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Open Access
The 341C/T polymorphism in the GSTP1 gene is associated with increased risk of oesophageal cancer
(BioMed Central Ltd, 2010) Li, Dongping; Dandara, Collet; Parker, M Iqbal
BACKGROUND: The Glutathione S-transferases (GSTs) comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study the effects of polymorphisms in these genes on the risk of developing oesophageal squamous cell carcinoma (OSCC) were evaluated in a hospital-based case-control study in two South African population groups. Genetic polymorphisms in GSTs were investigated in 245 patients and 288 controls samples by PCR-RFLP analysis. RESULTS: The GSTP1 341T variant was associated with significantly increased risk of developing OSCC as observed from the odds ratios for the GSTP1 341C/T and GSTP1 341T/T genotypes (OR = 4.98; 95%CI 3.05-8.11 and OR = 10.9; 95%CI 2.43-49.1, respectively) when compared to the homozygous GSTP1 341C/C genotype. The risk for OSCC in the combined GSTP1 341C/T and T/T genotypes was higher in tobacco smokers (OR = 7.51, 95% CI 3.82-14.7), alcohol consumers (OR = 15.3, 95% CI 1.81-12.9) and those using wood or charcoal for cooking and heating (OR = 12.1, 95% CI 3.26-49) when compared to those who did not smoke tobacco, or did not consume alcohol or user other forms of fuel for cooking and heating. Despite the close proximity of the two GSTP1 SNPs (313A>G and 341C>T), they were not in linkage disequilibrium in these two population groups (D':1.0, LOD: 0.52, r2: 0.225). The GSTP1 313A/G polymorphism on the other hand, did not display any association with OSSC. The homozygous GSTT1*0 genotype was associated with increased risk of OSCC (OR = 1.71, 95%CI 1.18-2.46) while the homozygous GSTM1*0 genotype was associated with significantly decreased risk of OSCC in the Mixed Ancestry subjects (OR= 0.39, 95%CI 0.25-0.62). CONCLUSIONS: This study shows that the risk of developing OSCC in the South African population can be partly explained by genetic polymorphisms in GST coding genes and their interaction with environmental factors such as tobacco smoke and alcohol consumption.
Open Access
50 years of Emmonsia disease in humans: the dramatic emergence of a cluster of novel fungal pathogens
(Public Library of Science, 2015) Schwartz, Ilan S; Kenyon, Chris; Feng, Peiying; Govender, Nelesh P; Dukik, Karolina; Sigler, Lynne; Jiang, Yanping; Stielow, J Benjamin; Muñoz, José F; Cuomo, Christina A; Botha, Alfred; Stchigel, Alberto M; De Hoog, G Sybren
New species of Emmonsia-like fungi, with phylogenetic and clinical similarities to Blastomyces and Histoplasma, have emerged as causes of systemic human mycoses worldwide. They differ from classical Emmonsia species by producing a thermally-dependent, yeast-like phase rather than adiaspores, and by causing disseminated infections, predominantly in immunocompromised patients and often with high case-fatality rates. Such differences will be important for clinicians to consider in diagnosis and patient management, and for microbiologists who may encounter these fungi with increasing frequency.
Open Access
9β Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease
(Public Library of Science, 2014) Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus
BACKGROUND: Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.
Open Access
A 40-50kDa Glycoprotein Associated with Mucus is Identified as α-1-Acid Glycoprotein in Carcinoma of the Stomach
(2012) Chirwa, Nthato; Govender, Dhirendra; Ndimba, Bongani; Lotz, Zoe; Tyler, Marilyn; Panieri, Eugenio; KAHN, DELAWIR; Mall, Anwar S
Background and Aim: Secreted gastric mucins are large O-glycosylated proteins of crude mucus gels which are aberrantly expressed in malignancy. An albumin associated 55-65kDa glycoprotein was previously shown in mucus gels in gastric cancer. The aim of this study was to investigate its expression and identification in human gastric tissue. Methods: Mucins were purified from crude mucus scrapings of 16 partial and 11 total resections and a rabbit polyclonal antibody was raised to the 55-65kDa glycoprotein. The location and expression of the glycoprotein was examined in normal gastric mucosa (n=20), intestinal metaplasia (n=18) and gastric cancer (n=27) tissue by immunohistochemistry. Mucins were analyzed by isoelectric focusing (IEF) on 2-D polyacrylamide gels. Identification of the 40-50kDa glycoprotein was by MALDI-TOF MS technique. Plasma levels were examined by Western blotting. Results: Extensive SDS-PAGE analysis gave a PAS positive glycoprotein in the 40-50kDa range, in patients with gastric cancer but not normals. It was expressed in parietal and columnar cells of normal gastric tissue and intestinal metaplasia respectively, and in 22 of 27 gastric cancer specimens. In 2-D PAGE stained with Coomassie Blue there were 3 spots positively identified as alpha-1-acid glycoprotein (AGP) by MALDI-TOF MS technique. PAS staining revealed a single bright spot in the same position but could not be identified. Preliminary measurements showed slightly higher levels of AGP in plasma of patients with gastric carcinoma. Conclusion: AGP levels are increased in gastric tissue and in the plasma of those with carcinoma of the stomach.
