OpenUCT :: Browsing by Subject "Middle Aged"

Browsing by Subject "Middle Aged"

Now showing 1 - 20 of 69

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
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
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
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
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.
Open Access
Development 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 H
OBJECTIVES: 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.
Open Access
Diagnosing tuberculosis in hospitalized HIV-infected individuals who cannot produce sputum: is urine lipoarabinomannan testing the answer?
(2017) Sabur, Natasha F; Esmail, Aliasgar; Brar, Mantaj S; Dheda, Keertan
Abstract Background Up to one third of HIV-infected individuals with suspected TB are sputum-scarce. The Alere Determine™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression. However, how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear. Methods This study represents a post hoc sub-group analysis of data from a randomized multi-center parent study. The study population consisted of hospitalized HIV-infected patients with suspected TB who were unable to produce sputum and who underwent urine LAM testing. The diagnostic utility of urine LAM for TB in this group was compared to the performance of urine LAM in patients who did produce a sputum sample in the parent study. Results There were a total of 187 and 2341 patients in the sputum-scarce and sputum-producing cohorts, respectively. 80 of the sputum-scarce patients underwent testing with urine LAM. In comparison to those who did produce sputum, sputum-scarce patients had a younger age, a lower Karnofsky performance score, and a lower weight and BMI at admission. A greater proportion of sputum-scarce patients were urine LAM positive, compared to those who were able to produce sputum (31% vs. 21%, p = 0.04). A higher proportion of sputum-scarce patients died within 8 weeks of admission (32% vs. 24%, p = 0.013). We inferred that 19% of HIV-infected sputum-scarce patients suspected of TB were diagnosed with tuberculosis by urine LAM testing, with an estimated positive predictive value of 63% (95% CI 43–82%). Conclusions Urine LAM testing can effectively identify tuberculosis in HIV-infected patients who are at a higher risk of mortality yet are unable to generate a sputum sample for diagnostic testing. Our findings support the use of urine LAM testing in sputum-scarce hospitalized HIV-infected patients, and its incorporation into diagnostic algorithms for this patient population.
Open Access
Does sentinel lymph node biopsy have a role in node-positive head and neck squamous carcinoma?
(2013) Edkins, O; Hofmeyr, C; Fagan, J
OBJECTIVES/HYPOTHESIS: The objective of the study was to determine whether sentinel lymph node biopsy (SLNB) can be used to reduce clinical overstaging of cervical nodes in head and neck squamous cell carcinoma (SCC) in a developing world setting. STUDY DESIGN: Sentinel and echelon lymph nodes were identified by means of a combination of lymphoscintigraphy, gamma probe and blue dye identification. They were analysed histologically and their pathological status was compared with the rest of the neck dissection specimen to determine diagnostic accuracy in patients with T1-4 N0-3 SCC of the oral cavity or oropharynx undergoing primary surgical resection and neck dissection. RESULTS: Thirty-three patients were included in the study, 13 in the node-negative (N0) and 20 in the node-positive (N+) group. In the clinically N0 group the sensitivity of SLNB was 100% and the negative predictive value (NPV) 100%. In the clinically N+ group the sensitivity was 71% and the NPV 60% for staging the nodal status of the neck. CONCLUSIONS; The accuracy of SLNB in the clinically N+ neck is too low for SLNB to be a means of avoiding comprehensive neck dissection. LEVEL OF EVIDENCE: 2B.
Open Access
Door-to-needle time for administration of fibrinolytics in acute myocardial infarction in Cape Town
(2012) Maharaj, Roshen C; Geduld, Heike; Wallis, Lee A
OBJECTIVES: To determine the current door-to-needle time for the administration of fibrinolytics for acute myocardial infarction (AMI) in emergency centres (ECs) at three hospitals in Cape Town, and to compare it with the American Heart Association/American College of Cardiology (AHA/ACC) recommendation of 30 minutes as a marker of quality of care. METHODS: A retrospective review of case notes from January 2008 to July 2010 of all patients receiving thrombolytics for AMI in the ECs of three Cape Town hospitals. The total door-to-needle time was calculated and patient demographics and presentation, physician qualification, clinical symptomology and reasons for delays in thromobolytic administration were analysed. RESULTS: A total of 372 patients with acute ST elevation myocardial infarction (STEMI) were identified; 161 patients were eligible for the study. The median door-to-needle time achieved was 54 minutes (range 13 - 553 mins). A door-to-needle time of 30 minutes or less was achieved in 33 (20.5%) patients; 51.3% of the patients arrived by ambulance; 34% of patients had a pre-hospital 12-lead ECG; and 88.8% had typical symptoms of myocardial infarction. Medical officers administered thrombolytics to 44.7% of the patients. The predominant infarct location on ECG was inferior (55.9%). CONCLUSION: A significant number of patients were not thrombolysed within 30 minutes of presentation. The lack of senior doctors, difficulty interpreting ECGs, atypical presentations and EC system delays prolonged the door-to-needle time in this study.
Open Access
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
