Risk factors of poor developmental outcome in children with tuberculous meningitis.

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. RESULTS: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87-6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. CONCLUSION: Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness.

The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting.

Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.

High-risk neuroblastoma that achieved post-induction chemotherapy metastatic remission and have undergone resection, is curable, even in limited resource settings.Achieving metastatic complete remission was the only factor that significantly predicated if surgery was done.The age at diagnosis, stage and hospitals with expertise in neuroblastoma surgery were of prognostic significance in South Africa.If a patient with high-risk neuroblastoma achieves metastatic complete remission in a resource limited setting, it should be an indication for resection of the primary tumor.

Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS).

BACKGROUND: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS. METHODS: Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described. RESULTS: Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. CONCLUSIONS: Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.

Decisional Conflict is Associated with Treatment Modality and not Disease Knowledge in South African Men with Prostate Cancer: Baseline Results from a Longitudinal Prospective Observational Study.

BACKGROUND: Decisional conflict (DC) is a psychological construct that an individual experiences in making a decision that involves risk, loss, regret, or challenges to one's values. This study assessed DC in a cohort of South African men undergoing curative treatment for localised prostate cancer (LPC). The objectives were to (1) to examine the association between DC and prostate cancer knowledge (PCK), demographics, state anxiety, prostate cancer anxiety and time to treatment and (2) to compare levels of DC between treatment groups [prostatectomy (RP) and external beam radiation (RT)]. METHOD: Data, comprising the Decisional Conflict Scale (DCS), Prostate Cancer Knowledge (PCK), State-Trait Anxiety Inventory (STAI-S), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and demographic data from 83 participants of a larger prospective longitudinal observational study examining depression, anxiety and health related quality of life (DAHCaP) were analysed. RESULTS: The mean age of participants was 63 years (RP 61yrs and RT 65yrs; p< 0.001). Most were of mixed ancestry (72.3%). The total DCS scores between the treatment groups (RP 25.00 and RT 18.75; p = 0.037) and two DCS sub-scores-uncertainty (p = 0.033), and support (p = 0.048), were significantly higher in the RP group. A statistically significant negative correlation was observed between state anxiety and time between diagnosis and treatment in the RP group (Spearman's rho = -0.368; p = 0.030). There was no correlation between the DCS score and PCK within each treatment group (Spearman's rho RP = -0.249 and RT = -0.001). CONCLUSION: Decisional conflict was higher in men undergoing RP. Men were more anxious in the RP group regarding the time treatment was received from diagnosis. No correlation was observed between DC and PCK. Pre-surgical management of DC should include shared decision making (SDM) which is cognisant of patients' values facilitated by a customised decision aid.

Depression, Anxiety, and Their Association to Health-Related Quality of Life in Men Commencing Prostate Cancer Treatment at Tertiary Hospitals in Cape Town, South Africa.

BACKGROUND: Comorbid depression and anxiety in men with localised prostate cancer (CaP) largely go undiagnosed and untreated and their effects on health-related quality of life (HRQOL) in men with CaP should not be underestimated. We examined the prevalence of depression and anxiety and its association with HRQOL in men about to commence treatment for CaP and the differences between treatment groups, radical prostatectomy (RP) and radiation therapy (RT). METHOD: One hundred and seven participants from a longitudinal prospective observational study assessing depression, anxiety and HRQOL in men with localised CaP (DAHCaP), were used in this cross-sectional analysis. Data were collected shortly before participants were scheduled to receive their treatment. The Centre for Epidemiologic Studies Depression Scale (CES-D), the State Trait Anxiety Inventory (STAI), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the European Organisation for Research and Treatment in Cancer Quality of Life questionnaire (EORTC QLQ-C30) and (EORTC QLQ-PR25) were used in this analysis. RESULTS: Symptoms of depression pre-treatment were noted in 39.3%, state anxiety 28%, trait anxiety 31.4% and prostate cancer anxiety in 12.1% of participants. Statistically significant correlations (P ≤ .05) with the CES-D and a cluster of symptoms on the EORTC QLQ-C30 domains for Global Health (rs = -.35), fatigue (rs = .38), pain (rs = .32), dyspnoea (rs = .28), insomnia (rs = .30) and finance (rs = .26) and EORTC QLQ-PR25 domains for urinary symptoms (rs = .43), bowel (rs = .43) and hormone replacement therapy (HRT) (rs = .41) were observed.Statistically significant correlations were also noted between the STAI-S and EORTC QLQ-C30 and EORTC QLQ-PR25. No statistically significant difference was noted between treatments. CONCLUSION: More men were depressed than anxious with significant associations with HRQOL prior to commencement of treatment. CaP treatments should focus not only on the prevailing indisposition but include a psychooncological and HRQOL assessment at pre-treatment in high-risk individuals.

