The rise in task-shared interventions that address the mental health treatment gap in low- and middle-income countries (LMICs) has highlighted the need for additional support and supervision of nonspecialist mental health workers (NHWs). The supervision of NHWs in most resource-limited settings is still primarily disorganized, without clear guidelines that provide the necessary structure for supervision. The need for supervision is even greater for NHWs working in the context of trauma, not only to provide training and ensure adequate delivery of care but also to provide support to minimize the psychological impact of their work. In South Africa, women face intersecting epidemics of HIV, intimate partner violence, and sexual trauma. This syndemic highlights the importance of integrating mental health treatment in HIV care, especially in settings like South Africa, where mental health services are limited. In this context, our group developed and is evaluating the effectiveness of ImpACT+, a task-shared coping intervention to improve clinical and mental health outcomes among HIV-infected women with sexual trauma in South Africa. We describe the ImpACT+ supervision model that is currently being implemented in the context of a hybrid effectiveness-implementation clinical trial. Combining experiences from clinical psychology, task-shared interventions, and trauma-informed care, the supervision model integrates formal elements of clinical supervision into categories that are suitable for use in task-shared trauma interventions in low-resource settings. To the best of our knowledge, such a trauma-informed supervision approach has not been widely documented in the literature, particularly in task-shared interventions in LMICs. In this article, we describe the ImpACT+ intervention, provide an overview of the supervision model, and provide illustrative examples of how the supervision model has been implemented.

Acute pancreatitis is an often-overlooked cause of acute abdominal pain in children and adolescents. Severe hypertriglyceridaemia is an important cause of recurrent acute pancreatitis. Monogenic causes of hypertriglyceridaemia, such as familial chylomicronaemia caused by lipoprotein lipase deficiency, are more frequently encountered in children and adolescents, but remain rare. Polygenic hypertriglyceridaemia is more common, but may require a precipitant before manifesting. With the global increase in obesity and type 2 diabetes, secondary causes of hypertriglyceridaemia in children and adolescents are increasing. We report two cases of severe hypertriglyceridaemia and pancreatitis in adolescent females. Hypertriglyceridaemia improved markedly with restriction of dietary fat. An inhibitor to lipoprotein lipase was found to be the cause in one patient, while in the other limited genetic investigation excluded chylomicronaemia owing to deficiency of lipoprotein lipase, its activators and processing proteins.

Abnormalities in the lipid profile are common, but it is often not easy to determine their cause. After exclusion of secondary causes, a primary (genetic) cause of dyslipidaemia should be considered. The most common monogenic dyslipidaemia is familial hypercholesterolemia (FH), but there are other clinically relevant genetic dyslipidaemias, including familial dysbetalipoproteinaemia (FD), monogenic chylomicronaemia and hypoalphalipoproteinemia. It is important to make a genetic diagnosis because it may influence the prognosis of the patient, for determining appropriate treatment goals and because it is relevant for family members. This clinical viewpoint explains the diagnostic process of genetic dyslipidaemias using two cases.

