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Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Background The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. Objective The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. Methods Data of patients recently (≤5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. Conclusion Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies. [ABSTRACT FROM AUTHOR]

The epidemiology of systemic lupus erythematosus (SLE) in Africa is largely undetermined, and the perception persists that the incidence of SLE on the continent is very low. Recent studies as well as our own experience, however, suggest that this is not the case. We have conducted a survey amongst medical practitioners in Africa to determine their experiences of diagnosing and treating SLE patients, and the results suggest that significant numbers of African patients are presenting with SLE. The apparent low incidence rate in Africa may be the result of underdiagnosis due to poor access to health care, low disease recognition within primary health care settings, limited access to diagnostic tools and inadequate numbers of specialist physicians. Treatment of SLE in Africa is also restricted by availability and affordability of immunosuppressive drugs. We have established the African Lupus Genetics Network (ALUGEN), an informal network of clinicians and researchers in Africa who have an interest in SLE, in order to facilitate combined clinical and research efforts towards improved outcomes for African SLE patients. [ABSTRACT FROM PUBLISHER]

There are few published studies on biopsy proven lupus nephritis (LN) from sub-Sahara Africa, mainly due to lack of expertise and pathology back-up for performing and interpreting renal biopsies in many centres. The purpose of this study was to document factors associated with biopsy proven LN and to determine clinical and laboratory models that best predict proliferative LN in South Africans. Of the 251 patients studied, 84.1% were females and 79.3% were of mixed ancestry. There were more observed cases of proliferative LN (63%) than non-proliferative LN. Factors associated with proliferative LN were male gender (p = 0.049), haematuria on dipstix (p < 0.0001), proteinuria on dipstix (p = 0.042), low serum albumin (p = 0.032), low complement C3 (p < 0.0001), low complement C4 (p = 0.009) and positive double-stranded DNA (p = 0.039). Using four models designed from various combinations of the factors associated with proliferative LN, the specificity and positive predictive values were highest for the model that combined gender (male), presence of dipstix haematuria and proteinuria, hypoalbuminaemia, low C3 and low C4 and positive double-stranded DNA (100% respectively). Further study is recommended to identify the value of using these demographic and laboratory parameters in identifying patients with proliferative LN in resource limited centres where the performance of a biopsy is not possible. [ABSTRACT FROM PUBLISHER]

Humidification for mechanical ventilation and high flow gas applications is more complicated than most clinicians are taught to believe and as a result is often not well understood. Several misconceptions survive despite growing evidence to the contrary. This article attempts to debunk some of these myths including why temperature is not a surrogate for humidity, why 100% humidity is not always optimal and the problems with humidity using heated wire circuits. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is a common paediatric soft tissue sarcoma that resembles developing foetal skeletal muscle. Tumours of the alveolar subtype frequently harbour one of two characteristic translocations that juxtapose PAX3 or PAX7, and the forkhead-related gene FKHR (FOXO1A). The embryonal subtype of RMS is not generally associated with these fusion genes. Here, we have quantified the relative levels of chimaeric and wild-type PAX transcripts in various subtypes of RMS (n=34) in order to assess the relevance of wild-type PAX3 and PAX7 gene expression in these tumours. We found that upregulation of wild-type PAX3 is independent of the presence of either fusion gene and is unlikely to contribute to tumorigenesis. Most strikingly, upregulated PAX7 expression is almost entirely restricted to cases without PAX3-FKHR or PAX7-FKHR fusion genes and may contribute to tumorigenesis in the absence of chimaeric PAX transcription factors. Furthermore, as myogenic satellite cells are known to express PAX7, this pattern of PAX7 expression suggests this cell type as the origin of these tumours. This is corroborated by the detection of MET (c-met) expression, a marker for the myogenic satellite cell lineage, in all RMS samples expressing wild-type PAX7. [ABSTRACT FROM AUTHOR]

