SAMJ Vol 107, No 8 (2017)

AUGUST 2017

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CME Wilderness medicine (part 2) IN PRACTICE Adolescents and HIV research: Ethical considerations Superficial scalp arteries as source of migraine pain CASE REPORT Ocular metastases in breast cancer RESEARCH Corneal donations in South Africa Effect of HIV status on clinical outcomes of surgical sepsis

For first-line treatment in bleeding oesophageal varices 1

NEW

At the ready to save lives References: 1. Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage (Review). Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002147.

DOI:10.1002/14651858.CD002147. 2. Levacher S, Letoumelin P, Pateron D, et al. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet 1995; 346: 865-868. 3. Söderlund C, Magnusson I, Törngren S, Lundell L. Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. Scand J Gastroenterol 1990; 25: 622-630. 4. Feu F, D’Amico G, Bosch J. The acute bleeding episode: advances in drug therapy. In: Arroyo V, Bosch J, Rodés J (eds). Treatments in Hepatology. Masson, Barcelona 1995: 9-22.

S4 GLYPRESSIN® 0,1 mg/ml (Solution for Injection). One ampoule of 8,5 ml solution contains 1 mg terlipressin acetate. Reg. No.: 43/21.13/0829.

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION: FERRING (Pty) Ltd. Route 21 Corporate Park, 6 Regency Drive, Irene Ext 30. Pretoria, South Africa.

Tel: +27 12 345 6358/9 Fax: +27 12 345 1156. www.ferring.co.za. For full prescribing information refer to the package insert approved by the medicines regulatory authority. 2017/032

Ready mixed, ready to go...

GLYPRESSIN terlipressin Solution acetate

®

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AUGUST 2017 PRINT EDITION

FROM THE EDITOR 3

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

Seeing through another’s eyes B Farham

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

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EDITOR’S CHOICE

CORRESPONDENCE

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Paraffin ingestion in children: Rationalising antibiotic treatment K Balme, C Stephen

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Human dignity and the future of the voluntary active euthanasia debate in South Africa A Donkin

IZINDABA 8 What can we expect from the leadership of the recently elected World Health Organization Director-General, Dr Tedros?

Y Pillay, A-E Birn, T Holtz 10

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30 days in medicine B Farham BOOK REVIEWS The ECG Atlas of Cardiac Rhythms A Doubell Darwin’s Hunch: Science, Race and the Search for Human Origins A S Mall

EDITORIAL

CONTINUING MEDICAL EDUCATION 20

GUEST EDITORIAL Growing wilderness and expedition medicine education in southern Africa R Hofmeyr, J Matthew, S Buchanan, G Tölken, R De Decker

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ARTICLES Expedition medicine: A southern African perspective R Hofmeyr, G Tölken, R De Decker

CEO AND PUBLISHER Hannah Kikaya Email: hannahk@hmpg.co.za MANAGING EDITORS Claudia Naidu Naadia van der Bergh

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 Simpson Ismail Davids ONLINE SUPPORT Gertrude Fani

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Heat-related illness in the African wilderness R Hofmeyr, C D’Alton

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Human factors: Predictors of avoidable wilderness accidents?

R De Decker, G Tölken, J Roos

FINANCE Tshepiso Mokoena

IN PRACTICE HEALTHCARE DELIVERY 38 A retrospective study evaluating the efficacy of identification and management of sepsis at a district-level hospital internal medicine department in the Western Cape Province, South Africa, in comparison with the guidelines stipulated in the 2012 Surviving Sepsis Campaign R Bhikoo, S Versfeld, M M De V Basson, A H Oosthuizen MEDICINE AND THE LAW 43 Enrolling HIV-positive adolescents in mental health research: A case study reflecting on legal and ethical complexities N Woollett, J Peter, L Cluver, H Brahmbhatt

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HMPG

TECHNICAL EDITORS Emma Buchanan Christelle Cronje Kirsten Morreira Paula van der Bijl

18 Short-course adjuvant trastuzumab will increase cure rates in patients with human epidermal growth factor receptor 2-positive breast cancer R P Abratt

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ASSOCIATE EDITORS Q Abdool Karim, A Dhai, N Khumalo, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman, J M Pettifor, W Edridge, R P Abratt, D L Clarke

CLINICAL UPDATE Does access to private healthcare influence potential lung cancer cure rates?

T-J John, D Plekker, E M Irusen, C F N Koegelenberg A method for determining when the superficial scalp arteries are the source of migraine pain E Shevel

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August 2017, Print edition

HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574 SAMA website: www.samedical.org Journal website: www.samj.org.za

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CASE REPORT Ocular metastasis as initial presentation in breast cancer M Maliepaard, M Mesham, Z Aleksic, R Scholtz, J Edge

ONLINE CONTENTS LISTED IN Index Medicus (Medline) Excerpta Medica (EMBASE) Biological Abstracts (BIOSIS) Science Citation Index (SciSearch) Directory of Open Access Journals (DOAJ) Current Contents/Clinical Medicine

RESEARCH 58

Corneal donations in South Africa: A 15-year review* N J York, C Tinley

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The effect of HIV status on clinical outcomes of surgical sepsis in KwaZulu-Natal Province, South Africa* S Green, V Y Kong, J Odendaal, B Sartorius, D L Clarke, P Brysiewicz, J L Bruce, G L Laing, W Bekker

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Pancreatitis in a high HIV prevalence environment* F Anderson, S R Thomson

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*Abstract only, full article available online.

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IN PRACTICE 684

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Confidentiality and fitness to drive: Professional, ethical, and legal duties in the case of the diabetic bus driver C Wareham

RESEARCH 710

Cardiovascular risk factors and mortality in children with chronic kidney disease A Mudi, C Dickens, C Levy, D Ballot

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Suicide in Pretoria: A retrospective review, 2007 - 2010 C Engelbrecht, R Blumenthal, N K Morris, G Saayman

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Background photo: Nurse visiting a patient | Damien Schumann Box photos: Rescue of a climber with heatstroke on Table Mountain, Cape Town. Poor decisionmaking is the prime cause of heat injuries | Rik De Decker; Migraine | Shutterstock; Corneal transplant | Nick York

CME Wilderness medicine (part 2) IN PRACTICE Adolescents and HIV research: Ethical considerations Superficial scalp arteries as source of migraine pain CASE REPORT Ocular metastases in breast cancer RESEARCH Corneal donations in South Africa Effect of HIV status on clinical outcomes of surgical sepsis

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August 2017, Print edition

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

FROM THE EDITOR

Seeing through another’s eyes On 9 September 2009, I lost two very dear friends in an appalling motor vehicle accident on the M3 just outside Cape Town, when their car was crushed by a truck that fell from the other side of the motorway. I am sure that people who were in Cape Town at that time will remember the accident – it was that sort of event. Some of Alan’s organs – kidneys, I seem to remember – were harvested for transplantation the following day. Marita lived for a few days more and no solid organs could be used, but the family agreed to her corneas being harvested. They are now keen advocates for organ donation and said that, apart from the comfort of knowing that Alan and Marita’s deaths could help someone else, the organ donation co-ordinators went out of their way to make the family’s time in hospital more bearable with their kindness. In their daughter Karin’s words, ‘Although my mom’s organs didn’t save a life, somebody else can see the world through her eyes due to her cornea organ donation, and what a lovely view of the world it is.’

Organ donation can be an emotive subject, and this and the previous edition of the SAMJ carry articles on a topic that is extremely important in South Africa (SA), given that we have a major shortage of organ donors.[1-3] Issues surrounding it range from cultural differences in how a dead body is viewed and disposed of to the practical aspects of harvesting, transport of harvested organs, donor waiting lists and availability of resources. Solid-organ donation may be a more emotive issue than something like corneal donation, although interestingly in SA it would appear that cultural beliefs and superstitions play a more significant role in the donation of corneas than that of solid organs.[4] There are emotions associated with the heart, for example. The very idea of removing part of a person after death will be difficult for some people to deal with. And then there are cultural issues around ideas of resurrection, the role of the ancestors, and so on. All these seem to be more of an obstacle to organ donation in the developing world than elsewhere, and, coupled with a relatively resource-poor environment, mean that people stay on organ donation lists for a very long time. And now it would seem that good intentions have paradoxically made corneal donation, in particular, even more difficult in SA. In this issue of the SAMJ, York and Tinley[3] show that the number of corneal donations in SA has declined significantly, which means that the burden of corneal disease requiring transplantation has risen steadily. The rapid drop in numbers between 2005 and 2008 came at the same time as legislation that affected SA’s forensic mortuaries. When the South African Police Services controlled and managed the forensic mortuaries, the eye bank directors had easy

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access to the details of the deceased in these mortuaries and so could contact the next of kin, and these mortuaries were the main source of corneal donors at the time. However, from 2006, the governance of mortuaries shifted to the National Department of Health, with new legislation placing a heavy emphasis on confidentiality and ethics, making it hard to access next of kin and also introducing a requirement for written consent for corneal donation from a family member who had identified the deceased in person. Corneas should ideally be harvested within 12 hours, and this new requirement makes this almost impossible. As a result, most donated corneas now come from registered organ donors who die in private hospitals, or individuals whose families have agreed to organ donation after death.

This source of corneal donors has not changed much in the 15-year study period, but was already low. Hence our now critical shortage of corneal donors.

At the same time, almost two-thirds of donated corneas are allocated to the private sector at all three of the major eye banks in the country, when the greatest need is in the public sector, mainly because of a distribution system heavily skewed in favour of the private sector and because the private sector can contribute to the costs of the eye banks – which are not-for-profit organisations.

Corneal transplants are a relatively simple but life-changing procedure. I would urge all involved in organ donation generally, and eye banks in particular, to look at ways in which the current system can be changed to benefit all those requiring corneal transplants in SA. The need is great.

Bridget Farham Editor ugqirha@iafrica.com 1. Crymble K, Fabian J, Etheredge H, Gaylard P. Perceptions of nurses’ roles in end-of-life care and organ donation – imposition or obligation? S Afr Med J 2017;107(7):573-575. https://doi.org/10.7196/ SAMJ.2017.v107i7.12487 2. Etheredge HR, Penn C, Watermeyer J. Interprofessional communication in organ transplantation in Gauteng Province, South Africa S Afr Med J 2017;107(7):615-620. https://doi.org/10.7196/SAMJ.2017. v107i7.12355 3. York NJ, Tinley C. Corneal donations in South Africa: A 15-year review. S Afr Med J 2017;107(8):697701. https://doi.org/10.7196/SAMJ.2017.v107i8.12482 4. Pike RE, Odell JA, Kahn D. Public attitudes to organ donation in South Africa. S Afr Med J 1993;83(2):91-94.

S Afr Med J 2017;107(8):645. DOI:10.7196/SAMJ.2017.v107i8.12741

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EDITOR’S CHOICE

CME: Wilderness medicine (part 2)

Time spent immersing ourselves deep into nature – away from the increasing busyness and clamour of modern life – allows the reflective practitioner time for introspection on challenges and the core values of life.

Currently, medical research in the wilderness helps to expand our understanding of conditions as diverse as congenital heart disease, pulmonary hypertension, sepsis, critical illness and diabetes.

Despite this, wilderness medicine has for many years been the domain of eclectic enthusiasts and adventurous amateurs. In hazardous environments, human physiology is stressed to its limits, and the health practitioner encounters both conventional and environmentally specific medical problems. Wilderness medicine incorporates medical response, with limited resource capabilities, and substantial delays to definitive care due to remote healthcare facilities, necessitating improvisations to deliver care in the face of austerity.

Internationally, the growth of wilderness, expedition, mountain and extreme medicine has been slow but steady. Historically, numerous international groups with experience in the field have provided commercial courses to address their educational needs, which have only recently become available in South Africa (SA).

Local enthusiasts and experts have provided insights into the scope and diversity of wilderness medicine, high-altitude illnesses, cold exposure, and submersion injuries. In this edition of SAMJ, we address the fundamental concepts of expedition medicine, from participant screening and selection of suitable medical supplies to the epidemiology, roles and psychological aspects encountered on expeditions. Continuing the human thread, human factors in the wilderness are addressed, including every human’s capacity to make mistakes – some deliberately, but most inadvertently – and how awareness of that error capacity can help in anticipating and preventing accidents. Finally, heat-exposure injury is discussed in the African context.

While far from a comprehensive review of wilderness and expedition medicine, it is the fervent hope of the authors that these topics provide a catalyst for awareness and a kernel for further discussion, interaction and development of the field in SA, and an emergence of the specialty on our continent.

Enrolling HIV-positive adolescents in mental health research: A case study reflecting on legal and ethical complexities

Adolescents living with HIV are an emerging group in the global HIV/AIDS epidemic. Mental health in this population affects HIV care, treatment, consequential morbidity and secondary transmission.

There is a paucity of research regarding these youth in SA, partly because section 71 of the National Health Act of 2003 (NHA) requires parental or guardian’s consent.

Woollett et al.[1] explored legal and ethical issues related to conducting adolescent mental health research in SA. After obtaining a High Court order permitting research on minors aged <18 years without prior parental or guardian’s consent, the authors used qualitative and quantitative methods to interview adolescents in five clinics serving HIV-positive adolescents in Johannesburg. Of 343 participants enrolled, 74% were orphaned and did not have legal guardians, 27% were symptomatic for depression, anxiety or post-traumatic stress disorder, 24% were suicidal, and almost 90% did not feel that they belonged in the family with which they lived.

Without court intervention, most of the participants could not have participated in this research because parental consent was impossible

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to obtain. This case study argues for exceptions to the parental consent requirement, which excludes orphaned and vulnerable children and youth from research.

Recommendations are made to promote ethical integrity in conducting mental health research with adolescents. A balance is needed between protecting adolescents from exploitation and permitting access to benefits of research. Requiring parental consent for all research does not necessarily give effect to policy. For the vast majority of SA HIV-positive adolescents, parental consent is not possible. Section 71 of the NHA ought to be amended to facilitate valuable and necessary research concerning HIV-positive orphan children and adolescents.

Cardiovascular risk factors and mortality in children with chronic kidney disease

Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD), and its progression is determined by the presence of single or multiple cardiovascular risk factors (CVRFs).

In a comparative cross-sectional study, Mudi et al.[2] determined the prevalence of CVRFs in children with CKD and their association with mortality. The subjects were aged 5 - 18 years with all stages of CKD. All had a short history taken along with a physical examination, and their blood samples were assessed for serum creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, total cholesterol, haemoglobin and C-reactive protein.

Urine samples were also assessed for proteinuria.

One hundred and six children who met the study criteria were recruited, 34 with CKD I, 36 with CKD II - IV and 36 with CKD V (dialysis). The overall median age was 11 years (range 8 - 14), and the male/female ratio was 2.1:1. The most common CVRF was anaemia (39.6%). The rate of anaemia was higher in the dialysis group than in the CKD II - IV and CKD I groups (77.8%, 33.3% and 5.9%, respectively). Other CVRFs detected were hypertension, proteinuria, hypercholesterolaemia and dysregulated mineral bone metabolism.

Seven deaths were recorded in the dialysis group during the study period. Severe hypertension and intracranial bleeding were the most common causes of death. Modifiable risk factors such as increased TC and decreased albumin levels were more common than other CVRFs in the dialysis patients who died.

CVRFs may be present in early CKD, even before the decline in GFR. Routine screening for CVRFs, along with timely intervention, may prevent the progression of CVD and mortality later in life.

Corneal donations in South Africa: A 15-year review

Corneal pathology is one of the leading causes of preventable blindness in SA. A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem.

York et al.[3] studied trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors using a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016.

There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8%

August 2017, Print edition

EDITOR’S CHOICE

originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%.

Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/ Asian. Donor age demonstrated a bimodal peak at 25 and 55 years.

The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.

Does access to private healthcare influence potential lung cancer cure rates?

Numerous studies show a link between poor socioeconomic status (SES) and late-stage cancer diagnosis. However, this has not been consistently shown looking at non-small-cell lung cancer (NSCLC) in isolation. Despite the extremely high prevalence of lung cancer and disparities in access to healthcare based on health insurance in SA, there is a paucity of data on the influence of health insurance (as a surrogate for SES) on stage at presentation of NSCLC. This study[4] assessed the relationship between health insurance status (and invariably SES) and staging (and therefore resectability) of patients with primary NCSLC at the time of initial presentation.

Health-insured patients with NSCLC (n=51) were retrospectively compared with NSCLC patients with no health insurance (n=532 with regard to demographics, tumour node metastasis (TNM) staging, and cell type at initial presentation.

Patients with no health insurance were younger (mean (standard deviation (SD)) 59.9 (10.1) years) than those with private health insurance (64.2 (9.6) years) (p=0.03). Poorly differentiated NSCLC was significantly more common in the privately health-insured group (23.6%) than among those with no health insurance (4.6%) (p<0.01).

Six of 51 NSCLC patients (11.8%) with private health insurance presented with early-stage, potentially curable disease (up to stage IIIA), compared with 55 patients (10.3%) in the uninsured group (p=0.75).

Access to private health insurance did not have a significant impact on stage at initial presentation. The only significant differences were the relatively advanced age at presentation and relatively higher percentage of poorly differentiated NSCLC seen in patients with health insurance.

BF 1. Woollett N, Peter J, Brahmbhatt H. Enrolling HIV-positive adolescents in mental health research: A case study reflecting on legal and ethical complexities. S Afr Med J 2017;107(8):679-683. http:// dx.doi.org/10.7196/SAMJ.2017.v107i8.12409 2. Mudi A, Dickens C, Levy C, Ballot D. Cardiovascular risk factors and mortality in children with chronic kidney disease. S Afr Med J 2017;107(8):710-714. http://dx.doi.org/10.7196/SAMJ.2017.v107i8.12271 3. York NJ, Tinley C. Corneal donations in South Africa: A 15-year review. S Afr Med J 2017;107(8):697701. http://dx.doi.org/10.7196/SAMJ.2017.v107i8.12482 4. John T-J, Plekker D, Irusen EM, Koegelenberg DFN. Does access to private healthcare influence potential lung cancer cure rates? S Afr Med J 2017;107(8):687-690. http://dx.doi.org/10.7196/SAMJ.2017. v107i8.12277

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

CORRESPONDENCE

Paraffin ingestion in children: Rationalising antibiotic treatment

To the Editor: We were delighted to see the recent CME articles on prevention of childhood injuries,[1] particularly highlighting the significant contribution of poisoning in injury-related morbidity and mortality in children. We noted with added interest the article

by Kimemia and Van Niekerk[2] on energy poverty, shack fires and childhood burns. It brings to the fore the serious potential fire-related dangers associated with the use of kerosene stoves as a cheap and readily available alternative source of energy for cooking, heating and lighting. In addition to the trauma-related burn injuries already discussed, it is important to remember the potential dangers of paraffin ingestion in children, as paraffin is often decanted from cumbersome large containers into smaller cooldrink bottles, placing thirsty and inquisitive toddlers at great risk of exposure.[3] In low- and middle-income countries, including South Africa (SA), ingestion of paraffin remains a common cause of childhood poisoning.[4,5] In 2006, it was estimated that there were 40 000 60 000 cases per annum in SA.[6] Although the absolute numbers have dropped since the 1990s, paraffin ingestion presentations still constituted on average over 20% of all poisoning cases seen at Red Cross War Memorial Children’s Hospital in Cape Town between 2003 and 2015 (1 151 paraffin cases with 2 deaths).[5,7] Although the majority of paraffin ingestions do not result in poisoning,[8] the primary clinical concern is the risk of aspiration leading to a sterile chemical inflammatory pneumonitis.[9] The mainstay of treatment is symptomatic, with appropriate respiratory support, and the majority of children who require hospital admission are discharged within a few days.[5,10,11] In patients with pneumonitis, the potential for secondary bacterial infection exists, but the difficulty of clinically determining inflammation v. infection has raised doubts about the use of antibiotics in treatment. As routine use of antibiotics in cases of paraffin ingestion is common practice,[12] and in light of the recent emphasis on antibiotic stewardship, it should be noted that a growing body of evidence points to the rarity of secondary infection and that prophylactic antibiotics are unwarranted.[10,11,13] Although further research is required, we suggest that antibiotic therapy should be reserved for children with concomitant infections or suspected secondary bacterial infection 48 hours after ingestion, or those who have an increased risk of developing complications, e.g. children with HIV/ AIDS, severe malnutrition or underlying respiratory illness.

It is evident that paraffin ingestion and burns remain common preventable childhood injuries. One can only hope that these commentaries will fuel both government and industry’s commitment to hastening the delivery of safer, more efficient and affordable energy alternatives.

Kate Balme, Cindy Stephen Poisons Information Centre, Red Cross War Memorial Children’s Hospital and Department of Paediatrics and Child Health, Faculty of Heath Sciences, University of Cape Town, South Africa kate.balme@uct.ac.za 1. Van As AB, van Niekerk A. Prevention of childhood injuries. S Afr Med J 2017;107(3):182. https://doi. org/10.7196/SAMJ.2017.v107i3.12364 2. Kimemia DK, van Niekerk A. Energy poverty, shack fires and childhood burns. S Afr Med J 2017;107(4):289-291. https://doi.org/10.7196/SAMJ.2017.v107i4.12436 3. Schwebel DC, Swart D, Hui SA, Simpson J, Hobe P. Paraffin-related injury in low-income South African communities: Knowledge, practice and perceived risk. Bull World Health Organ 2009;87(9):700-706. https://doi.org/10.2471%2Fblt.08.057505 4. Kohli U, Kuttiat VS, Lodha R, Kabra SK. Profile of childhood poisoning at a tertiary care centre in North India. Indian J Pediatr 2008;75(8):791-794. https://doi.org/10.1007%2Fs12098-008-0105-7 5. Balme K, Roberts JC, Glasstone M, Curling L, Mann MD. The changing trends of childhood poisoning at a tertiary children’s hospital in South Africa. S Afr Med J 2012;102(3):142-146. https://doi. org/10.7196%2Fsamj.5149

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6. Matzopoulos R, Carolissen G. Estimating the incidence of paraffin ingestion. Afr Saf Promot 2006;4(3):4-14.

7. Balme KH, Stephen CR, Mohamed F, Curling L. The profile of paediatric poisoning from Red Cross War Memorial Children’s Hospital: 2009-2015. Poster presented at the Biennial South African Paediatric Association and South African Association of Paediatric Surgeons Congress, Durban South Africa, 1 - 4 September 2016.

8. Anas N, Namasonthi V, Ginsburg CM. Criteria for hospitalizing children who have ingested products containing hydrocarbons. JAMA 1981;246(8):840-843. https://doi.org/10.1001%2Fja ma.1981.03320080026021 9. Eade NR, Taussig M, Marks MI. Hydrocarbon pneumonitis. Pediatrics 1974;54(3):351-357.

10. Reed RP, Conradie FM. The epidemiology and clinical features of paraffin (kerosene) poisoning in rural African children. Ann Trop Paediatr 1997;17(1):49-55. https://doi.org/10.1080% 2F02724936.1997.11747863 11. Simmank K, Wagstaff L, Sullivan K, Filteau S, Tomkins A. Prediction of illness severity and outcome of children symptomatic following kerosene ingestion. Ann Trop Paediatr 1998;18(4):309-314. https:// doi.org/10.1080%2F02724936.1998.11747965 12. Malangu N, du Plooy WJ, Ogunbanjo GA. Paraffin poisoning in children: What can we do differently?

S Afr Fam Pract 2005;47(2):54-56. https://doi.org/10.1080%2F20786204.2005.10873189 13. Balme KH, Zar HJ, Swift DK, Mann MD. The efficacy of prophylactic antibiotics in the management of children with kerosene-associated pneumonitis: A double-blind randomised controlled trial. Clin Toxicol (Phila) 2015;53(8):789-796. https://doi.org/10.3109%2F15563650.2015.1059943

S Afr Med J 2017;107(8):646. DOI:10.7196/SAMJ.2017.v107i8.12598

Human dignity and the future of the voluntary active euthanasia debate in South Africa

To the Editor: I would like to comment on the article by Jordaan. [1] I thank him for setting out some of the details of the recent Stransham-Ford case. However, in the second half of his article, as he sets out his pro-euthanasia opinion on the definition of ‘human dignity’, he loses sight of the human consequences of what he is advocating.

One of the real problems with legalising euthanasia, should we adopt Jordaan’s definition of human dignity, is that there will be many victims. I was recently confronted with the reality of our society’s indifference to the vulnerable. An elderly patient of mine who had advanced dementia was in need of some medical equipment for the sake of her comfort. Her carer expressed doubt that the family would buy it for her. I was surprised, as I knew that this patient had more than enough money to cover her medical expenses. The carer remarked that she thought that the family would rather try and keep her expenses to a minimum, even though she had more than enough money, as they were hoping that she might die before too long, and they did not want to use up too much of their inheritance before then.

Is this not an obvious pitfall of legalising euthanasia? How can anyone claim that people would not end the lives of family members for the sake of money, or that elderly people would not ask for or acquiesce to euthanasia out of a sense of guilt that they would otherwise be a burden on their families’ emotions and finances?

Jordaan proposes that individual autonomy is central to the definition of human dignity. This is highly debatable. However, proeuthanasia activists frequently hijack the word ‘dignity’ and use it as a euphemism when they actually mean ‘autonomy’. It would not sound as convincing to call your organisation ‘Autonomas’ or ‘Dying with Autonomy’.

Jordaan failed to mention that individual autonomy can never be absolute, and constantly has to be balanced against the harm that might be caused to others in the surrounding community. We do not have autonomy to speed on public roads, as it puts others in danger.

Furthermore, I would encourage Jordaan to research the concept of autonomy a little more deeply. Even his own choices are not as autonomous as he would like to think. The more one thinks about it, the more the issue of choice becomes a complex one. Particularly of note is Rene Girard’s mimetic theory, which is becoming more prominent in philosophy now that neuroscience is confirming

August 2017, Print edition

CORRESPONDENCE

the nature of humans’ developing, learning, behaving, desiring and choosing through mimicry of others.[2] As Westerners, we might find it surprising to hear that what we desire or choose could be based on mimicry of others rather than our own pure autonomy.

To quote Rene Girard (French historian, literary critic and philo­sopher of social science, whose work belongs to the tradition of anthropological philosophy): ‘The experience of death is going to get more and more painful, contrary to what many people believe.

The forthcoming euthanasia will make it more rather than less painful, because it will put the emphasis on personal decision in a way which was blissfully alien to the whole problem of dying in former times. It will make death even more subjectively intolerable, for people will feel responsible for their own deaths and morally obligated to rid their relatives of their unwanted presence. Euthanasia will further intensify all the problems its advocates think it will solve.’[3] We in South Africa have a chance to prevent euthanasia and its terrible consequences, though the threat of collapsing into standard Western individualist cultural ideology remains a looming possibility.

Preventing euthanasia will require us to be more active than the activists, and we will constantly need to keep the voice of the victims alive.

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Allan Donkin General practitioner, Somerset West, Western Cape, South Africa donkinaj2@gmail.com 1. Jordaan DW. Human dignity and the future of the voluntary active euthanasia debate in South Africa. S Afr Med J 2017;107(5):383-385. http://dx.doi. org/10.7196/SAMJ.2017.v107i5.12339 2. Garrels SR. Imitation, mirror neurons and mimetic desire: Convergence between the mimetic theory of Rene Girard and empirical research on imitation.

Contagion: Journal of Violence, Mimesis, and Culture 2005-2006;12-13:47-86. http://dx.doi.org/10.1353/ctn.0.0004 3. Girard R, author, Williams JG, ed. The Girard Reader. Crossroad Herder, 1996.

S Afr Med J 2017;107(8):647. DOI:10.7196/SAMJ.2017.v107i8.12599

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What can we expect from the leadership of the recently elected World Health Organization Director-General, Dr Tedros?

On 23 May 2017, the World Health Assembly (WHA) elected a new Director-General (DG) to replace the outgoing Dr Margaret Chan.

From a shortlist of three candidates, members of the WHA elected Dr Tedros Adhanom Ghebreyesus to lead the premier United Nations (UN) organisation on global health.

As has been widely reported, the World Health Organization (WHO) faces a series of critical challenges with which the new DG will be confronted, including reforming the institution to make it relevant to global health in the 21st century, attracting the necessary resources, etc. (see for example Horton[1]).

Ahead of the election, the authors of the recently published Textbook of Global Health[2] asked all three shortlisted candidates to respond to the following four questions: 1. How seriously will you take the societal determinants of health, and what specific actions will you lead in this regard?

2. How will you ensure that non-state actors do not capture the WHO and thereby neuter the role of UN member states in decisionmaking?

3. What specific novel policies will you propose to improve health equity and strengthen health outcomes in low- and middle-income countries (LMICs)?

4. What specific plans do you have to counter the climate change denialists, given the wealth of data on the negative impact of climate change on health?

We published, with a short commentary, the responses of the three candidates prior to the elections.[3] Here we provide the elected candidate’s responses. There are great expectations from Dr Tedros, and he has a huge task ahead. Given that Tedros is the first African candidate to be elected as WHO DG, African health professionals, practitioners and activists have a special responsibility in ensuring that he succeeds in reforming the WHO in favour of health equity and social justice, and in improving health status, especially for the poor and the marginalised.

How seriously will you take the societal determinants of health, and what specific actions will you lead in this regard?

I will take the social determinants of health very seriously if elected DG of the WHO, because without acknowledging and addressing these issues, we won’t solve health challenges at their roots. I will specifically address these first by working at all levels to break the silos down between our development objectives. At the international level, I will work to position the WHO as a leader in building strong partnerships across UN organisations. I will engage key regional and sub-regional groups to build the political leadership necessary to create multisectoral approaches. At the country level, I will also advocate for strong commitments to health not only from health ministries, but also finance, social and planning, among others. Where programmes have been effective at addressing the social determinants of health, the WHO can draw out evidence-based best practices and ensure they are shared

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regionally and globally. Lastly, as I have throughout my career, I will focus especially on the needs of vulnerable groups and those disproportionately affected by the social determinants of health.