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 case for integrating human rights in public health policy
(2006) London, Leslie
In a global environment where human rights and well-being are coming under increasing threat, both from the spectre of terrorism and from the counter-reaction to it,1 and where international governance systems continue to pay lip service to poverty reduction while encouraging unbridled private accumulation of wealth resulting in huge inequalities between and within countries,2,3 the need to make human rights considerations an integral part of how public health policies are formulated cannot be overemphasised. Contestation over entitlements to socio-economic rights has troubled health care systems worldwide, from resource-poor settings in Africa, where questions have been raised as to whether human rights approaches are best suited to addressing the problem of AIDS in Africa,4,5 through to the over-consumptive USA where universal access to health care remains a policy objective doomed to unfulfilment under market-fixated economic systems.6,7
Open Access
A comparative analysis of pharmacists’ perspectives on codeine use and misuse – a three country survey
(BioMed Central, 2018-03-27) Carney, Tara; Wells, John; Parry, Charles D H; McGuinness, Padraig; Harris, Richard; Van Hout, Marie C
Background The misuse of codeine is of increasing concern in a number of countries, particularly as this relates to over -the-counter pain and cough relief medication, and is also supplied as a prescription medicine. The study aimed to obtain and analyse the opinions and experience of pharmacy staff with regard to codeine misuse. Methods A cross-sectional web-based survey of pharmacy staff’s perspectives on this issue was administered through professional or regulatory bodies and completed by samples drawn in South Africa (n = 124), Ireland (n = 464) and the United Kingdom (n = 129). Results The majority of participants reported combination codeine-containing products as most popular, but significantly more pharmacy staff in South Africa reported codeine-containing cough syrups as most commonly popular (X2 = 122.7(2), p < 0.001). Codeine use was also seen significantly more of a public health problem in South Africa than in the other two countries (X2 = 7.6(2), p = 0.02). There was no difference across countries in the level of codeine misuse reported by pharmacy staff. Further findings indicate that professional training and education is desired, with unequivocal findings for the need for greater codeine control (X2 = 12.0(2), p = 0.002). Conclusion In conclusion, there were some inter-country differences, but overall the findings seem to suggest that pharmacists across all three countries view codeine misuse as a problem among their customers. Recommendations centre on risk management, surveillance and staff training.
Open Access
A comparative evaluation of PDQ-Evidence
(BioMed Central, 2018-03-15) Johansen, Marit; Rada, Gabriel; Rosenbaum, Sarah; Paulsen, Elizabeth; Motaze, Nkengafac V; Opiyo, Newton; Wiysonge, Charles S; Ding, Yunpeng; Mukinda, Fidele K; Oxman, Andrew D
Background A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. Methods We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. Results A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. Conclusions PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. Trial registration The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .
Open Access
A comparative risk assessment for South Africa in 2000: Towards promoting health and preventing disease
(2007) Norman, Rosana; Bradshaw, Debbie; Schneider, Michelle; Joubert, Jane; Groenewald, Pam; Lewin, Simon; Steyn, Krisela; Vos, Theo; Loubscher, Ria; Nannan, Nadine; Nojilana, Beatrice; Pieterse, Desiréé; the South African Comparative Risk Assessment Collaborating Group
A landmark project of the Medical Research Council, the first South African National Burden of Disease (SA NBD) study, identified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. (1) These estimates were recently revised (2) on the basis of additional data to estimate the disability-adjusted life years (DALYs) for single causes for the first time in South Africa. DALYs are a comprehensive measure of the disease burden combining the years of life lost (YLLs) as a result of premature mortality and years lived with disability (YLDs) related to illness or injury. (3) Compared with the use of mortality as a measure of disease burden, DALYs also capture the contributions of conditions that do not result in large numbers of deaths. For example, mental health disorders have a large disability component relative to the number of deaths. The SA NBD study highlighted the fact that despite levels of uncertainty there is important information to guide public health responses to improve the health of the nation.
Open Access
A comparison of indices of glucose metabolism in five black populations: data from modeling the epidemiologic transition study (METS)
(2015-09-15) Atiase, Yacoba; Farni, Kathryn; Plange-Rhule, Jacob; Luke, Amy; Bovet, Pascal; Forrester, Terrence G; Lambert, Vicki; Levitt, Naomi S; Kliethermes, Stephanie; Cao, Guichan; Durazo-Arvizu, Ramon A; Cooper, Richard S; Dugas, Lara R
Background: Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries. Methods: We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 ± 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day [min/day]), daily sedentary time (min/day), anthropometrics, and body composition. Results: Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m2 in men and from 25.8 to 34.8 kg/m2 in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 ± 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA. Conclusion: Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics.
