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- ItemOpen AccessA 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 ABACKGROUND 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.
- ItemOpen AccessA Qualitative study of language barriers between South African health care providers and cross-border migrants(2017) Hunter-Adams, Jo; Rother, Hanna-AndreaAbstract 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.
- ItemOpen AccessAcute 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, EugèneAbstract 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.
- ItemOpen AccessAdolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa(2014) Fatti, Geoffrey; Shaikh, Najma; Eley, Brian; Jackson, Debra; Grimwood, AshrafBACKGROUND: South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy OBJECTIVE: To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories METHODS: A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years as the comparison group RESULTS: Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25 CONCLUSION: An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals
- ItemOpen AccessAntenatal depressive symptoms and perinatal complications: a prospective study in rural Ethiopia(2017) Bitew, Tesera; Hanlon, Charlotte; Kebede, Eskinder; Honikman, Simone; Fekadu, AbebawAntenatal depressive symptoms affect around 12.3% of women in in low and middle income countries (LMICs) and data are accumulating about associations with adverse outcomes for mother and child. Studies from rural, low-income country community samples are limited. This paper aims to investigate whether antenatal depressive symptoms predict perinatal complications in a rural Ethiopia setting.
- ItemOpen AccessAPOL1 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 TBackgroundThe 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.
- ItemOpen AccessAssisted reproductive technology in South Africa: first results generated from the South African register of assisted reproductive techniques(2012) Dyer, Silke Juliane; Kruger, Thinus FransOBJECTIVE: 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.
- ItemOpen AccessAssociation 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, ThandiAbstract 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.
- ItemOpen AccessAssociations 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 CAbstract 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.
- ItemOpen AccessCardiovascular 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, AmyAbstract 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.
- ItemOpen AccessCases 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, KarenAbstract 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.
- ItemOpen AccessChanges 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 SHIV 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).
- ItemOpen AccessChylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test(2001)We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism. In type I hyperlipemia, the phenotype is extreme hypertriglyceridemia due to a lack of lipoprotein lipase activity, which causes the failure of remnant formation. The type III dyslipidemia phenotype is caused by the inefficient removal of chylomicron remnants from plasma, generally because of homozygosity for apolipoprotein E2 alleles. The breath test was predicted to be abnormal in type III hyperlipemia, whereas a priori in type I hyperlipemia defective remnant clearance was not anticipated. Subjects were injected with lipid emulsions prepared with a composition similar to normal chylomicron remnants. The emulsions contained cholesteryl ester incorporating the stable nonradioactive isotope
- ItemOpen AccessComparative 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 FBackgroundIn 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.
- ItemOpen AccessConference on "Multidisciplinary approaches to nutritional problems". Symposium on "Diabetes and health". Nutrition interventions for the prevention of type 2 diabetes.(2009) Steyn, Nelia P; Lambert, Estelle V; Tabana, HananiDiabetes mellitus is escalating globally and it is predicted that 200 million individuals worldwide will have diabetes by 2010 and 300 million by 2025. However, there is compelling evidence from many studies that for subjects with impaired fasting glucose or impaired glucose tolerance the presentation of type 2 diabetes can be delayed by lifestyle modification. The aim of the present review is to present a summary of lifestyle modification interventions that have included a dietary component in their overall diabetes prevention programme. Medline, allied health literature and diabetes journals were searched for peer-reviewed literature using the terms 'diet*' and 'diabetes' and 'intervention'. Inclusion criteria were: peer-reviewed studies from 1975 to 2008; a sample of at least fifty subjects; a healthy eating and/or physical activity component; prevention of diabetes as a primary goal. Generally, the participants were in a high-risk category for the development of diabetes. Outcomes were evaluated at two points in time (pre- and post-intervention) in terms of knowledge, behaviour change and clinical improvement, which included weight, blood pressure, BMI, body fat, waist circumference, waist:hip ratio and physiological and/or biochemical measures. Findings indicate that the most successful interventions combine individual dietary counselling with an activity component. Further factors predicting success are weight loss achieved, duration and intensity of the intervention and dietary compliance.