The MDM2 protein is known to be overexpressed in some sarcomas including rhabdomyosarcoma. However, the extent to which the MDM2 protein influences sensitivity to chemotherapeutic drugs is unclear. We have analysed this further using stable transfection of the mdm2 gene into 4 well-characterised human paediatric rhabdomyosarcoma cell lines. Transfection with themdm2 gene resulted in increased levels of the MDM2 protein in all the cell lines. In 2 of the lines, SCMC and RD, the mdm2 gene caused between 2-fold and 61-fold increase in resistance to vincristine, etoposide and doxorubicin but not to cisplatin. In these lines there was an increase in expression of themdr-1 gene which encodes P-glycoprotein, but not themrp1 gene which encodes the multidrug resistance protein (MRP). The resistance was reversible using the MDR modulator PSC833, confirming the presence of P-glycoprotein. We conclude that MDM2 overexpression may be a mechanism by which multidrug resistance is regulated in some rhabdomyosarcomas. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 68-year-old woman with dermatochalasis and vision obstruction. It mentions that bepharoplasty is a cosmetic procedure which is carried around the world. It mentions that DNA extracted from the paraffin tissue depicted the presence of T-cell clone. It offers information on folliculotropic mycosis fungoides (MF).

What would happen if respiratory therapists became the most engaged employees in an organization? Engaged employees are more creative, more productive, more loyal, use fewer sick days, and experience higher workplace satisfaction. What leader does not want these characteristics in every member of their workforce? In this respect, respiratory therapists are no different from manufacturing, retail, or finance employees. They value three basic work factors of engaged employees—mastery, purpose, and autonomy. These three critical factors have been well documented and, if an RT supervisor, coordinator, or manager wants engaged employees, they must address these factors. But if the general workforce only has 17%-25% of its workforce highly engaged, how is a mid-level manager in a huge, multi-tiered organization supposed to create a work atmosphere of engaged employees? This presentation will identify the foundational principles for creating an environment where engaged employees can be the standard and not the exception. It will be a strategic look into what conditions must be created (because you must be strategic before you implement tactics) and what practical outcomes can be expected from even simple changes. Leaders of two or 200 can apply these three factors to improve their workplace, their employees, and their team’s productivity-even in an organization that may not, or cannot, support them. Don’t settle for average. Start on the high purpose of making respiratory therapists the example of employee engagement in your organization. [ABSTRACT FROM AUTHOR]

Abstract Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number variation have also been identified; and an effect of ethnicity on susceptibility has been described.

Abstract Background Fetal alcohol syndrome (FAS) is a serious global health problem and is observed at high frequencies in certain South African communities. Although in utero alcohol exposure is the primary trigger, there is evidence for genetic- and other susceptibility factors in FAS development. No genome-wide association or linkage studies have been performed for FAS, making computational selection and -prioritization of candidate disease genes an attractive approach. Results 10174 Candidate genes were initially selected from the whole genome using a previously described method, which selects candidate genes according to their expression in disease-affected tissues. Hereafter candidates were prioritized for experimental investigation by investigating criteria pertinent to FAS and binary filtering. 29 Criteria were assessed by mining various database sources to populate criteria-specific gene lists. Candidate genes were then prioritized for experimental investigation using a binary system that assessed the criteria gene lists against the candidate list, and candidate genes were scored accordingly. A group of 87 genes was prioritized as candidates and for future experimental validation. The validity of the binary prioritization method was assessed by investigating the protein-protein interactions, functional enrichment and common promoter element binding sites of the top-ranked genes. Conclusion This analysis highlighted a list of strong candidate genes from the TGF-β, MAPK and Hedgehog signalling pathways, which are all integral to fetal development and potential targets for alcohol's teratogenic effect. We conclude that this novel bioinformatics approach effectively prioritizes credible candidate genes for further experimental analysis.