Open Access
A comparison of linkage to HIV care after provider-initiated HIV testing and counselling (PITC) versus voluntary HIV counselling and testing (VCT) for patients with sexually transmitted infections in Cape Town, South Africa
(2014-08-18) Leon, Natalie; Mathews, Catherine; Lewin, Simon; Osler, Meg; Boulle, Andrew; Lombard, Carl
Abstract Background We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIV-positive via the provider-initiated HIV testing and counselling (PITC) approach, as compared to the voluntary counselling and testing (VCT) approach, as little is known about the impact of expanded testing strategies on linkage to care. Methods In a controlled trial on PITC (Cape Town, 2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients. We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes. Secondary outcomes were HIV immune status and time taken to be linked to HIV care. Logistic regression was performed to analyse the difference between arms. Results There was no difference in the main outcomes of patients with a record of CD4 testing (69.9% in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526) and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI: 0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on low CD4 test result), accessed viral load testing approximately 2.5 months sooner than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221-0.784; p = 0.007). Conclusion The PITC intervention did not improve linkage to CD4 testing, but shortened the time to viral load testing for ART-eligible patients. Major gaps found in follow-up care across both arms, indicate the need for more effective linkage-to-HIV care strategies. Trial registration Current Controlled Trials ISRCTN93692532
Open Access
A comparison of physician emigration from Africa to the United States of America between 2005 and 2015
(2017) Duvivier, Robbert J; Burch, Vanessa C; Boulet, John R
BACKGROUND: Migration of health professionals has been a cause for global concern, in particular migration from African countries with a high disease burden and already fragile health systems. An estimated one fifth of African-born physicians are working in high-income countries. Lack of good data makes it difficult to determine what constitutes "African" physicians, as most studies do not distinguish between their country of citizenship and country of training. Thus, the real extent of migration from African countries to the United States (US) remains unclear. This paper quantifies where African migrant physicians come from, where they were educated, and how these trends have changed over time. METHODS: We combined data from the Educational Commission for Foreign Medical Graduates with the 2005 and 2015 American Medical Association Physician Masterfiles. Using a repeated cross-sectional study design, we reviewed the available data, including medical school attended, country of medical school, and citizenship when entering medical school. RESULTS: The outflow of African-educated physicians to the US has increased over the past 10 years, from 10 684 in 2005 to 13 584 in 2015 (27.1% increase). This represents 5.9% of all international medical graduates in the US workforce in 2015. The number of African-educated physicians who graduated from medical schools in sub-Saharan countries was 2014 in 2005 and 8150 in 2015 (304.6% increase). We found four distinct categorizations of African-trained physicians migrating to the US: (1) citizens from an African country who attended medical school in their own country (86.2%, n = 11,697); (2) citizens from an African country who attended medical school in another African country (2.3%, n = 317); (3) US citizens who attended medical school in an African country (4.0%, n = 537); (4) citizens from a country outside Africa, and other than the United States, who attended medical school in an African country (7.5%, n = 1013). Overall, six schools in Africa provided half of all African-educated physicians. CONCLUSIONS: The number of African-educated physicians in the US has increased over the past 10 years. We have distinguished four migration patterns, based on citizenship and country of medical school. The majority of African graduates come to the US from relatively few countries, and from a limited number of medical schools. A proportion are not citizens of the country where they attended medical school, highlighting the internationalization of medical education.
