively low (having not kept pace with inflation) and not strictly enforced, and no rigorous

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Leadership/governance Healthcare financing Health workforce Medical products, technologies Information and research Service delivery

}

problems.[13] As Bishai et al. [13] explain, ‘People who own the problem can anticipate the most likely social obstacles to its resolution, and their participation is essential.’ Without the vision and oversight of all those using and working in the health system, the NHI may face resistance from personnel at ground level.

Goals/outcomes

Access Coverage

Quality Safety

}

System building blocks

Improved health (level and equity) Responsiveness

Health workforce

Financial risk protection

Improved efficiency

Fig. 1. The World Health Organization Health Systems Framework.[3]

means test is in place to decipher income bracket.[4] Therefore, the majority of South Africans pay little or nothing for public healthcare, and so do not risk incurring catastrophic health costs. As seen in Kenya,[5] low fees for hospital service reduce the incentive for potential contributors to enrol in an NHI system.[4] How can we justify to the people that they should pay for a service that they used to get free? This is similar to the argument used by trade unions opposing the NHI in 1997.[4] The quality of the current SA public health sector is poor, performing worse than the average for an upper-middle-income country.[6] Low perceived quality of care can result in continuing out-of-pocket payments and expensive private health insurance,[4] as demonstrated in Thailand.[7] Lack of perceived benefit can also affect participation. This was the case in Kazakhstan, where very few self-employed individuals registered with the NHI, despite its being legally required.[8] For an NHI to be feasible and acceptable to the payers, it must offer significant advantages over existing services.[4] Systemic problems within the current system could adversely affect the ability of the NHI to translate additional finances into better quality healthcare, and the government risks introducing further inefficiencies into an already-struggling system.[6] Not only would this arouse animosity among those paying for but not benefiting from the NHI, but it would also impose a financial burden on all households, with or without private health insurance, with no significant improvement in the quality of care received.[6]

Governance

Alex van den Heever[9] of the University of the Witwatersrand suggests that financing the NHI is the least of the health system’s problems; rather, the main problem is with how the money is to be spent. ‘Lack of governance and accountability, and corruption, has led to several provinces going into chronic budget deficit.’[9] A fundamental criticism of the NHI is that its implementation will be constrained by the poor administrative and managerial capacity of the state.[10] The system is threatened by poor co-ordination between national, provincial and district levels.[11] The NHI system will need to provide clarity regarding roles, and mechanisms of communication, to ensure the effectiveness of management on the macro, meso and micro levels. Nigeria’s experience shows that interest and strong political leadership when implementing an NHI enhances the pace of the policy process.[12] However, when new systems are implemented, local politicians who could help to identify obstacles are often excluded. [13] Although political will is essential, it is necessary to involve all stakeholders when attempting any reform.[11] Vision, collaboration and oversight of the NHI will require co-operation and input from multiple levels, getting community members, service users, health workers and politicians together from the start, to share their views about the system and to commit to working together to solve

The Minister of Health, Dr Motsoaledi, has said that the country needs to triple its number of doctors for the NHI to work.[9] Currently, 70% of medical practitioners work in the private sector. This is not surprising, since a doctor in public practice, working in an under-resourced environment, will see up to 17 times the patient load of a private practitioner.[6] The country is currently funding new medical schools to increase the number of doctors produced yearly.[9] However, instead of focusing on training new professionals (who will almost certainly end up supplying the private sector), the problem that should be addressed is: why are the staff leaving? Low levels of staff motivation, owing to a discouraging work environment, with poor equipment, short supplies, high vacancy rates and mounting workloads, are the norm in public health facilities. [6] These ‘push factors’ need to be addressed in order to retain the number of health workers required for the new system to function. The public sector will need to utilise, support and motivate the available health workers by effective human-resource management and quality management tools, to create working environments that improve morale and job satisfaction, and enable staff to achieve their personal and professional goals.[6]

Service delivery

A history of colonialism, apartheid and separate development has impacted heavily on the misdistribution of and differential access to health services in SA.[14] The country was founded on principles of inequity, and to this day suffers the consequences, being regarded by analysts as having one of the most iniquitous health systems in the world.[9] The NHI claims to prioritise services to those populations most in need.[1] However, capacity varies between provinces, making their ability to implement service uneven.[15] This poses the risk of widening the equity gap, unless targeting and incentives can support the poorest-served provinces.[15] It is unclear how the NHI will redistribute the human resources and infrastructure that have been firmly set in centuries of unequal distribution along public-private, rural-urban, primary-tertiary and poor-rich lines.[6]

Information and research

The NHI will bring with it the proposed National Health Information Repository and Data system. This aims to improve monitoring and to track health status, quality assurance and healthcare utilisation.[1] However, there is a lack of monitoring and evaluation mechanisms at all levels of the health system, and inadequate human resources to provide such services.[11] Furthermore, past studies have shown SA to be ‘data rich but information poor’,[15] since data systems do not always provide nationally representative, good-quality information in a timely manner.[15] Capacity building to improve data collection, and making use of new digital technology, must be considered to improve implementation. Streamlining of translation into policy, programmes and practice should be prioritised to avoid the waste of this valuable resource.

Medical products and technologies

The private sector has a major role to play in developing innovative uses of medical products and technology, such as new diagnostics.[16]

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The NHI plans to purchase services from accredited and contracted private specialists and private hospitals.[1] The unsuccessful privatepublic partnership (PPP) in the neighbouring country Lesotho, along with international evidence, shows that PPPs can be risky and costly, and can fail to advance universal and equitable health coverage.[17] Furthermore, the high cost of private-provider fees is currently a barrier to expanding partnerships with the NHI, resulting in the need for the current Competition Commission enquiry into the drivers of prices in the private health sector.[16] PPPs will require a close, transparent relationship between government and private providers.[16] The SA health system will need to develop skilled management, and the capacity to choose PPPs that are strategically important to national goals.[16]

Conclusion

Equitable access and universal coverage through an NHI was envisioned in SA as early as the 1920s.[14] With the prospect finally on the horizon, leaders need to make efforts, at every level of the health system, to ensure a smooth transition for the people who will become a part of it. The public should understand the value and reap the benefits of an extra payroll tax. Good governance is required, with a plan to eliminate corruption, and vision must be sought from stakeholders throughout society. Human resources could be more highly valued and efforts made to create acceptable working environments, to retain staff. Inequities of the past have to be accounted for by rigorous efforts to target those least capable of delivering, yet most in need of service. Data collection should be facilitated in a feasible and sustainable manner that adds value to future policy. Using PPPs with caution, technologies can be optimised by building relationships between competent management personnel. Through considerations such as these, we recognise that the health system is, above all, a human system. Upon implementation of the NHI, and reform of the SA health system, government must therefore become attentive to all concerns, needs and aspirations of the people it serves.

Acknowledgements. Dr Dina Balabanova, London School of Hygiene and Tropical Medicine, for guidance and teaching in Health Systems. Author contributions. Sole author. Funding. None. Conflicts of interest. None. 1. Department of Health, South Africa. National Health Insurance for South Africa: Towards Universal Health Coverage. https://www.health-e.org.za/wp-content/uploads/2015/12/National-Health-Insurance-for-SouthAfrica-White-Paper.pdf (accessed 10 July 2017). 2. World Health Organization. What is universal health coverage? Geneva: WHO, 2014. http://www.who. int/features/qa/universal_health_coverage/en/ (accessed 10 February 2016). 3. World Health Organization Western Pacific Region. The WHO Health Systems Framework. Geneva: WHO, 2017. https://www.wpro.who.int/health_services/health_systems_framework/en/ (accessed 10 July 2017). 4. McIntyre D, Doherty J, Gilson L. A tale of two visions: The changing fortunes of Social Health Insurance in South Africa. Health Policy Plan 2003;18(1):47-58. https://doi.org/ 10.1093/heapol/18.1.47 5. Kraushaar D. The Kenya National Hospital Insurance Fund: What can we learn from thirty yearsâ&#x20AC;&#x2122; experience. Boston: Management Sciences for Health, 1997. 6. Okorafor OA. National health insurance reform in South Africa: Estimating the implications for demand for private health insurance. Appl Health Econ Health 2012;10(3):189-200. https://doi. org/10.2165/11594830-000000000-00000 7. Tangcharoensathien V, Supachutikul A, Lertiendumrong J. The social security scheme in Thailand: What lessons can be drawn? Soc Sci Med 1999;48(7):913-923. 8. Ensor T. Developing health insurance in transitional Asia. Soc Sci Med 1999;48(7):871-879. 9. Baleta A. South Africa rolls out pilot health insurance scheme. Lancet 2012;379(9822):1185. https:// doi.org/10.1016/S0140-6736(12)60495-4 10. National Planning Commission, South Africa. Diagnostic Overview. http://www.education.gov. za/Portals/0/Documents/Publications/National%20Planning%20Commission%20Diagnostics%20 Overview%20of%20the%20country.pdf?ver=2015-03-19-134928-000 (accessed 10 July 2017). 11. Marais DL, Petersen I. Health system governance to support integrated mental health care in South Africa: Challenges and opportunities. Int J Ment Health Syst 2015;9(1):1-21. https://doi. org/10.1186%2Fs13033-015-0004-z 12. Onoka CA, Hanson K, Hanefeld J. Towards universal coverage: A policy analysis of the development of the National Health Insurance Scheme in Nigeria. Health Policy Plan 2015;30(9):1105-1117. https:// doi.org/10.1093/heapol/czu116 13. Bishai D, Ghaffar A, Kelley E, Kieny MP. Honouring the value of people in public health: A different kind of p-value. Bull World Health Organ 2015;93(9):661-662. https://doi.org/10.2471/BLT.14.149369 14. van Rensburg HC. South Africa's protracted struggle for equal distribution and equitable access â&#x20AC;&#x201C; still not there. Hum Resour Health 2014;12:26. https://doi.org/10.1186/1478-4491-12-26 15. Mayosi BM, Lawn JE, Niekerk A, Bradshaw D, Karim SSA, Coovadia HM. Health in South Africa: Changes and challenges since 2009. Lancet 2012;380(9858):2029-2043. https://doi.org/10.1016/S01406736(12)61814-5 16. Kula N, Fryatt RJ. Public-private interactions on health in South Africa: Opportunities for scaling up. Health Policy Plan 2014;29(5):560-569. https://doi.org/10.1093/heapol/czt042 17. Webster PC. Lesotho's controversial public-private partnership project. Lancet 2015;386(10007):19291931. https://doi.org/10.1016/S0140-6736(15)00959-9

Accepted 11 July 2017.

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Evaluating 5 years’ NIMART mentoring in South Africa’s HIV treatment programme: Successes, challenges and future needs M Jones,1 RN, MSc; D Cameron,2 MB ChB, M Prax Med, MPhil, FCFP (SA) 1 2

East Sussex Healthcare NHS Trust, UK; and Evaluation Unit, Foundation for Professional Development, Pretoria, South Africa Department of Family Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa; and Evaluation Unit, Foundation for Professional Development, Pretoria, South Africa

Corresponding author: M Jones (martinjones6@nhs.net)

Task shifting has enabled South Africa (SA) to rapidly expand its HIV treatment programme. This has been achieved by training and mentoring primary-care nurses in nurse initiation and management of antiretroviral therapy (NIMART). Five years into its clinical mentoring programme, the Foundation for Professional Development conducted an evaluation that identified improved knowledge, attitudes and confidence perceived by nurses who received NIMART mentoring. Low completion rates for the Department of Health (DoH) NIMART training process were identified and therefore targeted mentoring was introduced; this increased the percentage of primary nurses eligible for DoH certificates of clinical competence in NIMART from 12%, adding a further 30%. There remain a large number of primary nurses who require mentoring in order to complete the NIMART process. For those who have completed the process, there remains a need for ongoing mentoring as SA’s HIV programme evolves, complex cases emerge and primary care undergoes change. S Afr Med J 2017;107(10):839-842. DOI:10.7196/SAMJ.2017.v107i10.12392

The Foundation for Professional Development (FPD) has contributed to the rapid expansion of South Africa (SA)’s HIV treatment programme. We wanted to evaluate FPD’s clinical mentoring programme, in order to identify its achievements and shortcomings, with a view to planning for the future. Over the past 10 years, research has shown that shifting the initiation and management of antiretroviral therapy (ART) from specialised, hospital-based clinics to primary-care nurses is complex and challenging.[1-6] Such task shifting has been shown to improve access to and early initiation of ART, reduce mortality and improve retention in care,[7] and has resulted in a reduced burden on referral hospitals.[8] Further benefits that have been demonstrated include reduced patient waiting times, less costly healthcare provision[9,10] and improved health-related quality of life in patients living with HIV.[11] The clinical mentorship of primary-care nurses by mentors with experience and expertise in HIV management has been shown to increase confidence and enhance professional development, and should be considered essential to ensure universal ART access in resource-limited settings.[12,13] We undertook a multifaceted review of the clinical mentoring of professional nurses initiating and maintaining HIV-positive patients on ART in primary-care clinics in 4 districts of SA, over a period of 5 years. These districts cover an area of 62.7 km2 (5% of SA’s landmass), and contain a population of 6.5 million people (12% of its total population). We reviewed the mentoring process that is set out in the Department of Health (DoH)’s Clinical Mentoring Manual for Integrated Services (‘the manual’),[14] and assessed the effectiveness of clinical mentoring by roving teams of mentors in equipping nurses with the knowledge, attitudes and skills required for nurse initiation and management of ART (NIMART).