- ItemOpen AccessDecreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia(1997) Marais, A David; Naoumova, R P; Firth, J C; Penny, C; Neuwirth, C K Y; Thompson, G RApheresis only partially controls raised low density lipoprotein cholesterol levels in patients with homozygous familial hypercholesterolemia, who usually respond poorly to lipid-lowering drugs. The efficacy and mechanism of action of a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin, was therefore investigated in seven homozygotes undergoing apheresis. One receptor-negative and six receptor-defective homozygotes undergoing plasma exchange or LDL apheresis every 2 weeks were studied during 2 months each on placebo and on atorvastatin 80 mg daily. Changes in plasma lipids and mevalonic acid, an index of cholesterol synthesis, were measured and the kinetics of the rebound of low density lipoprotein cholesterol and apolipoprotein B after apheresis were analyzed. All subjects had significant improvements on atorvastatin. Mean decreases in low density lipoprotein cholesterol were 31% greater both pre- and post-apheresis on atorvastatin compared with placebo, accompanied by a 63% decrease in mevalonic acid. Percentage changes in low density lipoprotein cholesterol and mevalonic acid were closely correlated (r = 0.89, P = 0.007). The mean production rates of low density lipoprotein cholesterol and apolipoprotein B were 21% and 25% lower, respectively, on atorvastatin than on placebo (P < 0.005 and <0.02) but changes in mean fractional clearance rates were not statistically significant. We conclude that atorvastatin enhances the efficacy of plasma exchange and low density lipoprotein apheresis in patients who lack low density lipoprotein receptors. This effect appears to be due to marked inhibition of cholesterol synthesis which results in a decreased rate of production of low density lipoprotein.
- ItemOpen AccessDetection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis(2016) Gupta-Wright, Ankur; Peters, Jurgens A; Flach, Clare; Lawn, Stephen DBackgroundSimple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay’s prognostic value.MethodsWe searched MEDLINE and Embase databases using comprehensive search terms for ‘HIV’, ‘TB’, ‘LAM’ and ‘sub-Saharan Africa’. Identified studies were reviewed and selected according to predefined criteria.ResultsWe identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44%) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6months, overall case fatality rates among HIV-TB cases varied between 7% and 53%. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95% confidence interval 1.6–3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95% confidence interval 1.4–4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count.ConclusionsWe have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0603-9) contains supplementary material, which is available to authorized users.
- ItemOpen AccessDevelopment and validation of a prognostic score during tuberculosis treatment(2017) Pefura-Yone, Eric Walter; Balkissou, Adamou Dodo; Poka-Mayap, Virginie; Fatime-Abaicho, Hadja Koté; Enono-Edende, Patrick Thierry; Kengne, André PascalBACKGROUND: Death under care is a major challenge for tuberculosis (TB) treatment programs. We derived and validated a simple score to predict mortality during tuberculosis treatment in high endemicity areas. METHODS: We used data for patients aged ≥15 years, diagnosed and treated for tuberculosis at the Yaounde Jamot Hospital between January 2012 and December 2013. Baseline characteristics associated with mortality were investigated using logistic regressions. A simple prognosis score (CABI) was constructed with regression coefficients for predictors in the final model. Internal validation used bootstrap resampling procedures. Models discrimination was assessed using c-statistics and calibration assessed via calibration plots and the Hosmer and Lemeshwow (H-L) statistics. The optimal score was based on the Youden's index. RESULTS: A total of 2250 patients (men 57.2%) with a mean age of 35.8 years were included; among whom 213 deaths (cumulative incidence 9.5%) were recorded. Clinical form of tuberculosis (C), age (A, years), adjusted body mass index (B, BMI, kg/m2) and status for HIV (Human immunodefiency virus) infection (I) were significant predictors in the final model (p < 0.0001) which was of the form Death risk = 1/(1 + e - (-1.3120 + 0.0474 ∗ age - 0.1866 ∗ BMI + 1.1637 (if smear negative TB) + 0.5418(if extra - pulmonary TB) + 1.3820(if HIV+))). The c-statistic was 0.812 in the derivation sample and 0.808 after correction for optimism. The calibration was good [H-Lχ2 = 6.44 (p = 0.60)]. The optimal absolute risk threshold was 4.8%, corresponding to a sensitivity of 81% and specificity of 67%. CONCLUSIONS: The preliminary promising findings from this study require confirmation through independent external validation studies. If confirmed, the model derived could facilitate the stratification of TB patients for mortality risk and implementation of additional monitoring and management measures in vulnerable patients.