Resilience of adolescents living with HIV in the Cape Metropole of the Western Cape.

Resilience shapes the experiences of adolescents living with HIV (ALWH), enabling them to come to terms with their diagnosis, have hope for the future and maintain meaningful relationships. Yet, little is known about contextual factors associated with resilience resources in South Africa. We aimed to describe individual, relational and community resilience resources, and identify contextual factors associated with resilience. We recruited 385 adolescents, aged 13-18, over a period of 5 months from 11 different public health HIV clinics. The Child and Youth Resilience Measure (CYRM-12) was used to measure resilience resources. Data on demographic variables, psychological attributes, and environmental factors such as HIV-related stigma and stressful life events were collected. ALWH lacked resilience in some aspects of the individual, relational and community domains. For every one-unit increase in the HIV-related stigma and stressful life events scores, resilience decreased by 0.29 (p = 0.01) and 0.37 (p = 0.04) units, respectively. Higher levels of resilience were associated with being virally suppressed (Mann-Whitney U, p = 0.028) although this association was no longer present in the regression model. Efforts to improve resilience amongst ALWH should be focused on fostering individual coping skills, interconnectedness, and positive relationships, to mitigate adverse environmental factors.

How much time do doctors spend providing care to each child in the ED? A time and motion study.

BACKGROUND: The total time per patient doctors spend providing care in emergency departments (EDs) has implications for the development of evidence-based ED staffing models. We sought to measure the total time taken by doctors to assess and manage individual paediatric patients presenting to two EDs in the Western Cape, South Africa and to compare these averages to the estimated benchmarks used regionally to calculate ED staffing allocations. METHODS: We conducted a cross-sectional, observational study applying time and motion methodology, using convenience sampling. Data were collected over a 5-week period from 11 December 2015 to 18 January 2016 at Khayelitsha District Hospital Emergency Centre and Tygerberg Hospital Paediatric Emergency and Ambulatory Unit. We assessed total doctor time for each patient stratified by acuity level using the South African Triage Scale. RESULTS: Care was observed for a total of 100 patients. Median age was 21 months (IQR 8-55). Median total doctor time per patient (95% CI) was 31 (22 to 38), 39 (31 to 63), 48 (32 to 63) and 96 (66 to 122) min for triage categories green, yellow, orange and red, respectively. Median timing was significantly higher than the estimated local benchmark for the lowest acuity 'green' triage category (31 min (22 to 38) vs 15 min; p=0.001) and the highest acuity 'red' category (96 min (66 to 122) vs 50 min; p=0.002). CONCLUSION: Doctor time per patient increased with increasing acuity of triage category and exceeded estimated benchmarks for the highest and lowest acuities. The distinctive methodology can easily be extended to other settings and populations.

HIV infection and anaemia do not affect HbA1c for the detection of diabetes in black South Africans: Evidence from the Durban Diabetes Study.

OBJECTIVE: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS: In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: ß  = -3.4 mmol/mol or -0.31%, p < 0.001 [macrocytic anaemia] to ß = 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART-treated HIV (2.9% vs. 1.2%, p = 0.08). CONCLUSIONS: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub-Saharan African populations.