Training and competency of the clinical mentors

To equip its professional staff to mentor NIMART-trained nurses, FPD orientated its doctors to become clinical mentors and to provide 6 months’ clinical-skills training and work-based supervision to its professional nurses, who had been working in ART clinics for several years. All these nurses had attended a 5-day NIMART training course as a prerequisite to becoming a clinical mentor. During the 6 months of supervision, the nurses attended 36 days of training in: HIV counselling and testing, prevention of mother-to-child transmission (PMTCT), adherence counselling, diagnosis and management of tuberculosis (TB), management of sexually transmitted infections, isoniazid prophylactic therapy, integrated management of childhood illnesses, Practical Approach to Lung Health and HIV/AIDS in SA (PALSA PLUS), paediatric HIV management, maintaining ART registers and SA’s electronic medical record system (TIER.net).

The mentoring process

These nurses kept a logbook of 80 patients who they had managed, as set out in the manual. The competence of these nurses as clinical mentors was tested in a series of three 12-station objective structured clinical examinations, moderated by experienced external examiners. Between 2010 and 2012, 39 professional nurses were assessed as competent, and deployed to provide clinical mentoring to professional nurses working in primary-care clinics supported by FPD. From 2012, the doctors, nurses and data management mentors – a health information system mentor and a data capturer – were grouped into roving mentor teams of four, who travelled together and visited clinics according to a set schedule. Specialist mentors in maternal and infant care, TB and community liaison provided additional support in accordance with the districts’ priorities.

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The teams each travel in a double-cab pick-up truck, from a convenient central starting point, and visit between one and four clinics a day. The total average daily distance covered is 94 km per team. The shortest distance may be only 3 km, while the farthest clinics in the rural districts of Nkangala and Vhembe are respectively 125 and 190 km from the central starting point. As a result, a significant period of time is spent travelling. Some clinics are visited weekly, while the more distant clinics only receive a monthly visit. The DoH requires all professional nurses working in primary care to undertake NIMART training. Clinical mentoring was introduced to ensure the continuing professional development of nurses following the theoretical part of NIMART training, and to support progress towards the 54 clinical competencies that are set out in the manual. The mentor encourages the mentee to follow the relevant DoH clinical guidelines, and if necessary, to phone for advice between visits. The mentee records in a logbook brief details of all the cases seen, and these are reviewed by the mentor at the next visit. Each NIMART nurse is required to see a minimum of 80 patients of various age groups (including infants), both men and women (including women who are pregnant) and those co-infected with HIV and TB. When the logbook is complete and the mentor satisfied with the clinical competence of the mentee, a portfolio of evidence (POE) is submitted to the DoH Regional Training Centre. The DoH then acknowledges the competency of the NIMART nurse by issuing a certificate of clinical competence.

The evaluation

The aim of our evaluation was to describe and analyse the achievements and evolution of clinical mentoring for NIMARTtrained professional nurses by roving mentor teams in primaryhealthcare facilities in the health districts of Tshwane (Gauteng Province), Nkangala (Mpumalanga Province), and Capricorn and Vhembe (Limpopo Province) over a period of 5 years. These are the four health districts that were supported by FPD at the time of the evaluation. In order to evaluate the roving mentorship programme, the following questions were considered: • What are the strengths and weaknesses of the mentoring process set out in the manual? • How many nurses completed the mentorship process and received certificates of clinical competence from the DoH, and how long did this take? • What was the coverage of mentorship provided by the roving mentor teams? • Is the model of roving mentor teams cost-effective and sustainable? • How should the process of clinical mentoring adapt as the HIV epidemic evolves and changes in donor funding occur? Semi-structured interviews were conducted with a convenience sample of NIMART nurses, facility managers, roving mentors and their operational managers. Data were also obtained from routine monitoring and evaluation reports, and from the DoH District Health Information System. Signed consent was obtained from all participants; interviewee responses and comments were recorded anonymously. The data analysis included statistical calculation and thematic analysis of the qualitative data. Ethical approval was obtained from the Research Ethics Committee of FPD on 10 December 2013 (ref. no. 2013/12/10). During the first quarter of 2014, a clinical nurse specialist from the UK with 25 years’ experience in HIV care, including 3 months establishing NIMART mentoring in the Eastern Cape Province,[15] visited 66 primary-care facilities in the four districts. He accompanied

the roving mentor teams on their routine visits, and interviewed 92 professional nurses who had completed classroom training in NIMART, 20 facility managers, 4 subdistrict programme managers, 45 roving mentors and 12 FPD operational managers.

Results

The NIMART-trained nurses who were interviewed were experienced professional nurses, many of whom had attended a number of related courses (Table 1).

Strengths and weaknesses of the mentoring process

Eighty-seven percent of the NIMART nurses interviewed said that mentoring had met their expectations, and 78% felt that the frequency of mentoring visits had been ‘just right’. Factors leading to this positive response included maintaining scheduled visits, the easy availability of the mentor for telephonic advice and the mentors’ supportive attitude, which made the nurses feel that they were not being ‘policed’: ‘The mentor corrects us very nicely.’ (Nurse) Effective mentoring requires a commitment to a long-term relationship of support and guidance, and nurses appreciated this: ‘One of the reasons it has worked is that it is the same team over a long period of time that can start to build real relationships.’ (Nurse) There was a great deal of initial apprehension on the part of professional nurses that the down referral of patients from centralised ART clinics would overwhelm them. However, despite the increased workload, 94% agreed that mentoring had helped to bring about a positive change in their attitude towards taking on the responsibility for initiating and managing patients on ART: ‘I feared down referral but now it’s an easy job to me; ART works.’ (Nurse) ‘There has been no increase in staffing in facilities, but HIV has increased the number of attendances, and on top of this the community’s awareness of health issues has improved.’ (Nurse) As a result of personal experience of HIV, some nurses were highly motivated to treat HIV-positive patients: ‘Many relatives and friends have died. I am trying to help those that are left.’ (Nurse) Table 1. The characteristics of the NIMART nurses interviewed (N=92) Female, %

Median age (years)

Median duration of professional experience (years)

Median time since NIMART training (months)

Additional training attended, % Diagnosis and management of TB

PMTCT

HIV counselling and testing

Integrated management of childhood illnesses

Paediatric HIV management

Primary healthcare diploma

Dispensing licence

PMTCT = prevention of mother-to-child transmission of HIV; TB = tuberculosis.

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Despite their NIMART training, prior to mentoring, some nurses were anxious about providing HIV care: ‘I previously feared even touching patients with HIV until the mentor explained things, motivated listening skills and empathy.’ (Nurse) While some knowledge is gained during classroom instruction, most learning occurs in the workplace. It is during this initial phase of translating theory into practice, and using the guidelines in practice, that mentoring plays such a vital role: ‘I did not feel clear after the NIMART course, but my mentor used the guidelines to help me to choose regimens, refer appropriately and deal with side effects.’ (Nurse)

Completion of the mentoring process

Nurses exhibited high levels of knowledge, confidence and competence in NIMART, but reported limited motivation to provide written evidence: by March 2014, only 13% (12) had completed the POE, and 8% (7) had received the certificate of clinical competency: ‘The requirement for 80 cases is too many – it is discouraging. Get rid of the annual presentation of certificates of clinical competency – it causes delay’. (Nurse) While the manual provided a valuable template to guide mentoring, many factors interfered with the completion of the process and the issuing of certificates of clinical competence. The following reasons were given by the NIMART nurses for not completing the process: • Not seeing enough HIV-positive children – this was seen as resulting from the success of the PMTCT programme. • Not being involved in the management of complex cases such as pregnant women co-infected with HIV and TB. • Being unaware that there was a logbook, or too busy to maintain or complete it. Mentors were praised for their accessibility, and their support in managing complex cases such as advanced HIV disease, treatment failure, initiation of ART in children and interpreting abnormal biochemistry results. However, the mentoring process was undermined by high patient numbers, reported absenteeism of parttime clinic doctors, nurse rotation to other aspects of primary-care provision, inadequate consultation space and the non-availability of essential medicines.

Coverage and sustainability

FPD’s 32 roving teams mentored 2 010 (60%) of 3 359 professional nurses in 409 health facilities in the 5 years reviewed. During this time, the 32 teams travelled a total of 3 700 560 km, at a cost of R6 216 941 (R1.68/km). The salaries for the 32 teams amounted to R267 200 million (R1.67 million/team/year). The total cost of this work-based mentoring programme was R268 million. The average cost per nurse mentored was R133 391 (Table 2).

Evolution

The evaluation found that 94% of nurses felt confident in initiating ART, and many had a growing sense of independence from their mentor. They felt that their skills in listening to their patients, performing physical examinations, making comprehensive assessments, interpreting laboratory results, providing adherence counselling and solving clinical problems had improved significantly: ‘Nurses are more knowledgeable and I get fewer phone calls.’ (Mentor)

‘We have a weekly meeting to discuss cases and ring FPD if we cannot resolve challenges together.’ (Nurse) While the initial phase of gaining confidence and competence in ART initiation is easily achieved, the skills required to recognise and manage the complications that may occur in patients taking ART take time to develop: ‘I think now we are moving away from [ART] initiation because most of the nurses are comfortable with that. We have stepped into reviewing side-effects and everything they are picking up. But we are getting patients that are having resistance and treatment failures so we need to build their confidence there.’ (Mentor) It was encouraging to see the professional maturity and competence that continues to grow in the NIMART nurses. Being a competent primary-care clinician requires life-long learning. The following comment is thus realistic and understandable: ‘Don’t stop coming – we need 2 years’ mentoring in order to be stable, independent.’ (Nurse) The temptation to ‘cut corners’ can be a danger with a complex process such as NIMART. However, ‘Mentoring visits prevent the clinic from complacency.’ (Nurse) ‘Having outside scrutiny helps to maintain sound minds on HIV.’ (Nurse) There is a need for a balance between encouraging independent practice and maintaining mentoring, as HIV care and patient needs evolve: ‘HIV is always changing so mentoring will always be needed.’ (Nurse) ‘Without the roving team we would be experiencing big problems.’ (Nurse) Professional isolation in a community primary clinic is a reality. The objectivity of a mentor provides encouragement and invaluable support. With ART guidelines subject to frequent revision, mentoring provides necessary updating of these.

Discussion

Our evaluation considered the evolution of a large PEPFAR (the US President's Emergency Plan for AIDS Relief)-funded clinical mentoring programme supporting primary-care nurses to deliver the NIMART programme over a 5-year period. We demonstrated the effectiveness of mentoring NIMART-trained professional nurses using teams of roving mentors, which has improved their knowledge, attitudes and skills. This was true in both urban and remote rural primary clinics. Mentoring also encouraged nurses to complete Table 2. The cost of work-based mentoring in four health districts Item

Cost per annum

Cost over 5 years

Transport (calculated at R1.68/km × 740 112 km/ annum)

ZAR1 143 470 USD96 090

ZAR5 717 350 USD480 449

Salaries (calculated at R1.67 million/annum/ team)

ZAR52 480 000 USD4 410 084

ZAR262 400 000 USD22 050 420

Total

ZAR53 623 470 USD4 505 174

ZAR268 117 350 USD22 530 870

Exchange rate = ZAR11.90:USD1.00 (at the time of the study).

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the POE: prior to this evaluation, 241 (12%) of 2 010 professional nurses in the four health districts had completed the POE. When mentors focused on encouraging its completion, a further 600 (30%) completed the DoH process. Participants agreed that NIMART mentoring has enabled nurses to successfully take on the role of initiating and maintaining HIVpositive patients in primary-care clinics. The DoH process of submitting POEs and being awarded certificates of competence was found to be dysfunctional, although rates of completion were improved through intensive, focused mentoring. Both processes require the investment of significant resources and amounts of time. In order to sustain the NIMART programme, professional nurses identified the need for ongoing mentoring to maintain standards of care and for support when managing complex cases. Multidisciplinary team case discussions were cited as a useful approach.

Conclusion

The key findings of the evaluation are summarised as follows: • Clinical mentoring by roving mentor teams has enabled primarycare nurses to become competent in initiating and maintaining ART. • While clinical mentoring is costly, it has improved access to ART. • Nurses delivering the NIMART programme require ongoing mentoring in order to increase the numbers who have completed the DoH mentoring process, and to deal with complex HIV-related problems. • With the integration of clinical services at primary-care clinics, work-based mentoring will need to be broadened to include the full spectrum of programmes delivered in primary care.