These include migrant, displaced and disabled individuals, people living in rural, urban slum and low-income areas, and other marginalised populations.

How will you ensure that non-state actors do not capture the WHO and thereby neuter the role of UN member states in decision-making?

The growing number of non-state actors around the WHO provides both an opportunity and a challenge. The opportunity lies in bringing diverse perspectives and skills to bear on some of the world’s greatest health challenges through partnership and collaboration. However, the WHO is the global leader for developing norms, standards and guidelines. This normative work must be firewalled from the wide variety of non-state actors that today need to be engaged in the programmatic work in order to fully address health issues.

Having this in mind, the WHO’s Framework for Engagement of Non-State Actors (FENSA) is a welcome step towards strengthening partnerships between the WHO and non-state actors, including civil society. If elected, I will work toward FENSA’s full implementation in pursuit of effective partnership with all stakeholders. In addition, where we do form partnerships, we must operate on the principle of complementarity, but not be afraid to challenge partners, for example to ensure that their work is evidence-based and responsive to countries’ needs.

What specific novel policies will you propose to improve health equity and strengthen health outcomes in LMICs? If I am elected, my top priority will be achieving universal health­ care (UHC) that is equitable and affordable for all. I am convinced that UHC, with financial protection and strong primary healthcare linked to community engagement, is the key to give us a world where everyone can lead healthy and productive lives regardless of who they are or where they live. It can also help us address public health emergencies and give us a safer world because a strong health system becomes our first line of defence to detect, monitor and respond to health emergencies. Achieving universal healthcare, of course, is an ambitious goal, and it is one which will require strong country-level ownership. To get there, I will work to raise the issue of UHC to the highest political levels, championing UHC as essential for the political agenda of every nation and as a basic right of every individual. I will work to unlock earmarked funding and mobilise new resources to achieve these goals. And I will lead a WHO 2 that looks to form deep partnerships with countries and regions to design and implement UHC approaches that are right for their unique contexts.

What specific plans do you have to counter the climate change denialists, given the wealth of data on the negative impact of climate change on health?

August 2017, Print edition

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On this issue, we need to first start with the facts – that climate and environmental change are real and unfortunately are having and will continue to have a negative impact on health. That evidence-driven reality is why I included climate change as one of my five top priorities if elected to become DG. This is an issue I was fortunate to have been able to work on with Ethiopia’s late Prime Minister, Meles Zenawi, who was a vocal champion and wanted to ensure that Ethiopia was a part of the solution, despite contributing nothing to the problem. Ethiopia now depends predominantly on renewable energy to reduce carbon emissions and is planting seven billion seedlings a year to trap carbon. Within these efforts, I advocated for mitigation strategies in addition to adaptation strategies, so we can prevent further environmental and climate change. The WHO also has an opportunity to be a part of the solution and should become a vocal advocate for mitigation strategies. It can champion global and regional coalitions which promote capacity building within countries around these strategies. It can advocate for increased financial allocations at the global, regional and national levels through active engagement with climate financing instruments, donors and national governments. It can work to strengthen country governments’ ability to understand and use climate

services and information for health policy, planning and research.

And it can promote sustainability within the health sector itself, championing the use of renewable energy sources.

Yogan Pillay National Department of Health, South Africa ypillay@intekom.co.za Anne-Emanuelle Birn University of Toronto, Canada Timothy Holtz Rollins School of Public Health, Emory University, Atlanta, Ga., USA 1. Horton R. Offline: Dear Tedros... Lancet 2017;389(10085):2177. http://dx.doi.org/10.1016/S01406736(17)31503-9 2. Birn AE, Pillay YG, Holtz TH. Textbook on Global Health. London: Oxford University Press, 2017.

3. Birn A-E, Pillay Y, Holtz TH. WHO DG candidates respond to fundamental questions on WHO and global health. PLoS Blogs: Diverse perspectives on science and medicine, 4 May 2017. http://blogs. plos.org/yoursay/2017/05/04/where-do-the-3-candidates-for-the-whos-next-director-general-standon-the-most-challenging-global-health-issues-of-our-time/ (accessed 8 July 2017).

S Afr Med J 2017;107(8):648-649. DOI:10.7196/SAMJ.2017.v107i8.12713

30 days in medicine Human papillomavirus testing leads to faster diagnosis of cervical disease

A large observational study has found that testing for human papillomavirus (HPV) in women with abnormal cervical cytology leads to faster diagnosis of cervical disease and fewer missed cases.

Researchers analysed results of cervical cytology from 457 317 women with a mean age of 39.8 years who were in screening programmes in New Mexico, USA, from January 2007 to December 2012. They assessed the effect that HPV testing after an abnormal screening cytology result had on diagnosis of cervical cancer and rates of biopsy and loop electrosurgical excision procedures.

Their results were reported in JAMA Oncology and showed that nearly 4.5% of the first cytology results per woman in the screening programme were reported as atypical squamous cells of undetermined significance. Of these, 80% were tested for HPV and in these women, the time to detecting abnormalities of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was much shorter in those who were being tested for HPV. In addition, the rate of loop electrosurgical excision procedures over 5 years was 20% higher in women who had HPV testing, resulting in increased detection of CIN2+ and CIN3+, than in women who were not tested for HPV. The authors point out that nearly all the high-grade disease occurred in the 43.1% of women who were HPV-positive, allowing colposcopy and related resources to be focused on this group.

Cuzick J, Myers O, Lee J-H, et al. Outcomes in women with cytology showing atypical squamous cells of undetermined significance with vs without human papillomavirus testing. JAMA Oncol 2017 (epub 22 June 2017). https://doi.org/10.1001/jamaoncol.2017.1040

Eating fish frequently helps rheumatoid arthritis

Eating fish at least twice a week is associated with reduced disease activity in patients with rheumatoid arthritis (RA), according to

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research reported in Arthritis Care and Research. The study, a crosssectional analysis of data from 176 patients who were taking part in a large study investigating subclinical cardiovascular disease in RA, found higher levels of joint swelling and tenderness in patients who ate fish less than once a month.

Most participants in the study had longstanding RA and were taking disease-modifying antirheumatic drugs. Patients filled in a food frequency questionnaire that detailed their diet over the previous year, and their frequency of fish consumption was analysed in relation to RA activity.

There was a clinically significant reduction in RA symptoms in people who ate fish frequently when compared with those who never ate fish, or who ate it less than once a month. The difference remained, even after taking fish oil consumption into account.

Tedeschi SK, Bathon JM, Giles JT, Lin TC, Yoshida K, Solomon DH. The relationship between fish consumption and disease activity in rheumatoid arthritis. Arthritis Care Res 2017 (epub 21 June 2017). https://doi.org/10.1002/acr.23295

Label vegetables differently to increase consumption

Labelling vegetables using language usually used with more indulgent foods increases their consumption more than plain labels or those describing health effects, according to a study published in JAMA Internal Medicine. The study was carried out on staff and students at a cafeteria at Stanford University, California. Each day of the autumn term of 2016, one vegetable dish was labelled randomly in one of four ways – basic (e.g. green beans), describing what was absent (e.g. low-sodium bok choy), health-positive (e.g. vitamin-rich corn) or indulgent (e.g. rich buttery roasted sweetcorn). The labelling changed, but there was no change in the way that the vegetables were prepared.

Labelling a vegetable dish indulgently was associated with a 25% increase in the number of people selecting the dish compared

August 2017, Print edition

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with when it was given a basic label, a 41% increase over a healthy restrictive label and a 35% increase over a health-positive label.

Indulgent labelling was associated with a 23% higher mass of vegetables eaten than basic labelling.

Turnwald BP, Boles DZ, Crum AJ. Association between indulgent descriptions and vegetable consumption: Twisted carrots and dynamite beets. JAMA Intern Med 2017 (epub 12 June 2017). https://doi.org/10.1001/ jamainternmed.2017.1637

Female athletes with naturally high levels of testosterone have a competitive edge

Some elite women athletes have naturally high levels of testosterone, and a study published in the British Journal of Sports Medicine suggests that this gives them a significant competitive advantage in sports that require stamina and visuospatial ability. Researchers say that this advantage should be taken into consideration when judging women’s eligibility for these events in the light of the suspension of International Association of Athletics Federations (IAAF) rules around the use of hormone treatment to lower testosterone levels.

These rules were suspended unless or until there is evidence that circulating androgens are found to affect women’s sporting performance, after a challenge by Indian athelete Dutee Chand.

Researchers drew on 2 127 observations of best performance by elite male and female athletes competing in events during the IAAF World Championships in 2011 and 2013 as well as measurements of androgens in their blood. Athletes were classified into three groups depending on how much free testosterone was circulating.

Women in the top third of circulating blood testosterone levels performed significantly better than those with the lowest levels in certain events – the 400 m sprint (2.7%), the 400 m hurdles (2.7%), the 800 m hurdles (1.78%), the hammer throw (4.5%) and the pole vault (2.9%). This pattern was not seen in male athletes with similar differences in testosterone levels.

As an observational study, no conclusions can be drawn about cause and effect. However, the authors conclude that the quantitative relationship between increased testosterone levels and improved

12

athletic performance should be taken into account in women with hyperandrogenism competing in the female category.

Bermon S, Garnier P-Y. Serum androgen levels and their relation to performance in track and field: Mass spectrometry results from 2127 observations in male and female elite athletes. Br J Sports Med 2017 (epub 3 July 2017). https://doi.org/10.1136/bjsports-2017-097792

No benefit from levothyroxine in older adults with subclinical hypothyroidism

Research published in the New England Journal of Medicine suggests that there is no benefit in the controversial use of levothyroxine when treating older adults with subclinical hypothyroidism.

Researchers conducted a double-blind, randomised, placebocontrolled, parallel-group trial involving 737 adults at least 65 years old (mean age 74.4 years) with persisting subclinical hypothyroidism (thyroid-stimulating hormone (TSH) levels in the range 4.6 19.9 mIU/L, free thyroxine normal). A total of 368 patients received levothyroxine at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease, with dose adjustment according to the TSH level; 369 patients received placebo with mock dose adjustment.

Patients reported on any changes in the hypothyroid symptoms score and tiredness score on a thyroid-related quality of life questionnaire at 1 year. Although there were changes in the TSH level in both the treated and the placebo groups, there were no differences in symptoms reported at 1 year and no beneficial effects of levothyroxine were seen.

The conclusion is that there is no benefit from levothyroxine in older adults who have subclinical hypothyroidism.

Stott DJ, Rodondi N, Kearney PM, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;376(26):2534-2544. https://doi.org/10.1056/NEJMoa1603825

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August 2017, Print edition

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BOOK REVIEWS The ECG Atlas of Cardiac Rhythms

By Rob Scott Millar. Cape Town: Clinics Cardive Publishing, 2015.

ISBN: 978-0-620-64044-2 In the introduction to his book, Rob Scott Millar states: ‘This is not a textbook. Its core value depends on the variety of real ECG traces and their interpretation which will, hopefully, assist you in interpreting similar rhythms that you encounter in your practices.’

In stating this, his humility may lead you to underestimate the value of this book, which is filled with pearls that only an experienced electrophysiologist and enthusiastic teacher of Rob Scott Millar’s stature can provide.

His humble description should rather read: ‘Its core value depends on the variety of real ECG traces and their interpretation, which will definitely assist you in interpreting similar rhythms that you encounter in your practices.’

Scott-Millar’s approach to arrhythmias, based on systematic observation prior to the application of basic principles, equips the reader with a lasting skill in assessing any arrhythmia. This is far preferable to relying on snap judgements and algorithmbased approaches, which may provide the right answer sometimes but in reality stand between the clinician and the growth in skilled ECG interpretation that comes with the experienced operator making systematic and meticulous observations and finding explanations that respect the basic principles of the de- and repolarisation of the heart and the methods we use to record them.

There are a few minor points that can be addressed to improve the publication, the first of these being the binding of the atlas. Scott Millar is known to place emphasis on the value of having a full-size standard 12-lead ECG at one’s disposal to formulate an opinion. This principle has clearly impacted upon the format of the atlas, and hence upon the method used to bind it. However, the ring binding with the overlay-type front cover may soon result in an atlas without a front cover, and content that gradually transforms into a collection of loose pages. I don’t judge a book by its cover, but having said that, I do enjoy a

book that has been bound in an appealing and lasting manner. Further to express my view on the binding perspective, I have to confess that I am a bit of a bibliophile and that I find pleasure in the feel and look of a good book in my hands. Having said that, an electronic format of this book will be well received.

The cross-references provided in the atlas are valuable in reinforcing important principles and examples. A few crossreferencing mistakes provided minor irritation, e.g. on p. 64 a reference is made to Figure 2.09A, which could not be found.

Similarly, on p. 183 a reference is made to an earlier diagram which should read 5.06 and not 5.05. Reference to alternative sources, such as the reference to an updated list of drugs to avoid in patients with QT prolongation, is also valuable. However, the reference given (www.azcert.org) takes one to the Crediblemeds.org website, which is maintained by the Arizona Centre for Education and Research on Therapeutics.

It requires registration with the website, presumably with some commercial goals leading to unwanted electronic traffic in one’s email in-box. I found the website of a British-based organisation (SADS Foundation), which offers help, support and counselling to affected families, to be more user friendly (http://www.sads.org. uk/drugs-to-avoid/).

Prior to the thoroughly enjoyable ECG quiz, a chapter dealing with the role of computers in ECG registration is also included.

In the section on transmission to distant

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August 2017, Print edition

sites the value of scanned ECGs transmitted by email is underlined, this in preference to faxed ECGs, which are often of poor quality.

In my experience the most common modality used to transfer ECGs are photographs sent from cellphones via SMS or WhatsApp. The miniaturised size of the images presents a problem, and solutions to overcome this are eagerly awaited.

The experience provided by working through this atlas is overwhelmingly positive. The layout, text and beautiful ECG examples all combine to provide an easy and thoroughly enjoyable read that can easily be followed by the beginner, but will prove equally interesting and informative to the experienced ECG interpreter. It is certainly a source that can be recommended to the undergraduate medical student as well as the specialist training in cardiology.

Acknowledgement. Republished with permission from the South African Heart Journal, the primary source of publication and with which copyright resides.[1]

Anton Doubell Division of Cardiology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa afd@sun.ac.za 1. Doubell A. Book Review: The ECG Atlas of Cardiac Rhythms.

S Afr Heart J 2016;13(2):126-127.

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Darwin’s Hunch: Science, Race and the Search for Human Origins

By Christa Kuljian. Johannesburg: Jacana Media, 2016. ISBN: 978-1-4314-2425-2

Christa Kuljian of the Wits Institute for Social and Economic Research has made an in-depth historical analysis of the personalities behind the study of human origins in southern Africa, spanning approximately a century. The hunt for fossils and fossil-finds

on the African continent, the ‘Cradle of Humankind’ made headline news all over the world, with the Out of Africa hypothesis the favoured one – it was Darwin’s hunch that this was so. In South Africa (SA) the names of Robert Broom, Raymond Dart and Phillip Tobias are synonymous with the story of our origins. Kuljian focuses on the personalities behind the science, weaving into the story their attitudes on issues of race, and the methodologies they employed to throw light on the evolution of the human race. As discomfiting as her story is, it is an honest piece of work that is relevant for the dominating discourse of the day in SA on race, racism, transformation and decolonisation.

The history of modern-day Homo sapiens is marred by racism, and a century-long view was that the races were created separately. The reference point was the ‘Boskop race’, a foundation of a race typology based on the finding of a skull in 1913. It was this idea that drove the research of Broom, Dart, and very disappointingly Tobias!

Dart’s discovery of the Taung skull in 1924, a momentous event in this history, seemed to have had no effect on his racist views, and generally he did not credit the African for any achievement. He would go to any lengths to secure a skeleton for his collection, which seemed more important than his study subjects. The demeaning scientific methodology employed reflected the view that the African was inferior, coinciding

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with the political ideas of British colonial rule and later apartheid. As recently as 2007 the Nobel laureate James Watson is known to have remarked that Africans were of a lesser intelligence! With the advent of modern genetics in the mid-20th century, a paradigm shift away from typology occurred when Hertha de Villiers showed that there were no distinguishing features between different SA tribes, but a ‘range of variation in a cluster of closely related populations’. A new direction in biological thinking was born.

Apartheid was dismantled in 1994, and in 2002 Phillip Tobias, who gradually abandoned the ideas of his predecessors, introduced himself on television with ‘Hello, my name is Phillip Tobias and I am an African.

We’re all African … because this was our cradle’ (my italics). Darwin’s hunch becomes fact and Tobias’s evolution with respect to his thinking is complete.

This highly recommended study should be part of discussions on science, race, decolonisation and transformation in all our classrooms in high schools and tertiary institutions as we envision a new SA society.

Anwar Suleman Mall Emeritus Professor and Senior Scholar, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, South Africa anwar.mall@uct.ac.za

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

EDITORIAL

Short-course adjuvant trastuzumab will increase cure rates in patients with human epidermal growth factor receptor 2-positive breast cancer Internationally, breast cancer is the commonest cancer in women, comprising 25% of cancers. It is also the most frequent cause of cancer death in women, comprising 14.3% of the total in economically lessdeveloped regions.[1] Human epidermal growth factor receptor 2 (HER2) is over­ expressed or positive in 20 - 25% of patients with early breast cancer.

Trastuzumab is an antibody that blocks the HER2 receptor, and adjuvant trastuzumab has been shown to increase overall survival (OS) and disease-free survival (DFS) in HER2-positive patients, but is associated with a risk of adverse cardiac events.[2] Despite the significant clinical benefit associated with adjuvant trastuzumab, ~90% of patients in South Africa (SA) with HER2positive breast cancer do not currently have access to adjuvant trastuzumab. The main reason for the lack of access to trastuzumab in SA is the cost.[3] This is the case for patients managed in both the public sector and the less well-resourced of the private medical schemes.

Trastuzumab is conventionally given for a 12-month period.

However, a new study confirms that it is probable that a much shorter course, given for 9 weeks, will increase the survival and DFS rates in patients compared with no trastuzumab, as there is no major loss of effectiveness.[4] It is estimated that the 9-week course of trastuzumab has a hazard ratio (HR) of 0.7 compared with no trastuzumab, and results in a 30% increase in patient survival. It is also associated with fewer cardiac complications and will be more affordable.[4]

The studies

A Cochrane systematic review and meta-analysis of adjuvant trastuzumab has shown a clinically significant improvement in survival. For OS, the HR was 0.66 (95% confidence interval (CI) 0.57 - 0.77; p<0.00001) and for DFS it was 0.60 (95% CI 0.50 0.71; p<0.00001).[2] There was also cardiac risk associated with this treatment. For adverse cardiac events, the relative risk (RR) was 5.11 (90% CI 3.00 - 8.72; p<0.00001), and for a decline in left ventricular ejection fraction it was 1.83 (90% CI 1.36 - 2.47; p=0.0008).[2] The 12-month adjuvant trastuzumab regimen was chosen empirically, and was supported by the HERceptin Adjuvant (HERA) trial.[5] In 5 102 patients, a regimen of adjuvant chemotherapy with no adjuvant trastuzumab was compared with regimens of either 1 or 2 years of adjuvant trastuzumab. One-year trastuzumab regi­ mens compared with regimens with no trastuzumab resulted in better DFS and OS. The 2-year regimen showed no further benefit. The 10-year survival rates for regimens with no adjuvant trastuzumab and for the 1-year trastuzumab regimens were 63% and 69%, respectively. The rates of cardiac events in regimens with no trastuzumab and for the 1-year trastuzumab regimens were 0.9% and 4.4%, respectively.

In the PHARE trial,[6] 6 months of adjuvant trastuzumab was shown to be marginally less effective than the 12-month regimen in terms of DFS in a non-inferiority study. The 2-year DFS was 93.8% (95% CI 92.6 - 94.9) in the 12-month group and 91.1% (95% CI 89.7 92.4) in the 6-month group.

To date, shorter courses of trastuzumab have not been prospectively compared with no trastuzumab in an adequately powered trial. The FinHer study was designed primarily to evaluate different chemo­ therapy agents; however, it included a subset analysis of 232 patients

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in whom a 9-week course of trastuzumab was compared with no trastuzumab.[7] This showed that this regimen had efficacy that was numerically similar to the 1 year of trastuzumab, but the study was not powered to demonstrate statistical significance. For distant DFS, the HR was 0.65 (95% CI 0.38 - 1.12; p=0.12). In patients with positive nodes there was a statistically significant increase in DFS, with an HR of 0.57 and a p-value of 0.047.

New evidence of the activity and lower toxicity of the short course of trastuzumab has now come from the Italian Short HER study,[4] presented at the prestigious meeting of the American Society of Clinical Oncology recently but not yet fully published. In this study, 1 253 patients from 82 centres were randomised to 12 months’ or 9 weeks’ adjuvant trastuzumab (long v. short HER). This was a noninferiority study. Comparing long HER with short HER, the 5-year DFS rates were 87.5% v. 85.4%, respectively, and the 5-year OS rates were almost identical at 95.1% and 95.0%. However, non-inferiority criteria were not reached in the frequentist analysis, with an upper limit of the CI set at 1.289 for DFS. For OS, the HR was 1.06 (90% CI 0.73 1.55) and for DFS the HR was 1.15 (90% CI 0.91 - 1.46). However, importantly, the researchers also carried out a Bayesian analysis that showed a 78% probability that the 9-week regimen was not inferior to the 12-month one.

This study also showed that prognostic factors in patients influenced the relative benefit of long HER as opposed to short HER. Patients with stage III disease or with four or more positive nodes, 15% of the group overall, benefited most from long HER. The evidence of non-inferiority was highest in the remaining patients.

In addition, cardiac toxicity was less with the short HER regimen.

Long HER compared with short HER showed a statistically significant decrease in left ventricular ejection fraction over time (p=0.023), and the rates of cardiac events of grade 2 or more were 14.4% and 5.1%, respectively, with an HR of 0.32 (95% CI 0.21 - 0.50; p<0001).

The drug cost of a 9-week trastuzumab regimen is a fifth of a 12-month one. The total doses of trastuzumab administered are 20 mg/kg and 110 mg/kg, respectively.

An estimate of the HR for overall survival for 9 weeks’ trastuzumab compared with no trastuzumab is 0.7, which is calculated as follows: for 1 year’s trastuzumab compared with no trastuzumab, the HR is 0.66,[2] and for 9 weeks’ trastuzumab compared with 1 year’s trastuzumab, the HR is 1.06.[4] An estimate of the HR of 9 weeks’ trastuzumab compared with no trastuzumab would therefore be ~0.66 × 1.06 = 0.70.

An estimate of the HR for disease-free survival for 9 weeks’ trastuzumab compared with no treatment is 0.69. For 1 year’s trastu­ zumab compared with no trastuzumab, the HR is 0.60,[2] and for 9 weeks’ trastuzumab compared with 1 year’s trastuzumab, the HR is 1.15.[4] An estimate of the HR for DFS of 9 weeks’ trastuzumab compared with no trastuzumab would therefore be ~0.66 × 1.15 = 0.69. The HR in the underpowered FinHer study was 0.65.

In a recent publication in the SAMJ,[3] the affordability and value of trastuzumab were reviewed. Using value (outcome divided by cost) as a parameter, it was proposed that there were two ways forward to provide this important and effective therapy within the finite resources of our healthcare system. These were: (i) the use of shorter courses of trastuzumab, which would be both active and more affordable; and (ii) identifying those prognostic groups that would

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EDITORIAL

benefit the most from adjuvant trastuzumab. The short HER studies support these proposals.

Acknowledgements. The author is grateful to Drs Fergus Macbeth and David Eedes for very helpful comments.

Conclusions

Raymond P Abratt Head of Clinical Governance, Independent Clinical Oncology Network, Cape Town, South Africa; and Emeritus Professor of Radiation Oncology, Faculty of Health Sciences, University of Cape Town, South Africa raymond.abratt@cancernet.co.za

Randomised trials of short courses of trastuzumab compared with no trastuzumab cannot now be done, as a ‘no adjuvant trastuzumab’ arm would be ethically unjustified in a study setting, even though this question is very relevant to low- and middle-income countries.

Nevertheless, the studies done provide us with strong and coherent evidence of the clinical value of a short-course trastuzumab regimen.[8] There will be further debate about 12-month trastuzumab v. shorter treatments in all countries, balancing benefits, costs and toxicity. Patients with stage III disease or four or more positive nodes are likely to continue with 1 year’s trastuzumab in well-resourced healthcare systems.

In SA, however, a decision needs to be made about how to make best use of this important treatment across all sectors of the healthcare system. Is it defensible to restrict adjuvant trastuzumab to the minority of people who can afford the 1-year course? Or should we accept the current evidence that a 9-week course is almost as effective and certainly less toxic, as well as an effective use of our healthcare resources? Moreover, the best available evidence indicates that 9 weeks of trastuzumab increases patient survival by about 30% compared with patients who receive no trastuzumab. Why should we not make it available to the large proportion of patients who currently have no access to it?

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1. Globocan. Breast cancer estimated incidence, mortality and prevalence worldwide in 2012. http:// globocan.iarc.fr/old/FactSheets/cancers/breast-new.asp (accessed 9 June 2017).

2. Moja I, Tagliabue I, Balduzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012, Issue 4. Art. No.: CD006243. http://dx.doi: 10.1002/14651858.CD006243 3. Abratt RP. Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer. S Afr Med J 2016;106(10):981-982. http://dx.doi.org/10.7196/SAMJ.2016.v106i10.11141 4. Conte PF, Bisagni G, Frassoldati A, et al. 9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: Results of the phase III multicentric Italian study Short-HER. Oral presentation at American Society of Clinical Oncology. J Clin Oncol 2017;35(15 Suppl):501-501. http://dx.doi. org/10.1200/JCO.2017.35.15_suppl.501 5. Cameron D, Piccart-Gebhart MJ, Gelber RD. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: Final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017;389(10075):1195-1205. http://dx.doi.org/10.1016/S0140-6736(16)32616-2 6. Pivot X, Romieu G, and the PHARE Trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): A randomised phase 3 trial. Lancet Oncol 2013;14(8):741-748. http://dx.doi.org/10.1016/S1470-2045(13)70225-0 7. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al., FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006;354:809-820. http:// dx.doi.org/10.1056/nejmoa053028 8. Wasserstein RL, Lazar NA. The ASA’s statement on p-values: Context, process, and purpose. Am Stat 2016;70(2):129-133. http://dx.doi.org/10.1080/00031305.2016.1154108

S Afr Med J 2017;107(8):654-655. DOI:10.7196/SAMJ.2017.v107i8.12673

August 2017, Print edition

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

CME

GUEST EDITORIAL

Growing wilderness and expedition medicine education in southern Africa ‘Look deep, deep into nature, and then you will understand everything better.’ (Albert Einstein, 1951 – A and E Television Biography) ‘One should not pursue goals that are easily achieved. One must develop an instinct for what one can just barely achieve through one’s greatest efforts.’ (Albert Einstein, 1915 – quote to Walter Daellenbach) Albert Einstein’s words give us pause to consider not only the means to understand the physical universe through the natural world, but also the nature of the inquisitive human soul. In our search for fundamental answers to the questions of both normal physiology and disease, we seek the phylogeny of our constitution: the myriad adaptations of life in all forms through the ages to survive under adversity, illness and injury. Looking deep into nature – be it the true depths of the ocean or the jungle, or the hypoxic heights of mountain peaks – has granted us an understanding of how humans can defeat pathogens, withstand thermal stressors and hypoxia, and endure extreme exertion.[1,2] It has also provided us with countless therapies for our ailments: analgesics, antibiotics, antivirals, anticoagulants, antihypertensives, haemostatics, and novel cancer treatments are all prime examples.[3] Furthermore, time spent immersing ourselves deep into nature – away from the increasing busyness and clamour of modern life – allows the reflective practitioner time for introspection on challenges and the core values of life.

Currently, medical research in the wilderness helps to expand our understanding of conditions as diverse as congenital heart disease, pulmonary hypertension, sepsis, critical illness, and diabetes.[1,4-9] Despite this, wilderness medicine has for many years been the domain of eclectic enthusiasts and adventurous amateurs. In hazardous environments, human physiology is stressed to its limits, and the health practitioner encounters both conventional and environmentally specific medical problems. Wilderness medicine incorporates medical response, limited resource capabilities, and substantial delays to definitive care due to remote healthcare facilities, necessitating improvisations to deliver care in the face of austerity.[10] Internationally, the growth of wilderness, expedition, mountain and extreme medicine has been slow but steady. Historically, numerous international groups with experience in the field have provided commercial courses to address their educational needs, [11-14] which have only recently become available in South Africa (SA).[15] Development has reflected the originally segregated expertise in multiple fields, such as high-altitude and hyperbaric medicine, tropical health and hygiene, and sports medicine. Fortunately, increasing interest has led to an increase in formal structures, guidelines, and training opportunities.

In recent years, amalgamated programmes have united under the auspices of groups such as the Wilderness Medical Society (WMS, www.wms.org), the International Society for Mountain Medicine (ISMM, www.ismm.org) and the Alpine Emergency Medical Commission (ICAR-MED, www.alpine-rescue.org). Great strides have been made in advanced medical research within the wilderness environment, and examples of unique insights into human physiology abound. Aspirant individual practitioners now have the option of numerous international training programmes in the field (Table 1). Examples include the holistic and largely

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self-directed Fellowship in Wilderness Medicine (FAMW) offered by the WMS Academy of Wilderness Medicine,[16,17] qualifications from postgraduate certificate to MSc level in expedition, wilderness and extreme medicine from institutions such as the Royal College of Physicians and Surgeons of Glasgow and the University of Exeter,[17,18] and the Diploma in Mountain Medicine (DiMM) offered under the auspices of the International Climbing and Mountaineering Federation (Union Internationale des Associations d’Alpinisme (UIAA), www.theuiaa.org) by multiple organisations worldwide.

