Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and ...Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.
Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.
There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval CI, 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer.
In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).
Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients' prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The ...optimal dose of clofazimine (CFZ), a repurposed medicine for DR-TB, that is safe and effective in the South African (SA) population is unknown.
To report on dose-related final treatment outcomes in patients receiving CFZ plus a background regimen for DR-TB.
In a retrospective review of patient folders from 2012 to 2014, treatment outcomes documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR-TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and outcomes.
A total of 600 patients were included, of whom 169 (28.2%) received 100 mg. Of these, 87 (51.5%) weighed <50 kg and 82 (48.5%) ≥50 kg. Four hundred and thirty-one (71.8%) received ≥200 mg, of whom 41 (9.5%) were <50 kg and 390 (90.5%) ≥50 kg. Overall 77.2% were HIV-positive, with 93.95% on antiretroviral medicine. The majority of patients presented with extremely drug-resistant TB (55.3%). Forty-seven and a half percent of patients received a standardised background regimen, and 52.5% received an individualised regimen containing a new or repurposed medicine including CFZ. On multivariate analysis, adjusting for age, gender, HIV status and concomitant antiretrovirals, previous TB history, type of TB and background regimen, patients ≥50 kg prescribed 100 mg CFZ were 60% less likely to have a successful outcome (adjusted odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2 - 0.8; p=0.009) compared with patients <50 kg receiving 100 mg CFZ. Patients <50 kg who received ≥200 mg were 40% less likely to have a successful treatment outcome (adjusted OR 0.6, p=0.3), and were found to have a higher risk of adverse events than patients <50 kg receiving 100 mg CFZ (82.9% v. 65.5%).
Dose-weight interaction plays a role in the odds of a successful outcome. There is an association between dose-weight interactions, outcomes and adverse events. Weight-based dosing in patients <50 kg and ≥50 kg must be considered to achieve optimal treatment outcomes and reduce adverse events. Active drug safety monitoring must be implemented as a package of care for patients receiving CFZ as part of a DR-TB treatment regimen.
Alterations in sleep duration and quality are linked to the development of cardiovascular risk factors and the metabolic syndrome (MetS). The aim of this study was to determine a sex stratified ...analysis on the role and associations of sleep duration on cardiometabolic risk factors, and the MetS.
Data from 1375 randomly selected participants (15-64 years) was collected for demographic, anthropometric, blood pressure and biochemistry data after overnight fasting, and derangements diagnosed according to published guidelines. Analysis of association between the MetS (harmonised criteria modified for South Asians), sleep duration (self-reported for a 24-hour period), and cardiometabolic risk factors was done using stepwise logistic regression.
The BMI, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), fasting plasma glucose, total cholesterol, low density lipoprotein were higher (p< 0.05) in subjects who slept <6 hours, with lower HDL. Under 6 hours of sleep was independently associated with raised FPG in men (OR 1.71 95% CI 1.53,5.52) only. More than 10 hours of sleep was independently associated with increased triglyceride levels in men (1.720.56, 5.23) and women (2.251.93,5.42).
The individual components of the Mets, particularly, increased triglycerides and blood glucose are associated with sleep deprivation or excess.
Background. Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis ...(TB). The optimal dose and dose-related safety of clofazimine (CFZ), a repurposed medicine for DR TB, in the South African (SA) population are unknown.Objectives. To report on dose-related adverse events in patients receiving CFZ plus a background regimen for DR TB.Methods. In a retrospective review of patient folders from 2012 to 2014, adverse events documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and adverse events.Results. Of 600 patients included, 78.7% (n=472) weighed ≥50 kg. Of these, 17.4% (n=82) received 100 mg CFZ and 82.6% (n=390) received >200 mg. Of 128 patients (21.3%) who weighed Conclusions. There is an association between dose-weight interaction and adverse events. The odds of any adverse event occurring were higher when low-weight patients (
The effect of interactions between organic solvents or water on the interfacial and bulk properties of 1-benzyl-3-methylimidazolium dicyanamide, BzMIMDCA and 1-benzyl-3-methylimidazolium ...bis{(trifluoromethyl)sulfonyl}imide, BzMIMNTf 2 were determined via measurement of activity coefficients γ ∞13 at infinite dilution for 64 solutes. The data were obtained using the gas–liquid chromatography technique. Measurements were undertaken at six temperatures, in 10 K intervals, in the range of 318.15 to 368.15 K. The solutes studied included both non-polar and polar compounds, such as alkanes, alkenes, and alkynes, as well as aromatic hydrocarbons, alcohols, water, ethers, ketones, acetonitrile, pyridine, 1-nitropropane, thiophene, and esters. Density, ρ , and viscosity η , measurements for a range of temperatures, T for the chosen ionic liquids (ILs), BzMIMDCA and BzMIMNTf 2 were also undertaken at pressure, p = 101 kPa. The gas–liquid partition coefficients, K L at infinite dilution, and the fundamental thermodynamic functions, partial molar excess Gibbs energy, enthalpy and entropy at infinite dilution were calculated from the experimental data measurements. The values of selectivity and capacity for three separation cases, viz. hexane/hex-1-ene, cyclohexane/cyclohexene, and ethylbenzene/styrene were calculated from γ ∞13 values and compared to literature for imidazolium-based or dicyanamide-based, or bis{(trifluoromethyl)sulfonyl}imide-based ionic liquids (ILs). The results from the study indicate that BzMIMDCA has large selectivity values for all three of the separation cases studied.