Recommendations

HIV is an evolving epidemic; as guidelines and patient needs change, clinical mentoring will similarly need to adapt in a climate where cost is an unavoidable consideration. Participants suggested a number of ways that mentoring could adapt, including: fewer and less-frequent mentoring visits, more telephonic mentoring and multidisciplinary complex-case discussions. Mentoring should focus on the DoH process in order to achieve higher rates of POE submission and increase the number of certificates of competence awarded. With the integration of clinical services at primary care clinics, work-based mentoring will need to be broadened to include the full spectrum of programmes delivered in primary care.

Acknowledgements. None. Author contributions. MJ: design, data gathering, analysis, writing; DC: design, analysis, writing. Funding. Foundation for Professional Development. Conflicts of interest. None. 1. Chan AK, Ford D, Namata H, et al. The Lablite project: A cross-sectional mapping survey of decentralized HIV service provision in Malawi, Uganda and Zimbabwe. BMC Health Serv Res 2014;14:352. https://doi.org/10.1186/1472-6963-14-352 2. Uebel K, Guise A, Georgeu D, Colvin C, Lewin S. Integrating HIV care into nurse-led primary health care services in South Africa: A synthesis of three linked qualitative studies. BMC Health Serv Res 2013;13:171. https://doi.org/10.1186/1472-6963-13-171 3. Emdin CA, Millson P. A systematic review evaluating the impact of task shifting on access to antiretroviral therapy in sub-Saharan Africa. Afr Health Sci 2012;12(3):318-324. https://doi. org/10.4314/ahs.v12i3.11 4. Fairall L, 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. https://doi.org/0.1016/S0140-6736(12)60730-2 5. Davies NE, Homfray M, Venables EC. Nurse and manager perceptions of nurse initiated and managed antiretroviral therapy (NIMART) implementation in South Africa: A qualitative study. BMJ Open 2013;3(11):e003840. https://doi.org/10.1136/bmjopen-2013-003840 6. Grimsrud A, Kaplan R, Bekker LG, Myer L. Outcomes of a nurse-managed service for stable HIVpositive patients in a large South African public sector antiretroviral therapy programme. Trop Med Int Health 2014;19(9):1029-1039. https://doi.org/10.1111/tmi.12346 7. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007 - 2009: Systematic review. Trop Med Int Health. 2010; 15(s1): 1-15. https:// doi.org/10.1111/j.1365-3156.2010.02508.x 8. Nyazulu JC, Muchiri E, Mazwi SL, Ratshefola M. NIMART rollout to primary healthcare facilities increases access to antiretrovirals in Johannesburg: An interrupted time series analysis. S Afr Med J 2012; 103(4): 232-236. https://doi.org/10.7196/samj.6380 9. Boullé C, Kouanfack C, Laborde-Balen G, et al. Task shifting HIV care in rural district hospitals in Cameroon: Evidence of comparable antiretroviral treatment-related outcomes between nurses and physicians in the Stratall ANRS/ESTHER trial. J Acquir Immune Defic Syndr 2013;62(5):569-576. https://doi.org/10.1097/QAI.0b013e318285f7b6 10. Long L, Brennan A, Fox MP, et al. Treatment outcomes and cost-effectiveness of shifting management of stable ART patients to nurses in South Africa: An observational cohort. PLoS Med 2011;8(7):e1001055. https://doi.org/10.1371/journal.pmed.1001055 11. Suzan-Monti M, Blanche J, Boyer S, et al. Benefits of task-shifting HIV care to nurses in terms of health-related quality of life in patients initiating antiretroviral therapy in rural district hospitals in Cameroon [Stratall Agence Nationale de Recherche sur le SIDA (ANRS) 12110/Ensemble pour une Solidarité Thérapeutique Hospitalière en Réseau (ESTHER) substudy]. HIV Med 2015;16(5):307-318. https://doi.org/10.1111/hiv.12213 12. Green A, de Azevedo V, Patten G, Davies MA, Ibeto M, Cox V. Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha, South Africa: A quality of care assessment. PLoS One 2014;9(6):e98389. https://doi.org/10.1371/journal.pone.0098389 13. Cameron D, Gerber A, Mbatha M, Mutyabule J, Swart H. Nurse initiation and maintenance of patients on antiretroviral therapy: Are nurses in primary care clinics initiating ART after attending NIMART training? S Afr Med J 2012;102:98-100. https://doi.org/10.7196/samj.5195 14. National Department of Health, South Africa. Clinical Mentorship Guide for Integrated Services. Pretoria: DoH, 2011. 15. Jones M, Stander M, van Zyl M, Cameron DA. The recall of lost to follow-up pre-antiretroviral therapy patients in the Eastern Cape and the impact of mentoring on patient care. S Afr Med J 2012; 102(9):768-769. https://doi.org/10.7196/samj.5957 16. Swart AM, Chisholm BS, Cohen K, Workman LJ, Cameron D, Blockman M. Analysis of queries from nurses to the South African National HIV & TB Health Care Worker Hotline. S Afr J HIV Med 2013;14(4):179-182. https://doi.org/10.7196/sajhivmed.948

Accepted 17 July 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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CASE REPORT

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa R Hassan-Moosa,1 MB BCh, MPH; T Chinappa,1 LRCP LRCS LM (Ireland); L Jeena,1 6th year medical student; L Visser,3 MB ChB, FCOphth (SA); K Naidoo,1, 2 MB ChB, PhD Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa 2 MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa 3 Department of Ophthalmology, Nelson Mandela Medical School of Medicine, University of KwaZulu-Natal, Durban, South Africa 1

Corresponding author: R Hassan-Moosa (razia.hassan-moosa@caprisa.org) Background. Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis. Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60. Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24. Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. Conclusion. CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis. S Afr Med J 2017;107(10):843-846. DOI:10.7196/SAMJ.2017.v107i10.12740

Cytomegalovirus (CMV) is a common opportunistic infection and a significant contributor to visual loss in patients with advanced stage HIV.[1] CMV seropositivity in Africa, specifically in subSaharan Africa, is highly endemic with reported seropositivity rates approaching 100%.[2] Despite antiretroviral therapy (ART), CMV infection in AIDS patients remains a significant risk factor for end organ disease and AIDS-related mortality.[3,4] Prior to the introduction of ART) 30 - 40% of HIV-infected individuals developed CMV retinitis.[5] However, the introduction of ART has resulted in a precipitous decline in CMV retinitis infections, which is particularly evident in the developed world.[6] Reported prevalence rates of CMV retinitis in HIV-infected patients varied between <5% in South Africa (SA) to >30% in South East Asia,[7] with a study in Cape Town reporting a prevalence rate of 0.8% (p<0.001) in patients with CD4+ cell counts <200 µ/L.[8] Data on local incidence rates are limited with the literature reporting sub-Saharan African incidence rates of <10%.[9] Resource-limited settings are challenged by inaccessibility of ocular care for HIV-infected patients on ART programmes, owing to a lack of skilled staff to conduct ophthalmic examinations. The mainstay of diagnosis of CMV retinitis is fundoscopy through a dilated pupil.[10] However, as CMV retinitis is asymptomatic in almost half of affected patients in the early stages of disease,[11] routine

screening fundoscopy for those at high risk of CMV disease by a trained clinician, not necessarily an ophthalmologist, is necessary. A review of the data from a 3-year pilot programme in Myanmar[12] showed the feasibility of CMV retinitis management at primary care level in resource-poor settings. Like other HIV-associated major opportunistic infections, CMV retinitis was diagnosed and treated by AIDS clinicians (non-ophthalmologists), with the appropriate training and support, prompting calls for the WHO to include routine ophthalmoscopy for all patients presenting for ART initiation with low CD4+ cell counts (<100 cells/µL) in AIDS treatment guidelines.[4,12] CMV retinitis is a slow and progressive disease in patients with advanced stage HIV.[2] Initial symptoms include visual field defects, the visualisation of floaters, flashes and a decline in vision, which initially occurs in one eye.[13] The disease is diagnosed presumptively by means of fundoscopy, unlike systemic CMV disease, which requires confirmation by biopsy.[11] Characteristic findings on fundoscopy include dense retinal whitening, haemorrhage, and a typical ‘brushfire’ retinitis pattern that distributes along blood vessels with small white satellite lesions at the border.[2] CMV retinitis is commonly confused with HIV retinopathy; however, the latter fades and condenses over time while CMV retinitis progresses.[2] When left untreated, CMV retinitis can progress to retinal detachment with

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direct damage to the macula or optic nerve, resulting in permanent blindness.[2] Blindness caused by CMV retinitis is irreversible and can occur prior to complete retinal destruction, which was responsible for >90% of HIV-associated blindness in the pre-ART era.[2] A total of 1 815 patients were enrolled into the PEPFAR-funded CAPRISA AIDS Treatment Programme (CAT) at the eThekwini site in Durban, South Africa (SA) between June 2004 and August 2013. In this report, we highlight the three patients in this cohort who developed CMV retinitis. Approval for data collection and analysis for the CAT programme was obtained from the University of KwaZulu-Natal Biomedical Research Ethics Committee (ref. no. E248/05).

Case reports Case 1

In June 2011, a 37-year-old man presented for ART initiation with a baseline CD4+ cell count of 35 cells/µL. He complained of a 5-month history of painless visual loss in the left eye. ART was commenced and he was referred to the ophthalmology clinic. Fundoscopy of the right eye showed a clear cornea, normal lens, a pink disc and cotton wool spots (Fig. 1), with a baseline visual acuity of 6/18. Poorer visual acuity of 3/60 was evident in the left eye, with fundoscopic examination showing dense retinal whitening and full-thickness necrosis (Fig. 2).

A diagnosis of CMV retinitis in the left eye and HIV retinopathy in the right eye was concluded. Weekly intravitreal ganciclovir injections into the left eye were commenced, and maintained for a total of 6 months. At 6 months post ART initiation, the patient’s CD4+ cell count was 63 cells/µL and his viral load was 42 copies/mL. His last ophthalmology report showed an improvement in visual acuity to 6/6 with no other pathology in the right eye. No visual improvement was noted in the left eye; visual acuity remained static at 3/60. The patient remained clinically stable otherwise.

Case 2

A 31-year-old woman, who was on TB treatment, presented for ART initiation in June 2007 with a baseline CD4+ cell count of 39 cells/µL. She complained of a 2-month history of deteriorating vision in both eyes, with the left eye being worse than the right. She was referred to the ophthalmology clinic and fundoscopy showed pigmented keratic precipitates on the cornea and frosted branch angiitis in the left eye. Retinitis, angiitis and hyperaemic discs were observed in the right eye. Bilateral CMV retinitis was confirmed. The patient was initiated on intravitreal ganciclovir injections in both eyes, and she started ART 6 weeks later. She received ganciclovir injections for 8 months and the visual acuity in her right eye improved to 6/9, and in her left eye to 6/24. The patient maintained viral suppression and had increased CD4+ cell counts of 220 and 440 cells/µL at 6 and 18 months, respectively.

Case 3

Fig. 1. Fundoscopy of the right eye (case 1) showing a clear cornea, normal lens, a pink disc and cotton spots.

Fig. 2. Left eye fundoscopy (case 1) showing dense retinal whitening and fullthickness necrosis.

A 29-year-old woman, who was on TB treatment, presented for ART initiation in October 2006 with a baseline CD4+ cell count of 24 cells/µL. The patient complained of blurred vision at her 2-month ART follow-up visit, and was referred to the ophthalmology clinic. Decreased visual acuity and impaired peripheral vision with a bilateral hemianopia was noted. Furthermore, bilateral retinal detachment secondary to CMV retinitis was observed on fundoscopy. The right eye was repaired with silicone oil tamponade. However, owing to poor prognosis secondary to extensive damage from complete retinal detachment in the left eye, surgical repair was not an option. Retinectomy and a repeat silicone oil tamponade was performed on the right eye ten months later. She was blind in the left eye and had impaired vision in the right eye that did not resolve after right eye surgery. The patient remained clinically stable over 5 years of followup and her last known CD4+ cell count was 479 cells/µL.