Other qualifications in tropical, aviation and hyperbaric medicine are well established.

While the FAWM and DiMM are well entrenched (and have been awarded to several SA candidates), the more formal International Diploma in Expedition and Wilderness Medicine (Royal College of Physicians and Surgeons of Glasgow[18]) and the MSc in Extreme Medicine (University of Exeter[17]) are novel programmes, and their ultimate success remains to be determined. There are two significant barriers to participation of candidates from southern Africa, i.e. the requirement to attend several contact sessions in Europe, and the cost of the tuition (between ZAR100 000 and ZAR150 000 per annum). Despite this, there is significant interest and demand from southern African medical practitioners for education in this exciting field. Clearly, a local need exists, and it requires African solutions!

Local enthusiasts and experts have provided insights into the scope and diversity of wilderness medicine, high-altitude illnesses, cold exposure, and submersion injuries.[2,20-22] In this edition of SAMJ, we address the fundamental concepts of expedition medicine, from participant screening and selection of suitable medical supplies to the epidemiology, roles and psychological aspects encountered on expeditions. Continuing the human thread, human factors in the wilderness are addressed, including every human’s capacity to make mistakes – some deliberate, but most inadvertently – and how awareness of that error capacity can help anticipate and prevent accidents. Finally, heat-exposure injury is discussed in the African context.[23-25] While far from a comprehensive review of wilderness and expedition medicine, it is the fervent hope of the authors that these topics provide a catalyst for awareness and a kernel for further discussion, interaction and development of the field in SA, and an emergence of the specialty on our continent.

As each new dawn draws the denizens of the bush to the waterhole, we have sought to create a gathering place for wilderness medicine enthusiasts in Africa. Although wilderness emergency

Fig. 1. Wilderness and Expedition Medicine Society of Southern Africa (www.wemssa.org).

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Table 1. Examples of current wilderness, expedition, mountain and extreme medicine courses and qualifications in SA and abroad* Programme/qualification

Organisation/institution

Short course examples Mountain Expedition Medicine, Winter Wilderness Medicine, Canyoneering Medicine, Wilderness Medicine monthly lecture series

WildMedix, Cape Town, South Africa (including open-access lectures streamed online)

Expedition and Wilderness Medicine, Polar Medicine, Mountain Medicine, Ocean Medicine, Prehospital Trauma Care, Jungle Medicine

World Extreme Medicine, UK

Mountain Medicine, Expedition Medicine and Field Skills, Expedition Medic

Wilderness Medical Training, UK

Mountain Medicine Avalanche Rescue

Mountain Medicine Institute and Silverton Avalanche School, Colorado, USA

Resident Physician Elective in Wilderness Medicine

McGill University and Wilderness MD Medical Solutions, Montreal, Quebec, Canada

Postgraduate certificate, diploma, fellowship and degree examples Diploma in Tropical Medicine and Hygiene, Diploma in Public Health in Rural Health, MPH in Disaster Management

University of the Witwatersrand, Johannesburg, SA

BSc Hons in Hyperbaric/Underwater Medicine, MSc in Baromedical Sciences

Stellenbosch University, Cape Town, SA

BSc Hons and MSc in Aerospace Medicine, Aviation Medical Examiners Course

University of Pretoria, SA

Fellowship of the Academy of Wilderness Medicine (FAWM)

Academy of Wilderness Medicine, Wilderness Medical Society, Utah, USA

Wilderness Medicine fellowships (1 - 3-year PG training programmes, aimed at graduates in emergency medicine)

Multiple institutions in the USA (see http://www.emra.org/match/wildernessmedicine-fellowships/)

Diploma in Mountain Medicine (DiMM)

Multiple organisations worldwide, under the auspices of the International Climbing and Mountaineering Federation/Union Internationale des Associations d’Alpinisme (UIAA), International Commission for Alpine Rescue (ICAR), and International Society for Mountain Medicine (ISMM)

International Diploma in Expedition and Wilderness Medicine (1-year PG certificate - 3-year MSc)

Royal College of Physicians and Surgeons of Glasgow, Scotland, UK

MSc in Extreme Medicine (1-year PG certificate - 3-year MSc)

University of Exeter, UK

SA = South Africa; PG = postgraduate.

[19]

*NB: This list is not intended to be exhaustive. Excellent repositories exist online.

medicine training forms a component of many prehospital training programmes in SA, and several short courses exist, there is currently no formal postgraduate academic programme supported by a higher education institution. To this end, the Wilderness and Expedition Medicine Society of Southern Africa (WEMSSA, www.wemssa.org) was formally constituted in 2016, and is open to membership of practitioners from all disciplines (Fig. 1). A vibrant online discussion group, web portal, society blog and openaccess wilderness medicine lecture series provide free resources and interaction throughout the region and beyond. Ultimately, the intention is to develop and offer a locally grown, internationally relevant postgraduate qualification in the field. In SA, this is of greater benefit than simply in the wilderness setting: practitioners capable of working in resource-limited difficult environments may be able to support a conventional health system with stringent resource restrictions.[26] Clearly, however, the success of any such endeavour relies on the engagement of colleagues with mutual interests in altruistic goals.

In the eyes of those who dream, Africa has the potential to become a world-class contributor in the field of wilderness medicine, although this will not be easy to achieve. In the words of Einstein, however, one should ‘… develop an instinct for what one can just barely achieve through one’s greatest efforts’, and pursue this goal.

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As with any great peak or destination deep in the wilderness, great efforts will be required to grow wilderness medicine in southern Africa. We have taken the first small steps, and invite you to join us on this expedition: ‘... a journey with a purpose’.

R Hofmeyr Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town; WildMedix, Cape Town; and Wilderness and Expedition Society of Southern Africa, South Africa ross.hofmeyr@uct.ac.za J Matthew Wilderness and Expedition Society of Southern Africa; Department of Emergency Medicine, Faculty of Health Sciences, University of KwaZulu-Natal, Durban; and Lifesaving South Africa, Durban, South Africa

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S Buchanan Wilderness and Expedition Society of Southern Africa; Africa Institute of Emergency Medicine, Cape Town; and Emergency Medical Society of South Africa, South Africa G Tölken WildMedix, Cape Town; and Mountain Club of South Africa, Mountain Rescue, Hottentots-Holland Section, Cape Town, South Africa R De Decker Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, and Red Cross War Memorial Children’s Hospital, Cape Town; and Mountain Club of South Africa, Cape Town, South Africa 1. Imray CH, Grocott MP, Wilson MH, et al. Extreme, expedition, and wilderness medicine. Lancet 2015;386(10012):2520-2525. https://doi.org/10.1016/S0140-6736(15)01165-4 2. Hofmeyr R, Matthew J, De Decker R. Wilderness medicine in southern Africa. S Afr Med J 2017;107(7):554-555. https://doi.org/10.7196/SAMJ.2017.v107i7.12608 3. Strumillo A. Medicines from nature. Biodiversity and human health. 2017. http://www.chgeharvard. org/topic/medicines-nature (accessed 19 April 2017).

4. Bailey DM, Willie CK, Hoiland RL, et al. Surviving without oxygen: How low can the human brain go?

High Alt Med Biol 2017;18(1):73-79. https://doi.org/10.1089/ham.2016.0081

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5. Dillard TA, Khosla S, Ewald FW Jr, et al. Pulmonary function testing and extreme environments. Clin Chest Med 2005;26(3):485-507,vii. https://doi.org/10.1016/j.ccm.2005.05.006 6. Grocott MP, Martin DS, Levett DZ, et al. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 200;360(2):140-149. https://doi.org/10.1056/NEJMoa0801581 7. Leach J. Psychological factors in exceptional, extreme and torturous environments. Extrem Physiol Med 2016;5(1):7. https://doi.org/10.1186/s13728-016-0048-y 8. Steel GD. Whole lot of parts: Stress in extreme environments. Aviat Space Environ Med 2005;76(6 Suppl):B67-B73.

9. West JB. Acclimatization and tolerance to extreme altitude. J Wilderness Med 1993;4(1):17-26.

10. Curran-Sills G, McDonald N, Auerbach PS, et al. Embracing the wild: Conceptualizing wilderness medicine in Canada. Can Fam Physician 2013;59(5):581-584.

11. World Expedition Medicine. http://www.expeditionmedicine.co.uk/ (accessed 20 March 2017).

12. Medical Expeditions. http://www.medex.org.uk/ (accessed 20 March 2017).

13. Wilderness Medical Training. http://wildernessmedicaltraining.co.uk/ (accessed 20 March 2017).

14. National Outdoor Leadership School. Wilderness Emergency Medical Technician. 2017. https://www. nols.edu/en/courses/courses/wilderness-emt-WEMT/ (accessed 20 March 2017).

15. WildMedix. http://www.wildmedix.com (accessed 14 April 2017).

16. Fellow of the Academy of Wilderness Medicine. https://wms.org/fawm/ (accessed 14 April 2017).

17. University of Exeter. Extreme Medicine MSc. Postgraduate Study and Research. http://www.exeter. ac.uk/postgraduate/taught/medicine/extrememedicinemsc/ (accessed 20 April 2017).

18. Royal College of Physicians and Surgeons of Glasgow. International Diploma in Expedition and Wilderness Medicine. https://rcpsg.ac.uk/diploma-in-expedition-and-wilderness-medicine (accessed 19 April 2017).

19. AventureMedic Resources. http://www.theadventuremedic.com/resources (accessed 19 April 2017).

20. Hofmeyr R. Wilderness cold-exposure injuries: An African perspective. S Afr Med J 2017;107(7):566570. https://doi.org/10.7196/SAMJ.2017.v107i7.12610 21. Hofmeyr R, Tölken G, De Decker R. Acute high-altitude illness. S Afr J Med 2017;107(7):556-561. https://doi.org/10.7196/SAMJ.2017.v107i7.12612 22. Matthew J, Robertson C, Hofmeyr R. Update on drowning. S Afr Med J 2017;107(7):562-565. https:// doi.org/10.7196/SAMJ.2017.v107i7.12609 23. Hofmeyr R, Tölken G, De Decker R. Expedition medicine: A southern African perspective. S Afr Med J 2017;107(8):659-663. https://doi.org/10.7196/SAMJ.2017.v107i8.12676.

24. Hofmeyr R, D’Alton C. Heat-related illness in the African wilderness. S Afr Med J 2017;107(8):664668. https://doi.org/10.7196/SAMJ.2017.v107i8.12710 25. De Decker R, Tölken G, Roos J. Human factors: Predictors of avoidable wilderness accidents? S Afr Med J 2017;107(8):669-673. https://doi.org/10.7196/SAMJ.2017.v107i8.12677 26. Matthew J. The role of wilderness medicine training in resource-limited settings. Afr J Emerg Med 2016;6(4):172-173. https://doi.org/10.1016/j.afjem.2016.11.004

S Afr Med J 2017;107(8):656-658. DOI:10.7196/SAMJ.2017.v107i8.12675

August 2017, Print edition

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

CME

Expedition medicine: A southern African perspective R Hofmeyr,1,2 MB ChB, DipPEC, DA, MMed (Anaes), FCA (SA), FAWM; G Tölken,2,3 MA; R De Decker,4 MSc, MB ChB, DCH, FCPaeds (SA), Cert Med Genet (Paeds) Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town, South Africa WildMedix, Cape Town, South Africa 3 Mountain Club of South Africa, Mountain Rescue, Hottentots-Holland Section, Cape Town, South Africa 4 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, and Red Cross War Memorial Children’s Hospital, Cape Town, South Africa 1 2

A growing number of people are undertaking expeditions and adventure travel to previously inaccessible areas. The risks posed by increasing accessibility of remote regions and interest in extreme sports have not been fully obviated by modern equipment and communications. Therefore, there remains a requirement for medical care during wilderness expeditions, for which expectations and formal standards continue to increase. Expedition medicine should take cognisance of the predicted problems, plan for contingencies, and be practised pragmatically in austere settings. Southern African medics have a broad skill set, which makes them ideally suited to the field, but they should seek to understand the epidemiology of expeditions in different environments, undergo specialised training, and become involved in all phases of planning and execution of an expedition. Routine general practice complaints and accidental trauma are ubiquitous; travel medical issues such as blisters, diarrhoea, insomnia, sunburn and dehydration occur commonly; area/activity-specific issues such as infectious disease risks and altitude illnesses must be addressed; and women’s health and dental problems are frequently overlooked. The expedition medic plays a wide range of roles, and should have knowledge and skills to match the requirements of the expedition. Fortunately, many resources exist to assist medics in becoming competent in the field.

S Afr Med J 2017;107(8):659-663. DOI:10.7196/SAMJ.2017.v107i8.12676

‘ Have you suffered, starved and triumphed, grovelled down, yet grasped at glory, Grown bigger in the bigness of the whole?

“Done things” just for the doing, letting babblers tell the story, Seeing through the nice veneer the naked soul?

Have you seen God in His splendours, heard the text that nature renders?

The simple things, the true things, the silent men who do things – Then listen to the Wild – it’s calling you.’

(Call of the Wild – Robert Service)

Scenario

A group of friends invites you to join a month-long overland fourwheel-drive trip through southern Africa. The three-vehicle convoy will visit wilderness areas in four countries, in many places spending several days between settlements, traversing remote game parks and unfenced camps in the bush. As you are the only doctor in the group, they offer to cover your costs if you serve as the expedition’s medic.

Eager for an adventure, you accept quickly. Only later do you begin to consider the implications of this role. What should you take with you? What mishaps and illnesses should you prepare for? How will you treat, transport or evacuate a member of the team? Suddenly, ‘winging it’ no longer feels like an adequate strategy.

Background

An expedition is described as a journey undertaken with a specific purpose, particularly for war, research, or exploration. Fortunately, as our antagonistic conquests for new territories have decreased, humans have sought to travel to remote regions for reasons of both scientific and, increasingly, personal discovery. Currently, many individuals undertake expeditions seeking personal challenges, promotion of worthy charitable causes, and extreme adventure

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activities. While detractors may accuse expedition participants of doing things ‘… just for the doing’, many actively seek out adversity in exchange for the beauty rendered by nature, and to see ‘… through the nice veneer the naked soul’. As technology and modern amenities steadily shrink the world into a global village, areas and destinations that would previously have required large, lengthy expeditions to reach can now be visited easily by adventure tourists with adequate financial means. Unfortunately, this may have decreased the average levels of skill and experience of participants.[1] Although modern equipment and communications have made wilderness expeditions much safer, they have not been able to obviate the vagaries of extreme conditions, fickle weather, thin air or gravity. When we listen to the call of the wild and explore far from formal healthcare systems, we must be prepared for medicine to travel with us.

Austerity does not constitute an excuse for poor care; ‘making do’ on ingenuity alone is not sufficient. Wilderness and expedition medicine, therefore, is as purposeful as the expedition itself: predicted, planned, and pragmatically performed. While expedition environments may differ dramatically – from seething oceans to desolate deserts, tropical jungles to frozen mountain peaks, and even to space – the unifying characteristics of expedition medicine remain the same: the patient and practitioner are in a remote location (in time and/or distance) under unusual physical and psychological demands (through exertion or environmental stressors). There is strong reliance on both clinical examination and good judgement within the context of location, available materials, and team dynamics.

Resource constraints require rationing, ingenuity and improvisation.

Fortunately, all of these characteristics are familiar to medics who have trained and practised in southern Africa.

Globally, wilderness medicine has grown organically with little organisation, driven by the needs of groups in a wide variety of environments. Traditionally, expedition doctors were wilderness

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enthusiasts with specific outdoor skills, who provided medical services as enthusiastic amateurs. Particularly in North America and Europe, however, these roles have become more formalised, and as expectations grew, medical standards (and ultimately research in the field) have expanded and continue to evolve rapidly.[2] Despite a strong history of participation in worldwide expeditions by South Africans, earlier development of wilderness and expedition medicine in South Africa (SA) was hampered by the limitation of international travel due to sanctions against the apartheid regime. However, the generally broad experience and skill sets of SA doctors make them well suited to provide care in extreme environments.

Epidemiology of expedition medicine

To the uninitiated, providing medical care on expeditions conjures up images of wild and venomous animal attacks, frostbite, spectacular falls and outlandish tropical diseases. While isolated locations and adverse environments do carry particular concerns, it is more important for the expedition medic to be prepared for the ordinary than the obscure.

Indeed, it is more likely that a participant will suffer injury as a result of a motor vehicle collision on the way to the trailhead rather than any other expedition-related risk.[3] Generally, the epidemiology of wilderness illness and injury can be considered in three classes of decreasing frequency: day-to-day ‘general practitioner’ ailments, travel medicine issues, and expedition/environment-specific problems.

On all but the largest expeditions, the medic is likely to be the only medical professional, and will therefore bear the brunt of any and all consultations. Immediate, free and unlimited access may encourage participants to consult the expedition medic for complaints with which they would not have presented to their general practitioner at home. Simple colds and influenza, headaches, muscle aches and strains, inconsequential gastrointestinal upsets, minor bumps and scrapes are common, and can be a drain on expedition medical supplies if treated aggressively.[4] Furthermore, consultations for women’s health issues and dental hygiene (especially on longer expeditions) are frequent, and often beyond the scope of experience of the practitioner. Therefore, while learning about trypanosomiasis and Crimean-Congo haemorrhagic fever for travels in Africa may seem desirable, acquiring competence in field management of toothache and caries is more important. To combat exhaustion of simple supplies (and encourage team members to use them sparingly), it is effective to encourage all participants to carry a small first-aid kit containing items such as adhesive plasters, analgesics, antispasmodics, rehydration solution, basic dressings and an antiseptic. Adding a few basic trauma supplies – for instance, a structural aluminium malleable (SAM) splint, trauma dressing and crêpe bandage – allows these kits to be pooled to manage emergencies, and reduces the bulk that must be carried by the expedition medic.

After routine general practitioner complaints, travel medicine issues are the most frequently encountered on expeditions.

Foremost among these is traveller’s diarrhoea, which is frequently caused simply by a change in dietary habits while on an expedition, or exposure to benign pathogens. However, gastroenteritis can be rapidly spread within a party unless meticulous attention is paid to personal hygiene, handwashing, clean water provision, and food preparation. Any gastrointestinal upset causing dehydration or lasting >48 hours should trigger symptomatic treatment and strong consideration of antimicrobials, especially after 72 hours. Powdered or effervescent sports drink preparations are commonly carried on expeditions, and can be used to both replace lost electrolytes and mask the taste of water purification tablets.

Other frequent travel issues include poor sleep (due to jet lag, unfamiliar environments or sharing quarters with noisy sleepers),

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blisters, and manifestations of solar exposure such as sunburn and dehydration. While simple exhaustion often solves the insomnia, it should be remembered that poor sleep at high altitudes can be both a consequence of poor acclimatisation and a diagnostic criterion for acute mountain sickness (AMS). Early initiation of prophylaxis/ treatment with acetazolamide may profoundly improve this situation. Blisters, sunburn and dehydration are best managed by pro­ active prevention.

Expedition-specific medical problems are determined by the nature of the activities, destination and wilderness environment.

For instance, high-altitude expeditions require planning for accli­ matisation and high-altitude illness,[5,6] but should also anticipate local and systemic cold exposure injuries,[7] and accidental trauma. In the African context, this is likely to include infectious disease. Malaria is a common threat that should not be discounted. Consideration should also be given to other transmissible conditions such as Dengue fever, cholera, typhoid, yellow fever and meningitis. Finally, the specific risks of specialised expedition tasks must be anticipated, such as dysbarism or decompression illness during diving.

The role of the expedition medic

Expedition medics clearly need a wide range of competencies to fulfil an unusually broad scope of roles, as described in Table 1.

Expedition medic qualifications and competencies

The nature of expedition medicine attracts individuals from diverse backgrounds, both personally and professionally. Although many expeditions may wish to be accompanied by a qualified expedition doctor, medics from fields such as nursing, prehospital or military field medicine and physiotherapy with appropriate skills and training can and do provide excellent care in the field.[8] Indeed, the breadth and depth of wilderness experience of the individual may be of more relevance than their specific medical qualification, and for some wilderness activities that carry a low risk and are without lengthy delays for evacuation, an expedition member who has been trained in advanced wilderness first aid may suffice.

Regardless of background, there are essential requirements for competency as an expedition medic. First and foremost, the medic should be competent to undertake the activities and cope well with the demands of the expedition, being comfortable to care for themselves in the specific wilderness environment. Adequate fitness and technical skill with regard to the expedition activities (e.g. mountaineering or kayaking skills) are essential. A doctor who cannot ski is a poor choice for a polar crossing, as is a nurse prone to motion sickness on a sailing trip.

Secondly, the medic must have the medical knowledge and skills to competently manage the most likely illnesses and injuries that may occur during the expedition. Generally, SA doctors have a broad skill set and can perform a wide range of minor procedures, which makes them well suited to serve on expeditions. However, as the itinerary becomes increasingly isolated from accessing a formal healthcare system, so does the level of intervention required to be practised in the field. A prospective wilderness medic should consider carefully where they may need to supplement their skills before departure (Fig. 1).

Finally, the expedition medic must consider his or her ability to perform medical care within an austere or adverse wilderness environment, with very limited support, possibly without the option of consulting colleagues, and with very limited equipment. It is a worthwhile exercise to perform wilderness simulations of potential medical emergencies, or to obtain formal wilderness medicine training, before embarking on an expedition. Crucially, wilderness

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Post-expedition

Expedition

Pre-expedition

Table 1. Roles of the medic before, during and after an expedition Planning

Integrate medical considerations into all aspects of planning Build close working relationship with expedition leadership Learn about the area, activities, challenges and risks Consider locally occurring infectious diseases: prevention, prophylaxis and specific treatments (if required) Consider all facets and periods of expedition, and formulate a medical evacuation plan for each area/activity/period Advise participants on suitable medical and evacuation insurance

Screening

Consider whether medical barriers to participation exist Perform appropriate screening and advise participants

Provisioning

Review/plan food and water provisioning Review/plan hygiene requirements Plan and pack medical supplies

Training

Acquire or improve any specifically required medical skills Ensure that the medical team has appropriate and adequate wilderness skills and fitness to take part in expedition activities Where possible, provide medical or wilderness first-aid training to expedition participants

Prevention

Maintain close liaison with expedition leadership Build rapport with participants Daily review of hygiene, food and water provisions Ongoing simple preventive medicine: hydration, stretching, sun protection, infectious disease prophylaxis, hand-washing, dental and other personal hygiene, sexual health Regular â&#x20AC;&#x2DC;clinicâ&#x20AC;&#x2122; times to ease access (but maintain medic sanity!)

Consider ongoing first-aid training (can be scenario-based)

Intervention

Ensure appropriate care is available to local staff and local people Manage routine medical issues during the expedition Provide psychological support to participants Maintain adequate records of consultations, treatments, challenges, supplies and other information, which may be of future use Manage medical emergencies

Follow-up

Advise participants with regard to medical conditions (eg. infectious diseases) which may only present in the weeks following return from the expedition Follow up on any medical problems which presented during the expedition, especially those requiring evacuation or early termination of participation

Document

Compile and submit an expedition medical report Document the supplies (medicines and disposables) used during the expedition, and consider making recommendations for future trips of the same nature Consider publication of useful information and findings in the literature Engage in networks of expedition medicine practitioners (e.g. wilderness medicine societies and online discussion groups) to share experience and help advance the speciality

practitioners need to be willing and able to think and act beyond the confines of their usual practice[9] (Fig. 2).

Until recently, there was little guidance on the competencies required for wilderness and expedition medicine. While numerous specialty courses exist (typically directed at specific environments, such as polar, mountain or jungle medicine) and there are several postgraduate wilderness medicine qualifications available worldwide, there has been little standardisation of requirements. In 2015, the Faculty of Pre-Hospital Care, Royal College of Surgeons of Edinburgh published a consensus report on medical provision for wilderness medicine.[10] This includes recommendations on the qualification levels of practitioners for wilderness activities, based on the perceived level of risk of the expedition, and the delay in accessing a higher level of outside care. At the most basic level, this person might be a non-medical member of the party with first-aid training. Where

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risk is higher, or delay to definitive care exceeds 12 hours, a doctor or advanced allied practitioner with adequate diagnostic and procedural skills and basic wilderness training is recommended. Qualified and experienced expedition doctors are recommended for remote or high-risk expeditions.

Expedition medical kits

Due to kit size and weight limitations inherent in participation in wilderness expeditions, the bag of the expedition medic must be packed with careful consideration and finesse. To keep the medical equipment within practical confines, the key determining factor becomes versatility of equipment and medication, rather than highly advanced niche applications. Every item should be either irreplaceable or have multiple uses. In addition to sufficient supplies for trauma and medical risks due to expedition area, remoteness, biome, altitude,

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Fig. 1. Mountain guides and doctors undertaking a mountain medicine training expedition on Mount Kilimanjaro participate in field management of a simulated casualty. (Photo: Dr Chanèl Rossouw, with permission.)

Fig. 2. An expedition medic performing field removal of a septic dental root after tooth avulsion at high altitude. Acquisition of a broad skill set is essential for providing pragmatic wilderness medicine. (Photo: Dr Chanèl Rossouw, with permission.)

duration and main activities, the medic should consider specific risks of the expedition participants. Taking advanced airway equipment, for example, should only be considered if the medic is sure that once in use, advanced airway management in the wilderness can also be sustained while waiting for a prolonged evacuation. Practical considerations such as temperature and water/humidity exposure of equipment and medications also come into play. This can be mitigated by packing supplies into waterproof containers (or simple zip-lock plastic bags) with accurate labelling, clustering/compartmentalising into practical sets such as airway management, haemorrhage control, wound closure, and pain management. This ensures that access to appropriate supplies is swift and easy in the field. As the medic on an expedition is as prone to all risks as every other expedition member, providing advice and training to selected expedition members on the contents, structure and usage of the expedition medical kit is advisable. This ensures continuity of medical care should the primary medic be incapacitated.

Ethics in expedition medicine

It is important that the medic is willing to sacrifice personal goals during the expedition to provide care to participants. This means that the expedition doctor should not be financially invested in the expedition – whether linked to a successful outcome, or because he/she has paid a fee to attain the expedition goal – as this compromises their decisionmaking.

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Expeditions are becoming safer, but society is also much less tolerant of risk. Every effort must be made to ensure that expedition participants have a realistic perception of the inherent dangers of the destination and activities, and are especially cognisant of the limited medical care that can be provided in the field. For example, the recent furore surrounding the death of a celebrity and lack of helicopter rescue during the night on Mount Kilimanjaro illustrates a pervasive lack of understanding of the local rescue capabilities in that area. The expedition medic must be au fait with available facilities on the ground, and help potential participants to understand the risks in relation to their goals, so that they can make an informed decision on participation.

Expedition doctors should be very aware of the challenges of balancing patient confidentiality with overall safety and expedition goals. Prior to an expedition, this may require significant efforts to gain the trust of prospective participants to disclose conditions that they feel may jeopardise their chances of being selected, and counselling to disclose potential medical risks to the expedition leadership. It is the contention of the authors that very few medical conditions are a complete barrier to participation in wilderness activities, provided the medic and participant are adequately informed. With full understanding of the risks, and informed consent, individuals should be able to experience the entire spectrum of challenges in the wilderness.

On an expedition, it can be difficult to create an environment in which participants can consult in private. It is useful to site the expedition doctor’s tent/accommodation on the outskirts of the camp, and in such a way as to allow privacy of interactions. Medics should be aware – especially at night – of the scant protection provided by tent walls. A final set of ethical challenges during expeditions centres upon denial of treatment and provision of futile care. In contrast to urban medicine, an expedition participant who declines or actively ignores medical advice can place fellow team members at risk. A more paternalistic care relationship is therefore required. Ideally, a consensus regarding management of these cases should be reached with the expedition leadership.

Resources for expedition medics

Fortunately, the increasing recognition of expedition medicine as a specialised field has led to the proliferation of good-quality resources for current and prospective expedition medics. These include professional groups such as the Wilderness Medical Society (www.wms.org) and the International Society for Mountain Medicine (www.ismm.org); online repositories such as Adven­ ture Medic (www.theadventuremedic.com) and Explorers Connect (www.explorersconnect.com); mountaineering organisations such as the Mountain Club of South Africa (cen.mcsa.org.za); professional wilderness medicine companies such as WildMedix (www.wildmedix. com); and health organisations such as the Centres for Disease Control and HealthMap (www.cdc.gov; www.healthmap.org). Peer-reviewed research and academic articles in this field can be obtained in journals such as the Wilderness and Environmental Medicine Journal, and High Altitude Medicine and Biology. There are also educational resources such as wilderness medicine podcasts (www.wemjournal.org).

The expedition doctor who prefers reading textbooks should consider the focused manual, Expedition and Wilderness Medicine, by Hudson and Knox,[11] the practical and comprehensive Oxford Handbook of Expedition and Wilderness Medicine, edited by Johnson et al.,[8] or the definitive encyclopaedia in the field, Auerbach’s Wilderness Medicine.[9]

Scenario resolution

Realising you have bitten off a little more than you can chew, you make two worthwhile investments: the electronic copy of an expe-

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dition and wilderness medicine textbook, and a hands-on course with an experienced company. The resulting increased understanding of the specific risks of the area and practical skills allow you to pack appropriate medical supplies for the expedition. In a remote camp in Botswana, one of the group who has been unwell with undifferen­tiated symptoms faints into the fire, sustaining seconddegree burns. You are able to provide effective immediate care, and, using a predetermined plan, evacuate her to Gaborone. By the time she arrives, you have already diagnosed the malaria that caused her collapse using a disposable rapid diagnostic kit, and have initiated treatment. After initial stabilisation, she is repatriated to SA and makes a full recovery while you re-join the expedition and enjoy an uneventful completion.