COVID-19 Related Anxiety in Men With Localized Prostate Cancer at Tertiary Hospitals in Cape Town, South Africa

INTRODUCTION: The health profile of older adults places them at risk of infirmity and death from COVID-19 which may induce anxiety or exacerbate pre-existing anxiety. We examined COVID-19 related anxiety in men undergoing treatment for prostate cancer (CaP). METHOD: This study was conducted between July and September 2020. Sixty participants from a larger prospective, longitudinal study assessing depression, anxiety and health related quality of life in men with localized prostate cancer (DAHCaP) were included. COVID-19 related anxiety was measured at a single time point using, the Corona Virus Anxiety Scale (CAS). In addition, the following, the State-Trait Anxiety Inventory (STAI-S), the Connor-Davidson Resilience (CD-RISC) scale and Multidimensional Scale of Perceived Social Support (MSPSS) that form part of the DAHCaP study were used in the analysis. We extracted pre-pandemic data for the STAI-S. RESULTS: Twenty-one percent had diabetes, 62.3% had hypertension and 24.6% had cardiac diseases, all known risk factors for severe COVID-19. Only 3% scored ≥9 on the CAS, indicating COVID 19 anxiety dysfunction. Half knew of family or friends that had contracted COVID-19 especially those scoring higher on the CAS (P = 0.042). There was a significant decrease in STAI-S scores pre-pandemic to the pandemic phase (34.7 to 29.8, P = 0.003). No correlation was observed between CAS and STAI-S (rho = 0.08), CD-RISC (rho = -0.06) or MSPSS (rho = -0.15). There was a weak positive correlation between the CAS and monthly income (rho = 0.33; P = 0.010). CONCLUSION: COVID-19 did not induce significant anxiety in men being treated for CaP nor did it place an additional psychological burden, nor was there any correlation with state anxiety, resilience or social support.

Neuroblastoma: The basis for cure in limited-resource settings.

BACKGROUND: Neuroblastoma (NB) contributes the most to the mortality of childhood malignancies worldwide. The disease spectrum is heterogenous and the management complex and costly, especially in advanced disease or disease with adverse biology. In low- and middle-income countries (LMICs) the majority of NB presents in advanced stages. Therefore, with limited resources and poor prognosis the treatment of NB is often not a priority. The aim of the study was to evaluate the research activities and perceptions of the management of NB that determine the research and treatment approaches in LMICs. METHODS: Data were sourced from https://www.clinicaltrials.gov/ identifying NB trials open to LMIC. Abstracts on NB research presented at the International Society for Paediatric Oncology (SIOP) Congresses between 2014 and 2020 were evaluated according to income status. An online survey evaluating medical views on NB in LMICs and the effect on the management was conducted. Descriptive analysis was done. Where appropriate categorical association between covariates was assessed using the Pearson chi-square (χ2 ) test or Fishers exact test. RESULTS: There were 15/562 (2.7%) trials open to LMIC. Only six of 138 (4.3%) LMIC participated in NB trials. Of the 688 abstracts presented between 2014 and 2020 at the SIOP International Congress on NB as primary subject, 297 (42.7%) were from LMICs. Only two were from low-income countries (LICs). Sixty-one countries responded to the NB survey. Positive views towards NB management were present when treatment was based on a national protocol, the availability of trimodal or advanced treatment options were present, and when a balance of metastatic or local disease were treated. CONCLUSION: Management of NB in LMICs should include increased advocacy and research as well as implementation of national management strategies.

Age at diagnosis as a prognostic factor in South African children with neuroblastoma.

PURPOSE: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. METHODS: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. RESULTS: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. CONCLUSION: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa: a retrospective cross-sectional study.

BACKGROUND: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different risk-factor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. METHODS: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. RESULTS: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3-4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd's ratio (OR) (95% CI): 3.12 (1.2-8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2-8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. CONCLUSIONS: We found an HIV-prevalence of 3.4% (95% CI 2.3-4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.

A comparison of the prevalence of sexually transmitted infections among circumcised and uncircumcised adult males in Rustenburg, South Africa: a cross-sectional study.