Open Access
A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa
(BioMed Central, 2017-09-29) Huerga, Helena; Shiferie, Fisseha; Grebe, Eduard; Giuliani, Ruggero; Farhat, Jihane B; Van-Cutsem, Gilles; Cohen, Karen
Background: Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods. Methods: Cross-sectional population-based survey in KwaZulu-Natal, South Africa. Individuals 15–59 years were eligible. Interviews included questions about ARV use. Rapid HIV testing was performed at the participants’ home. Blood specimens were collected for ARV detection, LAg-Avidity HIV incidence testing and viral load quantification in HIV-positive individuals. Multivariate logistic regression models were used to identify socio-demographic covariates associated with discordance between self-reported ART and ARV detection. Results: Of the 5649 individuals surveyed, 1423 were HIV-positive. Median age was 34 years and 76.3% were women. ART coverage was estimated at 51.4% (95%CI:48.5–54.3), 53.1% (95%CI:50.2–55.9) and 56.1% (95%CI:53.5–58.8) using self-reported ART, ARV detection and both methods combined (classified as ART exposed if ARV detected and/or ART reported) respectively. ART coverage estimates using the 3 methods were fairly similar within sex and age categories except in individuals aged 15–19 years: 33.3% (95%CI:23.3–45.2), 33.8% (95%CI:23.9–45.4%) and 44.3% (95%CI:39.3–46.7) using self-reported ART, ARV detection and both methods combined. Viral suppression below 1000cp/mL in individuals on ART was estimated at 89.8% (95%CI:87.3–91.9), 93.1% (95%CI:91.0–94.8) and 88.7% (95%CI:86.2–90.7) using self-reported ART, ARV detection and both methods combined respectively. HIV incidence was estimated at 1.4 (95%CI:0.8–2.0) new cases/100 person-years when employing no measure of ARV use, 1.1/100PY (95%CI:0.6–1.7) using self-reported ART, and 1.2/100PY (95%CI:0.7–1.7) using ARV detection. In multivariate analyses, individuals aged 15–19 years had a higher risk of discordance on measures of ARV exposure (aOR:9.4; 95%CI:3.9–22.8), while migrants had a lower risk (aOR:0.3; 95%CI:0.1–0.6). Conclusions: In KwaZulu-Natal, the method of identifying ARV use had little impact on estimates of ART coverage, viral suppression rate and HIV incidence. However, discordant results were more common in younger individuals. This may skew estimates of ART coverage and viral suppression, particularly in adolescent surveys.
Open Access
A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa
(2017) Huerga, Helena; Shiferie, Fisseha; Grebe, Eduard; Giuliani, Ruggero; Farhat, Jihane Ben; Van Cutsem, Gilles; Cohen, Karen
Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods.
Open Access
A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data
(2017) Nasejje, Justine B; Mwambi, Henry; Sabur, Natasha F; Lesosky, Maia
Abstract Background Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.
Open Access
A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics
(BioMed Central, 2018-06-14) Soko, Nyarai D; Masimirembwa, Collen; Dandara, Collet
Objective: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5′ nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent. Results We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student’s t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P < 0.001) in rosuvastatin exposure when compared to individuals carrying the wild type SLCO1B1 c.1929A allele. Polymorphism c.1929A>C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective.
Open Access
A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis
(2013) Irlam, James H; Mayosi, Bongani M; Engel, Mark E; Gaziano, Thomas A
Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children depends on prompt and effective diagnosis and treatment of pharyngitis at the primary level of care. Cost-effectiveness modeling shows that the most cost-effective strategy for primary prevention in South Africa (SA) is to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis in children presenting at the primary level of care and then to treat them with a single dose of intramuscular penicillin. Treat All and CDR2+ strategies are affordable and simple and miss few cases of streptococcal pharyngitis at the primary level of care. The CDR2+ strategy is the most cost-effective for primary prevention of ARF and RHD in urban SA and should complement primordial and secondary prevention efforts.
Open Access
A critical evaluation of the effectiveness of interventions for improving the well-being of caregivers of children with cerebral palsy: a systematic review protocol
(BioMed Central, 2016-07-13) Dambi, Jermaine M; Jelsma, Jennifer; Mlambo, Tecla; Chiwaridzo, Matthew; Tadyanemhandu, Cathrine; Chikwanha, Mildred T; Corten, Lieselotte
Background: Over the years, family-centered care has evolved as the “gold standard” model for the provision of healthcare services. With the advent of family-centered approach to care comes the inherent need to provide support services to caregivers in addition to meeting the functional needs of children with physical disabilities such as cerebral palsy (CP). Provision of care for a child with CP is invariably associated with poor health outcomes in caregivers. As such, there has been a surge in the development and implementation of interventions for improving the health and well-being of these caregivers. However, there is a paucity of the collective, empirical evidence of the efficacy of these interventions. Therefore, the broad objective of this review is to systematically review the literature on the effectiveness of interventions designed to improve caregivers’ well-being. Methods/design: This is a systematic review for the evaluation of the effectiveness of interventions designed to improve caregivers’ well-being. Two independent, blinded, reviewers will search articles on PubMed, Scopus, Web of Science, CINAHL, Psych Info, and Africa-Wide Information using a predefined criterion. Thereafter, three independent reviewers will screen the retrieved articles. The methodological quality of studies meeting the selection criterion will be evaluated using the Briggs Institute checklists. Afterwards, two independent researchers will then apply a preset data-extraction form to collect data. We will perform a narrative data analysis of the final sample of studies included for the review. Discussion: The proposed systematic review will provide the empirical evidence of the efficacy of interventions for improving the well-being of caregivers of children with physical disabilities. This is important given the great need for evidenced-based care and the greater need to improve the health and well-being of caregivers. Systematic review registration: PROSPERO CRD42016033975.
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.