Microbial data sharing underlies evidence-based microbial research, as well as pathogen surveillance and analysis essential to public health. While the need for data sharing was highlighted during the SARS-CoV-2 pandemic, some concerns regarding secondary data use have also surfaced. Although general guidelines are available for data sharing, we note the absence of a set of established, universal, unambiguous and accessible principles to guide the secondary use of microbial data. Here, we propose the Public Health Alliance for Genomic Epidemiology (PHA4GE) Microbial Data-Sharing Accord to consolidate consensus norms and accepted practices for the secondary use of microbial data. The Accord provides a set of seven simple, baseline principles to address key concerns that may arise for researchers providing microbial datasets for secondary use and to guide responsible use by data users. By providing clear rules for secondary use of microbial data, the Accord can increase confidence in sharing by data providers and protect against data mis-use during secondary analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: National Health Services (NHS) England mandates that an acute kidney injury (AKI) detection algorithm be embedded in laboratories. We evaluated the implementation of the algorithm and the consistency of alerts submitted to the United Kingdom Renal Registry (UKRR)., Methods: Code was developed to simulate the syntax of the AKI detection algorithm, executed on data from local laboratories submitted to the UKRR, including alerts and serum creatinine (SCr) results spanning 15 months before and after the alert submission. Acute kidney injury alerts were categorized into stages 0/1/2/3. Inter-rater agreement (Gwet's AC1) was used to compare local and centrally derived alerts at individual laboratory and commercial laboratory information management system (LIMS) levels, penalizing extreme disagreements., Results: The analysis included 9,096,667 SCr results from 29 labs (475,634 patients; median age 72 years, 47% female) between algorithm activation and data extraction (September 30, 2020). Laboratories and the central simulation generated 1,579,633 and 1,646,850 non-zero AKI alerts, respectively. Agreement was high within known laboratory information management system providers (0.97-0.98) but varied across individual laboratories (overall range 0.17-0.98, 0.17-0.23 in three). Agreement tended to be lower (Gwet's AC1 0.88) with the highest baseline SCr quartile (median 164 μmol/L)., Conclusions: Overall, alerts submitted to the UKRR are a valid source of AKI surveillance but there are concerns about inconsistent laboratory practices, incomplete adoption of the NHSE algorithm code, alert suppression, and variable interpretation of guidelines. Future efforts should audit and support laboratories with low agreement rates, and explore reasons for lower agreement in individuals with pre-existing CKD., (© 2024. The Author(s).)

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

In South Africa, PLHIV are eligible for free ART and kidney function screening. Serum creatinine (SCr) laboratory test data from the National Health Laboratory Service are collated at the Provincial Health Data Centre and linked with other routine health data. We analysed SCr and estimated glomerular filtration rate (eGFR) results for PLHIV and HIV-negative healthcare clients aged 18-80 years accessing healthcare in Khayelitsha, South Africa and comorbidity profiles at SCr and eGFR testing. 45 640 individuals aged 18-80 years with at least one renal test accessed Khayelitsha public health facilities in 2016/2017. 22 961 (50.3%) were PLHIV. Median age at first SCr and eGFR test for PLHIV was 33yrs (IQR: 27,41) to 36yrs (IQR: 30,43) compared to 49yrs (IQR: 37,57) and 52yrs (IQR: 44,59) for those without HIV. PLHIV first median SCr results were 66 (IQR: 55,78) μmol/l compared to 69 (IQR: 58,82) μmol/l for HIV-negative individuals. Hypertension, diabetes, and CKD at testing were more common in HIV-negative people than PLHIV. HIV, diabetes and tuberculosis (TB) are associated with higher eGFR results; whilst hypertension, being male and older are associated with lower eGFR results. These data reflect testing practices in the Western Cape: younger people without HIV have generally worse kidney function test results; younger PLHIV have generally good test results, and older people with/without HIV have generally similar test results, reflecting regular screening for kidney function in asymptomatic PLHIV whereas young HIV-negative people are tested only when presenting with renal symptoms. Our analysis suggests we cannot infer the future healthcare requirements of younger PLHIV based on the current ageing population, due to changing ART availability for different generations of PLHIV. Instead, routine health data may be used in an agile way to assess ongoing healthcare requirements of ageing PLHIV, and to reflect implementation of treatment guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Osei-Yeboah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The conduct of research is critical to advancing human health. However, there are issues of ethical concern specific to the design and conduct of research in conflict settings. Conflict-affected countries often lack strong platform to support technical guidance and monitoring of research ethics, which may lead to the use of divergent ethical standards some of which are poorly elaborated and loosely enforced. Despite the growing concern about ethical issues in research, there is a dearth of information about ethical compliance in conflict areas. Valid and ethically informed decision-making is a premier pact with research participants in settling possible ethical issues before commencing the research, which is ensured by gaining informed consent from prospective participants of the research., Aims: This research aimed to explore compliance with research ethics and consent validity in community-based epidemiological research conducted previously., Methods: Research participants were recruited in the western part of Ethiopia in three districts subjected to conflicts. A community-based cross-sectional study design was utilized, and 338 residents were enrolled as study participants. All participants had previously been enrolled as research participants in epidemiological studies. Data was collected using a questionnaire that was pilot-tested before the commencement of the main data collection. The questionnaire focused on participants' experiences of the informed consent process followed when they were recruited for an epidemiological study and covered themes such as essential information provided, level of comprehension, and voluntarism of consent., Results: Over half of the study participants, 176 (52%), were not provided with essential information before consenting. And 135 (40%) of them did not comprehend the information provided to them. One hundred and ninety (56%) participants freely and voluntarily agreed to partake in one of these epidemiological studies, with over a quarter (97; 28.7%) of them reporting they were subjected to undue influence. Written consent was obtained from only 32 (9.4%) of the participants., (© 2024. The Author(s).)

