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Open Access
A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
(2014) Blom, Dirk J; Hala, Tomas; Bolognese, Michael; Lillestol, Michael J; Toth, Phillip D; Burgess, Lesley; Ceska, Richard; Roth, Eli; Koren, Michael J; Ballantyne, Christie M; Monsalvo, Maria Laura; Tsirtsonis, Kate; Kim, Jae B; Scott, Rob; Wasserman, Scott M; Stein, Evan A
BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.
Open Access
A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa
(2011)
BackgroundTo better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts.MethodsSurveys were conducted in April 2009. Analysis data from the Asia cohort were collected in March 2009 from 12 centres in Cambodia, India, Indonesia, Malaysia, and Thailand. Data from the IeDEA Southern Africa cohort were finalized in February 2008 from 10 centres in Malawi, Mozambique, South Africa and Zimbabwe.ResultsSurvey responses reflected inter-regional variations in drug access and national guidelines. A total of 1301 children in the TREAT Asia and 4561 children in the IeDEA Southern Africa cohorts met inclusion criteria for the cross-sectional analysis.Ten percent of Asian and 3.3% of African children were on second-line ART at the time of data transfer. Median age (interquartile range) in months at second-line initiation was 120 (78-145) months in the Asian cohort and 66 (29-112) months in the southern African cohort. Regimens varied, and the then current World Health Organization-recommended nucleoside reverse transcriptase combination of abacavir and didanosine was used in less than 5% of children in each region.ConclusionsIn order to provide life-long ART for children, better use of current first-line regimens and broader access to heat-stable, paediatric second-line and salvage formulations are needed. There will be limited benefit to earlier diagnosis of treatment failure unless providers and patients have access to appropriate drugs for children to switch to.
Open Access
A decade of tobacco control: The South African case of politics, health policy, health promotion and behaviour change
(2013) Reddy, Priscilla; James, Shamagonam; Sewpaul, Ronel; Yach, Derek; Resnicow, Ken; Sifunda, Sibusiso; Mthembu, Zanele; Mbewu, Anthony
BACKGROUND: The South African (SA) government has implemented comprehensive tobacco control measures in line with the requirements of the Framework Convention on Tobacco Control. The effect of these measures on smoking prevalence and smoking-related attitudes, particularly among young people, is largely unknown. OBJECTIVE: To describe the impact of a comprehensive health promotion approach to tobacco control amongst SA school learners. METHODS: Four successive cross-sectional Global Youth Tobacco Surveys (GYTSs) were conducted in 1999, 2002, 2008 and 2011 among nationally representative samples of SA grades 8 - 10 school learners. We assessed the prevalence of current smoking (having smoked a cigarette on ≥1 day in the 30 days preceding the survey) and smoking-related attitudes and behaviours. RESULTS: Over the 12-year survey period current smoking among learners declined from 23.0% (1999) to 16.9% (2011) - a 26.5% reduction. Reductions in smoking prevalence were less pronounced amongst girls and amongst black learners. We observed an increase in smoking prevalence amongst learners between 2008 and 2011. Smoking-related attitudes and behaviours showed favourable changes over the survey period. CONCLUSION: These surveys demonstrate that the comprehensive and inter-sectorial tobacco control health promotion strategies implemented in SA have led to a gradual reduction in cigarette use amongst school learners. Of concern, however, are the smaller reductions in smoking prevalence amongst girls and black learners and an increase in smoking prevalence from 2008 to 2011. Additional efforts, especially for girls, are needed to ensure continued reduction in smoking prevalence amongst SA youth.