BACKGROUND: South Africa has a persistent burden of sexually transmitted infections (STIs). Male circumcision has been shown to be effective in preventing HIV and STIs, but data are scarce on the protective effect of circumcision in high-risk populations such as migrant miners. The objective of this study was to assess the effect of medical and traditional circumcision on the prevalence of STIs after adjusting for other risk factors in Rustenburg, a mining town in North West Province, South Africa. METHODS: This cross-sectional study used baseline data collected from a cohort study. Adult males in a mining town were assessed for STIs (gonorrhea, chlamydia, and trichomoniasis) using syndromic assessment. Data on circumcision status and other risk factors for STI syndromes were collected using an interviewer-administered questionnaire. The following symptoms were assessed; penile discharge, painful urination, dyspareunia or penile sores. These symptoms indicate sexually transmitted infection in general since laboratory tests were not performed. Multivariable log binomial regression was used to assess the independent effect of circumcision on STI presence after adjusting for confounders. RESULTS: A total of 339 participants with a median age of 25 years (IQR 22-29) were included in the study, of whom 116 (34.2%) were circumcised. The overall STIs prevalence was 27.4% (95% CI 22.8 to 32.6%) and was lower in the circumcised participants compared with those who were uncircumcised (15.5% vs 33.6%, respectively, p < 0.001). Both medical (OR 0.57, 95% CI 0.34-0.95, p = 0.030) and traditional circumcision (OR 0.34, 95% CI 0.13-0.86, p = 0.022) were strongly associated with a lower risk of STIs after adjustment for employment and condom use. CONCLUSION: In this high-risk population in a mining town in South Africa, with a relatively high prevalence of STIs, and where one third of males are circumcised, both medical and traditional circumcision appear to be protective against STIs.

Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018.

BACKGROUND: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying anti-rheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province. METHODS: A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018. RESULTS: We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10). CONCLUSION: Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.

Statin prescription among patients with type 2 diabetes in Botswana: findings and implications.

BACKGROUND: There is evidence of statin benefit among patients with diabetes regardless of cholesterol levels or prior cardiovascular disease history. Despite the evidence, there is under-prescription of statins in clinical practice. This study aimed to assess statin prescriptions and associated factors among patients with type 2 diabetes in Botswana. METHODS: The study was a secondary data analysis of 500 randomly selected type 2 diabetes patients at a specialised diabetes clinic at Gaborone, Botswana. We assessed the proportion of statin-eligible patients who are prescribed statins and evaluated the adjusted associations between various factors and statin prescriptions. RESULTS: Overall, 477 (95.4%) participants were eligible for a statin prescription. Clinicians prescribed statins in 217 (45.5%) of eligible participants, and only one (4.4%) ineligible participant. The probability of a statin prescription was higher in participants with high baseline low-density lipoprotein cholesterol (risk ratio [RR]: 1.49; 95%CI: 1.17-1.89), increasing duration of diabetes (RR: 1.01; 95%CI 1.00-1.03) and the presence of chronic kidney disease (RR: 1.35; 95%CI: 1.06-1.74). CONCLUSION: A large proportion with type 2 diabetes in Gaborone is not receiving statins. Clinicians did not consider most guideline-recommended indications for statin prescriptions. The findings call for improvement in diabetes quality of care by implementing evidence-based guideline recommendations.

Calcium channel blockers for people with chronic kidney disease requiring dialysis.

BACKGROUND: Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. OBJECTIVES: To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. AUTHORS' CONCLUSIONS: The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.

Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya.

BACKGROUND: Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities. METHODS: Cases were defined as patients attending the health facility due to diarrhea or a respiratory infection while controls were patients attending the same health facility for a non-communicable disease defined as an event other than diarrhea, respiratory infection. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the risk of diarrheal or respiratory infection in association with exposure to the health education program. RESULTS: There were 324 cases and 308 controls recruited for the study with 57% of the cases and 59% of the controls being male. Overall, 13% of cases vs. 20% of control patients were exposed to the education program. Participants exposed to the program had 38% lower odds of diarrhea and respiratory infections compared to those not exposed to the program (adjusted OR 0.62, 95% CI 0.41-0.96). A similar risk reduction was observed for participants in the study who resided in areas with water improvement initiatives (adjusted OR 0.65, 95% CI 0.47-0.90). Variables in the adjusted model included water improvement projects in the area and toilet facilities. CONCLUSION: Findings from this study suggest participants exposed to the education program and those residing in areas with water improvement initiatives have a reduced risk of having diarrhea or respiratory infection.

The importance of local control management in high-risk neuroblastoma in South Africa.