Abstract Background Familial Dysbetalipoproteinemia (FD) is the second most common genetic lipid disorder (prevalence ranging from 1 in 1000–2500), characterized by impaired postprandial lipoprotein clearance and associated with increased cardiovascular (CVD) risk. The majority of FD patients do not achieve non-HDL-cholesterol treatment goals, indicating the medical need for additional lipid-lowering treatment options. Purpose To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in FD patients. Methods A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12 week treatment periods. At the start and end of each treatment period FD patients received an oral fat load. The primary endpoint was the 8 hour post fat load non-HDL-cholesterol level expressed as area under the curve (AUC). Levels of other fasting and post fat load lipids and (apo)lipoproteins were assessed with ultracentrifugation, polyacrylamide gels, retinyl palmitate and SDS-PAGE. Results In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an ɛ2ɛ2 genotype. Compared with placebo, evolocumab reduced fasting non-HDL-cholesterol with 51% (95% CI 43–57) and the 8 hours post fat load non-HDL-cholesterol AUC with 49% (95% CI 42–55). Fasting triglyceride levels were reduced with 24% (95% CI 14–37) and the 8 hours post fat load triglyceride AUC was reduced with 22% (95% CI 11–29). Except for HDL-cholesterol, all fasting and 8 hour post fat load lipids and (apo)lipoproteins were significantly reduced by evolocumab, including apolipoprotein B (8 hour post fat load AUC reduction 47% (95% CI 41–53) and remnant cholesterol (8 hour post fat load AUC reduction 49% (95% CI −38 to 59)), compared with placebo. After treatment with evolocumab, 89% of patients achieved their non-HDL-cholesterol treatment goal compared with 36% after placebo. Conclusion Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and post fat load non-HDL-cholesterol and other atherogenic lipids and lipoproteins in FD patients. This is the largest clinical trial in FD to date and the first to investigate evolocumab in this very high-risk group. The large decrease in fasting and post fat load lipids and lipoproteins will likely lower CVD risk in these patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AmgenThis project was funded by Amgen for an investigator-initiated research project. The University Medical Center Utrecht was the sponsor of the study. The financial funder had no role in the design, collection of the data, conduct of the analyses or reporting of the study results.

Background Addressing sexual trauma in the context of HIV care is essential to improve clinical outcomes and mental health among women in South Africa. Women living with HIV (WLH) report disproportionately high levels of sexual trauma and have higher rates of posttraumatic stress disorder. Adherence to antiretroviral therapy (ART) may be difficult for traumatized women, as sexual trauma compounds the stress associated with managing HIV and is often comorbid with other mental health disorders, further compromising care engagement and adherence. ART initiation represents a unique window of opportunity for intervention to enhance motivation, increase care engagement, and address the negative effects of trauma on avoidant coping behaviors. Mental health interventions delivered by non-specialists in low- and middle-income countries have potential to treat depression, trauma, and effects of intimate partner violence among WLH. This study will examine the effectiveness of Improving AIDS Care after Trauma (ImpACT +), a task-shared, trauma-focused coping intervention, to promote viral suppression among WLH initiating ART in a South African clinic setting. Methods This study will be conducted in Khayelitsha, a peri-urban settlement situated near Cape Town, South Africa. Using a hybrid type 1 effectiveness-implementation design, we will randomize 350 WLH initiating ART to the ImpACT + experimental condition or the control condition (three weekly sessions of adapted problem-solving therapy) to examine the effectiveness of ImpACT + on viral suppression, ART adherence, and the degree to which mental health outcomes mediate intervention effects. ImpACT + participants will receive six once-a-week coping intervention sessions and six monthly maintenance sessions over the follow-up period. We will conduct mental health and bio-behavioral assessments at baseline, 4, 8, and 12 months, with care engagement data extracted from medical records. We will explore scalability using the Consolidated Framework for Implementation Research (CFIR). Discussion This trial is expected to yield important new information on psychologically informed intervention models that benefit the mental health and clinical outcomes of WLH with histories of sexual trauma. The proposed ImpACT + intervention, with its focus on building coping skills to address traumatic stress and engagement in HIV care and treatment, could have widespread impact on the health and wellbeing of individuals and communities in sub-Saharan Africa. Trial registration Clinicaltrials.gov NCT04793217 . Retrospectively registered on 11 March 2021.

This case report describes a patient who failed to thrive and lagged in development in the first year of her life and did not grow as expected. Though a history of diarrhoea was present, stool analysis was not conclusive for malabsorption of fat. Fat malabsorption may be due to various disorders of exocrine function of the pancreas as well as problems in the intestine. Abetalipoproteinaemia is a rare inherited condition in which neither the intestine nor the liver can secrete lipoproteins. This diagnosis was made on lipoprotein investigation by demonstrating the absence of lipoproteins containing apolipoprotein B (apoB). Lipoprotein investigation is generally normal in the parents of the recessively inherited condition of microsomal triglyceride transfer protein (MTTP) deficiency but in homozygous hypobetalipoproteinaemia owing to mutations in apoB that also impair lipoprotein assembly, the parents have low cholesterol concentrations. Patients with abetalipoproteinaemia improve markedly on dietary fat restriction but may benefit from medium-chain triglycerides as part of supplying their energy needs and, importantly, require high doses of vitamin E as well as other fat-soluble vitamins, to avoid neuromuscular degeneration and retinitis pigmentosa.