Open Access
A Qualitative study of language barriers between South African health care providers and cross-border migrants
(2017) Hunter-Adams, Jo; Rother, Hanna-Andrea
Abstract Background Communication with health care providers represents an essential part of access to health care for the over 230 million cross-border migrants around the world. In this article, we explore the complexity of health communication from the perspective of cross-border migrants seeking antenatal care in Cape Town, South Africa in order to highlight the importance of high quality medical interpretation. Methods As part of a broader study of migrant maternal and infant nutrition, we conducted a secondary data analysis of semi-structured in-depth interviews (N = 23) with Congolese (n = 7), Somali (n = 8) and Zimbabwean (n = 8) women living in Cape Town, as well as nine focus group discussions (including men: n = 3 and women: n = 6) were conducted with migrant Somalis, Congolese, and Zimbabweans (N = 48). We first used content analysis to gather all data related to language and communication. We then analysed this data thematically. Results Zimbabwean participants described how the inability to speak the local South African language (IsiXhosa) gave rise to labelling and stereotyping by healthcare staff. Congolese and Somali participants described medical procedures, including tubal ligation, which were performed without consent. Partners often tried to play the role of interpreter, which resulted in loss of income and non-professional medical interpretation. Participants’ highlighted fears over unwanted procedures or being unable to access care. Challenges of communication without a common language (and without professional medical interpretation), rather than outright denial of care by healthcare professionals, mediated these encounters. Conclusion Although there are several factors impeding cross-border migrants’ access to health care, effective communication is a prerequisite for quality care. Free-to-patient professional medical interpretation would not only benefit migrant populations but would benefit the broader community where language and health literacy are barriers to accessing health care. Novel approaches to language access may include technology-enabled professional interpretation.
Open Access
Acute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults
(2016) Kenteu, Bernold; Noubiap, Jean Jacques N; Etoa, Martine Claude; Azabji-Kenfack, Marcel; Dehayem, Mesmin; Sobngwi, Eugène
Abstract Background Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults. Methods We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m 2 with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test. Results During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893). Conclusion Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.
Open Access
Anemia in type 2 diabetic patients and correlation with kidney function in a tertiary care sub-Saharan African hospital: a cross-sectional study
(2016) Feteh, Vitalis F; Choukem, Simeon-Pierre; Kengne, André Pascal; Nebongo, Daniel N; Ngowe-Ngowe, Marcelin
BackgroundAnemia is common in diabetic patients and increases morbidity and mortality, but its burden has been less well characterized in sub-Saharan Africans. We determined the prevalence of anemia and investigated the related factors, with a particular focus on the role of declining renal function, in type 2 diabetic patients attending a tertiary health care institution in Cameroon.MethodsHemoglobin (Hb) levels were measured in a consecutive sample of patients with type 2 diabetes, who reported for annual review at the outpatient section of the Douala General Hospital in 2013. Patients were classified as anemic according to the World Health Organisation criteria (Hb < 12g/dl for females and Hb < 13g/dl for males). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease Study Group formula. Determinants of Hb concentration and anemia were investigated using multivariable logistic regressions.ResultsA total of 636 patients were examined including 263 (prevalence rate 41.4%) who had anemia. The prevalence of anemia increased significantly with deteriorating kidney function, although up to 31.9% of patients with normal kidney function had anemia. Compared with their non-anemic counterparts, anemic diabetic patients were older, had longer duration of diabetes, lower eGFR, higher prevalence of proteinuria and diabetic retinopathy (all p < 0.05). In multivariable logistic regressions, eGFR (p = 0.001) and presence of retinopathy (p = 0.023) were the independent determinants of prevalent anemia.ConclusionsThe prevalence of anemia is high in type 2 diabetic patients attending referral institutions in Cameroon, including among those without chronic kidney disease. Routine screening for anemia in all diabetic patients may aid early identification and correction as appropriate.
Open Access
APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans
(2015) Matsha, Tandi E; Pheiffer, Carmen; Masconi, Katya L; Yako, Yandiswa Y; Erasmus, Rajiv T
BackgroundThe frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.ResultsThe frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6%, 3.4%, and 5.8%, resulting in a 1.01% frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ≤ 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics.ConclusionsAlthough the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population.