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1. Dallimore J, Mason NP, Moore J. Expedition medicine. In: Auerbach PS, Cushing T, Harris NS, eds.

Auerbach’s Wilderness Medicine. 7th ed. Philadelphia, PA: Elsevier, 2017.

2. Imray CH, Grocott MP, Wilson MH, et al. Extreme, expedition, and wilderness medicine. Lancet 2015;386(10012):2520-2525. https://doi.org/10.1016/S0140-6736(15)01165-4 3. Anderson SR, Johnson CJ. Expedition health and safety: A risk assessment. J R Soc Med 2000;93(11):557562. https://doi.org/10.1177/014107680009301102 4. McIntosh SE, Leemon D, Visitacion J, et al. Medical incidents and evacuations on wilderness expeditions.

Wilderness Environ Med 2007;18(4):298-304. https://doi.org/10.1580/07-WEME-OR-093R1.1 5. Hofmeyr R, Meyer W, James M, et al. Recognising and mitigating the risk of altitude-related illness.

S Afr Med J 2016;106(9):834-835. https://doi.org/10.7196/SAMJ.2016.v106i9.11389 6. Hofmeyr R, Tölken G, De Decker R. Acute high-altitude illness. S Afr J Med 2017;107(7):556-561. https://doi.org/10.7196/SAMJ.2017.v107i7.12612 7. Hofmeyr R. Wilderness cold-exposure injuries: An African perspective. S Afr Med J 2017;107(7):566570. https://doi.org/10.7196/SAMJ.2017.v107i7.12610 8. Johnson C, Anderson S, Dallimore J, et al. Oxford Handbook of Expedition and Wilderness Medicine.

2nd ed. Oxford: Oxford University Press, 2015.

9. Auerbach PS, Cushing T, Harris NS, eds. Auerbach’s Wilderness Medicine. 7th ed. Philadelphia, PA: Elsevier, 2017.

10. Mellor A, Dodds N, Joshi R, et al. Faculty of Prehospital Care, Royal College of Surgeons Edinburgh guidance for medical provision for wilderness medicine. Extrem Physiol Med 2015;4:22. https://doi. org/10.1186/s13728-015-0041-x 11. Hudson S, Knox C. Expedition and Wilderness Medicine. Devon, UK: Expedition Medicine Ltd, 2006.

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

CME

Heat-related illness in the African wilderness R Hofmeyr,1 MB ChB, DipPEC, DA, MMed (Anaes), FCA (SA), FAWM; C D’Alton,2 MB ChB, MSc (Sport Exercise Med) Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town; and WildMedix, Cape Town, South Africa 2 Sports and Exercise Medicine, Faculty of Human Biology, University of Cape Town, South Africa

1

Corresponding author: R Hofmeyr (ross.hofmeyr@uct.ac.za)

Wilderness heat­related illnesses span a variety of conditions caused by excessive or prolonged heat exposure, and/or the inability to compensate adequately for increased endogenous production during strenuous outdoor activities. Despite management of well­known risk factors, such as lack of fitness or acclimatisation, dehydration, underlying illness and certain medications, even highly trained individuals may exceed their physiological capability to dissipate increased core temperature. Heat illnesses range from benign cramps to the more concerning heat syncope and exercise­associated collapse (with or without hyperthermia), and culminate in life­threatening heat stroke.

The differential diagnosis in the wilderness is broad and should include exercise­associated hyponatraemia with or without encephalopathy.

Clinical guidelines for wilderness and hospital management of these conditions are available. Field management and evacuation are based on severity, and include cooling, rehydration and assessment of core temperature and serum sodium, if possible. Hyponatraemia should be corrected with the use of oral or intravenous hypertonic saline, depending on whether the patient can safely take oral fluids. Hospital management may include aggressive and potentially invasive cooling, careful assessment for organ dysfunction, and intensive multi­organ support, if required. Paracetamol, non­steroidal anti­inflammatory drugs and dantrolene should not be used.

S Afr Med J 2017;107(8):664­668. DOI:10.7196/SAMJ.2017.v107i8.12710

Scenario

A fit­looking 23­year­old male participant in a summer mountain trail run collapses 3 km from the end of the 25 km race. Despite the altitude, ambient temperatures are warm, and the participants have been exposed to the full sun for several hours. On your first assessment, he is very confused, with a weak, rapid pulse (160 beats per minute). His skin is wet and cool. A passing member of the same running club alleges that he is not known to have any medical conditions. You notice that his water bottles are both empty. As fellow runners help you carry him to the nearby medical­aid station, a rapidly expanding differential diagnosis fills your thoughts.

Background

Wilderness heat­related illnesses span a continuum of medical problems caused by the generation of, and/or exposure to, excessive heat in the wilderness environment. They can range from minor annoyances to life­threatening conditions. Endogenous heat production is directly dependent on the sum of that from inescapable sources, such as basal cellular metabolism and cardiorespiratory work, and heat generated by physical exertion. All heat exchange (gain or loss) occurs through four mechanisms: conduction, convection, radiation and evaporation. Conduction refers to the direct transfer of heat from one object to another through contact. Convection is heat gain or loss due to movement of a fluid (such as air); a convection oven or wind chill from an Antarctic breeze are similar examples.

Radiation describes transfer of heat through electromagnetic waves, epitomised by the heat of the sun on skin. Evaporation is the loss of heat induced by the phase change from liquid to gas, which is dramatically affected by ambient vapour pressure or relative humidity.

Many animals have developed ingenious strategies to adapt their physiology to control heat gain or loss. Indeed, it is hypothesised that particular human traits – our upright stance, complex bony structure of the foot, nuchal ligament, relatively hairless skin and copious capacity for perspiration – evolved to give us an advantage in chasing

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down prey in the prehistorical African heat.[1] Today, however, humans are unique in their ability to adapt the environment to control their physiology through behaviour and material means: use of clothing, shelter, and devices such as heaters and air conditioners. Despite this, we cannot alter the laws of thermodynamics, and people in the wilderness are subject to the same exposure and thermal exchange mechanisms as our primitive ancestors. Fortunately, the development of modern science, clothing technology, and an understanding of physiology allow us to function successfully in environments of extreme heat under many adverse circumstances (Fig. 1).

Risk factors traditionally considered to increase our susceptibility to the deleterious effects of heat stress include obesity, lack of acclimatisation to hot environments, poor physical fitness, extremes of age, underlying illness (e.g. cardiac conditions, hyperthyroidism), dehydration, certain medications (e.g. beta blockers, anticholinergics,

Fig. 1. Despite reduced temperatures at high altitudes, the increased solar radiation and physical exertion can lead to severe sunburn and heat stroke in the unwary.

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and diuretics) and illicit drugs (e.g. ampheta­ mines, cocaine, and Ecstasy).

Heat-related illnesses are usually prevent­ able. Mitigating factors include improved physical fitness, heat acclimatisation, selec­ tion of appropriate clothing, maintaining adequate hydration, sufficient rest periods, and enhancing evaporative cooling. These may be recalled using the CHAFER mne­ monic (Table 1). However, it is important to appreciate that exertional heatstroke and other forms of heat illness can occur in spite of the optimal control of these fac­ tors.[2] Similarly, it is normal for well-adapted individuals to experience an increase in core temperature above ‘normal’ values during

exercise, even in the setting of low environ­ mental temperatures (Fig. 2). Therefore, core temperature alone is not a reliable indicator of heat illness or injury in the absence of other signs, and illness only occurs when physiological compensation to balance heat gain/production with heat loss fails.

Definition and spectrum of heat-related illnesses

Heat-related illnesses are not neatly delinea­ ted conditions, but rather occur as a spec­ trum – from benign to catastrophic. To better understand the pathophysiology of heat ill­ ness, it is essential to clarify the defini­ tions thought to encompass these entities.

Core temperature Heart rate Ambient temperature 160

100 80

37.5

60 37.0

Heart rate

120 38.0

40 20

36.5

0 36.0

Heat cramps

Heat cramps are muscle spasms that typi­ cally occur in the large muscle groups of the leg, and may be debilitatingly severe. The precise aetiology is still being debated, but is thought to be a combination of calcium and other electrolyte derangements at tis­ sue level, plasma volume depletion, tissue acidosis in the light of respiratory alkalosis from hyperventilation, and altered neuro­ muscular control related to exertion.[3-5] As these cramps can occur without exposure to a warm environment and typically resolve rapidly, they are often considered not to be true heat illness.

Heat rash and sunburn

140

38.5

15:57:20…

18:51:26…

15:52:35…

18:42:35…

21:11:18…

4:57:28…

9:02:26…

12:03:26…

14:50:35…

17:51:52…

20:26:53…

5:56:53…

9:05:41…

12:05:41…

14:55:41…

17:34:17…

20:24:17…

23:09:26…

1:59:26…

4:49:26…

7:39:26…

12:08:57…

15:09:01…

17:52:10…

20:11:07…

23:01:07…

1:51:07…

6:21:07…

9:01:29…

11:43:45…

14:28:23…

17:18:27…

20:01:40…

22:51:46…

2:21:46…

7:21:46…

10:23:21…

13:13:35…

17:00:59…

20:30:59…

23:43:43…

3:23:43…

9:01:34…

12:15:34…

15:05:34…

17:58:04…

20:59:04…

0:40:48…

4:30:48…

7:31:45…

10:08:01…

12:52:00…

15:42:00…

18:41:16…

21:37:04…

0:27:04…

4:47:04…

Temperature (ambient and core), 0C

39.0

Classifying the manifestations into discrete categories, however, is useful to ascribe the correct urgency of management and level of severity.

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Time

Fig. 2. Exercise-associated hyperthermia, with routinely raised core body temperatures during periods of physical effort (as shown by raised heart rate) despite frigid conditions during a 7-day mountaineering expedition in Patagonia. (Data – R Hofmeyr.)

Prickly heat or miliaria rubra is infrequently seen in the South African (SA) context, but occurs in humid or tropical climates owing to exocrine sweat duct blockage during copious or prolonged sweating. It presents as an erythematous pruritic rash with papules, usually on the neck, trunk and limbs, but sparing hands and feet. While heat rash alone is more of an irritation than a serious illness, the reduction in sweat production by duct obstruction can greatly reduce efficiency of evaporative heat loss and predispose the sufferer to more severe injuries. Sunburn – epidermal and dermal damage due to exposure to ultraviolet radiation – also limits sweat production. In

Table 1. Mitigating/preventive factors for heat-related illness – CHAFER CHAFER Clothing

Hydration

Acclimatisation

Fitness

Evaporative cooling Rest

Mitigating/preventive factors Clothing should provide skin protection, reflection of solar radiation, and encourage evaporative cooling.

Loose-fitting, light-coloured, wicking and/or porous items are ideal. Protection for the head, face and neck should be included.

Evaporative cooling through sweating is essential to maintain heat loss during exertion in warm environments, and can approach 1 000 mL/h in acclimatised individuals. Prehydration and drinking to thirst are effective measures. Imbibing cold fluids improves comfort and may aid heat loss.

Gradual exposure to increasing levels of exertion in a hot environment induces heat acclimatisation over a period of days to weeks. The predominant mechanism is an increase in quantity and efficacy of sweat production, improving evaporative cooling. Acclimatisation can be accomplished by 60 - 90 minutes of exercise in the heat per day, ideally over a period of 1 - 2 weeks. Benefits are typically lost within a fortnight of withdrawal from a continuous exposure stimulus.

Physical fitness allows more efficient effort, reducing the rate of endogenous heat production at the same level of activity compared with a less fit individual. It increases the effectiveness and rate of acclimatisation to hot environments, and reduces body fat, which in turn allows more efficient heat loss.

In addition to remaining well hydrated to allow for evaporative cooling through sweating, dipping or soaking clothing in water can greatly increase cooling by this mechanism.

Rest breaks during acclimatisation, strenuous exertion, and the hottest periods of the day reduce the risk of heat illness. This is particularly effective if rest can be taken in a cooler area.

CHAFER = clothing, hydration, acclimatisation, fitness, evaporative cooling, rest.

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its severe form, it can result in a systemic inflammatory response manifesting with headache, nausea, fever or rigors, and delirium.

Heat syncope and exercise-associated collapse

This condition is traditionally defined as a transient collapse or brief loss of consciousness occurring immediately after strenuous exercise in a warm environment. The patient usually rapidly regains clear consciousness shortly after becoming supine, or with raising of the legs. It is often seen in athletes, where it is possibly a manifestation of exercise-associated syncope. It commonly occurs immediately after completion of intense exercise. There are sudden decreases in venous return when skeletal muscle contraction is halted and blood pools in the lower extremities, in the context of exercise-induced peripheral vasodilation and decreased systemic vascular resistance. This may be compounded by an abnormal baroreflex response, Bezold-Jarisch or Barcroft-Edholm reflex. As this condition can occur during intense exercise in the absence of hot conditions, it is frequently termed exercise-induced postural hypotension.

Heat exhaustion

While heat exhaustion is understood to be a manifestation of intra­ vascular volume depletion and dehydration caused by prolonged effort in a thermally stressful environment, many in the sports medi­ cine community believe that heat exhaustion is a more severe form of exercise-associated collapse or exercise-induced postural hypo­ tension, and not a separate entity. In the wilderness environment, it is typified by symptoms of fatigue, effort intolerance, weakness, headache, nausea, tachycardia and sometimes dyspnoea. The patient may have a warm or cool skin, with profuse sweating. Core tempera­ ture is either normal or mildly elevated (<39°C). Critically, there is no persistent change in mental state. If altered mentation remains for more than a few minutes after the patient is supine, with legs raised, it should be treated as heat stroke.

Exercise-associated hyperthermia

Raised core body temperature (<40°C) that results from strenuous exertion or exercise may be a normal consequence of increased endogenous heat production, and can occur in cold environments, particularly in athletes exercising at or close to maximum capacity (Fig. 1). Where exercise-associated hypothermia leads to collapse or altered level of consciousness, it indicates the development of heat exhaustion or heat stroke. In athletes, this typically occurs over medium distances (5 - 21 km). Previous occurrence is a risk factor.

Heat stroke

Heat stroke is a true medical emergency. The defining characteristics are a core temperature of >40°C and encephalopathy, manifested by altered mental status. While often distinguished as occurring as a result of prolonged exposure to high ambient temperatures (classic heat stroke) or pathological hyperthermia during exercise (exertional heat stroke), it is most commonly a combination of the two in the context of wilderness medicine. The patient may be sweating, but often has a dry skin. Clinical signs include confusion, disorientation, decreased level of consciousness, inappropriate behaviour, ataxia or collapse, tachypnoea, and tachycardia, or the patient may be in cardiovascular shock on presentation. Dysrhythmias can occur. Risk of brain, renal, hepatic and other organ damage depends on duration of hyperthermia, with systemic protein denaturation beginning at >42°C. The patient may develop a systemic inflammatory response syndrome (SIRS) owing to cytokine and heat-shock protein release, which mimics sepsis.[6] Hypoperfusion of the gastrointestinal tract is exacerbated by inflammatory-mediated increase in mucosal and

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vascular permeability, leading to endotoxin migration from the gut to the circulation.[7] This is thought to lead to the multi-organ failure that causes death in severe or untreated cases.[8]

Exercise-associated hyponatraemia

While not specifically a heat-related illness, exercise-associated hyponatraemia (EAH) often occurs in the setting of prolonged effort in hot conditions. It is therefore important to understand the condition, and to consider it as a differential diagnosis. Defined as a serum sodium concentration ˂135 mmol/L within 24 hours of prolonged physical activity, it is believed to be caused by an interplay between excessive fluid intake (especially hypotonic fluids such as clear water) and reduced water excretion under the influence of anti­ diuretic hormone due to the physical stress imposed by exercise.[9] Of these factors, overhydration (>1 500 mL/h) is considered the most prominent cause. While most cases are asymptomatic and go unde­ tected, EAH can cause fatigue, nausea/vomiting, headache, dizziness, blurred vision and tachycardia. Severe cases can result in cerebral oedema (even non-cardiogenic pulmonary oedema) and confusion, decreased level of consciousness, and seizures. In these cases, it is termed exercise-associated hyponatraemic encephalopathy (EAHE).

Exercise-associated hyponatraemic encephalopathy

As described above, EAHE is defined as the presence of altered mental status, seizures or coma in the presence of EAH. As a biochemically proved reduction in serum sodium is required to confirm the diagnosis, it should be considered in all patients presenting with appropriate risk factors (prolonged effort, particularly in a warm environment, combined with significant hypotonic fluid intake and oliguria).

Wilderness medicine guidelines for heat-related illnesses

The Wilderness Medical Society (WMS) has published practice guidelines for wilderness emergency care, heat-related illnesses, and EAH, most recently updated in 2014.[2,9,10] These peer-reviewed, expert-consensus guidelines form an excellent foundation upon which local recommendations can be made for the African context, drawing from local experts in fields such as wilderness, emergency and sports medicine.

Clinical diagnosis and temperature measurement

The practitioner is usually alerted to the initial presence of heatrelated illness by patient symptoms. In the wilderness, a presumptive diagnosis is made on the clinical signs described above, in the presence of heat exposure and/or excessive endogenous production.

However, as hyperthermia and heat stroke can exist in the absence of excessive ambient temperatures – even in patients with cool extremities and skin – contemporaneous measurement of core body temperature is very valuable in excluding or confirming the diagnosis, assessing severity, and monitoring response to treatment.

Unfortunately, accurate core temperature measurement in the field is challenging. Invasive gold-standard measurements (pulmonary artery catheter or oesophageal thermistor) are infrequently available, and skin, oral or infrared tympanic measurements lack accuracy.[11] A pragmatic approach is to treat lucid patients according to their perceived temperature (as they do not have heat stroke if fully conscious and orientated), use a rectal thermometer for patients with altered consciousness, and insert an oesophageal thermistor, when available, in unconscious patients who have an advanced airway in place.[12]

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Field management

Severity of outcome of heat-related illness is directly proportionally related to duration of exposure. Treatment should therefore be initiated in the field, both to limit the progression of severity and to limit duration. Fortunately, there are many interventions that can be commenced in resource-constrained settings that will improve patient outcome (Table 2).

Field testing of serum sodium is available using compact, batterypowered point-of-care devices, such as the i-STAT analyser (Abbott Point of Care, USA).[13] However, in very hot environments, these devices often have a limited operation temperature range (e.g. 16 30°C for the i-STAT[14]), and the device may have to be kept cool in the field to guarantee function when required.[15]

Hospital management

Cases of suspected heat-related illness should always be managed urgently on admission to hospital. In addition to swift primary assessment and any related advanced life-support interventions, a reliable (rectal or oesophageal) core temperature and serum sodium measurement should be obtained as a matter of priority. Intravenous access should be established. It is valuable to obtain haematological, electrolyte, creatinine kinase, renal and liver function tests at the same time. Patients with altered mental status and a core temperature of >39°C must be urgently cooled, using methods described below.

Invasive cooling using bladder, gastric, pleural or peritoneal lavage can be considered if the patient does not respond rapidly. Seizures

should be controlled with a benzodiazepine or propofol, which may necessitate intubation and ventilation. Treat hypotension or shock with fluid resuscitation, but avoid hypotonic fluids, especially if the serum sodium level is unknown. If EAHE is diagnosed, up to three 100 mL boluses of 3% hypertonic saline at 10-minute intervals are advocated. There is no risk of central pontine myelinolysis with this therapy in the context of EAHE.[9] Serum potassium and calcium should be assessed and corrected if abnormal. If there is biochemical evidence of rhabdomyolysis, promoting positive fluid balance, diuresis with furosemide, and alka­ linisation of urine with sodium bicarbonate can be considered.[7,8] In contrast to fever, there is no role for paracetamol and non-steroidal anti-inflammatory drug use in heat stroke, which may cause further harm.[10] Dantrolene has also not been shown to contribute to man­ agement.[16] Admission to an intensive care unit (ICU) with renal dialysis and management for multi-organ failure may be required.

The treating clinicians should be alert for acute respiratory distress syndrome, liver or kidney injury, coagulopathy and gastrointestinal ischaemia.

Scenario resolution

You consider the potentially differential diagnosis, including presen­ tation of underlying febrile illnesses such as malaria, hypoglycaemia, drug toxicity or intoxication, cardiac ischaemic events, epilepsy, an occult head injury or EAH. However, the hot conditions and strenuous exertion make heat exhaustion or heat stroke very likely.

Table 2. Field management of heat-related illness General interventions

Heat cramps Heat rash

Sunburn Heat syncope Heat exhaustion Symptomatic wilderness hyperthermia/heat stroke

EAH and EAHE

In all suspected heat-related illness, decreasing physical effort or enforcing rest, moving the patient to a cool environment (or taking steps to shade the patient and encourage evaporative cooling), encouraging oral hydration if thirsty, and considering replacement of electrolytes are essential steps to enhance recovery.

Rest and stretch the involved limb and muscle groups. Encourage hydration with electrolytes. Consider calcium/ magnesium supplementation.

Promote a cool environment and improved personal hygiene. Application of lotions will aggravate the condition, although some advocate a topical corticosteroid in severe cases. Acclimatisation and avoidance of sweating will reduce further incidences.

Prevention of further exposure using barriers (clothing and regularly applied high-factor sunscreen) is essential.

Hydrating lotions and oral anti-inflammatories may reduce severity.

Cool the patient where possible; place supine and elevate legs. Once recovered, decrease effort and encourage frequent rest. Avoid aggressive intravenous and other invasive therapies.

Cool environment, rest, rehydration (typically oral), and consider electrolytes (oral). Assess core temperature early if there is any evidence of change in mental status. Evacuation for severe cases or those who respond poorly.

Provide advanced life support as indicated. Administer oxygen if available and saturations are <92%. Aggressive cooling using any available means should be initiated, including shading the patient from sunlight, removing excess clothing, soaking, dousing or partially submerging the patient in cold water, fanning, cold IV fluids, or even an ice bath. Covering the patient with a soaked blanket/sheet with continuous fanning is an effective method, using convective and evaporative cooling. Ice packs can be applied to the neck, axilla and groin, but their use and effectiveness have been challenged. No paracetamol or NSAIDs should be administered. Invasive/ rectal temperature monitoring should be established. Cool until 39°C and then observe; beware of rebound hyperthermia, but also excessive cooling. If using cold water or ice baths to cool the patient, it is effective to continue until the conscious patient begins to complain of cold. All patients should be evacuated to definitive medical care urgently.

EAH/EAHE should form part of the differential diagnosis for heat-related illnesses in the field. Ideally, field testing of serum should be used, as this guides the selection of fluid (hypo-, iso- or hypertonic) used for treatment.

In the absence of measurement, hypotonic or isotonic IV fluids should be avoided unless there is a clear indication (e.g. hypotension/shock). If hyponatraemia (serum sodium <135 mmol/L) can be demonstrated in the field, oral or IV hypertonic saline (100 mL 3% NaCl) can be administered every 10 minutes until 3 doses have been completed or neurological symptoms improve.[9] An oral mixture of hypertonic saline can be created by adding 3 4 stock cubes to half a cup of water.

EAH = exercise-associated hyponatraemia; EAHE = exercise-associated hyponatraemic encephalopathy; IV = intravenous; NSAIDs = non-steroidal anti-inflammatory drugs.

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At the medical station, you elevate the athlete’s legs, rapidly com­ mence cooling by soaking his clothing in cool water and encouraging evaporation by fanning, and obtain a rectal temperature of 41.2°C. Recognising the medical emergency, you establish IV access, and recognising the risk of hyponatraemia, start isotonic fluid resuscita­ tion. You request an urgent evacuation, even though the patient is gradually becoming more lucid. On arrival at the emergency unit, he is found to have significant rhabdomyolysis and dehydration in addi­ tion to heat stroke, but despite spending a night in the ICU, he avoids more serious consequences because of your swift interventions.

1. Bramble DM, Lieberman DE. Endurance running and the evolution of Homo. Nature 2004;432(7015):345352. https://doi.org/10.1038/nature03052 2. Wilderness Medical Society Expert Panel. Heat-related illnesses. In: Forgey WW, ed. Wilderness Medical Society Practice Guidelines for Wilderness Emergency Care. Connecticut, USA: FalconGuides, 2006:62-63.

3. Schwellnus MP. Cause of exercise associated muscle cramps (EAMC) – altered neuromuscular control, dehydration or electrolyte depletion? Br J Sports Med 2009;43(6):401-408. https://doi.org/10.1136/ bjsm.2008.050401 4. Schwellnus MP, Derman EW, Noakes TD. Aetiology of skeletal muscle ‘cramps’ during exercise: A novel hypothesis. J Sports Sci 1997;15(3):277-285. https://doi.org/10.1080/026404197367281

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5. Schwellnus MP, Drew N, Collins M. Muscle cramping in athletes – risk factors, clinical assessment, and management. Clin Sports Med 2008;27(1):183-194, ix-x. https://doi.org/10.1016/j.csm.2007.09.006 6. Dallimore J, Dhillon S, Winser S. Hot, dry environments: Deserts. In: Johnson C, ed. Oxford Handbook of Expedition and Wilderness Medicine. Oxford: Oxford University Press, 2015:745-767.

7. Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002;346(25):1978-1988. https://doi.org/10.1056/ NEJMra011089 8. Leon LR, Bouchama A. Heat stroke. Compr Physiol 2015;5(2):611-647. https://doi.org/10.1002/cphy. c140017 9. Bennett BL, Hew-Butler T, Hoffman MD, et al. Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia: 2014 update. Wilderness Environ Med 2014;25(4 Suppl):S30-S42. https://doi.org/10.1016/j.wem.2014.08.009 10. Lipman GS, Eifling KP, Ellis MA, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness: 2014 update. Wilderness Environ Med 2014;25(4 Suppl):S55-S65. https://doi.org/10.1016/j.wem.2014.07.017 11. Strapazzon G, Procter E, Paal P, et al. Pre-hospital core temperature measurement in accidental and therapeutic hypothermia. High Alt Med Biol 2014;15(2):104-111. https://doi.org/10.1089/ham.2014.1008 12. Hofmeyr R. Wilderness cold-exposure injuries: An African perspective. S Afr Med J 2017;107(7):566570. https://doi.org/10.7196/SAMJ.2017.v107i7.12610 13. Backer HD, Collins S. Use of a handheld, battery-operated chemistry analyzer for evaluation of heatrelated symptoms in the backcountry of Grand Canyon National Park: A brief report. Ann Emerg Med 1999;33(4):418-422.

14. Herr DM, Newton NC, Santrach PJ, et al. Airborne and rescue point-of-care testing. Am J Clin Pathol 1995;104(4 Suppl 1):S54-S58.

15. Joslin J, Mularella J, Schreffler S, et al. Novel method for reducing temperature of i-STAT1 analyzer in extreme environments. Wilderness Environ Med 2014;25(3):357-358. https://doi.org/10.1016/j. wem.2014.01.002 16. Bouchama A, Cafege A, Devol EB, et al. Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Crit Care Med 1991;19(2):176-180. https://doi.org/10.1097/00003246-199102000-00011

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

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Human factors: Predictors of avoidable wilderness accidents?

R De Decker,1 MSc, MB ChB, DCH, FC Paeds (SA), Cert Med Genetics (SA), G Tölken,2 MA; J Roos,3 MB ChB, DA (SA), FCA (SA), MMed (Anaes) epartment of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town and Red Cross War Memorial Children’s D Hospital, Cape Town, South Africa; and International Commission for Alpine Rescue Emergency Medicine Commission representative for the Mountain Club of South Africa Mountain Rescue team, Cape Town, South Africa 2 WildMedix, Cape Town, South Africa; and Mountain Rescue, Hottentots-Holland Section – Mountain Club of South Africa, Cape Town, South Africa 3 Department of Anaesthesia, Mitchell’s Plain Hospital, Cape Town, South Africa; and South African Red Cross Air Mercy Service, Cape Town, South Africa 1

Corresponding author: R De Decker (rik.dedecker@uct.ac.za)

A common misconception is that wilderness adventure travel is risky owing to the nature of the objective dangers that are encountered, such as avalanches, rock falls, flash floods, failure of technical equipment and so forth. However, when one critically examines the proximal causes of wilderness accidents, even those caused by such ‘objective dangers’, it is apparent that many are due to ‘human factors’ or nontechnical skills. These are broadly defined as the continuous process of identifying and avoiding the activities, interactions and decisions that may jeopardise safe and effective response to adverse events. Objective dangers and adverse events are unavoidable, but the response to them is governed by how team dynamics, leadership and followership modes, situational awareness and experience may mitigate these risks or manage their consequences effectively. On the other hand, ignoring human factors during wilderness travel is predictive of wilderness accidents. This article outlines how an awareness of human factors may be used to reduce the risks of adventure travel significantly.

S Afr Med J 2017;107(8):669-673. DOI:10.7196/SAMJ.2017.v107i8.12677

‘ Experience is what you get when you need it most.’ (Unknown origin)

Scenario

Under the leadership of Pete, a ski-mountaineering guide, a group of six skiers make an early start from the Grands Montets cable car station above Chamonix – the start of the week-long Haute Route ski tour to Zermatt in Switzerland. On the big (2 200 m) but easy descent to the Argentière glacier, differences in the skiing competencies of the team members are already noticeable. Opting to reach the Trient hut that evening in one big push, they agree to forego an early finish to the day at the nearby Argentière hut. Then, on the ascent up the Chardonnet glacier to the Col de Chardonnet, their skill differences are further pronounced by the technical challenges of doing kick turns on the steep, frozen snow. To the growing irritation of the competent Sebastian, two of the skiers, Jo and Dave, have to be shown how to use their ski crampons effectively. Reaching the Col, the team now faces one of the steepest descents on the Haute Route, usually done with a rope belay.

