Plos One
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Multicenter Study Observational Study
Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study.
Immunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects. ⋯ The BMI correlated with the response to ipilimumab treatment in a cohort of metastatic melanoma patients.
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Randomized Controlled Trial Multicenter Study
Effects of supplemental vitamin D and calcium on markers of proliferation, differentiation, and apoptosis in the normal colorectal mucosa of colorectal adenoma patients.
To clarify the roles of vitamin D and calcium as potential chemopreventive agents against colorectal cancer in humans, and to develop "treatable", pre-neoplastic, phenotypic biomarkers of risk for colorectal neoplasms, we estimated the effects of supplemental vitamin D3 (1,000 IU/day [25 μg/day]) and calcium (1,200 mg/day), alone and in combination, on biomarkers of proliferation (mib-1), differentiation (p21), and apoptosis (bax [apoptosis-promoting] and bcl-2 [apoptosis-inhibiting]), in the normal-appearing rectal mucosa in a subsample of participants (n = 104) in a larger randomized, double-blind, placebo-controlled clinical trial among colorectal adenoma patients. The biomarkers were measured in rectal biopsies at baseline and after one year of follow up, using automated immunohistochemistry and quantitative image analysis. ⋯ All estimated treatment effects on bcl-2 expression were close to the null. These pilot study results support further investigation of whether 1) vitamin D and calcium promote colorectal epithelial cell differentiation, reduce proliferation, and promote apoptosis in the normal-appearing human colorectal mucosa, 2) vitamin D and calcium act as chemopreventive agents against colorectal neoplasms, and 3) mib-1, p21, and bax are potential "treatable", pre-neoplastic, biomarkers of risk for colorectal neoplasms.
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Randomized Controlled Trial Multicenter Study
Towards 90-90: Findings after two years of the HPTN 071 (PopART) cluster-randomized trial of a universal testing-and-treatment intervention in Zambia.
HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the "PopART" universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. ⋯ Overall coverage against the 90-90 targets was high after two years of intervention, but was lower among men, individuals aged 18-34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements.
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Randomized Controlled Trial Multicenter Study
The p38 mitogen activated protein kinase inhibitor losmapimod in chronic obstructive pulmonary disease patients with systemic inflammation, stratified by fibrinogen: A randomised double-blind placebo-controlled trial.
Cardiovascular disease is a major cause of morbidity and mortality in COPD patients. Systemic inflammation associated with COPD, is often hypothesised as a causal factor. p38 mitogen-activated protein kinases play a key role in the inflammatory pathogenesis of COPD and atherosclerosis. ⋯ In this plasma fibrinogen-enriched study, losmapimod had no effect on arterial inflammation and endothelial function at 16 weeks of treatment, although it was well tolerated with no significant safety concerns. These findings do not support the concept that losmapimod is an effective treatment for the adverse cardiovascular manifestations of COPD.
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Multicenter Study
Predictive performance of a multivariable difficult intubation model for obese patients.
A predictive model of scores of difficult intubation (DI) may help physicians screen for airway difficulty to reduce morbidity and mortality in obese patients. The present study aimed to set up and evaluate the predictive performance of a newly developed, practical, multivariate DI model for obese patients. ⋯ The predictive performance of the selected model showed limited benefit for preoperative screening to predict DI among obese patients.