Genotypic Influences on Actuators of Aerobic Performance in Tactical Athletes.

Background: This study examines genetic variations in the systemic oxygen transport cascade during exhaustive exercise in physically trained tactical athletes. Research goal: To update the information on the distribution of influence of eleven polymorphisms in ten genes, namely ACE (rs1799752), AGT (rs699), MCT1 (rs1049434), HIF1A (rs11549465), COMT (rs4680), CKM (rs8111989), TNC (rs2104772), PTK2 (rs7460 and rs7843014), ACTN3 (rs1815739), and MSTN (rs1805086)-on the connected steps of oxygen transport during aerobic muscle work.

Methods: 251 young, healthy tactical athletes (including 12 females) with a systematic physical training history underwent exercise tests, including standardized endurance running with a 12.

Growth in Virologically Suppressed HIV-Positive Children on Antiretroviral Therapy: Individual and Population-level References.

Background: Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ).

gems: An R Package for Simulating from Disease Progression Models.

Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The 𝖱 package is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.

Additive effect of anemia and renal impairment on long-term outcome after percutaneous coronary intervention.

Introduction: Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes.

Methods: Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline.

Tenofovir or zidovudine in second-line antiretroviral therapy after stavudine failure in southern Africa.

Background: There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analysed outcomes in cohorts from South Africa, Zambia and Zimbabwe

Methods: Patients aged ≥16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programmes in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa.

Background: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%.

Methods And Findings: ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included.

Cohort study of trials submitted to ethics committee identified discrepant reporting of outcomes in publications.

Objectives: To identify factors associated with discrepant outcome reporting in randomized drug trials.

Study Design And Setting: Cohort study of protocols submitted to a Swiss ethics committee 1988-1998: 227 protocols and amendments were compared with 333 matching articles published during 1990-2008. Discrepant reporting was defined as addition, omission, or reclassification of outcomes.

A practical guide to Bayesian group sequential designs.

Bayesian approaches to the monitoring of group sequential designs have two main advantages compared with classical group sequential designs: first, they facilitate implementation of interim success and futility criteria that are tailored to the subsequent decision making, and second, they allow inclusion of prior information on the treatment difference and on the control group. A general class of Bayesian group sequential designs is presented, where multiple criteria based on the posterior distribution can be defined to reflect clinically meaningful decision criteria on whether to stop or continue the trial at the interim analyses. To evaluate the frequentist operating characteristics of these designs, both simulation methods and numerical integration methods are proposed, as implemented in the corresponding R package gsbDesign.

Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study.

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study.

Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa.

Objectives: Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4+ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa.

HIV infection disrupts the sympatric host-pathogen relationship in human tuberculosis.

The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host.

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.

Objectives: Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.

Design: Mathematical modelling study based on data from ART programmes.

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy.

Objective: To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy.

Methods: We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions.

Predictors of clinical outcomes in patients with severe aortic stenosis undergoing TAVI: a multistate analysis.

Background: Patients with severe aortic stenosis at increased surgical risk continue to experience compromised long-term survival despite successful transcatheter aortic valve implantation. We used time-related pathways in a multistate analysis to identify predictors of adverse long-term outcome in patients who underwent transcatheter aortic valve implantation.

Methods And Results: In a cohort of 389 patients with a mean age of 82.

Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis.

Objectives: To assess the proportion of patients lost to programme (died, lost to follow-up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme.

Methods: Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults.

Variability of growth in children starting antiretroviral treatment in southern Africa.

Background: Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa.

Methods: Treatment naïve children aged <10 years were included.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.

Background: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS).

Methods: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011.

Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: a mathematical modelling analysis.

Objectives: In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.

The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring.

Objectives: We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa.

Design And Setting: Collaborative analysis of two ART programmes in Lusaka, Zambia and Lilongwe, Malawi.

Methods: We included all adult patients experiencing immunological failure based on WHO criteria.

Population-based analysis of 4113 patients with acute cholecystitis: defining the optimal time-point for laparoscopic cholecystectomy.

Objective: To compare clinical outcomes after laparoscopic cholecystectomy (LC) for acute cholecystitis performed at various time-points after hospital admission.

Background: Symptomatic gallstones represent an important public health problem with LC the treatment of choice. LC is increasingly offered for acute cholecystitis, however, the optimal time-point for LC in this setting remains a matter of debate.

Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa.

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts.

Methods: We included 18,706 adult patients starting ART in South Africa and 80,937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months.

Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.

Background: Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficiency virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population.

Methods: We evaluated the contribution of 22 SNPs identified in genome-wide association studies and of longitudinally measured clinical factors to DM.

Growth response to antiretroviral treatment in HIV-infected children: a cohort study from Lilongwe, Malawi.

Objective: Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi.

Methods: All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008.