Open Access
Assisted reproductive technology in South Africa: first results generated from the South African register of assisted reproductive techniques
(2012) Dyer, Silke Juliane; Kruger, Thinus Frans
OBJECTIVE: We present the first report from the South African Register of Assisted Reproductive Techniques. METHODS: All assisted reproductive technology (ART) centres in South Africa were invited to join the register. Participant centres voluntarily submitted information from 2009 on the number of ART cycles, embryo transfers, clinical pregnancies, age of female partners or egg donors, and use of fertilisation techniques. Data were anonymised, pooled and analysed. RESULTS: The 12 participating units conducted a total of 4 512 oocyte aspirations and 3 872 embryo transfers in 2009, resulting in 1 303 clinical pregnancies. The clinical pregnancy rate (CPR) per aspiration and per embryo transfer was 28.9% and 33.6%, respectively. Fertilisation was achieved by intracytoplasmic sperm injection in two-thirds of cycles. In most cycles, 1 - 2 embryos or blastocysts were transferred. Female age was inversely related to pregnancy rate. CONCLUSION: The register achieved a high rate of participation. The reported number of ART cycles covers approximately 6% of the estimated ART demand in South Africa. The achieved CPRs compare favourably with those reported for other countries.
Open Access
Association between perceived built environmental attributes and physical activity among adults in South Africa
(2017) Malambo, Pasmore; Pheiffer, Carmen; Lambert, Estelle V; De Villers, Anniza; Puoane, Thandi
Abstract Background To investigate the association between perceived environmental attributes and leisure-time and transport-related physical activity. Methods This was a cross-sectional survey involving 671 South Africans aged ≥35 years from urban and rural settings. International Physical Activity Questionnaire and Neighbourhood Walkability Scale were used to collect data. Multivariable logistic regressions were used to investigate the associations. Results Significant urban vs. rural differences were apparent in the distribution of most attributes of neighborhood environment. After adjusting for gender, age, setting and relevant interaction terms, proximity to local stores was significantly associated with leisure-time physical activity (OR: 4.26; 95% CI, 1.00–18.08); while proximity to transit stops (2.44; 1.48–4.02), pleasant scenery (1.93; 1.07–3.46), sidewalks (2.36; 1.25–4.44), shade from trees (2.14; 1.19–3.85), traffic (2.17; 91.21–3.91) and well-lit streets (2.01; 1.04–3.89) were significantly associated with walking for leisure. Four-way intersections (4.54; 1.54–13.43), pleasant scenery (3.84; 1.35–10.99), traffic (0.28; 0.09–0.89), sidewalks (3.75; 1.06-13.27) and crosswalks were associated with transport related physical activity. Proximity to transit stops (2.12; 1.17–3.84) and well maintained sidewalks (2.69; 2.20–10.02) were significantly associated with total physical activity. Significant interactions by setting were apparent in some of the associations. Conclusion Some, but not all attributes of a neighborhood environment were significantly associated in expected directions with the three physical activity domains in this mixed urban and rural population. This study highlights the need for policy strategies aimed at improving or maintaining these perceived environmental attributes to promote physical activity.
Open Access
Associations between lifetime potentially traumatic events and chronic physical conditions in the South African Stress and Health Survey: a cross-sectional study
(2016) Atwoli, Lukoye; Platt, Jonathan M; Basu, Archana; Williams, David R; Stein, Dan J; Koenen, Karestan C
Abstract Background This study examined the association between the type, and cumulative number of lifetime potentially traumatic events (PTEs), and chronic physical conditions, in a South African sample. PTE exposures have been associated with an increased risk for a wide range of chronic physical conditions, but it is unclear whether psychiatric disorders mediate this association. Given the established differences in trauma occurrence, and the epidemiology of posttraumatic stress disorder (PTSD) in South Africa relative to other countries, examining associations between PTEs and chronic physical conditions, particularly while accounting for psychiatric comorbidity is important. Methods Data were drawn from the South African Stress and Health Study, a cross-sectional population-representative study of psychological and physical health of South African adults. Twenty-seven PTEs, based on the World Health Organization Composite International Diagnostic Interview Version 3.0, DSM-IV PTSD module were grouped into seven PTE types (war events, physical violence, sexual violence, accidents, unexpected death of a loved one, network events, and witnessing PTEs). Five clusters of physical conditions (cardiovascular, arthritis, respiratory, chronic pain, and other health conditions) were examined. Logistic regressions assessed the odds of reporting a physical condition in relation to type and cumulative number of PTEs. Cochran-Armitage test for trend was used to examine dose-response effect of cumulative PTEs on physical conditions. Results After adjusting for sociodemographic variables and psychiatric disorders, respondents with any PTE had increased odds of all assessed physical conditions, ranging between 1.48 (95 % CI: 1.06–2.07) for arthritis and 2.07 (95 % CI: 1.57–2.73) for respiratory conditions, compared to those without PTE exposure. Sexual violence, physical violence, unexpected death of a loved one, and network PTEs significantly increased the odds of all or nearly all the physical conditions assessed. There was a dose-response relationship between number of PTEs and increased odds of all physical conditions. Conclusions Results from this study, the first in an African general population, are consistent with other population-based studies; PTEs confer a broad-spectrum risk for chronic physical conditions, independent of psychiatric disorders. These risks increase with each cumulative PTE exposure. Clinically, comprehensive evaluations for risk of mental and physical health morbidities should be considered among PTE survivors.