There is some delay while Pete explains that he wants them all to sideslip the descent while roped, but again Jo and Dave are uncertain precisely how this should be done. Sebastian then notes with agitation that the mountaintops have disappeared into cloud, and exclaims: ‘Let’s just ski down! We are wasting time!’ Pete simply ignores him.

Then, without further ado, and mumbling with clear irritation about the ‘incompetence’ of the others, Sebastian launches off the Col on his skis. He manages a few deft, tight turns in the narrow couloir, but then catches an edge and tumbles out of sight. The team looks on with shock at his abrupt action, but then shock turns to horror when Sebastian can be seen sliding to a stop on the slope below the couloir. His skis are gone, and his left leg is at an impossible angle.

A blood-curdling scream comes up from below and echoes from the

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shrouded cliffs around them, sharply emphasising the rapid change from a sunny, fun day to a grey nightmare. The Trient hut, on the other side of the Fenêtre de Saleina and the Trient glacier, now seems very, very far away …

Background

One’s first reaction is to ‘blame’ Sebastian for his ‘idiotic’ behaviour.

His needlessly impulsive act has not only caused him serious injury, but also thrust the group into a precarious situation. They need to seek urgent rescue from their remote location in rapidly deteriorating conditions, putting themselves at more risk. Yet, on reflection, perhaps one could ask: • What really caused the accident?

• Could it have been avoided?

• How? And perhaps one should think, before the outset of any wilderness trip: • Can one predict/forecast accidents or high-risk situations?

• What are those predictors?

• If recognised, how can they be mitigated?

• What specific leadership roles or actions are required to avoid risk and accidents?

• What are followership roles? How and when should followers speak up when leadership is below par?

These questions should be addressed at the outset and on an ongoing basis during all stages of any wilderness excursion. How is this done, and where do these non-objective dynamics fit into mitigation of the obvious and compelling risks of wilderness adventures?

There are at least three important and distinct sets of factors that may impact on the safety and efficiency of wilderness activities:

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environmental factors, technical skills, and non-technical skills, otherwise known as human factors (HFs). While much attention is usually paid to the first two categories (is the weather OK, how old are your ropes, what is your skill level?), the third – HFs – is often disregarded. In many, if not most, instances of serious medical problems in the wilderness, it is precisely the HFs that are most important in risk prevention and mitigation. Despite HFs being distinct from the actual ‘agents’ of accidents, such as rock falls, avalanches or a siphon in a whitewater river, they have been clearly shown to be the most common cause of accidents. A meticulous review[1] of skydiving accidents in the USA clearly showed that as many as 86% of all fatal skydiving accidents are caused by HFs, and not environmental or technical factors. This article will focus on why and how HFs are the ultimate cause of accidents, and how this knowledge can reduce risks in the wilderness environment.

Remarkably little has been written about the role of HFs in the wilderness environment,[2,3] but there is a vast literature on their causative risks in aviation[4] and more recently in healthcare.[5-7] However, unlike healthcare, in aviation and wilderness adventures practitioners share a commonality: they are personally involved in the accidents. Nonetheless, even in healthcare, behavioural factors of the practitioner or care team may be the ultimate cause of accidents.

Therefore, much of what is written on HFs in these diverse settings can be applied to causes of accidents in the wilderness.

Human failure

It is perceived that most accidents are caused by human errors, but human mistakes have a complex causality themselves. Using Fig. 1, we are able to classify Sebastian’s error as a deliberate exceptional violation (breaking the rules in an attempt to solve an acute problem) and therefore perceived with shock by his teammates. Yet we can argue that Pete could probably have avoided Sebastian’s impulsive behaviour by earlier assertive action. Pete’s fault can be classified as an inadvertent thinking error due to a knowledge-based mistake (lacking the insight and experience to recognise deteriorating circumstances).

As a guide, Pete should have known that frustration may induce irrational behaviour in some people. On the other hand, the other team members may be blamed for a rule-based inadvertent thinking error (they should have been aware that they should speak up in the absence of good leadership). Also, the team should have known that safety is not the sole responsibility of Pete as team leader. All these errors by Pete and his team members were proximal to and directly led to the collective failure in avoiding Sebastian’s ‘final’ irrational action that ‘caused’ their precarious situation.

Human errors are unavoidable (‘to err is human’), and are generally executed within a context or system that may be adapted to prevent such errors from happening in the first place. Sebastian’s error was probably avoidable, but what could have been different in the team’s context or system to predict and avoid this accident?

Is it possible, during all wilderness excursions, to monitor the nonconcrete, almost intangible HFs at work in a group? And will an acute awareness of these factors allow one to predict when risks are rising, and an accident is about to happen?

Human factors

Besides the many recognisable objective dangers of the wilderness environment and the (very rare) failure of technical equipment, there is a third causative component to consider when trying to understand why things go badly wrong: the knowledge, recognition and correct interpretation of human (or non-technical, subjective) factors.

There are several broad definitions of HFs commonly employed in various contexts:

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HUMAN FAILURE

INADVERTENT ERRORS

ACTION ERROR

Action-based

SLIP

THINKING ERROR

Memorybased

LAPSE

DELIBERATE VIOLATIONS

ROUTINE

Rule-based MISTAKE

SITUATIONAL

EXCEPTIONAL

Knowledgebased MISTAKE

SLIP (comission)

Skill-based, familiar tasks that may occur if attention is diverted momentarily

LAPSE (omission)

Resulting action is not intended: ‘not doing what you were meant to do’

RULE-BASED MISTAKE

Errors of judgement: mental processes linked to planning, information gathering, communication, etc.

KNOWLEDGEBASED MISTAKE

Action as planned, but ‘doing the wrong thing believing it to be right’

ROUTINE

Deliberate deviations from rules (violations)

SITUATIONAL

Knowingly fail to follow procedures, to save time or effort

EXCEPTIONAL

Well-meaning but misguided action to ‘get the job done’

Fig. 1. Human failure types (adapted from Health and Safety Executive[8]).

• HFs concern the interactions between people and technical components in complex systems.[6] • HFs (or ergonomics) is the scientific discipline concerned with the understanding of interactions among humans and other elements of a system, and the profession that applies theory, principles, data and methods to design in order to optimise human wellbeing and overall system performance.[9] • HFs science attempts to design systems that support human performance and are resilient to unanticipated events.[7] Even though these definitions are generic, they all share ‘the primary goal of human factors science to promote efficiency, safety and effectiveness by improving the design of technologies, processes and work systems’.[10] There is no definition of HFs specific to wilderness travel scenarios, but to be useful it should comprise both what they are and what they aim to achieve. Such a proposed definition could be that monitoring HFs is ‘the continuous process of identifying those activities and decisions during a risky wilderness endeavour that may prevent or contain human error’. Or, put in another, more practical way, that it is the continuous process of identifying and avoiding the activities, interactions and decisions that may jeopardise a safe and effective response to adverse events. HFs embody a collective habit of continuous and conscious decision-making: all actions are continuously weighed up against present as well as anticipated circumstances, and placed in the context of the team, its functioning, resources and capacity, and the external environment. This active awareness then informs critical personal and team decision-making, which is core to safety.

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Merely observing the interplay of HFs per se does not reduce human error. But by understanding how, in a risky context, HFs allow serious human errors to happen, timely systemic and behavioural safeguards may be introduced. It recognises the need to have checks and balances in place that will diminish those errors, or possibly mitigate their effects if and when they occur.

Broadly speaking, HFs can be grouped into three broad categories: 1. The interpersonal skills of teamwork, leadership and communication 2. The cognitive skills of situational awareness and decision-making 3. The psychophysiology of stress and fatigue.

There are said to be more than 300 HFs, but the so-called ‘Dirty Dozen’ (Table 1), originally developed for aircraft maintenance crews,[11] are readily transferable to the context of wilderness activities. Most are self-evident, but unless explicitly introduced to the members of a team, and then continuously monitored during the activities of the team, any one or a combination of these factors indicates imminent systemic failure. How then is the awareness of these factors made to function in reality, to improve safety for everyone?

Team building

Central to the effective implementation of HFs is the concept of working as a team, which relies on the awareness of HFs by all team members, from the leader to the least experienced, to become a strong team. But how is a strong team different from an informal group? Teams are synergistic entities, with mutiple and diverse skill inputs bonded by a team ethic that makes them cohesively responsive to dynamic demands. Table 2 outlines the characteristics that distinguish groups from teams.

A critical component of the success of team building and functioning lies in the balance between leadership and followership.

Leadership

One of the overarching roles of a leader is to bond an informal group of people into a team to serve a common purpose. In wilderness adventures, that purpose is to enhance safety and to avoid risk and error. The evolution from an informal group to a structured team Table 1. The ‘Dirty Dozen’ human factors[11] 1. Lack of communication

5. Complacency

9. Lack of knowledge

2. Distraction

6. Lack of teamwork

10. Fatigue

3. Lack of resources

7. Pressure

11. Lack of assertiveness

4. Stress

8. Lack of awareness

12. Norms

should be engaged in and facilitated as soon as possible – as an explicit activity.

To create an effective team, it is necessary that the following 10 aspects, as appropriate, are introduced by the team leader, then discussed, clarified, agreed upon and understood by all team members before the activity starts:[11] 1. A clearly defined and maintained aim, or goal 2. Each team member’s roles and responsibilities 3. Communication methods 4. Limitations and boundaries of team and individual action 5. Emergency procedures 6. Individual expectations and concerns 7. What defines a successful outcome 8. Debriefing arrangements 9. Team dismissal arrangements 10. Opportunities for questions and clarification.

Followership

On the other hand, members of the group need to actively engage in followership. Followership is the willingness and capacity of all individuals in a group to actively follow the leader of that group.

Importantly, however, followership is not the passive acceptance of guidance, but rather a constructively critical and engaged involvement in making a success of the aims of the team by:[13] 1. Actively questioning and evaluating the mission progress 2. Analysing the overall situation 3. Continuously revising one’s personal understanding of the mission based on these evaluations and analyses 4. Using assertive but constructive behaviour when necessary 5. Making suggestions 6. Providing relevant information without being asked 7. Asking questions as necessary 8. Confronting ambiguities 9. Stating opinions on decisions/procedures 10. Refusing unreasonable requests.

The best teams in a wilderness context are characterised by ‘leaderless leadership’ (J H Graafland, unpublished Mountain Club of South Africa Mountain Leadership Course Notes, undated, available from MCSA (Cape Town Section), Hatfield Street, Cape Town, email mcsacapetown@iafrica.com). This occurs when the climate is created for a team to function efficiently without the need for continuous reliance on the team leader. In this role, the team leader’s functions are similar to those of a conductor of fully engaged members of an orchestra. Team members may be skilled in very different ways, but they all contribute variously to a cohesive successful outcome. This is in stark contrast to ‘groupthink’,[14] which is the custom in many groups of thinking or making decisions

Table 2. Characteristics that distinguish an informal group from a strong team (adapted from Chand[12]) Informal GROUPS

Strong TEAMS

Lack of previous opportunity to engage in collective work requiring joint effort

Members work with both individual and mutual accountability, implementing complementary skills

Lack of positive synergy to create solutions to complex problems

Evidence of positive synergy: • bounce ideas off one another • correct one another’s mistakes • apply diverse knowledge base to problems • accomplish work too difficult for any individual to achieve

Parallel performances not greater than the sum of individual inputs

Performances overlap to become greater than sum of individual inputs

Less responsive to dynamic environments

Flexible response to dynamic environments

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by consensus in a way that discourages creativity or individual responsibility, usually to avoid disharmony and conflict. However, in the ‘leaderless’ group, differing opinions and options are compared by frank discussion to reach a best solution. The discussion is guided by the team leader, who holds team members’ opinions in the same regard as his or her own.

Situational awareness

Each team member experiences the demands and challenges of the wilderness environment in different ways, and some may therefore recognise circumstances leading to human error before other, even very experienced, team members. The ability to sense ‘trouble brewing’ before the trouble occurs – to trust and act on gut feel – is called situational awareness (SA).

SA is a skill learned by experience, and is defined as ‘the perception of the elements in the environment within a volume of time and space, the comprehension of their meaning, and the projection of their status into the near future’[15] – in other words, it is the degree of the accuracy of one’s perception of environmental reality. It is about every team member monitoring the ‘team-in-the-environment’ so that potential problems will be detected and corrected before they escalate. SA is the skill of anticipating future contingencies based on the knowledge of the past (experience) and the present (awareness), and then projecting current circumstances into the future.

Fig. 2 illustrates the concept of heightened team SA. In a team of four, each member will have a differing SA of a complex and dynamic process or environment. When all team members are actively situationally aware (A), the intersection of their awareness raises the team’s shared or ‘distributed’ SA to very high levels (the red kite). This is an example of the synergistic effect of good team functioning, which significantly mitigates risk. Yet, as soon as one or two team members are distracted (e.g. No. 4 in team B, who has a slight effect on No. 3), the combined team SA is seriously diminished (the red splinter).

Conclusion: The importance of HFs to mitigate risk

Risk avoidance relies firstly on adequate levels of experience, ability and competence of team members to deal with current circumstances and recognise potential problems. Secondly, risk avoidance relies on a team understanding that the norm is to communicate any concerns to the team and its leader with assertiveness. Poor knowledge and understanding of potential risks, poor team communication, and the pressure to avoid delays may discourage competent followership.

Complacency, distraction and fatigue are widely variable personal

Fig. 2. Team situational awareness in a focused team (A: red kite) and a less focused team (B: red splinter). (Figure developed from an idea of Endsley.[15])

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characteristics that blunt awareness and generate team stress, which handicaps the teamwork required to maintain SA. The maintenance of shared SA is a powerful resource to reduce risk and it, in turn, is directly dependent on these HFs. Ignorance of the influence of HFs will predictably jeopardise optimal team functioning: in a team that is not responsive to the dynamic wilderness environment, SA is significantly weakened, allowing risks to escalate dangerously. In contrast, if attention is paid to the HFs that shape a team, it is possible to avoid or minimise the risk of wilderness accidents.

Finally, when dealing with risk in complex systems, it is worth noting that experience is inferior to currency. Recent exposure to all the demands of the activity is more valuable to the efficient assessment of and response to high-risk events than experience only. We often assume (incorrectly) that activity is thoughtdirected, i.e. proactive rather than reactive. In reality, most activity is simply reactive and little or no attempt is made to think first, particularly in experienced team members. Reactive behaviour is firstly based on old value systems and personal perceptions. More importantly, the second driver of reactive behaviour is experience and the failure to recognise that past performance is not a measure of future success. Experience tends to shoehorn new situations into old solutions. High-risk situations demand experts with currency to devise novel approaches, every time: old skills, but requiring inventive solutions! (Duncan Nel, leadership consultant – personal communication, May 2017.)

Deconstructing the scenario: Comments to illustrate the practical application of HFs

1. Under the leadership of Pete, an experienced ski-mountaineering guide, a group of six skiers …

There is adequate time, but no attempt is made at the outset to begin to create a cohesive team from the informal group by a thorough pre-depature briefing.

2. … there are noticeable differences in the skiing competencies of the team members.

Obvious skill differences are not a problem as long as they are within the skill levels required to complete the Haute Route. If explicitly assessed, they may create opportunities for a team to address and enhance the skills of all, especially those who are less skilled – a shrewd tool to create team cohesion. Awareness and acknowledgement of differing levels of skill is important – this allows focus on, compensation for and explicit acceptance of lower levels of skill by all team members, and cognisance of a potential Achilles heel: recognition of the fact that in highrisk environments the group will perform to the level of its least competent member.

3. … they agree to forego an early finish to the day at the nearby Argentière hut.

Not stopping at the first hut fosters an atmosphere of time pressure, while compromised decision-making skills by fatigued bodies and minds increase the risk of accidents. In contrast, by stopping early, the extra time would offer the opportunity to forge team bonds, and further assess different skill levels in the stress-free ambiance of the hut’s safer environment.

4. … their skill differences are further pronounced by the technical challenges …

An opportunity is missed to replan progress and spend time to teach and demonstrate the special skills required on the difficult glacier terrain, and then descend back to the Argentière hut. This strategy will also validate and reinforce the acceptance of justified delays in progress.

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5. To the further irritation of the competent Sebastian, two of the skiers, Jo and Dave, have to be shown how to use their ski crampons effectively.

This is an opportunity to engage the skilled Sebastian to instruct those who are less skilled, thereby positively redirecting his frustration. An earlier open acknowledgement of lower levels of skill of some team members would have reduced Sebastian’s expectations of the group, thereby reducing his frustration at the lack of prowess and progress.

6. There is some delay while Pete explains that he wants all to sideslip the descent while roped, but again Jo and Dave are uncertain precisely how this is done.

Pete could have defused Sebastian’s frustration further by asking him to assist in demonstrating how one sideslips while belayed by a rope. One of the more skilled skiers could have done the belaying, thereby further engaging the other team members.

7. … the mountaintops have disappeared into cloud …

Clearly, there is a lack of situational awareness. The poor weather is only noted when faced by a tricky descent, a delay is mandatory and stress levels have increased.

8. Pete simply ignores him.

A demonstration of poor leadership skills – Pete’s failure to deal with Sebastian’s frustration is a recipe for disaster that destroys team cohesion. … with clear irritation about the ‘incompetence’ of the others, 9.

Sebastian launches off the Col …

Driven by frustration, Sebastian takes matters into his own hands.

Harnessing his energy and drive earlier would have strengthened the team significantly. Even before the accident, the team needed to face a decision: to continue, or ski back down to the Argentière hut.

On calm reflection by the team, they probably would have opted to turn back. Had Pete stopped the party and actively invited the opinions of other party members to gain consensus on a change of plan, Sebastian could have contributed to the discussion/consensus and Pete could have gained collective ‘buy-in’. Such a considered decision bonds a team well.

37

10. The team looks on with shock at his abrupt action …

The team has been passively guided so far, making no spontaneous contributions until Sebastian is driven to an extreme decision.

Team co-operation and active followership have not been established, and the team will now be harshly tested. Building an adequate response with a non-cohesive group-thinking team in this situation will be very difficult, and the risks to all have now escalated severely. ‘ Good judgement is the result of experience and experience the result of bad judgement.’ (Mark Twain) 1. Hart CL, Griffith JD. Human error: The principal cause of skydiving fatalities. J Hum Perform Extrem Environ 2003;7(2), Article 2. http://dx.doi.org/10.7771/2327-2937.1027 2. McCammon I. Human factors in avalanche accidents: Evolution and interventions. In: Schweizer J, Gansner C, eds. International Snow Science Workshop. 27 September - 2 October 2009, Davos, Switzerland. Programme and Abstracts. Birmensdorf: Swiss Federal Institute for Forest, Snow and Landscape Research, 2009:644-648. http://www.wsl.ch/dienstleistungen/publikationen/pdf/9893. pdf (accessed 19 June 2017).

3. Wickens CD, Keller JW, Shaw C. Human factors in high-altitude mountaineering. J Hum Perform Extrem Environ 2015;12(1), Article 1. http://dx.doi.org/10.7771/2327-2937.1065 4. Friedman MP, Carterette EC. Human Factors in Aviation. San Diego, Calif.: Academic Press, 2014.

5. Catchpole K. Spreading human factors expertise in healthcare: Untangling the knots in people and systems. Qual Saf Health Care 2013;22(10):1-5. http://dx.doi.org/10.1136/bmjqs-2013-002036 6. Catchpole K, Goldman A, Lyons M, Maran N, Shearer H, Rogers H. Human Factors Training in the National Health Service: A Scoping Study. Leeds, UK: NHS Institute for Innovation and Improvement, 2010.

7. Scanlon MC, Karsh BT. Value of human factors to medication and patient safety in the intensive care unit. Crit Care Med 2010;38(6 Suppl):S90-S96. DOI: 10.1097/CCM.0b013e3181dd8de2 8. Health and Safety Executive (UK). Understanding human failure. http://www.hse.gov.uk/ construction/lwit/assets/downloads/human-failure.pdf (accessed 9 May 2017).

9. Wikipedia. Human factors and ergonomics. https://en.wikipedia.org/w/index.php?title=Human_ factors_and_ergonomics&oldid=778376557 (accessed 9 May 2017).

10. Russ AL, Fairbanks RJ, Karsh B-T, Militello LG, Saleem JJ, Wears RL. The science of human factors: Separating fact from fiction. BMJ Qual Saf 2013;22(10). http://dx.doi.org/10.1136/ bmjqs-2012-001450 11. Skybrary: The single point link to aviation safety knowledge. The Human Factors ‘Dirty Dozen’. http://www.skybrary.aero/index.php/The_Human_Factors_%22Dirty_Dozen%22#cite_note-3 (accessed 9 May 2017).

12. Chand S. Group dynamics: Its characteristics, stages, types, factors, team building and other details. http://www.yourarticlelibrary.com/management/group-dynamics-its-characteristics-stages-typesand-other-details-management/5363/ (accessed 4 May 2017).

13. Shimanski C. Situational Awareness in Search and Rescue Operations. Training manuscript of the Colorado Mountain Rescue Team. Denver, Colo.: Mountain Rescue Association, 2015.

14. Wikipedia. Groupthink. https://en.wikipedia.org/w/index.php?title=Groupthink&oldid=775857382 (accessed 11 May 2017).

15. Endsley MR. Toward a theory of situation awareness in dynamic systems. Hum Factors J Hum Factors Ergon Soc 1995;37(1):32-64. http://dx.doi.org/10.1518/001872095779049543

August 2017, Print edition

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

IN PRACTICE

HEALTHCARE DELIVERY

A retrospective study evaluating the efficacy of identification and management of sepsis at a district-level hospital internal medicine department in the Western Cape Province, South Africa, in comparison with the guidelines stipulated in the 2012 Surviving Sepsis Campaign R Bhikoo,1 MB ChB; S Versfeld,1 MB ChB; M M De V Basson,1 MB ChB, Hons BSc (Epidemiol), MMed (Int Med); A H Oosthuizen,2 MB ChB (Cum Laude), Dip PEC (SA), MMed EM, FCEM (SA) 1 2

Department of Internal Medicine, Karl Bremer Hospital, Cape Town, South Africa Department of Emergency Medicine, Karl Bremer Hospital, Cape Town, South Africa

Corresponding author: R Bhikoo (raisa3121@gmail.com) Background. Currently there is little information on the identification, management and outcomes of patients with sepsis in developing countries. Simple cost-effective measures such as accurate identification of patients with sepsis and early antibiotic administration are achievable targets, within reach without having to make use of unsustainable protocols constructed in developed countries.

Objectives. To assess the ability of clinicians at a district-level hospital to identify and manage sepsis, and to assess patient outcome in terms of in-hospital mortality and length of hospital stay given the above management.

Methods. A retrospective descriptive study design was used, analysing data from the routine burden of disease audit done on a 3-monthly basis at Karl Bremer Hospital (KBH) in the Western Cape Province, South Africa.

Results. The total sample size obtained was 70 patients, of whom 18 (25.7%) had an initial triage blood pressure indicative of sepsis-induced hypotension. However, only 1 (5.5%) of these 18 patients received an initial crystalloid fluid bolus of at least 30 mL/kg. The median time that elapsed before administration of antibiotics in septic shock was 4.25 hours. Furthermore, a positive delay in antibiotic administration (p=0.0039) was demonstrated. The data also showed that 8/12 patients (66.7%) with septic shock received inappropriate amounts of fluids.

The in-hospital mortality rate for sepsis was 4/24 (16.7%), for severe sepsis 11/34 (32.3%) and for septic shock a staggering 9/12 (75.0%).

Conclusions. The initial classification process and management of sepsis by clinicians at KBH is flawed. This inevitably leads to an increase in in-hospital mortality.

S Afr Med J 2017;107(8):674-678. DOI:10.7196/SAMJ.2017.v107i8.11019

Sepsis, as defined by the Surviving Sepsis Campaign (SSC) in 2012,[1] is the presence of a probable or documented infection together with systemic manifestations of an infection.

In 2004, the World Health Organization[2] listed three infective causes, namely lower respiratory tract infection, diarrhoeal disease and tuberculosis, on their top ten list of causes of death, which is similar to mortality reports documented in the 2013 Western Cape Mortality Profile.[3] This highlights the fact that sepsis and its sequelae – which were originally caused by an infection – are major contributors to the local and global burden of disease.

To date there are virtually no accurate data on the incidence and prevalence of or mortality rates for sepsis, severe sepsis and septic shock in developing countries. Mortality rates have been reported to be as high as 30% for sepsis, 40% for severe sepsis and 80% for septic shock[4-6] in developed countries. Septic shock is still the leading cause of death in intensive care units worldwide. [5] Data from developed countries show a continuous increase in the incidence of sepsis, further emphasising the need to review management protocols in order to reduce morbidity and mortality.

In developed countries, the implementation of protocols for the identification of sepsis and for its management have contributed to a decline in mortality rates.[7] In low-income countries, prob­

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lems such as access to healthcare, cost constraints, lack of resources and delayed presentation of patients with sepsis make it difficult to implement protocols based on the patient profile of developed countries. In sub-Saharan Africa there has therefore been a widespread shift towards the development of cost-effective protocols specifically suited to the local epidemiological and ecological characteristics. [8,9] In 2006, a Ugandan-based prospective study assessed the management and outcomes of hospitalised patients with severe sepsis syndromes. Approximately 85% of their sample were HIV-positive. Factors contributing to mortality included inadequate fluid administration, lack of uniformity in administration of antibiotics appropriate to the source of sepsis, and delay in antibiotic administration.[8] A follow-up prospective study was done in 2008 using the previous study as the observation cohort.

Interventions included early appropriate antibiotic and intravenous fluid administration. Mortality at 30 days was significantly lower in the intervention cohort compared with the observation cohort, leading to the conclusion that simple and inexpensive management can improve outcome.[8,9] Currently no data are available regarding sepsis management in our unique setting in South Africa (SA). We hope to pilot the way for further research in this field.

August 2017, Print edition

IN PRACTICE

Objective

The primary objective was to determine the efficacy of sepsis identification and management by clinicians at Karl Bremer Hospital (KBH), a large district-level hospital in Cape Town, SA. Furthermore, we aimed to determine the demographics of patients presenting with sepsis, the burden of sepsis and its management, and mortality rates and length of hospital stay among patients admitted. Key determinants of efficacy were assessed using guidelines outlined in the SSC[1] as a means of comparison. The SSC, initially published in 2004, reviewed data on the management of severe sepsis and septic shock. The recommendations are intended to be best practice and not standard of care.

Methods Setting

KBH is a large district-level hospital with a total of 310 beds, servicing an average of 11 000 patients per month. The estimated total cost per patient per day is ZAR2 105.90 for a ward admission. However, ~72% of the patients are classified as earning either no income or <ZAR3 000 per month, and are therefore not obliged to pay the full fee. A fourbed high-care unit shared by all the departments is able to manage ventilated patients. However, if a prolonged high-care admission is anticipated, the patient will need to be transferred to a fully equipped intensive care unit managed by a dedicated team at a tertiary facility I. Sepsis Widespread systemic manifestations due to the existence of an infection. The systemic manifestations could be any of the following (adapted from SSC[1]): General variables: • Fever (>38.3°C) • Hypothermia (core temperature <36°C) • Heart rate >90 bpm • Tachypnoea, respiratory rate >25/min • Altered mental status • Significant oedema or positive fluid balance (>20 mL/kg over 24 h) • Hyperglycaemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in the absence of diabetes Inflammatory variables: • Leukocytosis (white cell count >10 × 109/L) or leukopenia (white cell count <4 × 109/L) • Plasma C-reactive protein >4 mg/L Haemodynamic variables: • Arterial hypotension (systolic blood pressure <90 mmHg, mean arterial pressure <70 mmHg) Organ dysfunction variables: • Arterial hypoxaemia (PaO2/FiO2 ratio <300) • Acute oliguria (urine output <0.5 mL/kg/h for at least 2 h despite adequate fluid resuscitation) • Raised creatinine (>44.2 µmol/L) • Coagulation abnormalities (INR >1.5 or aPTT >60 s) • Ileus (absent bowel sounds) • Thrombocytopenia (platelet count <100 × 109/L) • Hyperbilirubinaemia (plasma total bilirubin >22 µmol/L)

such as the nearby Tygerberg Hospital. Additionally, the emergency department (ED) at KBH has three resuscitation beds.

Study design

A retrospective descriptive study design was used. The internal medicine department at KBH performs a routine burden of disease audit on a 3-monthly basis. Data for the audit are obtained from triplicate discharge letters, hospital transfer notes and death certification summaries containing all relevant information on the patient’s hospital stay, from admission to discharge or death. Data from the burden of disease audit for November 2015 - January 2016 were reviewed. For a patient to be selected for the study, the data from the audit sheet had to state any one of the key words ‘sepsis’, ‘severe sepsis’ or ‘septic shock’ as the diagnosis at discharge or death. The suspected or confirmed infection had to have been present at ED presentation for the patient to qualify for the study. Data were assessed using a data collection sheet compiled by the authors that focused specifically on clinical and blood gas measurements that could be used in the ED to classify patients as having sepsis, severe sepsis or septic shock. Time to first-dose antibiotics (grade 1B evidence based on the SSC[1]), source-appropriate antibiotics (grade 1B), amount of intravenous fluids (grade 1C) and arterial blood gas/lactate measurement were also assessed.

Once the data were obtained, we retrospectively classified patients into the sepsis, severe sepsis or septic shock groups based on the II. Severe sepsis Sepsis PLUS acute organ dysfunction or tissue hypoperfusion.