PURPOSE OF REVIEW:The functions, genetic variations and impact of apolipoprotein E on lipoprotein metabolism in general are placed in the context of clinical practice dealing with moderate dyslipidaemia as well as dysbetalipoproteinemia, a highly atherogenic disorder and lipoprotein glomerulopathy.RECENT FINDINGS:Additional variants of apolipoprotein E and participation of apolipoprotein E in inflammation are of interest. The mostly favourable effects of apolipoprotein E2 as well as the atherogenic nature of apolipoproteinE4, which has an association with cognitive impairment, are confirmed. The contribution of remnant lipoproteins of triglyceride-rich lipoproteins, of which dysbetalipoproteinemia represents an extreme, is explored in atherosclerosis. Mimetic peptides may present new therapeutic approaches. Apolipoprotein E is an important determinant of the lipid profile and cardiovascular health in the population at large and can precipitate dysbetalipoproteinemia and glomerulopathy. Awareness of apolipoprotein E polymorphisms should improve medical care.

Pregnancy represents a time of increased risk for intimate partner violence (IPV), and an HIV diagnosis further increases the vulnerability of this at-risk group. This study explores experiences of recent IPV using qualitative interviews with N = 12 HIV-positive pregnant women recruited from a clinical setting in South Africa, a location with a high global prevalence of IPV and HIV. Partner dynamics around IPV resulted in HIV shame and stigma and adversely affected engagement in HIV care and HIV treatment behaviors. The results highlight the challenges women face in navigating disclosure of both IPV and HIV, accessing necessary support, and engaging in both HIV-related and pregnancy-related care in the context of an abusive relationship.

Familial hypercholesterolaemia (FH) is a common autosomal dominantly inherited disorder in which impaired clearance of plasma low-density lipoprotein cholesterol causes premature atherosclerotic vascular disease and tendon xanthomata. This workshop aimed to consolidate information on the diagnosis and management of FH in South Africa. The genetic causes include mutations in the LDL receptor, apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 (PCSK9). Additionally, the concatenation of multiple gene variants can result in polygenic FH. Therapeutic measures include a healthy lifestyle, statins and cholesterol-absorption inhibitors that will achieve control of the dyslipidaemia in the majority of cases. The recently introduced monoclonal antibodies to PCSK9 can improve achievement of target concentration in severe cases. FH is present in all sectors of the South African population but there is sparse documentation in the indigenous African populations. FH should be actively sought, diagnosed and treated with judicious pharmacotherapy and screening of relatives.

MPV17-related mitochondrial neurohepatopathy is a rare genetic disorder worldwide. We report on a novel pathogenic variant in the MPV17 gene in 24 unrelated neurohepatopathic infants of non-consanguineous Black South African heritage. Exome sequencing identified homozygosity for a c.106C>T nonsense variant in exon 3 of the human MPV17 gene in 2 unrelated index patients. mRNA analysis revealed transcripts both with and without exon 3, indicating both reduced splice efficiency and premature termination as mechanisms for disease. Carrier frequency in this population was found to be 1 in 68 (95% CI; 1/122-1/38) with an estimated newborn incidence of 1 in 18 496 (95% CI; 1/59 536-1/5776). Affected infants all presented with infantile onset neurohepatopathy with none surviving beyond infancy. This description of a relatively common pathogenic variant underlying a previously uncharacterized severe neurohepatopathy in South Africa will engender increased awareness, earlier diagnosis and possibly improve outcome if preventative or specific therapeutic options can be found.