Open Access
Avoiding allogenic blood transfusions in endoscopic angiofibroma surgery
(2016) Wasl, Hisham; McGuire, Jessica; Lubbe, Darlene
BackgroundSurgical approaches for many tumours are often limited by blood loss, exposure and risk to vital anatomical structures. Therefore, the standard of care for certain skull base tumours has become endoscopic transnasal resection. Other surgical disciplines often use cell salvage techniques, but review of the otolaryngology literature revealed very few case reports. This study investigated the value and safety of salvage-type autologous blood transfusion during the endoscopic resection of juvenile nasopharyngeal angiofibromas (JNA).MethodsJNA is a rare vascular nasal tumour and the study extended over a 3-year period to obtain adequate patient numbers. All patients undergoing endoscopic resection during this period were included in the population sample. Ten patients with JNA were identified and underwent embolization prior to the endoscopic resection. In all cases the intraoperative blood salvage apparatus was used. Close post-operative monitoring was performed.ResultsHomologous blood transfusion could be avoided in all cases. Postoperative monitoring revealed transient bacteraemia in two cases where the leukocyte filter was not used, but no evidence of septicaemia.ConclusionsPerioperative cell saver and autologous blood transfusion in endonasal JNA surgery is safe. Homologous blood transfusion can be avoided by using this technique. The use of cell salvage allows for single stage surgery without the need to abandon surgery due to excessive blood loss and its future use is promising.
Open Access
Blood cultures in sick children
(2013) Lochan, Harsha; Bamford, Colleen; Eley, Brian
BACKGROUND: Blood cultures (BCs) are frequently performed in sick children. A recent audit of BCs among adult patients documented high rates of contamination by coagulase-negative staphylococci (CoNS). OBJECTIVES: To describe BC contamination rates and common pathogenic organisms causing bloodstream infection in children at a tertiary- level children's hospital. METHODS: BC results for children admitted to Red Cross War Memorial Children's Hospital from 2008 to 2012 were extracted from the National Health Laboratory Service database. Pathogenic and non-pathogenic (contaminated) growth on BCs in children <1 year of age and >1 year of age, were analysed. Data analysis was performed using Epi Info version 3.5.1. RESULTS: A total of 47 677 BCs were performed in the 5-year period. The proportion of contaminated specimens ranged between 5.9% and 7.2% per year (p=0.4). CoNS was the predominant isolate in 53.8% of all contaminated BCs. Children <1 year of age experienced higher contamination rates than children >1 year of age (8.7% v. 4.7%; relative risk 1.84; 95% confidence interval (CI) 1.71 - 1.97). Pathogenic organisms were isolated in 6.2% (95% CI 6.0 - 6.4) of all BC specimens. Among Gram-positive organisms, the proportion of Streptococcus pneumoniae isolates declined from 14.3% to 4.7% (p<0.00001), while there was a significant increase in Gram-negative organisms (51.8% - 57.9%; p=0.04) over the 5-year period. Klebsiella pneumoniae, the predominant Enterobacteriaceae isolated, decreased from 45.8% to 31.7% (p=0.004). CONCLUSION: This study identified unacceptably high BC contamination rates, emphasising the importance of collecting BC specimens under sterile conditions.