Discussion

Case 1 presented with mixed ocular pathology. HIV retinopathy presents in 70% of patients with advanced stage HIV disease[14] and affects the posterior segment of the eye, as does CMV retinitis. HIV retinopathy is an occlusive microangiopathy,[15] which presents as cotton wool spots, telangiectasia, microaneurysms and retinal haemorrhages. Cotton wool spots are the only common clinical feature in both HIV retinopathy and CMV retinitis;[16] however, cotton wool spots associated with HIV retinopathy are usually superficial, smaller lesions that resolve within a few months.[16] Immediate visual loss may not occur with HIV retinopathy and most often patients are asymptomatic.[16] However, there may be significant damage to the retinal nerve fibre layer, deterioration in colour vision and visual field deficits.[6] HIV retinopathy is a risk factor for CMV retinitis prompting the recommendation for routine ophthalmic examination every 3 months in patients with HIV retinopathy.[17] It is hypothesised that the microvasculopathy associated with HIV retinopathy aids the transit of CMV-infected leukocytes across vessel walls. Data from the Longitudinal Studies of the Ocular Complications of AIDS (LSOCA)

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cohort[4] concluded that the presence of HIV retinopathy increased the risk of CMV retinitis (hazard ratio 11.6; 95% CI 3.3 - 40.2; p=0.0001). It is important to note that other HIV-associated infectious causes of a retinitis such as varicella zoster virus, Toxoplasma gondii and choroidopathy caused by Pneumocystis carinii, should be excluded.[15] Cryptococcal ocular complications can manifest in patients with advanced stage HIV disease who develop cryptococcal meningitis and subsequent optic neuritis and papilloedema.[18] Ocular TB has been described in HIV-infected patients with disseminated TB affecting both the anterior and posterior segments of the eye with a variety of presentations that include: vitritis, retinal vasculitis, optic neuritis, choroiditis and choroidal tubercules.[6,19] Retinal toxicity secondary to ARTs, and to drugs used to treat commonly occurring HIV-associated comorbidities such as tuberculosis therapy, has been described in the literature. Didanosine, which was one of the earliest nucleoside reverse transcriptase inhibitors, resulted in retinal toxicity in patients initiated on ART,[20] and ritonavir- and efavirenzinduced retinal pigment eptheliopathy (RPE) initiating a ‘bull’s eye maculopathy’ have also been reported in the literature.[21,22] Owing to its cost-effectiveness, intravitreal ganciclovir injection is the current standard treatment in the SA public sector for active CMV retinitis infection,[23] even though systemic ganciclovir or valganciclovir therapy is standard of care in other countries as these drugs assist in the prevention of systemic dissemination and improving survival.[3,23] These injections are prescribed in combination with daily ART; the dose is based on clinical response and immune recovery and is stopped when CD4+ cell counts of >100 cells/µL are achieved.[24] The third case developed retinal detachment, which is a severe complication of CMV retinitis. Risk factors for retinal detachment include large anterior retinal lesions, intravitreal ganciclovir injections and bilateral disease.[25] While our patient demonstrated bilateral disease, she did not receive intravitreal injections, and we were unable to comment on the size of the anterior retinal lesion owing to the extent of the pathology on presentation. Retinal detachment is associated with poor visual outcomes leading to doubling of the visual angle and eventual blindness despite the initiation of ART, as was noted in our patient.[3,26] This patient reported an onset of visual loss post ART initiation and could have been a case of missed CMV retinitis at screening as she was asymptomatic. An important consideration in this patient would be an immune reconstitution inflammatory syndrome presenting as an immune recovery vitritis or immune recovery uveitis (IRU). IRU is a paradoxical worsening of intraocular inflammatory reactions that occurs during immune recovery after the administration of ART and can lead to substantial visual loss.[23] IRU can occur in 63% of patients with previous CMV retinitis[27] and can present as a mild decrease in vision with the presence of floaters, pain and redness in the affected eye.[28] Untreated CMV retinitis can lead to permanent blindness as a result of direct damage to the macula or optic nerve, or owing to retinal detachment. The need for surgical management to treat complications such as retinal detachment is often delayed in resource-limited settings and the persistent threat of developing CMV infection with chronic virological, immunological and clinical failure remains. The three cases presented here highlight the severe and irreversible visual complications characteristic of CMV retinitis. Despite early identification and rapid referral to a tertiary ophthalmology service, all patients developed permanent and irreversible visual impairment. The greatest risk factor for active CMV retinitis infection is a CD4+ cell count of <50 cells/µL[4,29,30] in HIV infected patients, irrespective

of whether patients are receiving ART. It is noteworthy that 90% of patients with incident CMV retinitis analysed in the LSOCA cohort[31] had a recent CD4+ cell count of <50 cells/µL, with 85% reporting ART use at the visit prior to CMV diagnosis.[4] The mainstay of CMV retinitis management is disease prevention through early ART initiation, especially before CD4+ cell count levels decline to <50 cells/µL. Furthermore, the importance of conducting routine ophthalmological examinations on patients presenting for ART initiation with advanced disease needs to be emphasised.[2,31,32] Visual loss adds to the overwhelming social and economic burden on patients and societies already plagued by HIV. We support the recommendation that routine fundoscopic examination be included in the standard WHO care package for HIV-infected patients with advanced disease.[10] Similar to other opportunistic infections in HIV, CMV screening, prevention, early diagnosis and treatment access should also be offered to patients at high risk for this complication. While all our patients presented with a history of visual loss, published data from elsewhere show high rates of asymptomatic CMV retinitis. Data from Myanmar showed that 31% of the 42 patients diagnosed with CMV retinitis by fundoscopy, were asymptomatic.[2] Asymptomatic CMV retinitis was also demonstrated in 44% of Cambodian patients, despite the use of a questionnaire designed specifically to elicit symptoms of CMV retinitis.[2] While studies advocate education of patients with low CD4+ cell counts (<100 cells/µL)[10] on the risk of CMV retinitis, and highlight the need for urgent medical evaluation in patients presenting with ophthalmic symptoms,[33] there are still large numbers of asymptomatic CMV retinitis cases. This underscores the need for the inclusion of routine fundoscopy in treatment guidelines for patients with advanced stage HIV as well as investment in training and infrastructure to enable frontline workers to conduct routine fundoscopic examinations on eligible patients. The training of nonophthalmologist clinicians in the use of telemedicine in screening for CMV retinitis, by means of digital fundus photography, should be explored.[34]

Study limitations

This was a retrospective data review and there was missing information with regard to ophthalmology visits and the relevant feedback reports. In addition, images for two of the cases reviewed here could not be retrieved from the ophthalmology department owing to technical errors with equipment.

Conclusion

CMV retinitis is a preventable condition that has debilitating and permanent sequelae. Our review highlights the importance of ART and diagnosing patients in the early stages of HIV infection, as well as the importance of routine ophthalmoscopy in patients with advanced stage disease. CMV retinitis frequently affects young individuals in the most productive stage of life. Despite virological suppression and immune recovery on ART, vision cannot be restored and blindness leads to a life of dependency in such cases.[2] CMV retinitis exists in the era of ART – we should not be lulled into believing otherwise. As we adopt the ‘test and treat’ strategy in SA, it is essential that frontline healthcare workers are trained in identifying CMV retinitis in high-risk individuals and that nonophthalmologist clinicians are equipped with the necessary skills to conduct ophthalmological examinations as part of routine HIV care. Furthermore, routine ophthalmological screening should be incorporated into standard treatment guidelines and algorithms for patients with CD4+ cell counts <100 cells/µL.

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Acknowledgements. The authors would like to thank the patients. Data were presented as a poster presentation at the 8th SA AIDS Conference held in Durban, SA on 13 June 2017. Author contributions. RHM and KN wrote the initial draft of the manuscript. TC, LJ, LV and RHM assisted with data collection and interpretation. All authors participated in the writing and editing of the article. Funding. Patients were enrolled into the CAT Programme, supported by the US President’s Emergency Plan for AIDS Relief (PEPFAR), the Global Fund to fight AIDS, Tuberculosis and Malaria, and the National Institute of Health Comprehensive International Program of Research on AIDS. KN was supported by the Columbia University-South Africa Fogarty AIDS International Training and Research Program (Grant D43 TW000231). Consent for publication. Written informed consent was obtained from the patients for publication of these case reviews and accompanying images. Conflicts of interest. KN received funding from PEPFAR, National Institutes of Health/NAID (Grant UM1AI069469) and Howard Hughes Medical Institute (Grant HHM1 55007065) for CAT. The other authors declare that they have no competing interests.

1. Butler NJ, Thorne JE. Current status of HIV infection and ocular disease. Curr Opin Ophthalmol 2012;23(6):517-522. https://doi.org/10.1097/ICU.0b013e328358ba85 2. Heiden D, Ford N, Wilson D, et al. Cytomegalovirus retinitis: The neglected disease of the AIDS pandemic. PLoS Med 2007;4(12):e334. https://doi.org/10.1371/journal.pmed.0040334 3. Jabs DA, Ahuja A, van Natta M, Dunn J, Yeh S. Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmology 2013;120(6):1262-1270. https://doi.org/10.1016/j.ophtha.2012.11.023 4. Sugar EA, Jabs DA, Ahuja A, et al. Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 2012;153(6):1016-1024.e5. https://doi.org/10.1016/j. ajo.2011.11.014 5. Martin-Odoom A, Bonney EY, Opoku DK. Ocular complications in HIV positive patients on antiretroviral therapy in Ghana. BMC Ophthalmol 2016;16(1):134. https://doi.org/10.1186/s12886016-0310-5 6. Agarwal A, Singh R, Sharma A, Gupta V, Dogra MR. Ocular manifestations in patients with human immunodeficiency virus infection in the pre-HAART versus the HAART era in the North Indian population. Ocular Immunol Inflamm 2016:396-404. https://doi.org/10.3109/09273948.2015.1133837 7. Ford N, Shubber Z, Saranchuk P, et al. Burden of HIV-related cytomegalovirus retinitis in resourcelimited settings: A systematic review. Clin Infect Dis 2013;57(9):1351-1361. https://doi.org/10.1093/ cid/cit494 8. Pathai S, Gilbert C, Weiss HA, McNally M, Lawn SD. Differing spectrum of HIV‐associated ophthalmic disease among patients starting antiretroviral therapy in India and South Africa. Top Med Int Health 2011;16(3):356-359. https://doi.org/10.1111/j.1365-3156.2010.02712.x 9. EL Fane M, Sodqi M, El Rherbi A, et al. Cytomegalovirus disease in patient with HIV infection. J Antimicrob Agents 2016;2(1). https://doi.org/10.4172/2472-1212.1000108 10. Heiden D, Saranchuk P, Tun N, et al. We urge WHO to act on cytomegalovirus retinitis. Lancet Glob Health 2014;2(2):e76-e77. https://doi.org/10.1016/S2214-109X(13)70174-8 11. Chiotan C, Radu L, Serban R, Cornăcel C, Cioboata M, Anghel A. Cytomegalovirus retinitis in HIV/ AIDS patients. J Med Life 2014;7(2):237.

12. Heiden D, Tun N, Maningding E, et al. Training clinicians treating HIV to diagnose cytomegalovirus retinitis. Bull World Health Org 2014;92(12):903-908. https://doi.org/10.2471/BLT.14.142372 13. Chakraborty D, Rama SK. CMV retinitis in an HIV patient with clinical and immunological failure on HAART. Int J Med Science Pub Health 2015;4(1):142-144. https://doi.org/10.5455/ ijmsph.2015.150820142 14. Jabs DA. AIDS retinopathy: Findings and significance. Ophthalmol Clin North Am 1988;1:101. 15. Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc 1995;93:623. 16. Holland GN. AIDS and ophthalmology: The first quarter century. Am J Ophthalmol 2008;145(3):397408.e391. https://doi.org/10.1016/j.ajo.2007.12.001 17. Nishijima T, Yashiro S, Teruya K, et al. Routine eye screening by an ophthalmologist is clinically useful for HIV-1-infected patients with CD4 count less than 200/muL. PLoS One 2015;10(9):e0136747. https://doi.org/10.1371/journal.pone.0136747 18. Moodley A, Rae W, Bhigjee A. Visual loss in HIV-associated cryptococcal meningitis: A case series and review of the mechanisms involved. South Afr J HIV Med 2015;16(1):1-9. https://doi.org/10.4102/ sajhivmed.v16i1.305 19. Gupta V, Shoughy SS, Mahajan S, et al. Clinics of ocular tuberculosis. Ocul Immunol Inflamm 2015;23(1):14-24. https://doi.org/10.3109/09273948.2014.986582 20. Gabrielian A, MacCumber MM, Kukuyev A, Mitsuyasu R, Holland GN, Sarraf D. Didanosineassociated retinal toxicity in adults infected with human immunodeficiency virus. JAMA Ophthalmol 2013;131(2):255-259. https://doi.org/10.1001/jamaophthalmol.2013.579 21. Pinto R, Vila-Franca M, Afonso CO, Ornelas C, Santos L. Ritonavir and bull’s eye maculopathy: Case report. GMS Opthalmol Cases 2013;3:Doc01. https://doi.org/10.3205/oc000011 22. Vaz Pereira C, Franco M, Guerra Pinto R, et al. Bull's eye maculopathy in a patient treated with efavirenz. Oftalmologia 2014;38(4):287-290. 23. Lapere SR, Rice JC. Cytomegalovirus retinitis in Cape Town, South Africa: Clinical management and outcomes. S Afr Med J 2017;107(6):514-517. https://doi.org/10.7196/samj.2017.v107i6.12250 24. Gore SK, Gore DM, Chetty K, Visser L. Cytomegaloviral retinitis-related retinal detachment: Outcomes following vitrectomy in the developing world. Int Opthalmol 2014;34(2):205-210. https:// doi.org/10.1007/s10792-013-9814-7 25. Yen M, Chen J, Ausayakhun S, et al. Retinal detachment associated with AIDS-related cytomegalovirus retinitis: Risk factors in a resource-limited setting. Am J Opthalmol 2015;159(1):185-192. https://doi. org/10.1016/j.ajo.2014.10.014 26. Thorne JE, Jabs DA, Kempen JH, et al. Incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology 2006;113(8):1432-1440. https://doi.org/10.1097/IEB.0b013e31802ddf5c 27. Urban B, Bakunowicz-Łazarczyk A, Michalczuk M. Immune recovery uveitis: Pathogenesis, clinical symptoms, and treatment. Mediators Inflamm 2014;2014(2014):Article ID 971417. https://doi. org/10.1155/2014/971417 28. Balamurugan S, Khodifad A. Immune recovery uveitis. The Official Scientific J Delhi Ophthalmol Soc 2015;25(4):233-237. https://doi.org/10.7869/djo.114 29. Ausayakhun S, Keenan JD, Ausayakhun S, et al. Clinical features of newly diagnosed cytomegalovirus retinitis in northern Thailand. Am J Ophthalmol 2012;153(5):923-931. https://doi.org/10.1016/j. ajo.2011.10.012 30. Leenasirimakul P, Liu Y, Jirawison C, et al. Risk factors for CMV retinitis among individuals with HIV and low CD4 count in northern Thailand: Importance of access to healthcare. Br J Ophthalmol 2016;100:1017-1021. https://doi.org/10.1136/bjophthalmol-2016-308556 31. Jabs DA, van Natta ML, Holbrook JT, Kempen JH, Meinert CL, Davis MD. Longitudinal study of the ocular complications of AIDS: 1. Ocular diagnoses at enrollment. Ophthalmology 2007;114(4):780786. https://doi.org/10.1016/j.ophtha.2006.11.008 32. Tun N, Smithuis FM, London N, Drew WL, Heiden D. Mortality in patients with AIDS-related cytomegalovirus retinitis in Myanmar. Clin Infect Dis 2014;59(11):1650. https://doi.org/10.1093/cid/ ciu648 33. Colby DJ, Vo DQ, Teoh SC, et al. Prevalence and predictors of cytomegalovirus retinitis in HIVinfected patients with low CD4 lymphocyte counts in Vietnam. Int J STD AIDS 2014;25(7):516-522. https://doi.org/10.1177/0956462413515197 34. Yen M, Ausayakhun S, Chen J, et al. Telemedicine diagnosis of cytomegalovirus retinitis by nonophthalmologists. JAMA Ophthalmol 2014;132(9):1052-1058. https://doi.org/10.1001/ jamaophthalmol.2014.1108