Type 2 diabetes mellitus (T2DM) is managed with combined lifestyle modifications and antidiabetic drugs, but people on treatment often fail to reach glycaemic control. Adherence is important for achieving optimal glycaemic control, and management of diabetes with drugs is a lifelong process, so understanding adherence through analysis of longitudinal medications data is important. Using retrospective routine health data and metformin dispensing records as a proxy for medication use, we describe longitudinal persistence and adherence to oral diabetes medication in a virtual cohort of 10541 people with diabetes (PLWD) in Khayelitsha subdistrict, Cape Town. Adherence was measured in 120-day sliding windows over two years and used to estimate metformin adherence trajectories. Multinomial logistic regression identified factors influencing these trajectories. Analysis of pharmacy dispensing records showed varying medication refill patterns: while some PLWD refilled prescriptions consistently, others had treatment gaps with periods of non-persistence and multiple treatment episodes-from one to five per individual across two years. There was a general trend of decreasing adherence over time across all sliding windows in the two-year period, with only 25% of the study population achieved medication adherence (> = 80% adherence) after two years. Four adherence trajectories; 'low adherence gradual decline (A), 'high adherence rapid decline' (B), 'low adherence gradual increase (C) and 'adherent' (D) were identified. Only trajectory D represented participants who were adherent at treatment start and remained adherent after two years. Taking HIV antiretroviral treatment before or concurrently with diabetes treatment and taking metformin in combination with sulphonylurea and/or insulin were associated with the long-term adherence (trajectory D). Routine data shows real life medication implementation patterns which might not be seen under controlled study conditions. This study illustrates the utility of these data in describing longitudinal adherence patterns at both an individual and population level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tamuhla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The increasing digitisation of personal health data has led to an increase in the demand for onward health data. This study sought to develop local language scripts for use in public sector maternity clinics to capture informed consent for onward health data use. The script considered five possible health data uses: 1. Sending of general health information content via mobile phones; 2. Delivery of personalised health information via mobile phones; 3. Use of women's anonymised health data; 4. Use of child's anonymised health data; and 5. Use of data for recontact. Qualitative interviews ( n  = 54) were conducted among women attending maternity services in three public health facilities in Gauteng and Western Cape, South Africa. Using cognitive interviewing techniques, interviews sought to:(1) explore understanding of the consent script in five South African languages, (2) assess women's understanding of what they were consenting to, and (3) improve the consent script. Multiple rounds of interviews were conducted, each followed by revisions to the consent script, until saturation was reached, and no additional cognitive failures identified. Cognitive failures were a result of: (1) words and phrases that did not translate easily in some languages, (2) cognitive mismatches that arose as a result of different world views and contexts, (3) linguistic gaps, and (4) asymmetrical power relations that influence how consent is understood and interpreted. Study activities resulted in the development of an informed consent script for onward health data use in five South African languages for use in maternity clinics.

Despite the expanding digitisation of individual health data, informed consent for the collection and use of health data is seldom explicitly sought in public sector clinics in South Africa. This study aims to identify perceptions of informed consent practices for health data capture, access, and use in Gauteng and the Western Cape provinces of South Africa. Data collection from September to December 2021 included in-depth interviews with healthcare providers ( n  = 12) and women ( n  = 62) attending maternity services. Study findings suggest that most patients were not aware that their data were being used for purposes beyond the individualised provision of medical care. Understanding the concept of anonymised use of electronic health data was at times challenging for patients who understood their data in the limited context of paper-based folders and booklets. When asked about preferences for electronic data, patients overwhelmingly were in favour of digitisation. They viewed electronic access to their health data as facilitating rapid and continuous access to health information. Patients were additionally asked about preferences, including delivery of health information, onward health data use, and recontacting. Understanding of these use cases varied and was often challenging to convey to participants who understood their health data in the context of information inputted into their paper folders. Future systems need to be established to collect informed consent for onward health data use. In light of perceived ties to the care received, these systems need to ensure that patient preferences do not impede the content nor quality of care received.

Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa., (© 2023. The Author(s).)

Evidence-based healthcare relies on health data from diverse sources to inform decision-making across different domains, including disease prevention, aetiology, diagnostics, therapeutics and prognosis. Increasing volumes of highly granular data provide opportunities to leverage the evidence base, with growing recognition that health data are highly sensitive and onward research use may create privacy issues for individuals providing data. Concerns are heightened for data without explicit informed consent for secondary research use. Additionally, researchers-especially from under-resourced environments and the global South-may wish to participate in onward analysis of resources they collected or retain oversight of onward use to ensure ethical constraints are respected. Different data-sharing approaches may be adopted according to data sensitivity and secondary use restrictions, moving beyond the traditional Open Access model of unidirectional data transfer from generator to secondary user. We describe collaborative data sharing, facilitating research by combining datasets and undertaking meta-analysis involving collaborating partners; federated data analysis, where partners undertake synchronous, harmonised analyses on their independent datasets and then combine their results in a coauthored report, and trusted research environments where data are analysed in a controlled environment and only aggregate results are exported. We review how deidentification and anonymisation methods, including data perturbation, can reduce risks specifically associated with health data secondary use. In addition, we present an innovative modularised approach for building data sharing agreements incorporating a more nuanced approach to data sharing to protect privacy, and provide a framework for building the agreements for each of these data-sharing scenarios., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Modern biomedical research is characterised by its high-throughput and interdisciplinary nature. Multiproject and consortium-based collaborations requiring meaningful analysis of multiple heterogeneous phenotypic datasets have become the norm; however, such analysis remains a challenge in many regions across the world. An increasing number of data harmonisation efforts are being undertaken by multistudy collaborations through either prospective standardised phenotype data collection or retrospective phenotype harmonisation. In this regard, the Phenotype Harmonisation Working Group (PHWG) of the Human Heredity and Health in Africa (H3Africa) consortium aimed to facilitate phenotype standardisation by both promoting the use of existing data collection standards (hosted by PhenX), adapting existing data collection standards for appropriate use in low- and middle-income regions such as Africa, and developing novel data collection standards where relevant gaps were identified. Ultimately, the PHWG produced 11 data collection kits, consisting of 82 protocols, 38 of which were existing protocols, 17 were adapted, and 27 were novel protocols. The data collection kits will facilitate phenotype standardisation and harmonisation not only in Africa but also across the larger research community. In addition, the PHWG aims to feed back adapted and novel protocols to existing reference platforms such as PhenX., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Lyndon Zass et al.)

Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH., Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period., Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults., Conclusions: Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: The Patient Master Index (PMI) plays an important role in management of patient information and epidemiological research, and the availability of unique patient identifiers improves the accuracy when linking patient records across disparate datasets. In our environment, however, a unique identifier is seldom present in all datasets containing patient information. Quasi identifiers are used to attempt to link patient records but sometimes present higher risk of over-linking. Data quality and completeness thus affect the ability to make correct linkages., Aim: This paper describes the record linkage system that is currently implemented at the Provincial Health Data Centre (PHDC) in the Western Cape, South Africa, and assesses its output to date., Methods: We apply a stepwise deterministic record linkage approach to link patient data that are routinely collected from health information systems in the Western Cape province of South Africa. Variables used in the linkage process include South African National Identity number (RSA ID), date of birth, year of birth, month of birth, day of birth, residential address and contact information. Descriptive analyses are used to estimate the level and extent of duplication in the provincial PMI., Results: The percentage of duplicates in the provincial PMI lies between 10% and 20%. Duplicates mainly arise from spelling errors, and surname and first names carry most of the errors, with the first names and surname being different for the same individual in approximately 22% of duplicates. The RSA ID is the variable mostly affected by poor completeness with less than 30% of the records having an RSA ID.The current linkage algorithm requires refinement as it makes use of algorithms that have been developed and validated on anglicised names which might not work well for local names. Linkage is also affected by data quality-related issues that are associated with the routine nature of the data which often make it difficult to validate and enforce integrity at the point of data capture., Competing Interests: Conflict of interest statement: The authors declare no conflicts of interests.