PURPOSE: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa. METHODS: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both. RESULTS: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries. CONCLUSION: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma.

Perioperative patient outcomes in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: There is a need to increase access to surgical treatments in African countries, but perioperative complications represent a major global health-care burden. There are few studies describing surgical outcomes in Africa. METHODS: We did a 7-day, international, prospective, observational cohort study of patients aged 18 years and older undergoing any inpatient surgery in 25 countries in Africa (the African Surgical Outcomes Study). We aimed to recruit as many hospitals as possible using a convenience sampling survey, and required data from at least ten hospitals per country (or half the surgical centres if there were fewer than ten hospitals) and data for at least 90% of eligible patients from each site. Each country selected one recruitment week between February and May, 2016. The primary outcome was in-hospital postoperative complications, assessed according to predefined criteria and graded as mild, moderate, or severe. Data were presented as median (IQR), mean (SD), or n (%), and compared using t tests. This study is registered on the South African National Health Research Database (KZ_2015RP7_22) and ClinicalTrials.gov (NCT03044899). FINDINGS: We recruited 11 422 patients (median 29 [IQR 10-70]) from 247 hospitals during the national cohort weeks. Hospitals served a median population of 810 000 people (IQR 200 000-2 000 000), with a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 (0·2-1·9) per 100 000 population. Hospitals did a median of 212 (IQR 65-578) surgical procedures per 100 000 population each year. Patients were younger (mean age 38·5 years [SD 16·1]), with a lower risk profile (American Society of Anesthesiologists median score 1 [IQR 1-2]) than reported in high-income countries. 1253 (11%) patients were infected with HIV, 6504 procedures (57%) were urgent or emergent, and the most common procedure was caesarean delivery (3792 patients, 33%). Postoperative complications occurred in 1977 (18·2%, 95% CI 17·4-18·9]) of 10 885 patients. 239 (2·1%) of 11 193 patients died, 225 (94·1%) after the day of surgery. Infection was the most common complication (1156 [10·2%] of 10 970 patients), of whom 112 (9·7%) died. INTERPRETATION: Despite a low-risk profile and few postoperative complications, patients in Africa were twice as likely to die after surgery when compared with the global average for postoperative deaths. Initiatives to increase access to surgical treatments in Africa therefore should be coupled with improved surveillance for deteriorating physiology in patients who develop postoperative complications, and the resources necessary to achieve this objective. FUNDING: Medical Research Council of South Africa.

Prevalence and risk factors of metabolic syndrome in HIV-infected adults at three urban clinics in a post-conflict setting, eastern Democratic Republic of the Congo.

OBJECTIVE: To determine the prevalence of and risk factors for metabolic syndrome (MS) in HIV-infected adults at three urban clinics in Bukavu, Democratic Republic of the Congo. DESIGN: Cross-sectional study. METHODS: From July to September 2016, baseline socio-demographics, risk factors and clinical characteristics were collected using a structured questionnaire or extracted from medical records. Fasting blood sugar and lipids were measured. MS was defined per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) criteria. Adjusted odds ratio (OR) was generated through multivariate logistic regression models. RESULTS: Of 495 participants, 356 (72%) were women and 474 (95.8%) were receiving antiretroviral therapy (ART). The median age (years) [interquartile range (IQR)] was 43 [36-51]. The overall prevalence of MS per NECP/ATP III and IDF criteria was 27% [95% CI: 20-35%] or 30% [95% CI: 23-38%], respectively. In a multivariate logistic regression, low physical activity (OR 2.47, 95% CI: 1.40-4.36); daily exposure to biomass fuel smoke (BMF) for more than 2 h (OR 2.18, 95% CI: 1.01-4.68); protease inhibitor containing ART (OR: 2.96, 95% CI: 1.07-8.18); and stavudine-containing ART regimen (OR: 2.57, 95% CI: 1.11-5.93) were independently associated with MS. CONCLUSIONS: MS was highly prevalent in this hospital-based study population. Beside known traditional risk factors and contribution of specific ART regimens to MS, daily exposure to BMF is new and of specific concern, necessitating targeted urgent prevention and management interventions.