Accepted 25 August 2017.

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Protection of the human research participant: A structured review L Roets, PhD Department of Health Studies, College of Human Sciences, University of South Africa, Pretoria Corresponding author: L Roets (roetsl@unisa.ac.za)

The history of health research, and concerns about the protection of human participants, dates back as far as the 1800s. The regulation, legislation and ethics-review requirements regarding the protection of the human research participants cause lively debates among researchers and scientists. The objective of this article is to share the findings of a structured review that was aimed at investigating the impact of and challenges with regard to the legislation, governance and research regulations aimed at protecting human research participants. The thematic analysis of the findings revealed dissatisfaction with diverse operational practices; different legislation and regulation practices; and institutional governance. Simplified and universally agreed-upon regulations and operational practices are needed, as is a common understanding of all concepts relating to ethical research conduct. S Afr Med J 2017;107(10):847-853. DOI:10.7196/SAMJ.2017.v107i10.12533

Research, and especially health research, benefits many people and communities, and sometimes society as a whole. Theoretical knowledge and the protection of the human participants are therefore justified, although the tension between scientific interests and the rights of individuals remains very prominent in discussions regarding research ethics. The Nuremberg Code and the Universal Declaration of Human Rights can be viewed as the bases for the development of universally accepted principles of research ethics that protect the human participant from harm and allow participants voluntary informed consent to the research. The Declaration of Helsinki, which is based on these, has therefore been recognised as one of the most authoritative statements on ethical standards for human research in the world.[1] The greatest and most notorious tragedies in human research, such as the injection of people with an organism that caused yellow fever, led to the development of a 10-point memorandum, titled Permissible Medical Experimentation, by Drs Ivy and Alexander. The memorandum was a set of rules for research on human participants, and later became the Nuremburg Code.[1] Researchers, however, have very diverse opinions of how a human participant is defined, and these divergent opinions have contributed to researchers claiming that they do not always have to seek ethical approval from a research ethics committee (REC) or institutional review board (IRB). However, the human participant, sometimes called the human subject, is defined by the South African (SA) National Department of Health (DoH)[2] as a living individual about whom a researcher obtains either (i) data, through interventions or interactions, or (ii) identifiable private information. There is also ongoing debate about when research can be identified as health-related, and, consequently, subject to regulation and ethical approval before it can proceed, as researchers differ on how to classify their research, which determines whether or not they really need to go through the ethical review processes managed by RECs and IRBs. This is fuelled by differences in how each researcher defines health research. According to the DoH,[2] health research includes any research that contributes to the knowledge of biological or social processes in human beings; suggests improved methods of provision of health services; examines human pathology, the causes of disease or the

effects of the environment on the human body; or contributes to the development of new applications of pharmaceuticals, medicines and related substances, or the development of new applications of health technology. The implication of this broad interpretation is that almost all healthrelated or social-science research involves a human participant. This interpretation of how a human participant is defined, and of what constitutes health research, has resulted in widespread discomfort and dissatisfaction with the model that currently governs research at most modern universities, which requires all health researchers to obtain ethical approval from RECs or IRBs.[3] Some researchers are of the view that ethics-review committees create a moral panic by means of distorted claims about potential harms to participants.[3] This structured review was motivated by these continual debates about what constitutes a human participant, and when research can be identified as health related, as well as other challenges, such as what type of research should be subjected to an ethics review process, and the impact that the legislation, governance and regulation of research by RECs and IRBs have on researchers, research and participants. The review aims to give an account of the impacts of and challenges pertaining to the legislation, governance and regulations that are aimed at protecting human research participants in the research process.

Methods

Data sources

A structured review of published literature from 2011 to 2016 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) framework.[4] The extensive and inclusive literature search was conducted using EBSCOhost, MEDLINE and the University of South Africa (Unisa) Library. This ensured the development of a relevant and conclusive structured review. The search terms used were ‘research ethics’, ‘human participants and research ethics’, ‘research ethics legislation’, ‘regulating research’ and ‘research ethics governance’. The terms were applied both individually and in combination, in an attempt to generate as much relevant literature as possible, with the added benefit of reduced risk of bias. The search was conducted in December 2016,

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with the assistance of a Unisa subject-specialist librarian. The search was confined to research and review articles published in English. All results were combined in order to prevent duplications.

Selection criteria

Studies and review articles reporting on ethics in research, research governance and legislation pertaining to the protection of human research participants were all included. Both qualitative and quantitative studies, as well as review articles, were included, to enhance generalisability and the validity of the outcome of the review. Nine studies were included in this review.

Assessment of study quality

I adopted a global assessment tool that divided the studies into two categories, namely weak and strong, as described by Bradbury-Jones et al.[5] The assessment tool was developed from the findings of a qualitative metasynthesis project.[6] The appraisal instrument focused on several key elements, including clear aims and objectives, a clear description of the data gathering and analysis processes, triangulation of data and clearly formulated findings (Table 1). The overall quality appraisal of the studies focused on methodological strengths and weaknesses, but also on the relevance of the research or review to addressing the aim of this review.

the tension between ethical decision-making as a regulatory activity, and researcher participation, and on researcher engagement in the decision-making processes, were obtained from a representative of each committee. The findings revealed that the RECs differ significantly in operational practices. Their levels of engagement with researchers, and with other committee members, differ widely. Gremillion et al.[7] were of the opinion that RECs should balance their collaboration with researchers with governance and oversight, and that a one-size-fits-all approach would not suffice. They considered that there ought to be a balance between the controlling and the enabling functions of RECs. Monaghan et al.[8] found that seeking research ethics approval in the humanities and social sciences has become overloaded by bureaucratic rules and regulations. Their review was conducted in England with the purpose of: augmenting existing literature that critiques research ethics governance; showcasing the problems encountered when multisite approval must be obtained; and assessing the cost of bureaucratic procedures in ethics approval. Narratives and literature were used for the review. They found that some researchers and authors were of the opinion that research ethics regulations are Studies/reviews identified through database MEDLINE (n=24) EBSCOhost (n=50) Unisa Library (n=21)

Data abstraction and assessment of risk bias

The major outcomes of all the studies included were individually extracted by the researcher and the co-coder, using a structured approach. The data extracted related to the aims of the studies or reviews, the methodology, the participants, the settings and the key findings.

Results

The initial search retrieved 95 articles, which were then handscreened by title and abstract. This process resulted in 45 articles for possible inclusion. A step-by-step approach was then followed to identify the final nine included in this review (Fig. 1).

Studies/reviews after screening of titles and abstracts (n=45)

Studies/reviews excluded owing to irrelevance to the research aim (n=50)

Full article/reviews further reviewed and rescreened (n=45)

Studies/reviews excluded owing to not passing the appraisal for good quality (n=31)

Full-text articles retrieved for final screening (n=14)

Full-text articles not completely meeting the criteria for inclusion (n=5)

Description of the studies

The nine studies included all focused on the regulation, legislation and governance of research ethics, or on RECs aimed at protecting human participants, and the implications thereof for research and researchers (Table 2). In the study by Gremillion et al.,[7] comparison was made between the operational practices of 10 RECs in New Zealand, in an attempt to identify best-practice options. In-depth narratives focusing on

Full articles (studies and reviews) included (n=9)

Fig. 1. Selection process for included studies/reviews.

Table 1. Assessment of study quality

1 2 3 4 5 6 7 8 9

Study Gremillion et al.[7] Monaghan et al.[8] McAreavey and Muir[3] Brunger and Russel[9] StĂźhlinger and Hackl[10] De Smit et al.[11] Silverman et al.[12] Macdonald and Spiegel[13] Spencer et al.[14]

Overall quality Good Good Good Good Good Good Good Good Good

Clear aims and objectives Yes Yes Yes Yes Yes Yes Yes Yes Yes

Ethical clearance NI Yes NI Yes NI Yes Yes NI Yes

NI = Not indicated.

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Clear data gathering and analysis Yes Yes Yes Yes Yes Yes Yes Yes Yes

Clear findings and conclusions Yes Yes Yes Yes Yes Yes Yes Yes Yes

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Table 2. Summary of included studies Study Gremillion et al.[7]

Country/ setting New Zealand

Monaghan et al.[8]

England

McAreavey and Muir[3]

Austria

Canada Brunger and Russel[9]

StĂźhlinger Austria and Hackl[10]

De Smit et al.[11]

Australia

Silverman et al.[12]

Egypt, SA and India

Macdonald and Spiegel[13]

USA and SA

Spencer et al.[14]

Methods Qualitative narratives

Participants 10 members of RECs

Aim/purpose To compare the review processes followed in 10 RECs

Findings Processes followed differ; committees must function within particular constraints, and balance the collaboration with researchers with ethical research governance Literature and Literature and To add to literature on the Ethical regulation is fundamentally narratives narratives from opinion of social researchers wrong because the damage that is researchers on research ethics caused to a democratic society far governance exceeds any possible harm to a human participant Literature and Authors, REC To describe the issues that A collaborative approach rather than a narratives members, research have contributed to the regulatory process needs to be adopted; applicant, supervisor, dissatisfaction with the meaningful meetings with researchers, university ethical review model that reviewers and potential participants administrator is prevalent in a specific will require extra time university Participatory Academic researchers To describe the politics Collective consent requires careful action research of community identity negotiation and should not be and the implications for simplified to make it look like re-imagining Canadian individual consent ethics guidelines Structured review Literature, policies To provide an overview European laws widely differ pertaining and legislation of European regulations to research with human subjects, in the field of ethics other than in medical research; in review committees, review some countries, one central REC requirements and Austrian exists, others rely on local committees legislation and some on institutional-related committees Observational Review of research To describe the The diverse expectations from study/ document submissions, heterogeneity in RECs create a heavy workload in review paperwork and documentation and requiring widespread ethical approval; correspondence administration required unnecessary administration must be from RECs of 25 by Human Research Ethics avoided and the processes simplified departments across Review Committees and seven Australian Research Governance states Quantitative Chairpersons of To assess the usefulness of The self-assessment tool can serve as research using an RECs in India, Egypt a self-assessment tool in a quality-improvement tool to assist online assessment and SA obtaining data on the extent in enhancing the operations of a tool to gather data to which RECs comply with committee international standards Case study One researcherâ&#x20AC;&#x2122;s To describe how the power The REC failed to understand experience of of institutional structures in qualitative research; they criticise the northern and the global North and South way in which another REC approved a southern RECs affect the work of students study, insist on changes not approved trying to conduct research by the other REC Multisite case 32 participants from To describe the perceptions, The key concern in data sharing is study using three sites experiences and concerns informed consent interview guides of 32 research stakeholders and focus groups regarding data-sharing practices

REC = research ethics committee; SA = South Africa.

not fit for the purpose of research. Sociologists argued that ethical regulation is fundamentally wrong, because the damage that is caused to a democratic society by inhibiting research far exceeds any possible harm that can come to a human participant in research. The findings

revealed a concern that ethics regulations and governance will kill social-science research, as differences in the opinions and procedures of different RECs can cause months of delays in obtaining ethics approval.