Sepsis-induced hypotension: • Systolic blood pressure <90 mmHg, or • Mean arterial pressure <70 mmHg, or • Systolic blood pressure decrease >40 mmHg Organ dysfunction variables: • Arterial hypoxaemia (PaO2/FiO2 ratio <300) • Acute oliguria (urine output <0.5 mL/kg/h for at least 2 h despite adequate fluid resuscitation) • Raised creatinine (>45 µmol/L) • Coagulation abnormalities (INR >1.5 or aPTT >60 s) • Ileus (absent bowel sounds) • Thrombocytopenia (platelet count <100 × 109/L) • Hyperbilirubinaemia (plasma total bilirubin >22 µmol/L) Tissue perfusion variables: • Hyperlactataemia (>1 mmol/L) • Decreased capillary refill or mottling III. Septic shock Severe sepsis PLUS evidence of tissue hypoperfusion not reversed with effective fluid resuscitation.

Sepsis-induced tissue hypoperfusion: Blood lactate concentration >4 mmol/L OR Sepsis-induced hypotension (as above)

Tissue perfusion variables: • Hyperlactataemia (>1 mmol/L) • Decreased capillary refill or mottling Fig. 1. Definitions used for the classification of sepsis. (SSC = Surviving Sepsis Campaign; PaO2 = partial pressure of arterial oxygen; FiO2 = fractional inspired oxygen; INR = international normalised ratio; aPTT = activated partial thromboplastin time.)

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August 2017, Print edition

IN PRACTICE

information that had been available to the casualty doctor at the time of presentation. Definitions used for the classification of sepsis are set out in Fig. 1.

Statistical analysis

All data collected were captured onto a Microsoft Excel database, version 2013 (Microsoft, USA). Data analysis was done in Microsoft Excel, version 2013, and statistical analysis in Statistica, version 12 (StatSoft, USA). The level of statistical significance was set at p<0.05.

The sign test was used to compare descriptive variables. To assess for data association, logistical regression testing and negative binomial regression testing were performed, with the data then being presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Ethics approval

Ethics approval was obtained from the Health Research Ethics Committee at the Stellenbosch University (ref. no. N15/10/103).

Furthermore, no patient who had an initial lactate level measured had a repeat level measured to assess lactate clearance or fluid responsiveness.

As a result, many patients who should probably have been classified as having septic shock were classified as having severe sepsis based on adherence to definitions. A total of 18/70 patients (25.7%) had an initial triage blood pressure indicative of sepsis-induced hypotension, but only 1/18 (5.6%) of these received an initial crystalloid fluid bolus of at least 30Â mL/kg and subsequent immediate blood pressure recheck for 6% 15% fluid responsiveness. Furthermore, 6/18 patients (33.3%) had no initial 3%

15%

3%

6% 3%

6% 3% 6% 3% 3%

Results

Of the 1â&#x20AC;&#x201E;000 patients reviewed in the burden of disease audit, 70 (7.0%) were included in the study. Of the 70 patients, 34 (48.5%) were male and 36 (51.4%) were female. The overall mean (standard deviation (SD)) age of patients presenting with a sepsis syndrome was 48 (9.5) years (minimum 17, maximum 85). A total of 25 patients (35.7%) were HIV-positive. The most common infective cause for sepsis identified by emergency personnel, across all the grades, was a lower respiratory tract infection. Not surprisingly, diarrhoeal disease/ acute gastroenteritis was the second most common diagnosis made (Figs 2 - 4).

Based on the data collection and subsequent sepsis subgrouping, evaluated using the initial information available to the casualty doctor, 24/70 patients (34.2%) were classified as having sepsis, 34/70 (48.6%) as having severe sepsis and 12/70 (17.1%) as having septic shock.

However, 18/24 (75.0%) of patients with sepsis, 8/34 (23.6%) with severe sepsis and 3/12 (25.0%) with septic shock did not have their arterial blood gas or lactate level measured at initial presentation.

4%

4%

64% 64% Acute gastroenteritis Bacterial meningitis Lower respiratory tract infection Acute gastroenteritis Malaria Bacterial meningitis Nosocomial sepsistract (ceftriaxone Lower respiratory infectionresistant) Unknown Malaria source Urinary tractsepsis infection Nosocomial (ceftriaxone resistant) Unknown source Urinary tract infection

Fig. 3. Suspected sources of severe sepsis.

9%

4%

17% 25%

8%

17% 25% 8%

8% 8%

63%

Acute gastroenteritis

50%

Bacterial meningitis Infective endocarditis Lower respiratory tract infection

Acute gastroenteritis

Nosocomial sepsis (ceftriaxone resistant)

Lower respiratory tract infection

Unknown source

Nosocomial sepsis (ceftriaxone resistant) Acute gastroenteritis

Urinary tract infection

Unknown source tract infection Lower respiratory Nosocomial sepsis (ceftriaxone resistant)

Fig. 2. Suspected sources of sepsis.

Fig. 4. Suspected sources of septic shock.

Unknown source

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August 2017, Print edition

50%

IN PRACTICE

No antibiotic

3

Gentamicin

1

Metronidazole

1

Antibiotic

Ertapenem Ciprofloxacin

3

2 1

Ceftriaxone + metronidazole

1

Ceftriaxone + cloxacillin

1

Ceftriaxone Azithromycin

1

3

3

Co-amoxiclav Ampicillin + gentamicin

11 1

24

3

1 16

1 1

1 0

5

10

15

20

25

30

35

40

Patients receiving antibiotic, n Bacterial meningitis Malaria Urinary tract infection

Acute gastroenteritis Lower respiratory tract infection Unknown source

Infective endocarditis Nosocomial sepsis (ceftriaxone resistant)

Patients, %

Fig. 5. Antibiotics prescribed during the first 24 hours after presentation.

90 80 70 60 50 40 30 20 10 0

83%

75%

68%

66%

34%

32%

25%

17%

Sepsis

Severe sepsis Alive

Septic shock

Total

Deceased

Fig. 6. In-hospital mortality rates for sepsis, severe sepsis and septic shock.

arterial blood gas or lactate level measured, so we had no way of knowing whether the patient was initially classified as having severe sepsis or septic shock, forcing us to assign patients to the severe sepsis group.

The antibiotic most frequently prescribed for sepsis, across all the grades, was ceftriaxone (Fig. 5). Bearing in mind the literature review[1] mentioned above regarding source-appropriate antibiotics, 55/70 patients (78.5%) were considered to have received the correct antibiotics for the respective source. However, no HIVpositive patient in the study received cover for Mycobacterium tuberculosis or Pneumocystis jiroveci pneumonia during the first 24 hours after presentation to hospital, despite the clinician having a documented suspicion thereof.

Interestingly, it is also important to note that 7/70 (10.0%) of the patients received no antibiotics during the first 24 hours after presentation, despite being identified by the casualty doctor as having a possible infective cause for their clinical symptoms. In these cases, the probable cause of sepsis was equally distributed between acute gastroenteritis and an unknown source. Of these patients, 3/7 (42.9%) could be classified as having septic shock based on the initial lactate level.

The median time that elapsed before administration of antibiotics during the first 24 hours after presentation, across all grades of sepsis, was 3.63 hours for sepsis (range 1.67 - 10.30), 1.58 hours for severe sepsis (range 1.00 - 2.83) and 4.25 hours for septic shock (range 1.00 - 23.98). Here it is important to note that the above are times from consultation with the attending doctor to antibiotic administration, which depending on how long patients had to wait to see a doctor, may differ considerably from the times from initial presentation at the emergency department to receiving an antibiotic. Unfortunately the latter could not be assessed because initial presenting times were not documented. To assess whether antibiotics were given within the 3-hour time frame for sepsis and severe sepsis, the sign test was used to extrapolate the data. The results showed that there was no delay in antibiotic administration for sepsis or severe sepsis (p=0.2706 for sepsis and p=0.9997 for severe sepsis), bearing in mind that the 3-hour mark was used as the cut-off for optimal time to initial antibiotic administration. For septic shock, however, a cut-off of 1 hour was used for optimal time

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August 2017, Print edition

to antibiotic administration, and here the sign test showed a positive delay in antibiotic administration (p=0.0039).

With regard to the early appropriate intravenous fluid administration discussed above, the data showed that 5/24 (20.8%) of patients with sepsis, 8/34 (23.6%) with severe sepsis and 8/12 (66.7%) with septic shock received inappropriate amounts of fluids. As mentioned above, only one patient received an initial fluid bolus of at least 30 mL/kg for sepsis-induced hypotension. Pearson’s χ2 test showed a positive association between septic shock and inappropriate intravenous fluid administration (p=0.009). Furthermore, the proportion of patients with septic shock who received appropriate intravenous fluids was less than half the proportions in the sepsis and severe sepsis groups. As mentioned above, no patient in our study had repeat arterial blood gas measurements to assess lactate clearance, a marker of response to therapy. Also, no invasive measures such as central venous pressures or arterial line blood pressure readings were used to assess fluid responsiveness optimally during the first 24 hours of management.

Overall, the outcome of patients in the study was determined by discharge or in-hospital mortality, the in-hospital mortality rate for sepsis being 4/24 (16.7%), that for severe sepsis 11/34 (32.3%) and that for septic shock a staggering 9/12 (75.0%) (Fig. 6). The mean (SD) age of the patients who died, across all sepsis syndromes, was 53 (9.5) years. The mean length of stay for all sepsis syndromes was 6.3 (2.3) days.

Logistic regression testing to investigate for possible associations between in-hospital mortality rates and various sepsis management principles revealed a positive association between in-hospital mortality and the following: • Time to first dose of antibiotic (OR 1.07, 95% CI 1.01 - 1.14; p=0.027). For every 1 hour’s delay in antibiotic administration, the chance of death increased by 7%.

• Source-appropriate antibiotics (OR 0.17, 95% CI 0.05 - 0.59; p=0.005). The chance of death for patients who received sourceappropriate antibiotics was 83% less than for those who did not.

• Early appropriate administration of intravenous fluid (OR 0.33, 95% CI 0.11 - 0.95; p=0.040). Appropriate intravenous fluids were associated with a 67% reduction in in-hospital mortality.

Discussion

The findings reported above reflect clear faults in the identification of sepsis at KBH and its resultant suboptimal management.

IN PRACTICE

Evidence to support poor recognition of sepsis syndromes includes lack of adequate fluid boluses for patients who met the definition for hypotension at admission, indicating that clinicians did not recognise the importance of hypotension as a clinical indicator of organ dysfunction in sepsis. Clinicians at KBH do not have access to laboratory results for a minimum of 12 hours after a consultation and are therefore forced to use their clinical judgement regarding the severity of disease, aided by blood pressure monitoring, urine output and blood gas measurement for lactate, and partial pressure of arterial oxygen/fractional inspired oxygen ratios to assess fluid responsiveness and organ dysfunction. Further evidence of inadequate identification of sepsis are the 3/7 patients who could be classified as having septic shock on the basis of the initial blood gas lactate measurement but did not receive antibiotics for the first 24 hours after presentation. This indicates a poor understanding of the effect of delayed antibiotic administration on mortality rates related to sepsis. The overall median time to initial antibiotic administration was 4.25 hours for septic shock v. 1.58 hours for severe sepsis. Because these three patients were included in the count for patients with septic shock, the median time to initial antibiotic administration in this subgroup increased significantly.

Kumar et al.[6] showed a 7.6% decrease in survival for every 1 hour’s delay in antibiotic therapy over the ensuing 6 hours. Similarly, we found a 7% increase in mortality for every hour’s delay in antibiotic administration. As mentioned above, the median time to the first dose of antibiotic was measured as the time from consultation with a doctor to initial antibiotic administration. The minimum waiting time in the ED from arrival at the hospital to doctor consultation is 45 - 60 minutes. None of the patients managed, regardless the grade of sepsis, are therefore achieving the targets of the 3-hour bundle and 1-hour administration time frames. This can be attributed to both poor identification, as discussed above, and resource limitations.

The nursing staff in the ED who are responsible for drug and fluid administration often oversee the management of 10 - 20 patients at a time, which makes it difficult for them to perform important tasks timeously. Bed constraints and lack of resuscitation room availability mean that severely ill patients often lie in the general ED area where there is no appropriate monitoring.

In our study, not receiving source-appropriate antibiotics had a positive association with mortality. Leibovici et al.[10] showed that survival improved when empirical antibiotic treatment matched the in vitro susceptibility of the likely pathogen. The concern in this regard is that we have limited evidence regarding source-appropriate antibiotics in an environment with a high prevalence of HIV infection. Infective aetiologies in sub-Saharan Africa differ from those reported in the SSC guidelines,[1] and in fact certain studies reviewed by the SSC committee excluded HIV-positive patients, giving rise to the questions which are the early source-appropriate antibiotics that should be administered given the unique sub-Saharan African environment, and what the effect on outcome is in HIV-positive patients.

Appropriate intravenous fluid administration is a further area for debate in the HIV-prevalent SA setting. The studies in Uganda and Zambia[8,9,11] reported concerns that in such a setting, large fluid boluses could worsen respiratory failure. However, we found a 67% reduction in in-hospital mortality with appropriate intravenous fluid administration. Again, lack of appropriate monitoring in the ED makes appropriate fluid administration difficult, as patients receiving large fluid boluses run the risk of becoming fluid overloaded unless they are adequately monitored.

Recommendations

It is evident that education for all healthcare providers involved in the identification and management of sepsis is necessary. Formulation of

42

a suggested process, perhaps in the form of a sepsis check sheet, could lead to improved management. Re-evaluation of outcomes in the form of length of hospital stay and in-hospital mortality will be necessary in order to evaluate the impact of such a process. Further areas that need attention are earlier availability of laboratory results, which aids decision-making, and more doctors in the ED to decrease waiting time.

Conclusions

The main aim of our study was to evaluate identification and management of the sepsis syndromes at a district-level hospital in the Western Cape. We concluded that the initial classification of sepsis, severe sepsis and septic shock by our clinicians is flawed. This is largely due to lack of understanding on the part of medical personnel of the clinical evidence needed to support the classification process.

This clinical evidence does not depend on delayed laboratory results, but on basic examinations and investigations available in the ED. Priorities in the management of the sepsis syndromes include early source-appropriate antibiotics and early appropriate intravenous fluid administration. These should be the cornerstones of management, and can be instituted regardless of resource availability. Finally, it is evident that additional research is needed in the field of sepsis identification and management in a resource-limited setting. However, basic management principles can nevertheless be implemented, with the potential for an enormous impact on patient survival.

Acknowledgements. Special thanks to Dr Zirkia Joubert and all the internal medicine medical officers at KBH for granting us the time we needed to work on this study, as well as for all their assistance with patient identification and data collection. We thank Mr M T Chirehwa for the data analysis and his subsequent interpretation of the statistical outcomes.

Finally, we thank Mr Iesrafeel Jakoet and Mr Brendon Versfeld for all their help with the write-up and editing of the article.

Author contributions. RB: primary author, literature review, data collection, interpretation and write-up; SV: assisted in data collection and write-up; MMDeVB and AHO: supervisors. All the authors consented to the publication of the article.

Funding. None.

Conflicts of interest. None.

1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2012;41(2):580-637. https:/doi. org/10.1097/CCM.0b013e31827e83af 2. World Health Organization. The Global Burden of Disease: 2004 Update. 2008. http://www.who.int/ healthinfo/global_burden_disease/2004_report_update/en/index.html (accessed 16 February 2017).

3. Morden E, Groenewald P, Zinyakatira N, et al. Western Cape Mortality Profile 2013. Cape Town: SA Medical Research Council, 2016. http://www.mrc.ac.za/bod/WC2013MortalityReport.pdf (accessed 27 June 2017).

4. Catenacci MH, King K. Severe sepsis and septic shock: Improving outcomes in the emergency department. Emerg Med Clin North Am 2008;26(3):603-623. https:/doi.org/10.1016/j.emc.2008.05.004 5. Degoricija V, Sharma M, Legac A, et al. Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital: Impact of intensive care unit performance and antimicrobial therapy.

Croat Med J 2006;47(3):385-397.

6. Kumar G, Kumar N, Taneja A, et al. Nationwide trends of severe sepsis in the 21st century (2000 - 2007).

Chest 2011;140(5):1223-1231. https:/doi.org/10.1378/chest.11-0352 7. Kaukonen KM, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000 - 2012. JAMA 2014;311(13):1308-1316. https:/ doi.org/10.1001/jama.2014.2637 8. Jacob ST, Banura P, Baeten JM, et al. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: A prospective intervention study. Crit Care Med 2012;40(7):2050-2058. https:/doi.org/10.1097/CCM.0b013e31824e65d7 9. Jacob ST, Moore CC, Banura P, et al. Severe sepsis in two Ugandan hospitals: A prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PLoS One 2009;4(11):e7782. https:/doi.org/10.1371/journal.pone.0007782 10. Leibovici L, Shraga I, Drucker M, et al. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998;244(5):379-386. https:/doi.org/10.1046/j.13652796.1998.00379.x 11. Andrews B, Muchemwa L, Kelly P, et al. Simplified severe sepsis protocol: A randomized controlled trial of modified early goal-directed therapy in Zambia. Crit Care Med 2014;42(11):2315-2324. https:/doi. org/10.1097/CCM.0000000000000541

Accepted 22 March 2017.

August 2017, Print edition

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

IN PRACTICE

MEDICINE AND THE LAW

Enrolling HIV-positive adolescents in mental health research: A case study reflecting on legal and ethical complexities N Woollett,1 MA (Psychology, Art Therapy); J Peter,2 SC, BCom, LLB, LLM; L Cluver,3 DPhil; H Brahmbhatt,4 MPH, PhD epartment of Paediatrics and School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg; D and Wits Reproductive Health and HIV Institute, Johannesburg, South Africa 2 Johannesburg Bar, South Africa; and New South Wales Bar, Australia 3 Centre for Evidence-Based Intervention, Department of Social Policy and Intervention, Oxford University, UK 4 Department of Population, Reproductive and Family Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA; and Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa 1

Corresponding author: N Woollett (woollettn@gmail.com) Background. Adolescents living with HIV are an emerging group in the global HIV/AIDS epidemic. Mental health in this population affects HIV care, treatment, consequential morbidity and secondary transmission. There is a paucity of research regarding these youth in South Africa (SA), partly because section 71 of the National Health Act of 2003 (NHA) requires parental or guardian’s consent.

Objective. To explore legal and ethical issues related to conducting adolescent mental health research in SA. Methods. After obtaining a High Court order permitting research on minors aged <18 years without prior parental or guardian’s consent, we used qualitative and quantitative methods to interview adolescents in five clinics serving HIV-positive adolescents in Johannesburg.

Results. Our study enrolled 343 participants; 74% were orphaned and did not have legal guardians, 27% were symptomatic for depression, anxiety or post-traumatic stress disorder, 24% were suicidal, and almost 90% did not feel that they belonged in the family with which they lived. Without court intervention, most of the participants could not have participated in this research because parental consent was impossible to obtain. This case study argues for exceptions to the parental consent requirement, which excludes orphaned and vulnerable children and youth from research.

Conclusions. Recommendations are made to promote ethical integrity in conducting mental health research with adolescents. A balance is needed between protecting adolescents from exploitation and permitting access to benefits of research. Requiring parental consent for all research does not necessarily give effect to policy. For the vast majority of SA HIV-positive adolescents, parental consent is not possible.

Section 71 of the NHA ought to be amended to facilitate valuable and necessary research concerning HIV-positive orphan children and adolescents.

S Afr Med J 2017;107(8):679-683. DOI:10.7196/SAMJ.2017.v107i8.12409

The adolescent burden of HIV

Adolescents living with HIV are an emerging group in the global HIV/AIDS epidemic. In 2012, there were 2.1 million HIV-positive adolescents in low- and middle-income countries (LMICs); globally there were 3.2 million HIV-positive children aged <15 years, 90% of whom were living in sub-Saharan Africa. [1,2] Nearly one-sixth of all new HIV infections are in adolescents aged 15 - 19 years,[3] making this group the most vulnerable incident infection population in South Africa (SA).[4] In addition, owing to significant improvements in accessing antiretroviral therapy, children born with HIV are growing into adolescence in large numbers, especially in LMICs.[5,6] Worldwide, adolescents are the only age group in which AIDSrelated deaths are not decreasing.[3] In 2013, there were >9 500 deaths of HIV-infected adolescents in SA.[7] Local studies contrasting adolescents with adults indicate lower retention in care and viral suppression among youth.[8,9] The cohort of sexually active, HIVpositive and viraemic youth makes a significant impact on HIV transmission rates, warranting consideration of public health investment. Engagement of adolescents is critical to a meaningful HIV response.

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Approximately 15 million children in sub-Saharan Africa have lost one or both parents to AIDS, 2.5 million of them in SA.[10] An orphanhood epidemic has matured alongside the HIV epidemic, with high rates of adolescent orphans. In 2012, the overall national level of orphans aged <18 years was 16.9% (maternal 4.4%, paternal 9.3%, double 3.2%).[4] Families of HIV-positive children and adolescents have high levels of mobility and migration, with inconsistent guardianship, care and supervision.[11-13] Typically when biological parents die, their children are taken into care by extended family or friends. Unless a child is placed in formal institutional care, the formal appointment of a legal guardian is extremely rare. Legal guardianship is often not meaningful to black African families.[14]

Rates of mental health problems in adolescents

In both developed and less-developed countries, almost 50% of people living with HIV/AIDS have a diagnosable mental disorder – in some instances a rate three times higher than that in the general population.[15-18] Reasons for this include premorbid mental conditions, the effect of HIV on the central nervous system, the psychological

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impact of living with HIV/AIDS, side-effects of medication, social stigma and discrimination.[15] Mental health disorders occur with increased frequency among HIV-positive children and adolescents in developed contexts.[12,19,20] In LMICs there is a paucity of research on this population and mental health outcomes. Studies in Western countries, measuring the association between HIV and mental health outcomes in adolescents, are not always comparable with black African populations, where adolescents are subjected to multiple additional risks and vulnerabilities. Poor mental health is strongly related to other health and development concerns in young people – lower educational achievements, neurocognitive delay, substance abuse, violence, and poor reproductive and sexual health.[21-25] Examination of the impact of HIV on mental health outcomes in adolescents locally is critical; mental health is likely to affect HIV care and treatment, the resulting adult burden of disease and secondary transmission.

Difficulties with undertaking research on this group

SA legislation requiring parental or guardian’s consent presents a significant barrier to research on HIV-positive adolescents aged <18 years. Using a study of mental health outcomes of HIV-positive adolescents in Johannesburg as a case study, we explore legal and ethical issues related to conducting adolescent mental health research.

The legal framework – the National Health Act of 2003 (NHA)[26]

Prior to March 2012, the SA framework governing research permitted children (<18 years) to consent independently to take part in research. [27] Where the research posed minimal risk and no community objection was anticipated, national ethical guidelines permitted an exemption from parental or guardian’s consent for participation in health research by older children.[14,28] On 1 March 2012, section 71 of the NHA came into effect, which has four prerequisites for research or experimentation on a minor for therapeutic purposes: (i) the best interests of the minor; (ii) conformity with the manner and conditions prescribed; (iii) consent of the parent or guardian; and (iv) consent of the minor where capable of understanding. Non-therapeutic research and experimentation require additional ministerial consent.[29] On 19 September 2014, the Regulations Relating to Research with Human Participants were promulgated, completing the new legal framework for regulating health research established by the NHA.[30] These regulations address three general issues relating to children. First, minors are considered a vulnerable population.

Health research ethics committees (HRECs) are required to balance child protection and research facilitation and pay special attention to protocols, recognising children as deserving beneficiaries of research outcomes.[31] Second, the participation of minors must be scientifically indispensable to the study design.[31] Third, minors can only participate in research when they will be exposed to particularly low levels of risk, an approach that corresponds with the risk categories described in national ethical guidelines.[30] The regulations define ‘therapeutic research’ as research that holds out the prospect of direct benefit to the participant. Neither the NHA nor the regulations defines ‘research’.

Impractical for researchers: Woollett case study

Our case study (a description of the mental health of HIV-positive adolescents accessing care in Johannesburg) highlights the legal

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process undertaken to facilitate research on vulnerable SA adolescents.

It could not be done with parental or guardian’s consent, as the proposed participants would be orphans without legal guardians.

Approval was initially refused by the University of the Witwatersrand medical HREC. In July 2013, the principal investigator applied to the High Court, Johannesburg, in its capacity as upper guardian of minors, for consent for the research. The application was served on the facility managers of the five clinics concerned, the provincial and district research committees, the Chris Hani Baragwanath and Charlotte Maxeke academic hospital research committees, the provincial health MEC and the health minister. Upon the order being granted, the university HREC granted unconditional approval of the study (M130258), as did the other research committees. This process took 8 months and without pro bono legal assistance would have been impossible.

The study integrated qualitative and quantitative methods in design and implementation. It took place in five clinics serving HIV-positive adolescents in Johannesburg. A survey was undertaken of 343 HIV-positive adolescents aged 13 - 19 years. It contained standard assessments for depression, anxiety, post-traumatic stress disorder (PTSD) and suicide and captured HIV, sexual reproductive health, adherence, disclosure and demographic information.

Of the 343 participants, 74% were orphaned and did not have legal guardians. Most were probably perinatally infected. Twenty-seven percent were symptomatic for depression, anxiety or PTSD, 24% indicated signs of suicidality (excluding 17 adolescents excluded for active suicidality), almost 90% did not feel that they belonged within the family fostering them, 90% did not receive praise from those they lived with, and 85% were not given the same things as other children in the home. But for the High Court order, most of the sample would probably not have participated in this research.

Issues related to parental consent

Much debate has taken place over allowing children to consent to health research.[14,27,32,33] SA HIV research is still abundant, and the greatest burden of disease has moved to vulnerable groups, including adolescents. Research on adolescents is critical, but inhibited by requiring parental consent.

Exclusion of most orphaned and vulnerable children and youth (OVCY)

The adverse outcomes of being orphaned include loss of effective guidance and supervision, inconsistent care, loss of educational opportunities, impoverishment, increased sexual vulnerability, high rates of risk-taking, psychological distress and significant mental health problems. [19] There is a higher prevalence of HIV infection among orphans due to AIDS causes than among non-orphans and orphans of non-AIDS causes, together with earlier sexual debut, an increased risk of intergenerational sex, and increased family violence and exploitation.[10,34-37] OVCY are increasingly recognised as a special population for HIV risk and transmission.[35] OVCY, child-headed households and children and youth without an official guardian are a unique and contemporary issue placing many SA institutions (including government) under tremendous pressure. Innovation and responsiveness are key factors to counter these challenges. This vulnerable group can ill afford to be neglected by research, which could assist in HIV prevention and yield effective treatment interventions.

Parental consent is impossible for minors not living with, or having access to, their parents, and for orphans, who comprise a significant proportion of HIV-positive children. Section 71 has the effect of impeding research on child-headed households and OVCY.

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Inconsistent and confusing legal policy

Section 129 of the Children’s Act of 2005[38] permits independent autonomous consent to general medical treatment by a child aged >12 years, including HIV counselling and testing. The Choice on Termination of Pregnancy Act of 1996[39] provides for autonomous decision-making by a pregnant child with no minimum age requirement. Policy recognises child and adolescent capacity to make decisions concerning themselves. An adolescent child may independently consent to an HIV test and receive medical treatment, but cannot consent to the observation of such for research to improve the quality of, or access to, treatment. Excluding autonomous participation in observational research of a low-risk nature undermines this policy.

Inadvertent harm or silence to voices that most need to be heard

Adolescents may opt not to seek care because they want to avoid telling their parents about their health problems and sexual activity. [1] The Children’s Act[38] facilitates confidentiality from parents, avoiding stigma, discrimination and potential punishment. Requiring parental consent for research removes confidentiality. Children who are unable to obtain parental consent to participate are often those most in need of mental health information and resources. Requiring parental consent excludes their experiences and needs from research findings.[40] Research identifying harm to children may expose the parents and caretakers as the perpetrators of such harm. Parental consent in these circumstances is highly likely to be refused and the harm undetected. SA prevalence rates for abuse in adolescents are 56.3% for lifetime physical abuse, 35.5% for lifetime emotional abuse and 9% for lifetime sexual abuse.[24] Historically, a requirement for parental consent in all cases would have precluded the ground-breaking research by radiologists correlating paediatric head trauma with long-bone fractures identifying child abuse.[41]

Requiring parental consent may be inconsistent with principles of justice, inclusiveness and autonomy

Requiring parental consent implicitly assumes that parents’ ability to understand research and assess risk is always superior to their children’s. Parents’ opinions are often informed by their own experience of adolescence rather than the realities of their children. [40] Mental health is highly stigmatised, difficult to communicate and often not discussed in families.

Most school-aged children are capable of meaningful assent for participation in many types of research studies. Adolescents from 14 years may be as capable as adults of making competent decisions about research participation, according to more stringent legal standards of competency.[42] SA adolescents view participation in research, particularly HIV vaccine trials, to be beneficial and would participate, their reasons ranging from altruism to direct benefit.[32,43] Adolescents report marginal levels of distress when self-reporting violence and suicidality.[44,45] In our study, the overwhelming majority of adolescents expressed relief and gratitude in being able to tell their story and did not report experiencing the interview as stressful – echoing findings in other studies of HIV-affected children.[46-48] The African Charter on the Rights and Responsibilities of the Child recognises rights to enjoy the best attainable state of physical, mental and spiritual health and scientific research. The right to life and the right to access to healthcare rank among the most fundamental of the human rights guaranteed by international human rights.[49] Excluding adolescent children from health research infringes on their constitutional rights to both basic healthcare and access to healthcare services.[50]

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Recommendations for mental health research with adolescents arising from this study

To promote ethical integrity, the following were implemented and are examples that may be helpful to other studies: • A community advisory board that can advise on all aspects of the research, including proposal, protocol, survey, informed consent and a dissemination plan, can ensure youth-friendliness and relevance if constituted by adolescents who utilise services. This is effective in addressing complex health disparities and facilitates local acceptability of the research practices.