BACKGROUND AND AIMS:Familial hypercholesterolaemia (FH) is the commonest monogenic disorder that accelerates atherosclerotic cardiovascular disease. We compared and contrasted the characteristics of patients from three specialist centres in the southern hemisphere.METHODS:Adult index-cases with molecularly diagnosed heterozygous FH attending specialist lipid centres in Cape Town, Perth and São Paulo were studied. Myocardial infarction, revascularisation, hypertension, diabetes, smoking and lipid-lowering treatment were recorded at the time of diagnosis and compared across the three centres.RESULTS:The spectrum of genetic variants causative of FH was significantly different in patients attending the centres in South Africa compared with Australia and Brazil. Hypertension and diabetes were more prevalent in Brazilian and Australian patients, than in South African patients, but the frequency of smoking was significantly greater in South Africa than the other two centres (p<0.01). Age, male sex and smoking were significant independent predictors of coronary artery disease (CAD) in all three countries (p<0.05).CONCLUSIONS:Patients with FH in three specialist centres in the southern hemisphere exhibit a high prevalence of non-cholesterol cardiovascular disease risk factors. Older age, male sex and smoking were more common among subjects with CAD. In all three countries, there should be vigorous programmes for the control of risk factors beyond good control of hypercholesterolaemia among patients with FH. Promotion of a healthy lifestyle, especially anti-smoking advice, is of paramount importance.

BACKGROUND:The classification of sexuality-related conditions and conditions relating to transgender identity has generated controversy. Growing evidence suggests that the distress and dysfunction reported by transgender individuals is more likely associated with social exclusion, stigmatization, and violence than as a result of gender incongruence per se. Our study aimed to explore the experiences of South African transgender individuals through: 1) their self-reported accounts of gender incongruence, and 2) associations between their experiences of social exclusion and violence, and their reports of psychological distress and dysfunction during adolescence. METHODS:Our sample of 57 South African transgender adults completed a structured interview, in English, including questions related to experiences of gender incongruence duration, distress, dysfunction, social exclusion, and violence. RESULTS:Many transgender individuals reported having experienced an intense desire to be a different gender, with all noting discomfort with several aspects of their bodies. Importantly, psychological distress and dysfunction were significantly associated with social exclusion (most commonly perpetuated by family and friends) and not with gender incongruence per se. CONCLUSIONS:This study adds to the growing evidence that experiences of social exclusion play a significant role in the psychological distress and dysfunction reported by transgender persons.

Letter by Nutten et al. on article by Levin et al. (Levin ME, Blackhurst DM, Kirstein F, Kok D, van der Watt GF, Marais AD. Residual allergenicity of amino acid-based and extensively hydrolysed cow's milk formulas. S Afr Med J 2017;107(9):763-767. S Afr Med J 2017;107(3):258-263. https://doi.org/10.7196/SAMJ.2017.v107i9.12137); and response by Levin et al.

Advances in the causes of disorders of lipid metabolism, and effective intervention in atherosclerosis with medication, have increased the reliance on laboratory investigation in clinical practice. The conventional lipid profile, comprising fasting triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, suffices for screening persons at risk of atherosclerosis. Additionally, lipoprotein (a) measurement enhances risk assessment and could explain atherosclerosis with a desirable lipid profile. Certain rare disorders in sterol and fatty acid metabolism do not alter the conventional lipid profile. Non-fasting samples are gaining popularity, as the triglycerides, although mildly increased, signify atherogenic lipoprotein remnant accumulation. Apoprotein A1 (apo A1) and apo B concentrations parallel HDL cholesterol and LDL cholesterol, respectively, and are of value in disorders of these lipoproteins. In severe dyslipoproteinaemia, special investigations establish the cause of the disease and may allow selection of better treatment. In such cases, not only apoprotein concentrations, but also enzyme or cell function, as well as genetic investigations, are relevant. The most important genetic disorders to recognise are familial hypercholesterolaemia, dysbetalipoproteinaemia and chylomicronaemia. Expertise in lipidology is limited in South Africa, but specialist centres can provide clinical and laboratory support to ensure best management of severe disorders.

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.