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McAreavey and Muir[3] found widespread dissatisfaction with the ethical-review model at Australian universities. In this study, multiple perspectives were gained through discussions with a REC member, a researcher, a supervisor, a research applicant and a university administrator, who each related their own experiences regarding the ethics-review process. The researchers found that the RECs, in themselves, do not behave unethically, but they follow a model that results in the inappropriate treatment of applications. The findings revealed that academics often feel that they have to ‘play the game’ in order to obtain ethics approval, resulting in RECs not being treated with respect. Major difficulties were encountered with REC members who come from a natural- and physical-science background, as they found it hard to understand qualitative research. Brunger and Russel’s[9] Canadian study was conducted with the aim of identifying how best to apply the Tri-Council Policy Statement guidelines in a community with complex and multiple political and cultural jurisdictions. Legislation (the Health Research Ethics Authority Act, SNL, 2006 Chapter H-1.2) had replaced regional-based review boards with centralised research ethics boards on a provincial level. All applications for health-research ethics approval now have to go through a centralised provincial review board. Participatory-action research was conducted, with research academics as participants. The findings revealed that far more collaboration is needed between researchers and boards, and that researchers and research ethics review board members should pay attention to the politics of risk – in other words, the ways in which collective identity and research are co-constructed. To simplify collective consent as equal to individual consent was considered inappropriate, and misleading to both the researcher and the communities participating in a study. Stühlinger and Hackl[10] conducted a structured review in Austria to provide an overview of European regulations in the field of ethics-review committees, specifically their review requirements. They critically analysed Austrian legislation and proposed an institutional solution to address legislative gaps. The keywords used in their research were ‘human research subject protection’, ‘research participant protection’, ‘research ethics committees’ ‘biomedical research’ and ‘European clinical trials regulation’. The findings revealed that European laws differ widely when it comes to research with human subjects, except for those concerning medical research. In some countries, a central research ethics committee exists, while in others there are local committees, and still others use institution-related committees. Some European countries have passed comprehensive laws on human research, but this is not necessarily so in others. It seems that research participants, therefore, are not equally protected. Twenty-five departments from seven states in Australia participated in the study conducted by de Smit et al.[11] The study purpose was to describe the heterogeneity in the administration and documentation required by human RECs across Australia. An observational study was made of the submission paperwork required by the various RECs, as well as the correspondence between the committees and the researchers from each of the collaborating sites. All participating states except Victoria employed a single ethics-review model; however, the application process, the guidelines provided for the number of documents needed for submission and the turnaround time varied significantly. The researchers concluded that these differences contributed to a very heavy workload in obtaining ethical approval, and that there is a need to simplify the processes. Silverman et al.[12] conducted a quantitative descriptive study using an online self-assessment tool to gather data from REC members in Egypt, India and SA. The purpose of their study was

to assess whether a self-assessment tool could be used to obtain data that reveal the extent to which RECs comply with recognised international standards. The findings revealed that RECs in India, Egypt and SA mostly performed well at aspects such as submission processes, the recording of minutes, the use of recommended criteria for review of protocols and informed-consent documentation. The aspects identified as challenging were policies and procedures, membership composition, ethics training, procedures for proposal reviews, elements in decision letters and criteria for further review. The dilemma of students or researchers who need ethics approval from RECs at different institutions (global North and South) were investigated in a case study by Macdonald and Spiegel.[13] The study highlighted the frustrations experienced when a researcher receives approval from one committee, while a second committee insists on changes to the research proposal before it can be approved. Either the proposal must go back and forth between the various RECs, or the researcher has to be unethical by changing the proposal without the first REC knowing about the changes. Spencer et al.[14] conducted a multisite case study involving 32 research stakeholders, who took part in interviews and focusgroup discussions. The purpose was to describe their perceptions, experiences and concerns about data-sharing practices. Some participants suggested that the argument should move beyond the question of whether or not to share data, to how to share it in ways that best minimises potential harm and respects participants’ reasonable expectations, such that the benefits would outweigh the potential harm. Junior researchers felt that more specific consent is needed if the purpose of the research deviates from that to which original consent was given. Senior researchers favoured broad consent for practical and administrative purposes. However, it seems that informed consent remains the key concern.

Methodology quality

All the studies included in this review had specific and clear aims and objectives. In six publications, the authors explicitly mentioned that ethical approval was received, and written consent obtained from the participants. In two publications, the qualitative data was provided by the authors themselves, and therefore they did not provide evidence of ethical approval to share their own experiences. The two review publications also did not indicate that ethical approval to conduct their studies was obtained. In some publications, the researchers and authors themselves were the participants, and in others the participants were either conveniently or purposefully selected. Gremillion et al.,[7] McDonald and Spiegel[13] and McAreavey and Muir[3] purposefully selected participants (the authors themselves) and undertook a thematic analysis of their narratives. Spencer et al.[14] made use of snowball sampling and used thematic analysis. Silverman et al.[12] purposefully selected chairpersons of RECs, and a statistical analysis of the data was done. Stühlinger and Hackl[10] conducted a structured review, with a thematic analysis, to present their data. Brunger and Russel,[9] Monaghan et al.[8] and De Smit et al.[11] purposefully selected participants and provide a thematic analysis of their data. Kasule et al.[15] sent an open invitation to all administrators of RECs in Africa whose contact details were available on the internet, and provided a statistical analysis of the data. Most of the studies reported on qualitative data, which was not a surprise, as it seems that it is mostly researchers involved in social-science research who are concerned about the legislation and regulation of research to protect the human research participant. All studies provided clear findings that contributed to the findings of this structured review.

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Results

The thematic analysis of the results of the included studies revealed three themes: operational practices, legislation and regulation, and organisational governance (Table 3).

Operational practices

It is evident from the review findings that the operational practices of RECs and IRBs are very diverse,[7] although they all strive to protect the human participant. For the researcher who needs to obtain ethical approval from different committees around the globe, this is a frustration, as such inconsistencies can be a hindrance that does not enhance research or contribute to a global culture of research. The submission requirements, communication and collaboration between the committees and researchers, and the meeting procedures and review processes, are different for each committee.[7,11] The National Health and Medical Council in Australia has developed a national approach, but this intervention has not streamlined the process.[11] The disparities were clearly highlighted when the same study was submitted to 24 RECs, and the feedback differed significantly; there were between 0 to more than 10 major concerns raised by the various committees, and the turnaround time for resubmission ranged from 2 weeks to 2 months.[11] Sometimes, ethical approval took as long as 1 year, or a specific REC did not grant such approval at all, which forced researchers to go to alternative committees to obtain ethical approval for their study.[8] These delays in turn cause delays in data gathering and graduation, and can have serious implications with regard to funding and so forth. It seems that inflexible and prescribed rules to protect human participants, without supportive structures and relevant procedures, lead to frustration for researchers. Some researchers defiantly stated that ‘breaking the rules imposed on researchers by RECs will not result in unethical behaviour’.[8] Although very specific training is required for REC members,[8] most of this training is focused on the committee chairpersons.[15]

Not all members are equally capacitated to undertake an objective review that protects the human participant without harassing the researcher, which inhibits a positive and ethical culture of research. Training is needed to simplify, but also to homogenise, human research ethics approval processes,[11] to protect not only the human participant, but also the researcher.

Legislation and regulation

Legislation and regulation differ from country to country,[13] and various registration and accreditation bodies exist. Some countries have passed comprehensive laws on human-subject research (Spain, Cyprus, Switzerland, Denmark, Norway, Luxembourg, Latvia, Estonia, Lithuania and SA), while this is not the case in others.[10] In the USA, IRBs are registered with the US Office for Human Research Protections, in an attempt to simplify and co-ordinate research ethics approval. In certain countries, all health ethics research committees must be accredited or registered with a National Health Research Council or other relevant institution.[16] Some countries extend their responsibility to also cover the social and behavioural sciences.[13] In some countries, such as SA, the National Health Act (Act No. 61 of 2003) requires that RECs be registered with a national body, and it also prescribes the criteria for membership and the expertise of members of a REC, and provides guidelines with regard to the training of committee members, as well as standing operational procedures.[2] RECs should facilitate the ethics review process and protect the rights and dignity of potential human research participants, and prevent inconsistency in the interpretation of guidelines[11] and definitions. It is also imperative that concepts such as ‘vulnerable human subjects’, ‘health research’ and ‘personal data’ are universally understood and agreed upon, to determine whether an ethics review is required or not – not all research involves a human participant or sensitive data.[10] Receiving ethical approval for research in the humanities and social sciences has become increasingly problematic due to the bureaucratic

Table 3. Themes identified Theme Operational practices

Category Submission requirements Communication Meetings

Review processes Legislation and regulation

Diverse accreditation and registration bodies

Different definitions of human participants Positive aspects Negative aspects

Institutional governance

Constraints

Subtheme Application documents Application processes Contact persons Timeframes Online Face to face Regularity Training requirements Expertise National Health Research Councils, institutional boards, Department of Health Acts Ethical decision-making, protection of the human participant Negative impact on social research Governing the researcher Unpredictable ethical decision-making Power games Lack of resources Diverse departments Lack of clear mandate Inconsistency in the application of governance

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rules and regulations.[8] The fact that ethical decision-making is inherently local, very specific, contextual and also contestable also implies that it cannot easily be accommodated in a bureaucratic system of rules.[8] Some researchers felt that the ethical-review process was a power game, which felt like an emotional war.[8] Unpredictable and inconsistent ethical reviews and results,[11] as well as inappropriate treatment of researchers,[3] cause the abovementioned experiences of researchers. Researchers are confronted with the tensions between their own ethical conscience and all the procedural demands of rules, regulations[8] and legislation, causing negativity towards pursuing research where human participation is involved. A question raised by researchers was: who is a REC protecting when it insists that a separate, local ethics approval process cannot alter or recommend alterations on a research proposal approved by them?[13]

Institutional governance

To develop a culture in research that supports ethical conduct requires unconditional support and commitment from the leaders of an institution. It is essential that every member of the REC demonstrates transparency, integrity and accountability. Adequate resources, legitimatising the authority of a committee and compliance with national laws[12] are crucial. In many African countries, a lack of financial resources to strengthen the capacity of the REC membership is a major challenge.[15] The administrative duties involved in the ethics review process contribute to a heavy workload for both the researcher and the REC members, and therefore there is a general call to reduce the number of administrative processes and procedures.[11] Inconsistency in the application of governance[11] is also a problem. University governance is and should be affected by the requirements for accreditation by or registration with a national body when the requirements are gazetted, as for example in SA. The parameters of ethical regulation are often determined by the demands of funders.[3] The global tendency is that research grants can only be obtained after approval from a formal REC or IRB,[3] without researcher or participant ever having a say in what they consider ethical or otherwise. This raises serious questions about who is currently protected by all the regulatory processes.[17]

Limitations of the review

The fact that the authors in four of the nine studies included in this review used their own research experience as data, thereby contributing to the narratives used for data gathering, might be construed as biasing their conclusions, but the contexts were very clearly described and their personal experiences were carefully examined. It is interesting to note that although all the studies were concerned with the issue of gaining ethical approval, four publications did not indicate whether or not their studies were ethically approved.