• Research staff need a balance of research, community and clinical experience. Lay counsellors, with experience in the clinics managing issues of adherence, disclosure, stigma and HIV counselling, and additional training that emphasises adolescent rights, the distinction between researchers and counsellors, modelling interview techniques, with practice sessions on dealing with informed consent processes, etc. are recommended. Staff also need weekly debriefing and supervision from a registered therapist.

• Consent procedures disclosed that confidentiality may be broken by the mandatory reporting requirements relating to suspected illtreatment, abuse or neglect of children (section 42 of the Children’s Act,[38] section 4 of the Prevention of Family Violence Act of 1993,[51] and sexual offences against children (section 54 of the Criminal Law (Sexual Offences and Related Matters) Amendment Act of 2007[52]). Study staff need training to identify reporting obligations, and understand and manage the processes triggered.

• Researchers must be mindful that there is evidence that compared with adults, adolescents are less likely to spontaneously consider risks and benefits, are less likely to evaluate long-term consequences of decisions, are more likely to place weight on benefit than risk, are more likely to be short-term focused, and are less likely to recognise the vested interests of others.[43] Recognition of immature decision-making is therefore necessary, and researchers should try to enhance adolescent understanding to the fullest extent possible. To assess understanding, our informed consent contained both multiple-choice questions and open-ended probing questions.

• The latent power dynamic between researchers and adolescent participants must be managed. Contextually, obedience to and respect for adults are values strongly emphasised; children seldom speak up or voice their opinions to adults.[53] Time needs to be provided for the adolescents to acquire trust in the researchers and the research process. Research counsellors were able to speak all the local languages, increasing their ability to answer all questions posed and alleviate potential anxiety of the participants.

• Authenticity in child participatory research is crucial: without it, the validity of what is reported is inevitably questionable and, at the level of tokenism, it is fundamentally unethical.[53] Research utilising non-verbal methods, such as drawings, can offer research subjects active participation in the research process, authenticating their voice through their engagement, offering more developmentally appropriate means of accessing data, diminishing stress in the child/adolescent-adult interaction, and providing a more comfortable method of engagement than language.[53-56] • Engaging youth in research can be facilitated with the use of mobile and computer devices, known to be appealing. Data were collected on tablet computers to improve reporting of sensitive questions.[57,58] • HRECs reviewing adolescent protocols should consult with one another to facilitate uniformity in response to similar research protocols.[43]

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Discussion

Evidence regarding the mental health of HIV-positive adolescents is fundamental to inform policy. In this case study, 27% of HIVpositive adolescents accessing treatment were experiencing common mental health problems that were previously unrecognised and could be treated in the public health system. But for a court order, this evidence would not have been available. Vulnerable groups such as adolescents are typically the last to benefit from research, and often need it the most.

Laws such as the NHA were developed to safeguard children, and in many cases do. Section 71 has the policy objective to protect them. Where the parental consent requirement is inappropriate or impossible, it operates to exclude children from research, further increasing their vulnerability and failing its policy objective. Research ethics legislation is vital and welcomed, but a balance is needed between protection from exploitation and access to benefits of research. Excessive regulation to protect adolescents from exploitative research may impede on their human rights and autonomy as individuals and circumvents research being undertaken to improve access to care and treatment and reform national policy.[27] It is also likely to delay their access to any improvement based on adult research undertaken.[59] Provision should be made for rigorous review

by HRECs and promoting clear communication to adolescents rather than restrictions that reduce research participation.[30] The NHA and its regulations ought to take into account the social contexts of SA adolescents. A rights-based approach is necessary in managing these tensions.[60] As highlighted by Mann (in Kirby[49]), ‘health and human rights are complementary approaches to the central problem of advancing human well-being’.

Failure to address mental health problems in terms of prevention and treatment, including developmental and intellectual disorders, in childhood and adolescents in low-resource settings is a public health issue with far-reaching consequences. A substantial proportion of adult mental health problems originate early in life, and such failure has long-lasting effects beyond childhood and adolescence[60] and impedes the achievement of basic development goals in LMICs. A commitment to evidence-based healthcare requires more, not less, effort to encourage research and clear evaluation of services.

Service and research entities need to assess whether their services/ interventions are helping children/adolescents and how they can be improved. Excluding the most vulnerable adolescents risks biasing the research capacity to assess their needs and services to them.

These findings suggest the importance of considering an amendment to section 71 of the NHA, in order to facilitate valuable and necessary research concerning HIV-positive and orphaned children. A mechanism ought to be introduced to permit research on children where parental or guardians’ consent is either not practicable or inappropriate. ‘Research’ ought to be defined. A distinction should be made to cater for HRECs to allow a dispensation from parental consent for classes of research that present minimal risk of harm to child participants, and an age threshold should be introduced for children to give autonomous consent. Further practical examples of how to address the challenges related to this work in diverse contexts are needed in order to build a consensus on best practices.

Conclusions

Ethical and sound health research is essential to promoting the health of highly vulnerable HIV-positive and affected adolescents. If research results are to be targeted to adolescents, it is essential that adolescents be included so that study outcomes are relevant to them.

Healthcare policy is best improved based on the evidence to meet the mental health needs of this population more effectively.

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Requiring parental consent for particular research does not necessarily give effect to policy. For the vast majority of HIV-positive adolescents, such consent is simply impossible. The result is that the most vulnerable are excluded from research that may yield great benefit. Resort to the High Court is practically unworkable and legislative amendment is urgently required.

Acknowledgements. We thank the participants for sharing their stories.

We acknowledge the impressive work of the research counsellors (Thamsanqa Jabavu, Nombulelo Shezi, Linda Mazibuko, Princess Mbatha, Tebogo Moloi, Honey Nyapoli, Bafana Gxubane, Shenaaz Randeria and Relebohile Maleka), both in their capacity as counsellors and for their enthusiasm in engaging in this research. We are grateful to the national and provincial departments of health for allowing access to the patients and facilities in Johannesburg. Thanks also to Ms Justine Michel of Fluxmans Attorneys, Johannesburg, for legal assistance.

Author contributions. NW conceived and undertook the study and drafted the manuscript for publication; JP secured the court order to undertake the study and contributed to the drafting and editing of the manuscript; HB and LC provided overall guidance on the protocol development and design of the study; and HB provided overall oversight of the study. All authors read and approved the final manuscript.

Funding. None.

Conflicts of interest. None.

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53. Clacherty G, Donald D. Child participation in research: Reflections on ethical challenges in the southern African context. Afr J AIDS Res 2007;6(2):147-156. https://doi.org/10.2989/16085900709490409 54. Coad J. Using art-based techniques in engaging children and young people in health care consultations and/or research. J Res Nurs 2007;12(5):487-497. https://doi.org/10.1177/1744987107081250 55. D’Amico M, Denov M, Khan F, Linds W, Akesson B. Research as intervention? Exploring the health and well-being of children and youth facing global adversity through participatory visual methods.

Glob Public Health 2016;11(5-6):528-545. https://doi.org/10.1080/17441692.2016.1165719 56. Willis N, Frewin L, Miller A, Dziwa C, Mavhu W, Cowan F. ‘My story’ – HIV positive adolescents tell their story through film. Child Youth Serv Rev 2014;45:129-136. https://doi.org/10.1016/j. childyouth.2014.03.029 57. Gorbach PM, Mensch BS, Husnik M, et al. Effect of computer-assisted interviewing on self-reported sexual behavior data in a microbicide clinical trial. AIDS Behav 2013;17(2):790-800. https://doi. org/10.1007/s10461-012-0302-2 58. Toska E, Cluver LD, Hodes R, Kidia KK. Sex and secrecy: How HIV-status disclosure affects safe sex among HIV-positive adolescents. AIDS Care 2015;27(Suppl 1):47-58. https://doi.org/10.1080/09540 121.2015.1071775 59. Pettifor A, Bekker LG, Hosek S, et al. Preventing HIV among young people: Research priorities for the future. J Acquir Immune Defic Syndr 2013;63(Suppl 2):S155-S160. https://doi.org/10.1097/ qai.0b013e31829871fb 60. Kieling C, Baker-Henningham H, Belfer M, et al. Child and adolescent mental health worldwide: Evidence for action. Lancet 2011;378(9801):1515-1525. https://doi.org/10.1016/s0140-6736(11)60827-1

Accepted 5 April 2017.

August 2017, Print edition

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

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Does access to private healthcare influence potential lung cancer cure rates?

T-J John,1 MB ChB, Dip HIV Man (SA); D Plekker,2 MB ChB, FCP (SA), MMed (Int), Cert Pulm (SA); E M Irusen,1 MB ChB, FCP (SA), PhD; C F N Koegelenberg,1 MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulm (SA), PhD ivision of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg D Academic Hospital, Cape Town, South Africa 2 Pulmonologist, Kuils River Hospital, Cape Town, South Africa 1

Corresponding author: T-J John (jessjohnt@gmail.com) Background. Numerous studies show a link between poor socioeconomic status (SES) and late-stage cancer diagnosis. However, this has not been consistently shown looking at non-small-cell lung cancer (NSCLC) in isolation. Despite the extremely high prevalence of lung cancer and disparities in access to healthcare based on health insurance in South Africa, there is a paucity of data on the influence of health insurance (as a surrogate for SES) on stage at presentation of NSCLC. Objective. To assess the relationship between health insurance status (and invariably SES) and staging (and therefore resectability) of patients with primary NCSLC at the time of initial presentation.

Methods. Health-insured patients with NSCLC (n=51) were retrospectively compared with NSCLC patients with no health insurance (n=532) with regard to demographics, tumour node metastasis (TNM) staging, and cell type at initial presentation.

Results. Patients with no health insurance were younger (mean (standard deviation (SD)) 59.9 (10.1) years) than those with private health insurance (64.2 (9.6) years) (p=0.03). Poorly differentiated NSCLC was significantly more common in the privately health-insured group (23.6%) than among those with no health insurance (4.6%) (p<0.01). Six of 51 NSCLC patients (11.8%) with private health insurance presented with early-stage, potentially curable disease (up to stage IIIA), compared with 55 patients (10.3%) in the uninsured group (p=0.75).

Conclusions. Access to private health insurance did not have a significant impact on stage at initial presentation. The only significant differences were the relatively advanced age at presentation and relatively higher percentage of poorly differentiated NSCLC seen in patients with health insurance.

S Afr Med J 2017;107(8):687-690. DOI:10.7196/SAMJ.2017.v107i8.12277

According to the World Cancer Report of 2014,[1] lung cancer remains the most common cause of cancer-related death, resulting in >1.59 million reported deaths in 2012. The situation in South Africa (SA) is no different, although studies have consistently shown that SA patients with non-small-cell lung cancer (NSCLC) have an inferior potential cure rate at presentation when compared with the USA and Western Europe.[2-4] Only ~10% of patients diagnosed with lung cancer in SA are offered treatment with curative intent.[2-4] The National Institute for Health and Clinical Excellence (NICE) guideline[5] recommends radical surgery for stage I - II NSCLC, with chemoradiotherapy with or without surgery (with curative intent) offered to patients with stage IIIA disease. Palliative chemotherapy and radiotherapy are recommended for later-stage NSCLC patients (stage IIIB and IV).[5] Stage at diagnosis is therefore an important indicator of survival in lung cancer.[6] Diagnosis at an advanced stage (IIIB or IV) usually precludes the possibility of cure and leads to poor long-term outcomes.[7-9] Five-year survival rates of patients diagnosed with late-stage disease range from ~4% to 6%, whereas those for early-stage disease range from 40% to 54%.[6,10-14] Health insurance status is commonly used as a surrogate marker of socioeconomic status (SES).[15] In turn, SES has been shown to be an independent contributor to health status, as a surrogate for lifestyle, diet, and working and living conditions.[16] Lower SES is known to be associated not only with an increased incidence of cancer but also with worsened survival.[17,18] Although numerous

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studies across various cancers have shown that poor SES has been associated with late-stage diagnosis, this has not been consistently observed in studies looking at NSCLC in isolation.[18-21] Disparities in access to healthcare and its use, as well as lack of preventive healthcare services including cancer screening, may contribute somewhat to differentials in cancer stage distributions, especially in late-stage diagnosis.[18,22-25]

Objective

There is a paucity of SA data comparing the staging of lung cancer patients at the time of presentation based on SES. The objective of this study was to assess the relationship between health insurance status (and invariably SES) and staging of patients (and therefore resectability and potential cure) with primary NSCLC at the time of initial presentation. The studyâ&#x20AC;&#x2122;s null hypothesis, based on previous international research, was that there is no notable difference in the resectability rates of patients with v. without private health insurance diagnosed with NSCLC at the time of presentation.

Methods

All cases of primary lung cancer presenting to Tygerberg Academic Hospital and the Kuils River Respiratory Centre (Kuils River Hospital) in Cape Town, SA, between August 2013 and September 2015 were identified. Tygerberg Academic Hospital, a 1 380-bed public hospital, is a primary referral centre serving approximately three million people. Kuils River Respiratory Centre is based in the suburb of

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Kuils River, with patients being admitted to the 180-bed Kuils River Hospital.[26] The two centres are in close proximity and serve a patient population group similar in demographics other than their SES. All patients in the study population diagnosed with an underlying primary NSCLC in either of the institutions were included in the study group. In the study group, all patients who had a confirmed histological diagnosis together with complete staging details were included in the analysis.

Patients were excluded if the presentation with primary lung malignancy was not their first presentation to the healthcare service with a malignancy, or if a second underlying malignancy was suspected at the time of presentation.

Information on individual patients was collected retrospectively from medical records, including routine demographic and clinical data. All patients had access to positron emission tomography/computed tomography, bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration with rapid on-site evaluation, transthoracic image (ultrasound or tomography)-guided biopsy and related diagnostic techniques that were performed at the discretion of the treating doctors as per standard operating procedures. A combined panel of at least a pulmonologist, thoracic radiologist, thora­cic surgeon, specialist oncologist and pathologist staged all patients as per the 2009 International Association for the Study of Lung Cancer tumour node metastasis (TNM) staging system. These findings were recorded prospectively in a lung cancer registry (administered by the investigators), which was retrospectively used to identify cases anonymously.

Pathological analyses were performed by the National Health Laboratory Services at Tygerberg Hospital (state patients) and Ampath Laboratories at N1 City Hospital in Cape Town (insured patients).

Statistical analysis

Data were collected on a customised Microsoft Excel spreadsheet, version 15.0.4797.1000 (Microsoft, USA). Chi-square or Fisher’s exact tests (where indicated) were performed on dichotomous categorical variables, and t-testing on continuous data.

A 5% significance level (p<0.05) was applied.

waiver of consent owing to the retrospective nature and anonymity of the study design.

Results

During the 2-year study period, 665 patients were seen between the two institutions with a confirmed histological diagnosis of primary lung malignancy. All the patients who presented to Tygerberg Hospital (n=610) had no health insurance, whereas all the patients who presented to Kuils River Respiratory Centre (n=55) had access to private health insurance.

The patients with no health insurance were younger (mean (standard deviation (SD)) 59.9 (10.1) years) than those with private health insurance (64.15 (9.6) years) (p=0.03). There was no significant difference in gender distribution between the two groups (Table 1). Overall, adenocarcinoma was the commonest form of lung malignancy (48.1%), followed by squamous cell carcin­ oma (29.2%). In the privately health-insured group, poorly differentiated NSCLC (25.5%) was more common than squamous cell carcinoma (23.6%). Poorly differentiated NSCLC was also significantly more common

Discussion

In this retrospective, observational study in patients with NSCLC, access to private health insurance (medical aid in SA) was shown not to have a significant effect on staging at initial presentation. The only significant differences were the relatively advanced age at presentation and relatively higher percentage of poorly differentiated NSCLC seen in private practice.

Potential theories regarding why a laterstage diagnosis would have been expected in

Table 1. Demographics, cell types and staging for all lung cancer patients by health insurance type (N=665) All* (N=665)

No health insurance (n=610)

Private health insurance (n=55) p-value

Age (yr), mean (SD)

60.49 (10.1)

59.9 (10.1)

64.15 (9.6)

0.03

Gender male, n (%)

404 (60.8)

372 (61.0)

32 (58.2)

0.68

Adenocarcinoma

320 (48.1)

298 (48.9)

22 (40.0)

0.26

Squamous cell carcinoma

194 (29.2)

181 (29.7)

13 (23.6)

0.35

Poorly differentiated

42 (6.3)

28 (4.6)

14 (25.5)

<0.01

Other

27 (4.1)

25 (4.1)

2 (3.6)

1

82 (12.3)

78 (12.8)

4 (7.3)

0.28

I

8 (1.4)

7 (1.3)

1 (2.0)

1

II

15 (2.6)

15 (2.8)

0 (0.0)

0.38

IIIA

38 (6.5)

33 (6.2)

5 (9.8)

0.37

IIIB

128 (22.0)

115 (21.6)

13 (25.5)

0.52

IV

394 (67.6)

362 (68.0)

32 (62.7)

0.44

Limited

11 (13.4)

10 (12.8)

1 (25.0)

1

Extensive

71 (86.6)

68 (87.2)

3 (75.0)

1

Demographics

Cell type, n (%) NSCLC (n=583)

SCLC Stage, n (%) NSCLC (n=583)

SCLC (n=82)

Ethical approval

Ethical approval for this retrospective analysis was provided by the Stellenbosch University Research Ethics Committee (ref. no. S16/04/077). The application included a

in the privately health-insured group (23.6%) compared with those with no health insur­ ance (4.6%) (p<0.01).

Sixty-one (10.5%) of the 583 patients with NSCLC were staged as early-stage disease (up to stage IIIA, Table 1). In total, 477 of 532 NSCLC state patients (89.7%) had incurable disease at presentation, compared with 45 of 51 privately insured patients (88.8%) (p=0.75). Conversely, 55 state patients (10.3%) presented with early-stage, potentially curable disease (up to stage IIIA) compared with 6 patients in the privately insured group (11.8%) (p=0.75).

SD = standard deviation; NSCLC = non-small-cell lung cancer; SCLC = small-cell lung cancer. *Stage I - IIIA v. stages IIIB - IV NSCLC.

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those of lower SES include fatalistic views and medical mistrust, which has been shown to be more common among the poor and minorities[27,28] and leads to delays in seeking care for symptoms suggestive of lung cancer as well as delaying prompt work-up once a tumour has been identified. The poor may also prioritise health to a lesser degree and therefore postpone seeing a doctor, which can contribute to later stage of presentation.[6,28] However, these findings were not reproducible in this study, which showed that although patients without health insurance presented with later-stage disease, there was no significant difference between the privately insured and uninsured groups.

A systematic review of the literature from 1995 to 2005 by Woods et al.[15] found that most studies report an association between low SES and later stage at diagnosis of various cancers. As with our study, this does not always hold true when looking at NSCLC in isolation. Various studies of lung cancer from Canada, Denmark and Sweden have only indicated limited socioeconomic differences in advanced-stage diagnosis.[17,29,30] Other studies from the UK have in fact shown a lower frequency of advanced stage at diagnosis in more deprived patients.[31] The findings of our study, although not showing independent evidence of an association (p=0.75), may reflect a lack of power due to the lack of numbers in the privately insured group.

To our knowledge, there are no available local data looking at the influence of SES or health insurance on the stage of presentation of primary lung malignancy.

The proportion of early-stage (up to stage IIIA) disease in the study group was calculated at 10.3% in our patients with no health insurance and 11.8% in those with private health insurance. This corresponds with reported resectability rates in patients with NSCLC in SA literature, where operability rates between 10% and 11% have been quoted in other studies from Johannesburg and Cape Town.[2-4,32,33] In the developed world, the proportion of patients who present with potentially curable disease is much higher. A study detailing >12 800 cases of lung cancer from Nebraska, Canada, revealed early-stage disease in 23.04% of patients.[34] Other studies from the developed world have revealed resectable disease in up to 33% of patients.[13] It must be noted that in the SA setting, other factors including the effect of the HIV pandemic on the stage of presentation must be kept in mind. A previous study from the Western Cape Province, SA, has shown that HIV-positive lung cancer patients were significantly less likely to have early-stage lung cancer compared with their HIVnegative counterparts.[4] Limited resources in the state sector and restricted funding by medical aids in the private sector also pose significant barriers to early detection of disease.

The present study revealed that poorly differentiated NSCLC was significantly more common in the privately health-insured group (23.6%) compared with those with no health insurance (4.6%) (p<0.01). Our data also support current worldwide lung cancer trends that have revealed an increase in the proportion of patients being diagnosed with adenocarcinoma in comparison with squamous cell carcinoma.[35-40] A steady decrease in daily smoking prevalence in association with switching to low-tar and filter cigarettes (enhancing delivery of smoke to peripheral regions of the lung) is believed to contribute to the decrease in rates of squamous cell carcinoma and the increase in rates of adenocarcinoma.[41-44] It has been postulated that filter tips effectively reduce deposition of larger particles in the central airway, resulting in a reduced risk of squamous cell carcinoma, but increase deposition of small-size particles in the deeper parts of the lung where adenocarcinoma preferentially occurs.[41,42]

Study limitations

A limitation of the study is possible selection bias, in that data from a single region that only includes <10% of the SA population may not

50

be generalisable to the whole population. Furthermore, the lack of documentation of race makes it even more difficult to generalise the results and findings to the SA population as a whole. Access to and quality of healthcare institutions may also vary between metropolitan areas. A further potential limitation may be the fact that different laboratories were used for analysis and typing of lung cancer.

Health insurance type as a measure of SES has limitations in that it may be affected by the wide lack of homogeneity within each group. In future studies, a multilevel framework examining individual and area-specific socioeconomic variables, including housing standards, family income, etc., may be a better classification of SES. Further, larger-scale studies involving multiple centres (both public and privately run) from around the country may aid in proving significance of the above findings and minimise any selection bias that may be present. A multilevel assessment of SES as outlined above may also give a better indication of the true impact of SES on stage of presentation with underlying malignancy.

Conclusions

We found a nominal and statistically insignificant difference between the stage of presentation in patients who had health insurance compared with those who did not have access to private health insurance. Larger-scale studies involving multiple centres may need to be carried out to identify whether a true difference exists between the two groups; this is of great importance, as a difference may have important public health implications for the future. It is also evident that lung cancer screening as well as other methods to improve earlystage disease detection remains one of the most important tools in improving lung cancer cure rates.

Acknowledgements. None.

Author contributions. CFNK and T-JJ conceived the idea. All authors collected the data. T-JJ and CFNK analysed the data and prepared the manuscript, and EMI and DP were responsible for critical revision of the manuscript.

Funding. None.

Conflicts of interest. None.

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Accepted 7 April 2017.

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

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A method for determining when the superficial scalp arteries are the source of migraine pain E Shevel, BDS, Dip MFOS, MB BCh The Headache Clinic, Johannesburg, South Africa Corresponding author: E Shevel (drshevel@headclin.com)

In some patients the pain of migraine originates in the extracranial cranial arteries. This article describes the location and a logical examination sequence of the vessels most frequently involved in migraine pain.

S Afr Med J 2017;107(8):691-693. DOI:10.7196/SAMJ.2017.v107i8.12417

Migraine is a common disorder with a worldwide lifetime prevalence of 16%, and a last-year prevalence of 10%.[1] There is a great deal of evidence showing that painful dilation of the terminal branches of the external carotid arteries is the source of the pain in many but not all migraine sufferers.[2] In a study of 63 migraineurs, digital compression of the ipsilateral superficial temporal artery during migraine headache temporarily reduced or eliminated the pain in 23 (36%) cases.[3] Migraine pain can also originate in the pericranial muscles.[4,5] Although migraine is one of the most common reasons for patients visiting their general practitioner, the study curriculum in medical schools does not include instruction on how to examine migraine sufferers to determine whether their pain originates in the terminal branches of the external carotid artery, the pericranial muscles, or both. The importance of accurate diagnosis of the source of the pain cannot be overemphasised. The abortive treatment of choice for migraine is one of the ergot alkaloids or triptans, which are vasoconstrictors that act upon the terminal branches of the external carotid artery.[6-9] In this article a protocol is described for the clinical evaluation of the terminal branches of the external carotid artery to diagnose which patients have vascular pain and in whom vasoconstrictors are the most likely to be effective.

Anatomy

The scalp derives its blood supply mainly from the four superficial branches of the external carotid artery, the superficial temporal, angular, occipital, and posterior auricular arteries, and the supraorbital and supratrochlear branches of the internal carotid.

There are extensive anastomoses between these arteries, homolateral and heterolateral, the latter crossing the midline, and therefore able to vascularise the opposite side of the scalp.[10] There is an anastomosis crossing between the left and right sides every 5 - 7 mm.

Intertemporal anastomoses are by far the most numerous, followed by inter-occipital. As a result of this vast network of anastomoses, the blood supply of the scalp takes the form of a rich network of interconnecting vessels. These connections vary among patients and from left to right in the same patient.[10]

main trunk is most accessible where it crosses superficial to the zygomatic process of the temporal bone just anterior to the tragus.[13] The superficial temporal artery is sometimes very small, in which case it may be replaced by the posterior auricular artery. It at times also communicates with the supraorbital artery to supply the forehead.[14]

Superficial temporal artery â&#x20AC;&#x201C; frontal branch

The frontal branch of the superficial temporal artery runs a tortuous course just subcutaneously, crossing the temple in an anterosuperior direction (Fig. 1). It is often visible, particularly during a migraine attack. Although it is a terminal branch of the superficial temporal artery, because of its extensive anastomoses in the scalp, the frontal branch is not supplied exclusively by the superficial temporal artery, but also by other scalp vessels.[12]

Posterior auricular artery

The posterior auricular artery emerges from the deeper tissues in the groove between the cartilage of the ear and the mastoid process (Fig. 1), and immediately divides into its auricular and occipital branches. When the posterior auricular is larger than usual it may be compensating for a deficiency in either the occipital or superficial temporal arteries.[14]

Occipital artery

The occipital artery emerges from the deep tissues of the neck, and pierces the fascia between the attachments of the sternomastoid and

Superficial temporal artery â&#x20AC;&#x201C; main trunk

The superficial temporal artery bifurcates anterior to the auricle to become two major branches, the frontal and the parietal.[11] The frontal branch runs toward the midline of the forehead above the eyebrow, and the parietal branch supplies the parietal region (Fig. 1).[12] The

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Fig. 1. The extensive arterial anastomotic network of the terminal branches of the external carotid artery.

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trapezius muscles at the level of the superior nuchal line. It then ascends in a tortuous course in the superficial fascia of the scalp, where it divides into numerous branches, which reach as high as the vertex of the skull, and anastomoses with the posterior auricular and superficial temporal arteries.[15] It also anastomoses with the contralateral occipital artery.[10]

Supraorbital and supratrochlear arteries

The supraorbital and supratrochlear arteries emerge superficially at or near the supraorbital foramen to supply the forehead, and anastomose with the frontal branch of the superficial temporal and the supraorbital and supratrochlear arteries of the opposite side (Fig. 1).[15]

Angular artery

The angular artery is the terminal branch of the facial artery. It runs up the lateral surface of the nose, and terminates in the frontal tissues (Fig. 1).[15]

Methods

In some patients with migraine headache, reduction of the blood pressure in the painful area by digital occlusion of one or more of the superficial arteries reduces or eliminates the pain while the pressure is being applied.[3,16-21] Before the examination commences, the patient is asked to estimate the severity of the headache according to a scale of 0 = no pain to 10 = the worst pain possible, and the severity is recorded.

As each artery is compressed, the patient is asked to estimate the percentage of pain relief, if any, and which is recorded. It is interesting that in patients who report pain relief with digital arterial compression, in some the pain returns the moment the pressure is relieved, and in others the pain takes time to return.

The arteries are examined in the following sequence: • superficial temporal – main trunk • superficial temporal – frontal branch • occipital • posterior auricular • angular • supraorbital and supratrochlear.

One or more of the abovementioned arteries may be involved in the pain process.

It is necessary to bear in mind that because of the variability of the anastomoses between these vessels, it may be difficult to diagnose accurately which arteries are contributing blood flow to the painful area. Arteries distant from the painful area may also be involved in the pain mechanism. A common finding, for example, is that compression of the occipital artery may alleviate ipsilateral periorbital pain.

When the pain is unilateral, the ipsilateral artery is compressed first, then the contralateral artery, then both left and right simultaneously.

If the pain is bilateral, the left and right sides are compressed simultaneously.

examiner stands in front of the patient and compresses the tissues anterior to the tragus against the zygomatic arch with the fingertip touching the tragus and the finger parallel to the arch. This ensures that all the tissues up to at least 2.5 cm anterior to the tragus are compressed (Fig. 2).

If the pain improves or disappears when the contralateral artery is compressed, it indicates a substantial anastomotic connection between left and right.

Superficial temporal artery – frontal branch

The examiner stands in front of the patient, with the patient’s head inclined backwards at ~45° to the horizontal. The flat part of the finger is applied to the temple to compress the tissues along a line extending from the outer canthus of the eye for 4 - 5 cm in a posterosuperior direction. The artery is often located near the hairline, and may be visible, particularly in thinner individuals (Fig. 3).

Occipital artery

The examiner stands in front of the patient and places the forefinger over the occipital tissues horizontally between the ear and the midline, just above the level of the superior nuchal line, exerting forward pressure and compressing 3 - 4 cm of tissue against the skull (Fig. 4).

Posterior auricular artery

The examiner stands behind the patient and exerts upward pressure with the fingertip into the depression between the cartilage of the pinna and the mastoid process (Fig. 5).

Supraorbital, supratrochlear, and angular arteries

The examiner stands behind the patient, and with the fingertip against the root of the nose compresses the supraorbital soft tissues against the supraorbital rim (Fig. 6).

Fig. 2. Compression of the main trunk of the superficial temporal artery.