The present work focussed on application of the environmental friendly 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide (BMIM+Tf2N−) ionic liquid for the separations of ...(alkane/aromatic), (alkane/alk-1-ene), (cycloalkane/aromatic) and (water/alkan-1-ol) using gas-liquid chromatography (GLC) technique. In this reason the activity coefficients at infinite dilution, γ13∞, for 31 organic solutes (alkanes, cycloalkanes, alkenes, alkynes, aromatics, alkanol and ketones) and water in ionic liquid were measured at temperatures of (323.15, 333.15, 343.15, 353.15 and 363.15) K. Stationary phase loadings of (42.83 and 68.66) % by mass were used to ensure repeatability of measurements. Density and viscosity values were measured to confirm the purity of ionic liquid. Partial molar excess enthalpies at infinite dilution, ΔH1E,∞, were also determined. The selectivities, Sij∞, and capacities, kj∞, were determined for the above separations. The separating ability of the investigated ionic liquid was compared with previously investigated ionic liquids and industrial solvents such as sulfolane, n-methyl-2-pyrrolidine (NMP) and n-formylmorpholine (NFM).
•Activity coefficients were measured in the ionic liquid BMIM+Tf2N−.•Selectivities for selected separations compared to other IL's and solvents•Capacities for selected separations were also calculated and discussed.•The expression and estimation of uncertainty have been described in detail.
Western Cape Province, South Africa.
To characterise tuberculosis (TB) epidemiology, disease presentation and treatment outcomes among adolescents (age 10-19 years) and young adults (age 20-24 years) ...in the Western Cape.
A retrospective, cross-sectional review of routine patient-level data from the Electronic TB Register (ETR.Net) for 2013. Site of TB disease, human immunodeficiency virus (HIV) status and TB treatment outcomes were analysed by 5-year age groups (<5, 5-9, 10-14, 15-19, 20-24 and 25 years of age). TB notification rates were calculated using census data.
Adolescents and young adults comprised 18.0% of all new TB notifications in 2013. The notification rate was 141 TB cases/100 000 person-years (py) among 10-14 year olds, 418/100 000 py among 15-19 year olds and 627/100 000 py among 20-24 year olds. HIV prevalence among TB patients was 10.9% in 10-14 year olds, 8.8% in 15-19 year olds and 27.2% in 20-24 year olds. Older adolescents (age 15-19 years) and young adults (age 20-24 years) with HIV co-infection had poor treatment outcomes: 15.6% discontinued treatment prematurely and 4.0% died.
Young people in the Western Cape suffer a substantial burden of TB, and those with TB-HIV co-infection are at high risk of treatment discontinuation.
Objective:
Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a ...plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164.
Methods:
Pregnant women (n = 300) were subdivided into low, medium and high NOx exposure groups, genotyped for the miRNA-146a G/C rs2910164 using polymerase chain reaction-restriction fragment length polymorphism, and further stratified based on HIV status.
Results:
Unstratified data (HIV+ and HIV− mothers combined): Mothers from the high NOx group with the variant C-allele had low blood iron levels (p = 0.0238), and had babies with reduced birthweights (p = 0.0283). As NOx increased, the prevalence of preterm birth and low birth weight also increased in mothers with the variant C-allele versus wildtype G-allele. HIV-infected mothers: In all NOx exposure groups, mothers with the variant C-allele had higher systolic blood pressure (low: p = 0.0386, medium: p = 0.0367 and high: p = 0.0109) and had babies with lower Appearance, Pulse, Grimace, Activity and Respiration scores at 1 min (low: p = 0.0190, medium: p = 0.0301 and high: p = 0.0361).
Conclusion:
Maternal rs2910164 variant C-allele, NOx pollution and HIV/AIDS might collectively play a role in intensifying gestational hypertension and ABO.
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