Conclusion

The types of research that require ethical approval have changed over time, from a focus purely on medical research, to the inclusion of new fields such as public-health research, biomedical research and other health-related fields. As a result, there is a need for new ethical standards to be established that equally protect all human participants, as well as researchers. In Europe and many other countries around the globe, national laws, as yet, have not been adapted to reflect this change, or its impact on the protection of

human participants.[10] These challenging developments require the establishment of new ethical-review principles. An ethics review is intended to be a transparent process that makes a positive contribution to the research itself and the culture of research in general, and that ensures the protection of human participants, but instead, the introduction of ethical scrutiny has incurred hostility.[3] Research should not be separated from ethical requirements, but it seems that REC regulations have raised concerns and ignited lively debate. To behave ethically means to protect others, minimise harm and increase the sum of good in the world. A REC, as a multidisciplinary, independent body charged with reviewing research proposals involving human participants, must ensure that the dignity, rights and wellbeing of human participants are protected. However, there are many more concerns in research than merely the protection of the human participant. Issues that cause contention in the power relationship between committee and researcher are: the choice of research questions; the relative distribution of burdens v. benefits; the ownership of data; the appreciation of intellectual capital; capacity building; and respect not only for local IRBs, RECs[13] and committee members, but also researchers. REC reviews should maintain and promote confidence, and guarantee transparency, in research, by protecting the rights of participants[10] and of the researcher. However, qualitative researchers perceive the ethical approval process as a hurdle to be overcome, and do not, in any way, view it as a collegial process that is there to support them. The relationship between a REC and a researcher should be one of mutual trust, and initiatives such as an international network, similar to UNESCO, to support and co-operate with researchers and ethics committees,[10] should be considered. There is also a need for diverse RECs from all over the world to interact and agree on what ethical research entails.[13] The abundance of research data that exists today, as well as the technology to distribute and make these data available, has enormous potential to contribute to advances in science[14] and to an interrelated and diversified health-research environment. Policies that mandate that researchers share their data are becoming common,[18] but how does this affect consent by participants and the ownership of the data? Commentators have advocated for the protection of the rights and the responsibilities of the researcher who is generating the data, while recognising the rights of the data assessors,[14] but where do these leave the human participants who gave consent to a specific study? These are the issues that ethics committees need to consider. The major differences in the standards of different RECs and IRBs also complicate international research collaboration, research funding and the publication of research findings. Differences in the interpretations of the concepts ‘human participant’, ‘health-related research’, ‘vulnerable group’ and ‘sensitive private data’ contribute to the frustration of researchers, especially in the social sciences, where researchers conducting collaborative research must adapt their research to conform to the requirements of diverse committees and boards to obtain approval. In addition to the lively debate around the various interpretations of the concepts mentioned above, there are other pertinent issues that need further investigation, such as the types of research that can be considered as involving human participants; the definition of health-related research; the diversity of RECs and their requirements; the lack of a global simplified process; the delays in obtaining approval; and the legislation, regulation and governance of research and research ethics, RECs and the protection of human participants.

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This structured review left me with a feeling of discomfort. Although human research participants must be protected, researchers and research should equally be supported and motivated. The ethicsreview process must be streamlined; the concepts need to be clear, well defined and transparent; and the process must contribute to capacity building. It should not be hostile to researchers, and must be carried out by knowledgeable and trained committee members, and overall, enhance a culture of ethical conduct in research. The question that I am still left with is: Is it possible for RECs around the globe to agree on one simplified, streamlined process that encourages a positive culture of research, while protecting the human research participant and the community as a whole? Acknowledgements. None. Author contributions. Sole author. Funding. None. Conflicts of interest. None. 1. Dhai A. The research ethics evolution: From Nuremburg to Helsinki. S Afr Med J 2014;14(3):178-180. http://doi.org/10.7196/SAMJ.7864 2. National Department of Health, South Africa. Ethics in health research: Principles, structures and procedures. http://www.mrc.ac.za/ethics/DOHEthics.pdf (accessed 10 March 2017). 3. McAreavey R, Muir J. Research ethics committees: Values and power in higher education. Int J Soc Res Methodol 2011;14(5):391-405. http://doi.org/10.1080/13645579.2011.565635 4. Moher D, Liberati A, Tetzlaff J, Altman DG & The PRISMA Group. Preferred reporting items for systematic reviews and meta-analysis: The PRISMA statement. Open Med 2009;3(3):123-130. http:// doi.org/10.1371/journal.pmed.1000097 5. Bradley-Jones C, Rattray J, Jones M, MacGillivray S. Promoting the health, safety and welfare of adults with learning disabilities in acute care settings. A structured literature review. J Clin Nurs 2013; 22:1479-1509. http://onlinelibrary.wiley.com/doi/10.1111/jocn.12109/pdf (accessed 10 March 2017). 6. Sandelowski M, Barroso J. Classifying the findings in qualitative studies. Qual Health Res 2003;13(7):905923. http://journals.sagepub.com/doi/10.1177/1049732303253488 (accessed 10 March 2017).

7. Gremillion H, Snell D, Crosthwaite J, Finch B, Paterson J, Tavinor G. What does organizational diversity in New Zealand tertiary sector research ethics committees teach us about balancing consultative and governance approaches to ethics review? N Z Sociol 2016;31(4):4-27. http://search.informit.com.au/fu llText;dn=339248951923644;res=IELFSC (accessed 10 March 2017). 8. Monaghan LF, O’Dwyer M, Gabe J. Seeking university research ethics committee approval: The emotional vicissitudes of a ‘rationalised’ process. Int J Soc Res Methodol 2013;16(1):65-80. https://doi. org/10.1080/13645579.2011.649902 9. Brunger F, Russel T. Risk and representation in research ethics: The NunatuKavut experience. J Empir Res Hum Res Ethics 2016;10(4):368-379. https://doi.org/10.1177/1556264615599687 10. Stühlinger V, Hackl M. Research ethics committees in the field of health-related human research – a European perspective and the case of Austria. Eur J Health Law 2014,21:387-400. http://booksandjournals. brillonline.com/content/journals/10.1163/15718093-12341329 (accessed 10 March 2017). 11. De Smit E, Kearns LS, Clarke L, Dick J, Hill CL, Hewitt AW. Heterogeneity of human research ethics committees and research governance offices across Australia: An observational study. Australas Med J 2016;9(2):33-39. https://doi.org/10.4066/AMJ.2015.2587 12. Silverman H, Sleem H, Moodley K, et al. Results of a self-assessment tool to assess the operational characteristics of research ethics committees in low and middle- income countries. J Med Ethics 2015;41:332-337. http://doi.org/10.1136/medethics-2013-101587 13. Macdonald H, Spiegel AD. Distraction from the real difficulties: Ethical deliberations in international health research. Anthropol S Afr 2013;36(3-4):146-154. http://doi.org/10.1080/02580144.2013.10887040 14. Spencer G, Silaigwana B, Wassenaar D, Bull S, Parker M. Developing ethical practices for public health research data sharing in South Africa: The views and experiences from a diverse sample of research stakeholders. J Empir Res Hum Res Ethics 2015;10(3):290-301. http://journals.sagepub.com/doi/ abs/10.1177/1556264615592386 (accessed 10 March 2017). 15. Kasule M, Wassenaar DR, Ijsselmuiden C, Mockatla B. Silent voices: Current and future roles of African research ethics committee administrators. IRB Ethics Hum Res 2016;38(1):13-19. http:// www.cohred.org/wp-content/uploads/2012/09/Silent-Voices-Current-and-Future-Roles-of-AfricanResearch.pdf (accessed 10 March 2017). 16. South Africa. National Health Act No. 61 of 2003. http://www.gov.za/sites/www.gov.za/files/a61-03. pdf (accessed 10 March 2017). 17. Watson R, Gelling L. Editorial: NHS research ethics committees: For whose protection? J Clin Nurs 2012;21:2097-2098. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2702.2011.03887.x/epdf (accessed 10 March 2017). 18. Department of Health and Human Services, National Institutes for Health, USA. NIH Genomic data sharing, 2014. https://www.nih.gov/news-events/.../nih-issues-finalized-policy-genomic-data-sharing (accessed 14 February 2017).

Accepted 16 May 2017.

October 2017, Print edition

These open-access articles are distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients M Held,1 PhD; M Laubscher,1 FCOrth (SA); L Workman,2 MPH; H J Zar,2 PhD; R Dunn,1 FCSOrth (SA) 1 2

Orthopaedic Research Unit, Department of Orthopaedic Surgery, Groote Schuur Hospital, University of Cape Town, South Africa Department of Pediatrics and Child Health, Red Cross War Memorial Childrenâ&#x20AC;&#x2122;s Hospital, University of Cape Town and MRC Unit on Child and Adolescent Health, University of Cape Town, South Africa

Corresponding author: M Held (michael.held@uct.ac.za) Background. GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. Objectives. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. Methods. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. Results. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIVuninfected patients (p=0.225). Conclusion. GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB. S Afr Med J 2017;107(10):854-858. DOI:10.7196/SAMJ.2017.v107i10.11186

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.11186

Deep-vein thrombosis in the era of high HIV and tuberculosis prevalence: A prospective review of its diagnosis and treatment in a quaternary centre K E Hodkinson, MB BCh; J N Mahlangu, MB BCh, FCPath (SA), MMed (Haem), Cert Clin Haem (SA) Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg; and National Health Laboratory Service, Johannesburg, South Africa Corresponding author: K E Hodkinson (drkatehodkinson@gmail.com) Background. Venous thromboembolic disease (VTE) is a leading cause of morbidity and mortality worldwide. HIV and tuberculosis (TB) infections have an aetiological association with VTE. Implementation of national HIV and TB programmes in South Africa (SA) has changed the burden of these two conditions, with resultant effects on VTE prevalence. Furthermore, with the increased use of direct oral anticoagulants (DOACs), baseline thrombosis data are needed to evaluate the effect of these new agents. Objectives. To determine real-life baseline VTE characteristics in a pre-DOAC era, and to document the association of HIV and TB infections with VTE. Methods. This was a single-centre prospective cohort study performed in a quaternary care centre at Charlotte Maxeke Johannesburg Academic Hospital, SA. Key inclusion criteria included signed informed consent by adults (â&#x2030;Ľ18 years) with a new episode of thrombosis. Procedures included physical examination, thrombosis risk factor assessment, duplex Doppler examination, thrombophilia screening, inpatient treatment and outpatient follow-up.

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RESEARCH

Results. Ninety-nine participants with confirmed thrombosis met the inclusion criteria. Participants were predominantly black (79.8%) and female (64.6%), with a median age of 46 (interquartile range 38 - 57) years. The prevalences of HIV and TB were 53.0% and 21.2%, respectively. The most common risk factors for thrombosis were TB (17.2%) and malignancies (14.1%). Thrombophilia screening had a low diagnostic yield. The median time to target international normalised ratio during hospitalisation was 5.5 (4.0 - 7.0) days and the median duration of hospitalisation was 9 (7 - 11) days. The overall mortality rate in the cohort at 3 months post hospitalisation was 12.1%. Conclusions. This prospective study provides real-life data on thrombosis diagnosis and management at a quaternary public healthcare facility, providing a valuable baseline against which the effect of new DOAC anticoagulants can be assessed. Further research is required to clarify the aetiological association between thrombosis and HIV and TB. S Afr Med J 2017;107(10):859-863. DOI:10.7196/SAMJ.2017.v107i10.12443

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.12443

Male involvement in prevention of mother-to-child transmission of HIV in the context of partner testing in Goba town, Ethiopia: A facility-based cross-sectional study M T Alemayehu,1 BSc, MPH; J Haidar,2 MD, MSc, CRM, CME, HD 1 2

Goba Hospital, Oromia Health Bureau, Goba, Ethiopia School of Public Health, Addis Ababa University, Ethiopia

Corresponding author: J Haidar (hjemal@gmail.com) Background. Antenatal care (ANC) is an entry point for the prevention of mother-to-child transmission (PMTCT), particularly when a man accompanies his spouse for voluntary counselling and testing (VCT), even though this seldom happens in Ethiopia. Objective. To study the role of male partners in improving PMTCT/ANC, which is essential to prevent HIV/AIDS transmission in this country. Our study focused on identifying barriers for the low involvement in PMTCT/ANC among male partners whose spouses received ANC. Methods. A total of 422 male partners in Goba town, Oromia regional state, Ethiopia, were recruited in September - October 2014 and enrolled by a systematic sampling method. A facility-based cross-sectional study and two focus group discussions (FGDs) were conducted. Binary logistic regression and odds ratios were calculated to ascertain sociodemographic and other important information compared with the outcome variable and PMTCT/ANC, while the findings of the FGDs were grouped according to the emerging themes and analysed manually by means of a thematic approach. Results. The percentage of male partners (22.7%) accompanying their spouses for HIV testing and counselling at antenatal clinics improved three-fold when an invitation letter was introduced as a new initiative to increase male participation. Individuals in the age group 15 - 29 years (adjusted odds ratio (AOR) 5.4, 95% confidence interval (CI) 1.66 - 17.85), and whose duration of marriage was 5 years (AOR 5.6, 95% CI 1.83 - 17.30), were more likely to be tested than their referent groups. Men without a higher education (AOR 0.1, 95% CI 0.02 - 0.50), who disagreed with legal enforcement (AOR 0.1, 95% CI 0.07 - 0.32), were less likely to be tested, while those who did not notify their partners (AOR 8.4, 95% CI 1.92 - 37.12) were more likely to use the service. Being busy, proxy testing, fears of testing HIV-positive, neglecting the importance of VCT, and inadequate knowledge about the PMTCT/ANC programme were other barriers that came to the fore in the FGDs. Conclusion. Identified barriers have to be addressed, and helpful practices, such as using invitation letters to increase the uptake of the service by male partners, have to be instituted. S Afr Med J 2017;107(10):864-870. DOI:10.7196/SAMJ.2017.v107i10.11371

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.11371

October 2017, Print edition

RESEARCH

Survival of patients with Kaposi’s sarcoma in the South African antiretroviral treatment era: A retrospective cohort study M M Sengayi,1,2,3 MB ChB, Dip HIV Man, PhD; D Kielkowski,1 PhD; M Egger,4,5 MD, MSc, FFPH (UK); L Dreosti,6 MB ChB, BSc Hons, FCP (SA); J Bohlius,4 MD, MScPH National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland 3 School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Institute of Social and Preventive Medicine, University of Bern, Switzerland 5 Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 6 Department of Medical Oncology, Steve Biko Academic Hospital and School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 1 2