Superficial temporal artery – main trunk

The superficial temporal artery passes superficial to the posterior root of the zygomatic arch just anterior to the tragus. Gentle palpation of this area often reveals the presence of a pulse, which is frequently more prominent during a migraine attack. Applying digital pressure over the zygomatic arch, thereby compressing the artery against the arch, temporarily occludes the artery. As the anteroposterior distance of the artery from the tragus is variable, the following method is used to ensure its compression: The

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Fig. 3. Compression of the frontal branch of the superficial temporal artery.

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(AD 936 - 1013), the renowned Moorish physician (known in the West as Abucalsis or Abulcasis). More recently, Hare observed ‘headache … to diminish in intensity locally when the particular artery which supplies the affected area is pressed on’.[16] He found that compressing the occipital, the superficial temporal, or the angular artery relieved the headache over the distribution of the relevant vessel. Since then, reduction in the pain of migraine headache by digital compression of one or more of the superficial extracranial arteries has been extensively documented.[17,20,22,23] In a study of 63 migraineurs, digital compression of the ipsilateral superficial temporal artery during migraine headache temporarily reduced or eliminated the pain in 23 (36%) cases.[3] The diagnosis of the origin of the pain in migraine is essential to ensure the prescription of the appropriate treatment. This highlights the importance of developing a protocol for determining the origin of the pain in each patient. A logical examination sequence has been presented that enables an accurate assessment to be made of which extracranial vessels, if any, are the source of pain in individual migraineurs.

Fig. 4. Compression of the occipital artery.

Acknowledgements. None.

Author contributions. Sole author.

Funding. None.

Conflicts of interest. None.

Fig. 5. Compression of the posterior auricular artery.

Fig. 6. Compression of the angular, supraorbital, and supratrochlear arteries.

Results

The longer an attack lasts, and the more severe the attack, the less likely that digital compression will provide an accurate diagnosis.

It is well known that the vasoconstrictors, the triptans, are less effective and sometimes have no effect, even in patients with proven arterial pain, if the headache has been allowed to become very severe before the medication is used. The same occurs with digital artery compression.

It is also of interest that arterial compression sometimes relieves pain in an area not supplied by the compressed artery. Commonly, compression of the occipital arteries relieves peri-orbital pain, and compression of the superficial temporal main trunk may on occasion relieve occipital pain. The reason for this may lie in the extensive anastomoses that exist between the terminal branches of the external carotid arteries, both ipsilateral and contralateral.[10]

Discussion

The first recorded reference to the involvement of the extracranial vasculature in headache is attributed to Abu Qasim al-Zahrawi

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1. Rasmussen BK, Jensen R, Schroll M, Olesen J. Epidemiology of headache in a general population – a prevalence study. J Clin Epidemiol 1991;44(11):1147-1157. https://doi.org/10.1016/0895-4356(91)90147-2 2. Shevel E, Spierings EH. Role of the extracranial arteries in migraine headache: A review. Cranio 2004;22(2):132-136. https://doi.org/10.1179/crn.2004.017 3. Drummond PD, Lance JW. Extracranial vascular changes and the source of pain in migraine headache.

Ann Neurol 1983;13(1):32-37. https://doi.org/10.1002/ana.410130108 4. Shevel E. Cervical muscles in the pathogenesis of migraine headache. J Headache Pain 2004;5(1):12-14. https://doi.org/10.1007%2Fs10194-004-0062-0 5. Tfelt-Hansen P, Lous I, Olesen J. Prevalence and significance of muscle tenderness during common migraine attacks. Headache 1981;21:49-54. https://doi.org/10.1111/j.1526-4610.1981.hed2102049.x 6. Andersen AR, Tfelt-Hansen P, Lassen NA. The effect of ergotamine and dihydroergotamine on cerebral blood flow in man. Stroke 1987;18(1):120-123. https://doi.org/10.1161/01.str.18.1.120 7. Hachinski V, Norris JW, Edmeads J, Cooper PW. Ergotamine and cerebral blood flow. Stroke 1978;9(6):594-596. https://doi.org/10.1161/01.str.9.6.594 8. Schumacher G, Wolff H. Experimental studies on headache: A. Contrast of histamine headache with the headache of migraine and that associated with hypertension. B. Contrast of vascular mechanisms in pre-headache and in headache phenomena of migraine. Arch Neurol Psychiat 1941;45(2):199-214. https://doi.org/10.1001/archneurpsyc.1941.02280140009001 9. Jansen I, Edvinsson L, Mortensen A, Olesen J. Sumatriptan is a potent vasoconstrictor of human dural arteries via a 5-HT1-like receptor. Cephalalgia 1992;12(4):202-205. https://doi.org/10.1046/j.14682982.1992.1204202.x 10. Marty F, Montandon D, Gumener R, Zbrodowski A. Subcutaneous tissue in the scalp: Anatomical, physiological, and clinical study. Ann Plast Surg 1986;16(5):368-376. https://doi.org/10.1097/00000637198605000-00004 11. Stock AL, Collins HP, Davidson TM. Anatomy of the superficial temporal artery. Head Neck Surg 1980;2(6):466-469. https://doi.org/10.1002/hed.2890020604 12. Imanishi N, Nakajima H, Minabe T, Chang H, Aiso S. Venous drainage architecture of the temporal and parietal regions: Anatomy of the superficial temporal artery and vein. Plast Reconstr Surg 2002;109(7):2197-2203. https://doi.org/10.1097/00006534-200206000-00003 13. Abul-Hassan HS, von Drasek Ascher G, Acland RD. Surgical anatomy and blood supply of the fascial layers of the temporal region. Plast Reconstr Surg 1986;77(1):17-28. https://doi.org/10.1097/00006534-198601000-00004 14. Bergman RA, Afifi AK, Miyauchi R. Illustrated Encyclopaedia of Human Anatomic Variation: Opus II. Cardiovascular System. Arteries: Head, Neck, and Thorax. 2002. http://www.vh.org/adult/provider/anatomy/ AnatomicVariants/Cardiovascular/Text/Arteries/TemporalSuperficial.html (accessed 21 June 2017).

15. Williams PL, Warwick R, Dyson M, Bannister L. Gray’s Anatomy. London: Churchill Livingstone, 1989.

16. Hare F. Mechanism of the pain in migraine. Med Pr 1905;1:583.

17. Louis S. A bedside test for determining the sub-types of vascular headache. Headache 1981;21 (3):8788. https://doi.org/10.1111/j.1526-4610.1981.hed2103087.x 18. Vijayan N. Head band for migraine headache relief. Headache 1993;33(1):40-42. https://doi. org/10.1111/j.1526-4610.1993.hed3301040.x 19. Graham JR, Wolff HG. Mechanism of migraine headache and action of ergotamine tartrate. Arch Neurol Psychiat 1938;39 (4):737-763. https://doi.org/10.1001/archneurpsyc.1938.02270040093005 20. Pickering GW. Experimental observations on headache. BMJ 1939;1(4087):907-912. https://doi. org/10.1136/bmj.1.4087.907 21. Tunis MM, Wolff HG. Analysis of cranial artery pulse waves in patients with vascular headache of the migraine type. Am J Med Sci 1952;224:565-568. https://doi.org/10.1097/00000441-195211000-00013 22. Lipton SA. Prevention of classic migraine headache by digital massage of the superficial temporal arteries during visual aura. Ann Neurol 1986;19(5):515-516. https://doi.org/10.1002/ana.410190521 23. Shevel E. The role of the external carotid vasculature in migraine. In: Clarke LB, ed. Migraine Disorders Research Trends. New York: Nova Science Publishers, 2007.

Accepted 28 March 2017.

August 2017, Print edition

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

IN PRACTICE

CASE REPORT

Ocular metastasis as initial presentation in breast cancer M Maliepaard,1 MB BS; M Mesham,2 MB ChB, FCS (SA); Z Aleksic,3 MD, FCS (SA); R Scholtz,4 MB ChB, DCH, FCS (SA); J Edge,5 MMed (Surg) Department of Surgery, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa Department of Ophthalmology, Life Peninsula Eye Hospital, Cape Town, South Africa 3 Department of Ophthalmology, Cape Town Mediclinic, Cape Town, South Africa 4 Department of Ophthalmology, Life Eye and Laser Centre, Life Peninsula Eye Hospital, Cape Town, South Africa 5 Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa 1 2

Corresponding author: J Edge (dr@jennyedge.co.za)

Two patients presented to their ophthalmologists with vision disturbances. On ocular examination, retinopathic lesions were observed.

On subsequent examination, these lesions were diagnosed as metastases of breast cancer. Neither patient had a history of breast cancer. In patients with breast cancer and multiple metastases, ocular metastases are well described. However, the latter is uncommon as a presenting complaint.

S Afr Med J 2017;107(8):694-696. DOI:10.7196/SAMJ.2017.v107i8.12352

Metastatic disease involving the eye is rare. In women, the primary cancer most commonly occurs in the breast. Ocular metastases from breast cancer are generally a feature of widespread disseminated disease. It is rare for ophthalmological symptoms to be the presenting symptoms of a breast primary carcinoma. We present two patients who were not known to have breast cancer and who were diagnosed with ocular metastases, which were subsequently shown to be from a breast primary lesion.

Case 1

A 74-year-old woman presented to her ophthalmologist with a 4-week history of deteriorating vision in her right eye. She noticed flashing lights for the first 2 weeks, followed by 2 weeks of decreased visual acuity.

On examination, the visual acuity on the right was 0.4 best corrected (left: 1.0) and the anterior segment was normal.

The dilated pupil fundus examination revealed exudative retinal detachment (retinal detachment with no visible retinal tears, holes or breaks) with subretinal haemorrhage and a choroidal mass ~2 disc diameters superior from her optic disc (Fig. 1).

The mass was provisionally diagnosed as a choroidal secondary lesion, as it did not appear to be a choroidal melanoma. The patient initially reported to be well, but on further questioning with regard to comorbidities she mentioned noticing a breast lump.

On examination of her breasts, she had locally advanced breast cancer of the left breast with overlying skin nodules and ipsilateral lymphadenopathy. Core biopsy showed the lesion to be grade 3 ductal carcinoma – oestrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2-negative. A computed tomography (CT) scan showed an intraocular lesion with widespread pulmonary and bony metastases. She was treated with endocrine therapy.

Case 2

An 80-year-old woman presented to her ophthalmologist with a 1-month history of blurred vision in her right eye. The vision was reduced to 6/18 and she had a large pale subretinal lesion nasal to the disc. She was otherwise well. An ultrasound scan of the eye

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Fig. 1. Fundoscopy showing retinal folds with retinal detatchment, and no obvious tear.

showed a single, 14 mm choroidal mass (Fig. 2). Magnetic resonance imaging (MRI) confirmed an intraocular mass (Fig. 3), in keeping with a metastatic lesion. She was unaware of any other problems.

On examination, her breasts were normal. Her mammogram showed a 6 mm lesion in the left breast. Biopsy revealed a grade 1 ER-positive, PR-positive, HER2-negative ductal carcinoma. A CT scan showed multiple pulmonary metastases and an adrenal mass. These were interpreted in keeping with metastatic breast cancer rather than melanoma. She was treated with an aromatase inhibitor and her vision has improved.

Background

The presenting symptoms of ocular tumours are blurred vision, loss of peripheral vision or floaters.

The differential diagnosis includes: • choroidal melanoma • choroidal metastases (commonly breast and lung)

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Fig. 2. Ultrasound scan showing ocular tumour.

Fig. 3. Magnetic resonance imaging showing intraocular tumour.

• choroidal haemorrhage • inflammatory lesions of the choroid (granulomatous diseases) • retinoblastoma (in children).

Orbital tumours tend to present differently. The common presenting symptoms are proptosis, pain, diplopia and blurred vision.

The differential diagnosis includes: • orbital pseudotumour • thyroid eye disease • haemangioma • meningioma • lymphoma • rhabdomyosarcoma • metastases.

Discussion

The eye is an uncommon site for metastatic lesions, as it does not have a well-developed lymphatic system. Therefore, metastatic spread to the eye is haematogenous. The uveal tract, which is the most vascular part of the eye, is the most likely to be affected.[1]

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Ninety percent of metastatic lesions deposit in the choroid, causing painless loss of vision. The most common presentations are blurred vision, visual field defects and floaters.[2-4] In ~10% of cases the iris and ciliary body are involved.[1,3] In such cases, patients present with chronic anterior uveitis or raised intraocular pressure owing to iris neovascularisation or trabecular meshwork block from metastatic deposits.[1] The inflammation and raised pressure are resistant to treatment. Less commonly, breast adenocarcinoma will deposit in the orbital lymphatic tissue behind the eye and present with exophthalmos and pain.[2,4] On examination, choroidal metastases appear as pale subretinal lesions. The lesions exude serous fluid into the subretinal space and frequently cause retinal detachment. Choroidal metastases are associated with a disproportionately large amount of subretinal fluid compared with primary choroidal melanomas.[1,3,5] Both of our patients had retinal detachment at presentation, which is not uncommon in women with metastatic breast cancer. In contrast, with melanomas, the deposit is usually of a significant size before an exudative retinal detachment can be seen.

Many choroidal metastases are asymptomatic, unless the macula is directly involved by tumour or the associated retinal detachment.

They tend to be pale and often have a characteristic leopard-spot appearance from retinal pigment epithelial change on the surface.

Lipofuscin from poorly functioning retinal pigment epithelium can be observed on the surface of metastatic deposits, which can also be seen in choroidal melanoma.[1] Fluorescein angiography of a metastatic deposit reveals hypofluoresence in the arterial phase followed by late hyperfluorescence, with no pooling of dye. Indocyanine green angiography of the deeper choroidal vasculature is useful to differentiate choroidal haemangioma from a metastatic deposit. However, the most helpful investigation is an ocular ultrasound scan. Metastases are typically placoid shaped with an undulating surface and show medium to high blood flow velocity.

Most ocular metastases are indistinguishable in terms of the original primary tumour; however, certain primary tumours are associated with a particular metastatic appearance. Carcinoid metastases in the choroid appear orange, as do thyroid metastases. Renal metastases are more likely to produce intraocular haemorrhage. A solitary ocular metastasis from a cutaneous melanoma is pigmented and difficult to distinguish from a primary choroidal melanoma, although retinal and vitreous pigmented seeding is an indication that the pigmented choroidal tumour may be a secondary lesion.

When investigating ocular tumours, a breast examination and chest radiograph should be performed to determine the possible presence of a primary lesion. A liver ultrasound scan and liver function tests should be done to investigate the presence of potential liver metastases. An MRI of the brain is an important investigation, as cerebral and intraocular cancers often coexist. If the primary source of the metastatic lesion is unknown, a positron emission tomography (PET) scan or CT scan should be considered. These are very helpful investigations for lymphoma and melanoma, which are metabolically active and therefore show good uptake of fludeoxyglucose F18 (FDG).[1] The proportion of ocular tumours caused by metastases depends on when the tumours are diagnosed. A survey of 716 patients with ocular disease leading to their death showed that 9.3% had metastatic disease to the eye. However, this is more commonly seen at postmortem examination than in routine practice.[1] Common primary sites include breast (47%) and lung (21%). Other primary sites are prostate, gastrointestinal tract, kidney and skin (melanoma).[6] The metastases usually present as unilateral disease.[2] However, bilateral disease does occur, with an incidence of 20%.[7]

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IN PRACTICE

In women with widespread metastatic breast cancer, 28 - 58% may have orbital metastases[1,6] that may be asymptomatic. The metastases generally present 4.5 - 6.5 years after the initial diagnosis.[7] However, ocular metastasis is seldom the initial presentation of a previously undetected cancer.

Conclusion

Although ocular metastases as primary presentation of breast cancer are rare, it is an important diagnosis to consider. When examining a patient with ophthalmological complaints suggesting an infiltrative process, a thorough history must be taken and, in women, a full clinical examination must include a breast examination.

Acknowledgements. We would like to thank both of the patients for sharing their history with us.

Author contributions. All authors contributed to the article.

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Funding. None.

Conflicts of interest. None.

1. Cohen VML. Ocular metastases. Eye 2013;27(2):137-141. https://doi.org/10.1038/eye.2012.252 2. Vlachostergios PJ, Voutsadakis IA, Papandreou CN. Orbital metastasis of breast carcinoma. Breast Cancer 2009;3:91-97.

3. Wickremasinghe S, Dansingani KK, Tranos P, Liyanage S, Jones A, Davey C. Ocular presentations of breast cancer. Acta Ophthalmologica 2007;85(2):133-142. https://doi.org/10.1111/j.1600-0420.2006.00737.x 4. Ahmada MS, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr Opin Ophthalmol 2007;18(5):405-413. https://doi.org/10.1097/ICU.0b013e3282c5077c 5. Georgalas I, Paraskevopoulos T, Koutsandrea C, et al. Ophthalmic metastasis of breast cancer and ocular side effects from breast cancer treatment and management: Mini review. BioMed Res Int 2015. https://doi.org/10.1155/2015/574086 6. Arepalli S, Kaliki S, Shields CL. Choroidal metastases: Origin, features, and therapy. Ind J Ophthalmol 2015;63(2):122-127. https://doi.org/10.4103/0301-4738.154380 7. Francone E, Murelli F, Paroldi A, Margarino C, Friedman D. Orbital swelling as a first symptom in breast carcinoma diagnosis: A case report. J Med Case Rep 2010;4:211. https://doi.org/10.1186/1752-1947-4-211

Accepted 29 March 2017.

August 2017, Print edition

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

RESEARCH

Corneal donations in South Africa: A 15-year review N J York,1 MB BCh, FC Ophth (SA), Dip Ophth (SA); C Tinley,2 MB ChB, FRC Ophth (Lond) 1 2

Department of Ophthalmology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa Department of Ophthalmology, Red Cross War Memorial Childrenâ&#x20AC;&#x2122;s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Corresponding author: N York (yorkn20@gmail.com) Background. Corneal pathology is one of the leading causes of preventable blindness in South Africa (SA). A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem.

Objectives. To describe trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors.

Methods. This was a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016.

Results. There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8% originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%. Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/Asian. Donor age demonstrated a bimodal peak at 25 and 55 years.

Conclusions. The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.

S Afr Med J 2017;107(8):697-701. DOI:10.7196/SAMJ.2017.v107i8.12482

Full article available online at http://dx.doi.org/10.7196/SAMJ.2017.v107i8.12482

The effect of HIV status on clinical outcomes of surgical sepsis in KwaZulu-Natal Province, South Africa S Green,1,2 BSc Hons, MSc, MB BCh, DA; V Y Kong,2 MSc, PhD, MRCS; J Odendaal,2 BSc, MMedSci; B Sartorius,3 PhD; D L Clarke,2 PhD, FCS (SA); P Brysiewicz,4 PhD; J L Bruce,2 FCS (SA); G L Laing,2 PhD, FCS (SA); W Bekker,2 FCS (SA) Department of Anaesthesia, Critical Care and Pain, University of KwaZulu-Natal, Pietermaritzburg, South Africa Pietermaritzburg Metropolitan Surgical Service, Department of Surgery, University of KwaZulu-Natal, Pietermaritzburg, South Africa 3 Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa 4 School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa 1 2

Corresponding author: V Y Kong (victorywkong@yahoo.com) Background. KwaZulu-Natal Province, South Africa (SA), has long been the epicentre of the HIV epidemic, but the impact of HIV co-infection on the clinical outcomes of emergency surgical patients with sepsis remains largely unknown.

Objective. To review our experience with the management of patients with HIV co-infection and to compare the disease spectrum and outcome with those without HIV infection.

Methods. A retrospective study was undertaken at the Pietermaritzburg Metropolitan Surgical Service (PMSS), SA over a 5-year period from January 2010 to December 2014.

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RESEARCH

Results. A total of 675 patients with a documented surgical source of sepsis were reviewed. Of these, 332 (49%) were male, and the mean age was 46 (standard deviation 19) years. HIV status was known in 237 (35%) patients, 146 (62%) were HIV-positive and the remaining 91 (38%) were HIV-negative. Other than tuberculosis of the abdomen being significantly more common in HIV-positive than HIV-negative patients (10% v. 2%, p=0.033), there were no differences in the spectrum of diseases between the two groups. There were no significant differences in overall morbidity or mortality. When adjusted for CD4 counts, the mortality in HIV-positive patients with a CD4 count <200 cells/µL was 60% (15/25) and in those with a CD4 count >200 cells/µL it was 2% (2/101) (p<0.001).

Conclusion. The clinical presentation and the spectrum of surgical sepsis in patients with HIV co-infection were not markedly different to those in patients who were not HIV-infected. HIV-infected patients with a CD4 count <200 cells/µL had a significantly higher mortality.

Management approaches should not differ based solely on the HIV status of patients with surgical sepsis.

S Afr Med J 2017;107(8):702-705. DOI:10.7196/SAMJ.2017.v107i8.12045

Full article available online at http://dx.doi.org/10.7196/SAMJ.2017.v107i8.12045

Pancreatitis in a high HIV prevalence environment F Anderson,1 FCS, MMed; S R Thomson,2 ChM, FRCS (Ed & Eng) epartment of Surgery, Inkosi Albert Luthuli Central Hospital and School of Clinical Medicine, College of Health Sciences, Nelson R Mandela D School of Medicine, University of KwaZulu-Natal, Durban, South Africa 2 Department of Gastroenterology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa 1

Corresponding author: F Anderson (andersonf1@ukzn.ac.za) Background. Acute pancreatitis is common in HIV-positive individuals in reports from regions with a low incidence of HIV infection. This association has not been reported in areas with a high incidence of HIV infection.

Objective. To examine the prevalence and outcomes of HIV-associated acute pancreatitis in a high HIV prevalence environment, and trends over the period May 2001 - November 2010.

Methods. The records of patients admitted with acute pancreatitis from 2001 to 2010 were reviewed, looking for HIV status, CD4 counts and medications at presentation. The Glasgow criteria, organ failure, local complications and mortality were assessed.

Results. One hundred and six (16.9%) of 627 patients admitted with acute pancreatitis during the study period were infected with HIV. Most were female (65.1%) and black African (91.5%). The serum amylase level was used to confirm acute pancreatitis in 50 patients, with a mean of 1 569 IU/L (range 375 - 5 769), and urinary amylase in 56 patients, with a mean of 4 083 IU/L (range 934 - 36 856). Alcohol was a less frequent cause of pancreatitis in the HIV-positive group than in patients who were HIV-negative (24.5% v. 68.3%), and the prevalence of gallstones as a cause was similar (23.6% v. 17.9%). Antiretroviral therapy was associated with pancreatitis in 35.8%, and 6 (5.7%) had abdominal malignancies. Sixteen (15.1%) had pancreatic necrosis, 20 (18.9%) had septic complications, and 6 (5.7%) died.

Conclusions. HIV-associated acute pancreatitis was most frequent in females and black Africans and was associated with malignancy.

Mortality was similar in HIV and non-HIV pancreatitis.

S Afr Med J 2017;107(8):706-709. DOI:10.7196/SAMJ.2017.v107i8.10296

Full article available online at http://dx.doi.org/10.7196/SAMJ.2017.v107i8.10296

59

August 2017, Print edition

CAREERS & CLASSIFIEDS Ladine Van Heerden Tel: 012 481 2121 | E-mail: ladinev@hmpg.co.za Makhadzi Mulaudzi Tel: 012 481 2156 | E-mail: makhadzim@hmpg.co.za We accept credit card payments - Visa or MasterCard.

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t it comfor for ready r University tably into y eference. S of Cape To o our hospit u th A fr ic w a al bag or co n n ’s Division Medicines publishers at pock o F f o C rmulary (S linical Pha for the Sou A r M m th MAKHADZI, TEL: +27 (12) 481 2156 a F c A ), o fr lo a ic jo g an Medica y and the H informatio int initiativ l AEMAIL: n, includin ealth and M ssociatiomakhadzim@hmpg.co.za g n , fu e p d ll r o ic d vides easy al Publishin rug profile 12th editio access to th s, clinical n gG n of SAMF e latest, scie otes and sp is your ess e n cial prescr ential refer tifically ac iber’s poin ence to the ts. The tho rational, co roughly up st-effective and safe us e of medic ines.

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DEPARTMENT OF SOCIAL DEVELOPMENT It is our intention to promote representivity (race, gender and disability) in the public service through the filling of this post and candidates whose transfer / promotion/ appointment will promote representivity, will receive preference.

APPLICATIONS: The Director General, Department of Social Development, Private Bag X901, Pretoria, 0001.

Physical Address: HSRC Building, 134 Pretorius Street.

FOR ATTENTION: Ms E Steenkamp CLOSING DATE: 1 September 2017 NOTE: Curriculum vitae (CV) with a detailed description of duties, the names of two referees, and certified copies of qualifications and identity document must accompany your signed application for employment (Z83). In the event of hand delivery of applications, applicants must sign an application register book as proof of submission. All shortlisted candidates for SMS posts will be subjected to a technical exercise that intends to test relevant technical elements of the job, the logistics of which will be communicated by the Department. Following the interview and technical exercise, the selection panel will recommend candidates to attend a generic managerial competency assessment (in compliance with the DPSA Directive on the implementation of competency based assessments). The competency assessment will be testing generic managerial competencies using the mandated DPSA SMS competency assessment tools. The successful candidate will sign an annual performance agreement, complete a financial disclosure form and will also be required to undergo a security clearance. If the candidate is applying for an OSD post, certificates of service must be attached to the CV. It is the applicant’s responsibility to have foreign qualifications evaluated by the South African Qualification Authority (SAQA). Failure to submit the requested documents will result in your application not being considered. Personnel suitability checks will be conducted on short listed candidates and the appointment is subject to positive outcomes of the checks. Correspondence will be limited to shortlisted candidates only. The selection of candidates will be done with due regard to the relevant aspects of the selection process as set out in the Public Service Regulations, 2016 Chapter 4/67. Applications received after the closing date will not be taken into consideration. No faxed or e-mailed applications will be considered. If you have not been contacted within three months after the closing date of this advertisement, please accept that your application was unsuccessful.

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In terms of the Chief Directorate’s employment equity target, African males and females, as well as persons with disabilities, are encouraged to apply.

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The convenient pocket-sized design enables you to fit it comfortably into your hospital bag or coat pocket, so it The convenient pocket-sized design enables you to fit it comfortably into your hospital bag or coat pocket, so it can always be at hand for ready reference. South African Medicines Formulary (SAMF), a joint initiative of the can always be at hand for ready reference. South African Medicines Formulary (SAMF), a joint initiative of the University of Cape Town’s Division of Clinical Pharmacologyyand the Health and Medical Publishing Group, University of Cape Town’s Division of Clinical Pharmacolog and the Health and Medical Publishing Group, publishers for the South African Medical Association, provides easy access to the latest, scientifically accurate publishers for the South African Medical Association, provides easy access to the latest, scientifically accurate information, including full drug profiles, clinical notes and special prescriber’s points. The thoroughly updated information, including full drug profiles, clinical notes and special prescriber’s points. The thoroughly updated 12th edition of SAMF is your essential reference to the rational, cost-effective and safe use of medicines.

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CPD

AUGUST 2017

The CPD programme for SAMJ is administered by Medical Practice Consulting.

CPD questionnaires must be completed online at www.mpconsulting.co.za.

True (A) or false (B): SAMJ Enrolling HIV-positive adolescents in mental health research: A case study reflecting on legal and ethical complexities 1. Nearly one-sixth of all new HIV infections are in adolescents aged 15 - 19 years.

2. In both developed and less-developed countries, almost 50% of people living with HIV/AIDS have a diagnosable mental disorder.

Does access to private healthcare influence potential lung cancer cure rates?

3. Only ~10% of patients diagnosed with lung cancer in South Africa (SA) are offered treatment with curative intent.

4. Stage at diagnosis is not an important indicator of survival in lung cancer.

Corneal donations in SA: A 15-year review 5. Corneal disease is the cause of visual loss in 11% of blind or severely visually impaired children and 4% of blind adults in SA. 6.

Most patients with corneal disease will experience improved vision with a corneal transplant.

The effect of HIV status on clinical outcomes of surgical sepsis in KwaZulu-Natal Province, SA 7. About 25% of KwaZulu-Natalâ&#x20AC;&#x2122;s adult population live with HIV, compared with a national average of 18%.

8. In this study, the most common HIV-associated cause of surgical sepsis was abdominal tuberculosis.

Cardiovascular risk factors and mortality in children with chronic kidney disease (online only) 9. Cardiovascular disease is the most common cause of death among paediatric patients with end-stage renal disease.

10.

The body mass index alone is sufficient for determining the nutritional status of chronic kidney disease patients on dialysis.

CME Expedition medicine: A southern African perspective 11. Injuries caused by motor vehicle accidents on the way to a wilderness area are more common than any other expeditionrelated risks.

12.

Being competent in the management of toothache is more important than knowing about tropical diseases.

13. Poor sleep at high altitudes may be a symptom of acute mountain sickness.

Heat-related illness in the African wilderness 14. All heat exchange (gain or loss) occurs through four mechanisms: conduction, convection, radiation and evaporation.

15. Beta-blockers, anticholinergics and diuretics can increase susceptibility to heat.

16. Core temperature alone is not a reliable indicator of heat illness or injury in the absence of other signs.

17.

Gradual exposure to increasing levels of exertion in a hot environment induces heat acclimatisation over a period of days to weeks.

Human factors (HFs): Predictors of avoidable wilderness accidents?

18. There are at least three important and distinct sets of factors that may impact on the safety and efficiency of wilderness activities: environmental factors, technical skills, and non-technical skills, otherwise known as HFs. 19. HFs are seldom the most common cause of accidents in the wilderness.

20. HFs science attempts to design systems that support human performance and are resilient to unanticipated events.

Readers please note: articles may appear in summary/abstract form in the print edition of the Journal, with the full article available online at www.samj.org.za

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August 2017, Print edition

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