Purpose: Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes., Methods: We tested 234 genetically naive South African children diagnosed with/possible DEE using gene panels, exome sequencing, and chromosomal microarray. Statistical comparison of electroclinical features in children with and children without candidate variants was performed to identify characteristics most likely predictive of a positive genetic finding., Results: Of the 41 (of 234) children with likely/pathogenic variants, 26 had variants supporting precision therapy. Multivariate regression modeling highlighted neonatal or infantile-onset seizures and movement abnormalities as predictive of a positive genetic finding. We used this, coupled with an emphasis on precision medicine outcomes, to propose the pragmatic "Think-Genetics" strategy for early recognition of a possible genetic etiology., Conclusion: Our findings emphasize the importance of an early genetic diagnosis in DEE. We designed the Think-Genetics strategy for early recognition, appropriate interim management, and genetic testing for DEE in resource-constrained settings., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis., (© 2023. The Author(s).)

Research involving human participants requires their consent, and it is common practice to capture consent information on paper and store those hard copies, presenting issues such as long-term storage requirements, inefficient retrieval of consent forms for reference or future use, and the potential for transcription errors when transcribing captured informed consent. There have been calls to move to electronic capture of the consent provided by research participants (e-consent) as a way of addressing these issues. A tiered framework for e-consent was designed using the freely available features in the inbuilt REDCap e-consent module. We implemented 'branching logic', 'wet signature' and 'auto-archiver' features to the main informed consent and withdrawal of consent documents. The branching logic feature streamlines the consent process by making follow-up information available depending on participant response, the 'wet signature' feature enables a timestamped electronic signature to be appended to the e-consent documents and the 'auto-archiver' allows for PDF copies of the e-consent documents to be stored in the database. When designing the content layout, we provided example participant information text which can be modified as required. Emphasis was placed on the flow of information to optimise participant understanding and this was achieved by merging the consent and participant information into one document where the consent questions were asked immediately after the corresponding participant information. In addition, we have provided example text for a generic human genomic research study, which can be easily edited and modified according to specific requirements. Building informed consent protocols and forms without prior experience can be daunting, so we have provided researchers with a REDCap template that can be directly incorporated into REDCap databases. It prompts researchers about the types of consent they can request for genomics studies and assists them with suggestions for the language they might use for participant information and consent questions. The use of this tiered e-consent module can ensure the accurate and efficient electronic capture and storage of the consents given by participants in a format that can be easily queried and can thus facilitate ethical and effective onward sharing of data and samples whilst upholding individual participant preferences., (© 2022. The Author(s).)

The SARS-CoV-2 virus is responsible for the COVID-19 global public health emergency, and the disease it causes is highly variable in its clinical presentation. Clinical phenotypes are heterogeneous both in terms of presentation of symptoms in the host and response to therapy. Several studies and initiatives have been established to analyse and review host genetic epidemiology associated with COVID-19. Our research group curated these articles into a web-based database using the python application-server framework Django. The database provides a searchable research tool describing current literature surrounding COVID-19 host genetic factors associated with disease outcome. This paper describes the COHG-SA database and provides an overview of the analyses that can be derived from these data., (© 2022. The Author(s).)

Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine. We discuss how the information gathered in the survey could instruct the policies of African institutions seeking to implement precision, and more specifically, genomic medicine approaches in their health care systems in the following areas: 1) Prioritization of infrastructures. 2) Need for translational research. 3) Information dissemination to potential users. 4) Training programs for specialized personnel. 5) Engaging political stakeholders and the public. A checklist with key requirements to assess readiness for implementation of genomic medicine programs is provided to guide the process from scientific discovery to clinical application., Competing Interests: MK is a non-executive director and shareholder of Gknowmix (Pty) Ltd., that developed a database resource for research translation under the auspices of the South African Research Council. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jongeneel, Kotze, Bhaw-Luximon, Fadlelmola, Fakim, Hamdi, Kassim, Kumuthini, Nembaware, Radouani, Tiffin and Mulder.)