Corresponding author: M M Sengayi (mazvita.sengayi@nhls.ac.za) Background. When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIVpositive Kaposi’s sarcoma (KS) patients shifted from symptomatic palliation to potential cure. Objective. To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. Methods. We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012. We used Kaplan-Meier survival functions to estimate 1- and 2-year survival, and Cox regression models to identify changes over time and prognostic factors. Results. Our study included 357 AIDS-KS patients, almost all of whom were black Africans (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37 (interquartile range (IQR) 30 - 43) years, and the median baseline CD4 count was 242 (130 403) cells/µL. Most patients received ART (n=332, 93.0%) before or after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%) with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95% CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR 2.88, 95% CI 1.36 - 6.09) predicted mortality. Conclusions. Our results show that large national ART roll-out programmes can successfully reduce KS-related mortality at the individual patient level. If ART coverage is extended, KS-associated morbidity and mortality are likely to drop. S Afr Med J 2017;107(10):871-876. DOI:10.7196/SAMJ.2017.v107i10.12362

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.12362

Short-term outcomes of inborn v. outborn very-lowbirth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa L Gibbs, MB BCh, DCH (SA), MMed (Paeds), FCPaed (SA); L Tooke, MB ChB, MMed (Paeds), FCPaed (SA), Cert Neonatology; M C Harrison, MB ChB, MRCP, FRCPCH Department of Neonatology, Groote Schuur Hospital, Cape Town; and School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: L Gibbs (lyndal.gol@gmail.com)

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RESEARCH

Background. The Groote Schuur Hospital (GSH) neonatal nursery provides level 3 care for the Metro West Health District in the Western Cape Province of South Africa. Worldwide, very-low-birth-weight (VLBW) neonates delivered in level 3 neonatal units have better outcomes than those transported from other facilities. Objectives. To identify the characteristics and outcomes of VLBW neonates at GSH, with emphasis on differences between inborns and outborns. Methodology. This was a retrospective cohort study. VLBW neonates admitted to the GSH neonatal nursery between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford Network database and reviewed. Results. Of 1 032 VLBW neonates enrolled, 906 (87.8%) were delivered at GSH and 126 (12.2%) were outborn. Access to antenatal care, antenatal steroids and inborn status were statistically significant predictors of mortality and survival without morbidity. The mothers of inborn patients were more likely than those of outborn patients to have received antenatal care (89.1% v. 57.9%; p<0.0001) and antenatal steroids (64.2% v. 15.2%; p<0.0001). Inborns required less ventilatory support (16.2% v. 57.9%; p<0.0001) and surfactant administration than outborns (25.3% v. 65.1%; p<0.0001), and developed less late infection (8.8% v. 23.4%; p<0.0001), severe intraventricular haemorrhage (3.7% v. 13.9%; p<0.0001) and chronic lung disease (5.3% v. 13.4%; p=0.003). The incidence of necrotising enterocolitis was similar in the two groups (5.9% v. 8.7%; p=0.227). The mortality rate was 18.4% for inborns and 33.3% for outborns (p<0.0001). Mortality declined as birth weight increased. Of the survivors, 85.0% of inborns and 70.2% of outborns did not develop serious morbidity (p=0.003). Conclusions. VLBW neonates delivered at GSH had better outcomes than their outborn counterparts. Perinatal regionalisation is beneficial to our patients, with antenatal care, timeous transfer in utero and antenatal steroids contributing to excellent outcomes. S Afr Med J 2017;107(10):900-903. DOI:10.7196/SAMJ.2017.v107i10.12463

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.12463

Respiratory comorbidity in South African children with atopic dermatitis C L Gray,1 MB ChB, FRCPCH, MSc, PhD; M E Levin,1 MB ChB, FCPaeds, PhD; G du Toit,2 MB ChB, FRCPCH Division of Allergology, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town, and Faculty of Health Sciences, University of Cape Town, South Africa 2 King’s Health Partners MRM and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, UK; and Department of Paediatric Allergy, Guy’s and St Thomas’ NHS Foundation Trust, London, UK 1

Corresponding author: C Gray (claudiagray.paediatrics@gmail.com) Background. Atopic dermatitis (AD) is an early and important step in the propagation of the allergic march, enhancing food and respiratory allergies via epicutaneous sensitisation to allergens. Objectives. To determine the prevalence and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South African (SA) children with AD. Methods. This was a prospective, observational study in a paediatric university hospital in Cape Town, SA. Children with moderate to severe AD, aged 6 months - 10 years, were recruited randomly and investigated for food sensitisation and allergy. They were assessed for sensitisation to aeroallergens by the immuno solid-phase allergen chip test. House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass, tree pollen, mould (Alternaria), cat and dog sensitisation patterns were analysed. Symptoms of asthma and allergic rhinitis were elicited using a questionnaire modified from the International Study of Asthma and Allergies in Childhood study questions. Results. One hundred participants (59 black Africans and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis; 89% tested positive to at least one aeroallergen, most commonly house-dust mite DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%). Asthma, allergic rhinitis and aeroallergen sensitisation all increased with increasing age, while food allergy decreased with age. Food allergy was not an independent risk factor for respiratory allergies. Children were sensitised to indoor allergens (house-dust mite, pets) from an early age, while pollen allergies increased with age. Conclusions. In this cohort of SA children with moderate to severe AD, comorbidity with respiratory allergies was high. The prevalence of respiratory allergies increased with age while food allergy decreased with age, in keeping with the pattern of the allergic march. Seasonal

October 2017, Print edition

RESEARCH

allergies increased with age, while house-dust mite and pet allergy peaked in younger children, in keeping with early exposure via a defective skin barrier. Early and effective restoration of the skin barrier in AD may be a target for reducing aeroallergen-related diseases. S Afr Med J 2017;107(10):904-909. DOI:10.7196/SAMJ.2017.v107i10.12418

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.12418

Preoperative fasting times: Prescribed and actual fasting times at Universitas Hospital Annex, Bloemfontein, South Africa G Lamacraft,1 MBBS (Lond), DA (SA), MRCP (UK), FRCA (UK), PhD; C Labuschagne,2 3rd-year medical student; S Pretorius,2 3rd-year medical student; M C Prinsloo,2 3rd-year medical student; M D Smit,2 3rd-year medical student; J-R Steyn,2 3rd-year medical student 1 2

Department of Anaesthesiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa School of Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

Corresponding author: G Lamacraft (lamacraftg@ufs.ac.za) Background. Guidelines recommend a preoperative fasting period of 6 hours for solid food and 2 hours for clear fluids. Because of fixed meal times and imprecise operation starting times, patients often fast for an extended period of time. Objective. To investigate the prescribed preoperative fasting times, and the actual duration of fasting, compared with the internationally accepted fasting times for solid food and clear fluids. Methods. Patients (N=105) aged 14 - 60 years, who were scheduled for elective surgery in the morning session (list starting time 07h00), were included in this prospective study. On arrival in theatre, all patients were asked when they last ate and drank. Anaesthetic records were used to determine the prescribed fasting times and operation starting times. Results. For solids, patients were most frequently prescribed to start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00 (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and 25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes). Conclusion. Most patients started fasting too early preoperatively, consequently withholding food and oral fluids for longer than recommended. An increased awareness regarding complications of unnecessarily long fasting times, and interventions to correct this problem, is required. S Afr Med J 2017;107(10):910-914. DOI:10.7196/SAMJ.2017.v107i10.10930

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.10930

October 2017, Print edition

RESEARCH

Bibliometric trends of South African environmental health articles between 1998 and 2015: Making local research visible and retrievable C Y Wright,1,2 PhD; F Dominick,3 BSc; Z Kunene,1 BCur Hons; T Kapwata,1 MSc; R A Street,1,4 PhD Environment and Health Research Unit, South African Medical Research Council, Pretoria, South Africa Department of Geography, Geoinformatics and Meteorology, Faculty of Natural and Agricultural Sciences, University of Pretoria, South Africa 3 Ludwig Maximilian University of Munich, Germany 4 Discipline of Occupational and Environmental Health, School of Nursing and Public Health, College of Health Sciences, University of KwaZuluNatal, Durban, South Africa 1 2

Corresponding author: C Y Wright (cwright@mrc.ac.za) Background. South Africa (SA) has to grapple with multiple burdens of disease for which environmental factors have a role to play in both causation and prevention. This article describes a bibliometric review of environmental health indexed literature for SA over an 18-year period. Objectives. To provide an overview of the nature of SA-based published environmental health indexed research and to identify search challenges, frequently researched topics, and gaps and opportunities for future research. Methods. The Web of Science, PubMed and Science Direct were used to search for original, peer-reviewed and review articles with the inclusion criteria ‘environmental health’ and ‘South Africa’ available online and published between 1998 and 2015, inclusively. Results. A total of 230 journal articles were included in the bibliometric analysis. The highest number of articles (n=54) was published in 2015. The majority of the first authors were affiliated with SA institutions (n=160, 69.5%). For the articles where funding was explicitly declared (n=148), the three most frequently occurring agencies that funded the published research were the National Research Foundation in SA (n=17), the South African Medical Research Council (n=13) and the Water Research Commission (n=9). There was little inter-annual/ environmental health category variation over time owing to the relatively small sample size. The largest number of retrieved journal articles was in the area of environmental pollution control (n=76), followed by environmental health lifestyle and behaviour-related topics (n=42) and then water monitoring (n=26). Conclusions. Despite the research needed to solve large environmental health challenges in SA, environmental health was only used as a keyword in title, author keywords or abstract for 230 SA-based studies over an 18-year period. This makes it extremely difficult for environmental health research to be located and used to inform the profession as well as the research agenda. Several issues that environmental health practitioners are typically tasked to implement and monitor are not indexed as environmental health topics. The need for authors to use ‘environmental health’ as a keyword is emphasised, particularly if research is to inform decision-making and policy support, as well as guide future research in the country. S Afr Med J 2017;107(10):915-924. DOI:10.7196/SAMJ.2017.v107i10.12429

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i10.12429

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True (A) or false (B): SAMJ Protection of the human research participant: A structured review 1. The Declaration of Helsinki has been recognised as one of the most authoritative statements on ethical standards for human research in the world. 2. The memorandum Permissible Medical Experimentation was a set of rules for research on human participants, and later became the Nuremburg Code. 3. The broad South African (SA) Department of Health definition of human research includes, but is not limited to, any research that contributes to the knowledge of biological or social processes in human beings. 4. The implication of this broad interpretation is that almost all health-related or social-science research involves a human participant. Survival of patients with Kaposi’s sarcoma (KS) in the SA antiretroviral treatment era: A retrospective cohort study 5. The start of SA’s antiretroviral therapy programme in 2004 resulted in a shift from symptomatic palliation to potential cure for HIV-positive KS patients. 6. The advent of antiretroviral therapy dramatically decreased KS incidence, morbidity and mortality in high-income countries. Therapeutic drug monitoring of amlodipine and the Z-FHL/ HHL ratio: Adherence tools in patients referred for apparent treatment-resistant hypertension 7. A patient’s usual BP is ‘strongly and directly’ associated with cardiovascular and overall mortality, and lowering the BP reduces this risk. 8. A consistent finding is that ~50% of treated patients fail to achieve a goal of <140/90 mmHg. Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, SA 9. The initial resuscitation and stabilisation of preterm infants after delivery affects their morbidity and mortality.

Bibliometric trends of South African environmental health articles between 1998 and 2015: Making local research visible and retrievable 10. It is easy to find SA environmental health articles in literature searches using ‘environmental health’ as the keyword. CME User perspectives on Implanon NXT in SA: A survey of 12 publicsector facilities 11. Removals were most common among married and cohabiting women. 12. In the Demographic and Health Survey 2016, ~4% of sexually active women in SA were using the implant. Uptake and early removals of Implanon NXT in SA: Perceptions and attitudes of healthcare workers 13. The SA government introduced Implanon NXT, a long-acting subdermal contraceptive implant, in 2014. 14. Nurses lacked confidence in providing implant services effectively, particularly removals, which they ascribed to the brief, cascadetype training received. 15. Side-effects, particularly irregular bleeding, are the most common reason for early removals. Gaps in monitoring systems for Implanon NXT services in SA: An assessment of 12 facilities in two districts 16. Implanon NXT offers 3 years of protection against pregnancy. 17. In the year after the launch of Implanon NXT, the Department of Health (DoH) reported that ~800 000 implants had been inserted and that >6 000 healthcare providers had been trained with regard to implant provision. 18. The DoH stated that by April 2015, according to their estimates, ~5 000 removals had been recorded and that this figure has been steadily rising over time. 19. The actual number of and reasons for implant removals are well known. 20. Clinical studies of Implanon NXT showed that complications occur in ~1% of insertions.

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