- ItemOpen AccessDevelopment and validation of a short questionnaire to assess sodium intake(2008) Charlton, Karen E; Steyn, Krisela; Levitt, Naomi S; Jonathan, Deborah; Zulu, Jabulisiwe V; Nel, Johanna HOBJECTIVES: To develop and validate a short food-frequency questionnaire to assess habitual dietary salt intake in South Africans and to allow classification of individuals according to intakes above or below the maximum recommended intake of 6 g salt day-1. DESIGN: Cross-sectional validation study in 324 conveniently sampled men and women. METHODS: Repeated 24-hour urinary Na values and 24-hour dietary recalls were obtained on three occasions. Food items consumed by >5% of the sample and which contributed > or =50 mg Na serving-1 were included in the questionnaire in 42 categories. A scoring system was devised, based on Na content of one index food per category and frequency of consumption. RESULTS: Positive correlations were found between Na content of 35 of the 42 food categories in the questionnaire and total Na intake, calculated from 24-hour recall data. Total Na content of the questionnaire was associated with Na estimations from 24-hour recall data (r = 0.750; P < 0.0001; n = 328) and urinary Na (r = 0.152; P = 0.0105; n = 284). Urinary Na was higher for subjects in tertile 3 than tertile 1 of questionnaire Na content (P < 0.05). Questionnaire Na content of <2400 and > or =2400 mg day-1 equated to a reference cut-off score of 48 and corresponded to mean (standard deviation) urinary Na values of 145 (68) and 176 (99) mmol day-1, respectively (P < 0.05). Sensitivity and specificity against urinary Na > or =100 and <100 mmol day-1 was 12.4% and 93.9%, respectively. CONCLUSION: A 42-item food-frequency questionnaire has been shown to have content-, construct- and criterion-related validity, as well as internal consistency, with regard to categorising individuals according to their habitual salt intake; however, the devised scoring system needs to show improved sensitivity.
- ItemOpen AccessDevelopment and validation of instruments measuring body image and body weight dissatisfaction in South African mothers and their daughters(2005) Mciza, Zandile; Goedecke, Julia H; Steyn, Nelia P; Charlton, Karen; Puoane, Thandi; Meltzer, Shelly; Levitt, Naomi S; Lambert, Estelle VOBJECTIVE: We sought to validate questionnaires concerning body image perception, body size dissatisfaction and weight-related beliefs in multi-ethnic South African mothers and their daughters. SETTINGS AND SUBJECTS: Girls attending primary school (ages 9-12 years, n = 333) and their mothers (n = 204) were interviewed regarding their demographics and body image. Weight, height and skinfold thicknesses were measured. Body image questions and body mass index (BMI) were compared with silhouettes adapted from the Pathways Study for girls and Stunkard's body image figures for mothers. A Feel-Ideal Difference (FID) index score was created by subtracting the score of the silhouette selected by the participants as 'Ideal' from the one selected as most closely representing their current appearance or 'Feel'. We hypothesised that a higher FID index score would be associated with greater body size dissatisfaction. RESULTS: BMI percentiles in girls (r = 0.46, P < 0.05) and BMI in mothers (r = 0.68, P < 0.05) were positively correlated with the selected silhouettes based on size. Participants who reported feelings of being 'fat' and those who perceived that their family and friends were more dissatisfied with their body size had significantly higher FID index scores. Scores were lower in black than white girls (all P<0.05). No differences were found in FID index scores between ethnic groups of mothers. Internal reliability of the 'thin' and 'fat' belief constructs for girls was demonstrated by standardised Cronbach's alpha values > or = 0.7. CONCLUSION: Silhouettes, FID index, 'fat' and 'thin' belief constructs (in girls) are age-appropriate, culturally sensitive and can be used in further intervention studies to understand body image.