There is an increasing recognition of the importance of including benefit sharing in research programmes in order to ensure equitable and just distribution of the benefits arising from research. Whilst there are global efforts to promote benefit sharing when using non-human biological resources, benefit sharing plans and implementation do not yet feature prominently in research programmes, funding applications or requirements by ethics review boards. Whilst many research stakeholders may agree with the concept of benefit sharing, it can be difficult to operationalise benefit sharing within research programmes. We present a framework designed to assist with identifying benefit sharing opportunities in research programmes. The framework has two dimensions: the first represents microlevel, mesolevel and macrolevel stakeholders as defined using a socioecological model; and the second identifies nine different types of benefit sharing that might be achieved during a research programme. We provide an example matrix identifying different types of benefit sharing that might be undertaken during genomics research, and present a case study evaluating benefit sharing in Africa during the SARS-CoV-2 pandemic. This framework, with examples, is intended as a practical tool to assist research stakeholders with identifying opportunities for benefit sharing, and inculcating intentional benefit sharing in their research programmes from inception., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Successful antiretroviral rollout in South Africa has greatly increased the health of the HIV-positive population, and morbidity and mortality in PLHIV can increasingly be attributed to comorbidities rather than HIV/AIDS directly. Understanding this disease burden can inform health care planning for a growing population of ageing PLHIV. Anonymized routine administrative health data were analysed for all adults who accessed public health care in 2016-2017 in Khayelitsha subdistrict (Cape Town, South Africa). Selected comorbidities and age of ascertainment for comorbidities were described for all HIV-positive and HIV-negative healthcare clients, as well as for a subset of women who accessed maternal care. There were 172 937 adult individuals with a median age of 37 (IQR:30-48) years in the virtual cohort, of whom 48% (83 162) were HIV-positive. Median age of ascertainment for each comorbidity was lower in HIV-positive compared to HIV-negative healthcare clients, except in the case of tuberculosis. A subset of women who previously accessed maternal care, however, showed much smaller differences in the median age of comorbidity ascertainment between the group of HIV-positive and HIV-negative health care clients, except in the case of chronic kidney disease (CKD). Both HIV-positive individuals and women who link to maternal care undergo routine point-of-care screening for common diseases at younger ages, and this analysis suggests that this may lead to earlier diagnosis of common comorbidities in these groups. Exceptions include CKD, in which age of ascertainment appears lower in PLHIV than HIV-negative groups in all analyses suggesting that age of disease onset may indeed be earlier; and tuberculosis for which age of incidence has previously been shown to vary according to HIV status., Competing Interests: The authors declare no competing interests., (Copyright: © 2021 Osei-Yeboah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Globally there is increasing awareness of the need for end-of-life care and palliative care in hospitalised patients who are in their final year of life. Limited data are available on palliative care requirements in low- and middle-income countries, hindering the design and implementation of effective policies and health services for these patients., Objectives: To determine the proportion of patients who die within 1 year of their date of admission to public hospitals in South Africa (SA), as a proxy for palliative care need in SA., Methods: This was a retrospective cohort study using record linkage of admission and mortality data. The setting was 46 acute-care public hospitals in Western Cape Province, SA., Results: Of 10 761 patients (median (interquartile range (IQR)) age 44 (31 - 60) years) admitted to the 46 hospitals over a 2-week period in March 2012, 1 570 (14.6%) died within 1 year, the majority within the first 3 months. Mortality rose steeply with age. The median (IQR) age of death was 57.5 (45 - 70) years. A greater proportion of patients admitted to medical beds died within 1 year (21.3%) compared with those admitted to surgical beds (7.7%)., Conclusions: Despite a median age &lt;60 years at admission, a substantial percentage of patients admitted to public sector hospitals in SA are in the final year of their lives. This finding should be seen in the context of SA's high communicable and non-communicable disease burden and resource-limited public health system, and highlights the need for policy development, planning and implementation of end-of-life and palliative care strategies for hospitals and patients.

Background: COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries., Methods: The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population., Findings: There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92)., Interpretation: Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa., Funding: This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC&#95;PC&#95;MR/T037733/1)., Competing Interests: Declaration of Competing Interest JAD has been a speaker and on advisory board for Novartis, Novo Nordisk, Sanofi, Lilly, Servier, MSD, Aspen, Abbott, AstraZeneca, MSD and Boehringer Ingelheim; ILR, WT, and PJR have been a speaker for Sanofi and Aspen. AC has been a speaker for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Medtronic, Merck, Novo Nordisk, Sanofi and on an advisory board for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk, Sanofi. All other authors declare no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)