(2015) Sabatine, Marc S; Giugliano, Robert P; Wiviott, Stephen D; Raal, Frederick J; Blom, Dirk J; Robinson, Jennifer; Ballantyne, Christie M; Somaratne, Ransi; Legg, Jason; Wasserman, Scott M; Scott, Robert; Koren, Michael J; 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 short-term studies. We conducted two extension studies to obtain longer-term data. METHODS: In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined. RESULTS: As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003). CONCLUSIONS: During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers, NCT01439880 and NCT01854918.).
Open Access
Erratum to: Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study
(2017) Nguimmo-Metsadjio, Aurelie; Atogho-Tiedeu, Barbara; Noubiap, Jean Jacques; Evehe, Marie-Solange; Djokam-Dadjeu, Rosine; Donfack, Olivier Sontsa; Nanfa, Dieudonne; Mato, Edith Pascale M; Ngwa, Elvis Ndonwi; Guewo-Fokeng, Magellan; Pokam-Fosso, Priscille; Mbacham, Wilfred F; Mbanya, Jean Claude; Sobngwi, Eugène
OBJECTIVE: This study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population. METHOD: This was a case-control pilot study including 61 obese and 61 non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure, fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T) polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes were correlated with clinical and biological parameters. RESULTS: The T allele was predominant in the study population with a frequency of 93%. No statistically significant difference was however observed between the genotypic (p = 0.50) and allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of clinical and biochemical parameters of C allele carriers (CX = CC + CT) with those of TT genotype showed that there was no significant difference between the lipid profile of these two groups. CONCLUSION: The rs7903146 (C/T) polymorphism of the TCF7L2 gene might not be associated with obesity in the Cameroonian population.
Open Access
Erratum to: Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials
(2016) Phillips, Patrick P J; Mendel, Carl M; Burger, Divan A; Crook, Angela M; Nunn, Andrew J; Dawson, Rodney; Diacon, Andreas H; Gillespie, Stephen H
BackgroundDespite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials.MethodsUsing data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome.ResultsTime to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP.ConclusionsCulture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.
Open Access
Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa: study protocol for a cluster randomized trial
(2017) Lippman, Sheri A; Pettifor, Audrey; Rebombo, Dumisani; Julien, Aimée; Wagner, Ryan G; Kang Dufour, Mi-Suk; Kabudula, Chodziwadziwa Whiteson; Neilands, Torsten B; Twine, Rhian; Gottert, Ann; Gómez-Olivé, F Xavier; Tollman, Stephen M; Sanne, Ian; Peacock, Dean; Kahn, Kathleen
Abstract Background HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care—including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Methods/design Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18–49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Discussion Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa. Trial Registration NCT02197793 Registered July 21, 2014.
Open Access
Fatal outcomes among patients on maintenance haemodialysis in sub-Saharan Africa: a 10-year audit from the Douala General Hospital in Cameroon
(2016) Kengne, André Pascal
Abstract Background End-Stage Renal disease (ESRD) is associated with increased morbidity and mortality. We assessed the occurrence, time-trend and determinants of fatal outcomes of haemodialysis-treated ESRD patients over a 10-year period in a major referral hospital in Cameroon. Methods Medical records of ESRD patients who started chronic haemodialysis at the Douala General Hospital between 2002 and 2012 were reviewed. Baseline characteristics and fatal outcomes on dialysis were recorded. Accelerated-failure time and logistic regression models were used to investigate the determinants of death. Results A total of 661 patients with 436 (66 %) being men were included in the study. Mean age at dialysis initiation was 46.3 ± 14.7 years. The median [25 th –75 th percentiles] duration on dialysis was 187 [34–754] days. A total of 297 (44.9 %) deaths were recorded during follow-up with statistical difference over the years (p < 0.0001 for year by year variation) but not in a linear fashion (p = 0.508 for linear trend), similarly in men and women (p = 0.212 for gender*year interaction). The death rate at 12 months of follow-up was 26.8 % (n = 177), with again similar variations across years (p < 0.0001). In all, 34 % of deaths occurred within the first 120 days. Year of study and background nephropathies were the main determinants of mortality, with the combination of diabetes and hypertension conveying a 127 % (95 % CI: 40–267 %) higher risk of mortality, relative to hypertension alone. Conclusion Mortality in dialysis is excessively high in this setting. Because most of these premature deaths are potentially preventable, additional efforts are needed to offset the risk and maximise the benefits from the ongoing investments of the government to defray the cost of haemodialysis. Potential actions include sensitisation of the population and healthcare practitioners, early detection and referral of individuals with CKD; and additional subsidies to support the cost of managing co-morbidities in patients with CKD in general.
Open Access
Glucose tolerance, MTHFR C677T and NOS3 G894T polymorphisms, and global DNA methylation in mixed ancestry African individuals
(2016) Matsha, Tandi E; Pheiffer, Carmen; Pheiffer, Carmen
The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both ) and in screen-detected diabetes compared to known diabetes on treatment (). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.