Open Access
Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease
(2016) Yusuf, Salim; Lonn, Eva; Pais, Prem; Bosch, Jackie; López-Jaramillo, Patricio; Zhu, Jun; Xavier, Denis; Avezum, Álvaro; Leiter, Lawrence A; Piegas, Leopoldo S; Parkhomenko, Alexander; Keltai, Matyas; Keltai, Katalin; Sliwa, Karen; Chazova, Irina; Peters, Ron JG; Held, Claes; Yusoff, Khalid; Lewis, Basil S; Jansky, Petr; Khunti, Kamlesh; Toff, William D; Reid, Christopher M; Varigos, John; Accini, Jose L; McKelvie, Robert; Pogue, Janice; Jung, Hyejung; Liu, Lisheng; Diaz, Rafael; Dans, Antonio; Dagenais, Gilles
BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events ...
Open Access
Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease
(2016) Lonn, Eva M; Bosch, Jackie; López-Jaramillo, Patricio; Zhu, Jun; Liu, Lisheng; Pais, Prem; Diaz, Rafael; Xavier, Denis; Sliwa, Karen; Dans, Antonio; Avezum, Álvaro; Piegas, Leopoldo S; Keltai, Katalin; Keltai, Matyas; Chazova, Irina; Peters, Ron JG; Held, Claes; Yusoff, Khalid; Lewis, Basil S; Jansky, Petr; Parkhomenko, Alexander; Khunti, Kamlesh; Toff, William D; Reid, Christopher M; Varigos, John; Leiter, Lawrence A; Molina, Dora I; McKelvie, Robert; Pogue, Janice; Wilkinson, Joanne; Jung, Hyejung; Dagenais, Gilles
Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)
Open Access
Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study
(2017) Dugas, Lara R; Forrester, Terrence E; Plange-Rhule, Jacob; Bovet, Pascal; Lambert, Estelle V; Durazo-Arvizu, Ramon A; Cao, Guichan; Cooper, Richard S; Khatib, Rasha; Tonino, Laura; Riesen, Walter; Korte, Wolfgang; Kliethermes, Stephanie; Luke, Amy
Abstract Background Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. Methods In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25–45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. Results The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. Conclusions These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.
Open Access
Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa
(2016) Njuguna, Christine; Swart, Annoesjka; Blockman, Marc; Maartens, Gary; Chisholm, Briony; Stewart, Annemie; Uys, Anri; Cohen, Karen
Abstract Background Gynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. Methods We identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes. Results We received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6–42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). Conclusions Gynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.
Open Access
Changes in self-reported HIV testing during South Africa's 2010/2011 national testing campaign: gains and shortfalls
(2016) Maughan-Brown, Brendan; Lloyd, Neil; Bor, Jacob; Venkataramani, Atheendar S
HIV counselling and testing is critical to HIV prevention and treatment efforts. Mass campaigns may be an effective strategy to increase HIV testing in countries with generalized HIV epidemics. We assessed the self-reported uptake of HIV testing among individuals who had never previously tested for HIV, particularly those in high-risk populations, during the period of a national, multisector testing campaign in South Africa (April 2010 and June 2011).
Open Access
Characteristics and outcome of children with juvenile dermatomyositis in Cape Town: a cross-sectional study
(2016) Okong’o, Lawrence Owino; Esser, Monika; Wilmshurst, Jo; Scott, Christiaan
Abstract Background Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory childhood myopathy of uncertain aetiology. The demographic and clinical presentation of JDM may differ by race and geographic regions. Few studies have described the characteristics of JDM patients from Africa. Methods We conducted a retrospective observational study to determine clinical characteristics and outcomes of patients satisfying the Bohan and Peter criteria for probable JDM seen between 2004 and 2013 in three hospitals in Cape Town, South Africa. Results Twenty five cases were identified: 16 female and 9 male; thirteen (52 %) were of indigenous African, eleven (44 %) mixed and one (4 %) European ancestry. The median ages at disease onset and diagnosis were 6.75 (range 2.0–9.7) and 7.9 (range 3.4–9.75) years respectively. Eleven patients had calcinosis while the mortality was 2/25 (8 %). Only 40 % of the patients had clinically inactive disease by PRINTO criteria (modified) at last review. There was no statistically significant difference in racial distribution (p-value = 1), age at disease onset (p-value = 0.87) and disease duration prior to treatment initiation (p-value = 0.75) between patients who had clinically active and inactive disease. Conclusion The demographic characteristics of children with JDM were similar to that from most other regions of the world with female predominance and similar age at onset. Majority of the patients remained with clinically active disease, which put them at risk of further disease complications. Long term follow up and use of appropriate treatment guidelines may be indicated in management of JDM patients for optimum treatment outcomes.
Open Access
Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function
(2017) Hemingway, Cheryl; Berk, Maurice; Anderson, Suzanne T; Wright, Victoria J; Hamilton, Shea; Eleftherohorinou, Hariklia; Goldgof, Greg M; Hickman, Katy; Kampmann, Beate; Schoeman, Johan; Eley, Brian; Beatty, David; Pienaar, Sandra; Nicol, Mark P; Griffiths, Michael J; Waddell, Simon J; Newton, Sandra M; Coin, Lachlan J; Relman, David A; Montana, Giovanni; Levin, Michael
The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.
Open Access
Comparative performance characteristics of the urine lipoarabinomannan strip test and sputum smear microscopy in hospitalized HIV-infected patients with suspected tuberculosis in Harare, Zimbabwe
(2015) Zijenah, Lynn Sodai; Kadzirange, Gerard; Bandason, Tsitsi; Chipiti, Maria Mary; Gwambiwa, Bevel; Makoga, Forget; Chungu, Pauline; Kaguru, Philip; Sabur, Natasha F
BackgroundIn Zimbabwe, sputum smear microscopy (SSM) is the routinely used TB diagnostic tool in hospitalised HIV-infected patients. However, SSM has poor sensitivity in HIV-infected patients. We compared performance of urine lipoarabinomannan strip test (LAM) and SSM among hospitalized HIV-infected patients with suspected TB.MethodsHospitalized HIV-infected patients with suspected TB were randomized to LAM plus SSM or SSM alone groups as part of a larger multi-country parent study. Here we present a comparison of LAM versus SSM performance from the Zimbabwe study site. LAM analyses (grade 2 cut-off) were conducted using (i) a microbiological reference standard (MRS; culture positivity for M.tb and designated definite TB) and (ii) a composite reference standard (CRS; definite TB plus probable TB i.e. patients with clinical TB excluded from the culture negative group). CRS constituted the primary analysis.Results82/457 (18%) of the patients randomized to the LAM group were M.tuberculosis culture positive. Using CRS, sensitivity (%, 95 % CI) of LAM was significantly higher than SSM [49.2 (42.1-56.4) versus 29.4(23.2-36.3); p < 0.001]. Specificity and PPV were 98.1%, and 95.8%, respectively. By contrast, using MRS, LAM sensitivity was similar to SSM and specificity was significantly lower, however, the combined sensitivity of LAM and SSM was significantly higher than that of SSM alone, p = 0.009. Using CRS, LAM sensitivity (%, CI) was CD4 count dependent [60.6(50.7-69.8) at ≤50 cells/μL; 40.0(22.7-59.4) at 51-100 cells/μL, and 32.8(21.0-46.3) at >100 cells/μL. The combined sensitivity of LAM and SSM was higher than SSM alone being highest at CD4 counts <50 cells/μL [67.6(57.9-76.3); p = <0.001]. Specificity of LAM or SSM alone, or of combined LAM and SSM was >97% in all the 3 CD4 strata.ConclusionAmong hospitalized HIV-infected patients with suspected TB, the sensitivity of LAM is significantly higher than that of SSM, especially at low CD4 counts. LAM and SSM are complimentary tests for diagnosis of TB in HIV-infected patients. We recommend a combination of LAM and SSM for TB diagnosis in HIV-infected patients with low CD4 counts in HIV/TB co-endemic countries, where alternative methods are unavailable.