ATM Mutations Associate with Distinct Co-Mutational Patterns and Therapeutic Vulnerabilities in NSCLC.

Purpose: Ataxia-telangiectasia mutated (ATM) is the most frequently mutated DNA damage repair gene in non-small cell lung cancer (NSCLC). However, the molecular correlates of ATM mutations and their clinical implications have not been fully elucidated.

Experimental Design: Clinicopathologic and genomic data from 26,587 patients with NSCLC from MD Anderson, public databases, and a de-identified nationwide (US-based) NSCLC clinicogenomic database (CGDB) were used to assess the co-mutation landscape, protein expression, and mutational processes in ATM-mutant tumors.

Evaluating a Cox marginal structural model to assess the comparative effectiveness of inhaled corticosteroids versus no inhaled corticosteroid treatment in chronic obstructive pulmonary disease.

Purpose: To evaluate the potential of a Cox marginal structural model (MSM) to estimate the time-varying causal inference of a known clinical trial association where the effectiveness of inhaled corticosteroid- (ICS-) versus non-ICS-containing treatments has been compared in patients with chronic obstructive pulmonary disease (COPD).

Methods: This retrospective study from 2006-2016 used linked data from Clinical Practice Research Datalink-GOLD, Hospital Episode Statistics, and Office for National Statistics mortality. A Cox MSM, incorporating a new-user design, was deemed capable of replicating a clinical trial-like pathway.

Glycaemic, weight, and blood pressure changes associated with early versus later treatment intensification with dapagliflozin in United Kingdom primary care patients with type 2 diabetes mellitus.

Aims: Early treatment intensification for type 2 diabetes mellitus (T2DM) is often required to achieve glycaemic control and avoid longer-term complications. We assessed associations between early versus later dapagliflozin initiation with changes in glucose control, weight, and blood pressure using UK Clinical Practice Research Datalink (CPRD) data.

Methods: People with T2DM aged ≥18 years, initiating dapagliflozin between November 2012 and August 2016 and with prior oral T2DM therapy (N = 3774), were included.

Glycated Hemoglobin, Body Weight and Blood Pressure in Type 2 Diabetes Patients Initiating Dapagliflozin Treatment in Primary Care: A Retrospective Study.

Introduction: The present study aimed to describe characteristics of patients with type 2 diabetes (T2D) in UK primary care initiated on dapagliflozin, post-dapagliflozin changes in glycated hemoglobin (HbA), body weight and blood pressure, and reasons for adding dapagliflozin to insulin.

Methods: Retrospective study of patients with T2D in the Clinical Practice Research Datalink with first prescription for dapagliflozin. Patients were included in the study if they: (1) had a first prescription for dapagliflozin between November 2012 and September 2014; (2) had a Read code for T2D; (3) were registered with a practice for at least 6 months before starting dapagliflozin; and (4) remained registered for at least 3 months after initiation.

Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population.

Purpose: The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. The aim of this study was to measure the concomitant exposure of patients to CYP3A4-metabolised statins and CYP3A4 inhibitors in the UK primary care population.

Methods: The co-administration of statins and CYP3A4 inhibitors during 2008 was examined in the General Practice Research Database, a large nationally representative UK primary care database.

A meta-analysis of six prospective studies of falling in Parkinson's disease.

Recurrent falls are a disabling feature of Parkinson's disease (PD). We have estimated the incidence of falling over a prospective 3 month follow-up from a large sample size, identified predictors for falling for PD patients repeated this analysis for patients without prior falls, and examined the risk of falling with increasing disease severity. We pooled six prospective studies of falling in PD (n = 473), and examined the predictive power of variables that were common to most studies.

Persistence with once-daily versus twice-daily bupropion for the treatment of depression in a large managed-care population.

In this study, the impact of dosing frequency [once daily with bupropion extended-release (XL) versus twice daily with bupropion sustained-release (SR)] on medication persistence was assessed over a 9-month period in a large cohort of patients with depression in a managed-care setting. Administrative claims data from the Integrated Health Care Information Services National Managed Care Benchmark database were analyzed for patients 18 to 64 years old with a documented diagnosis of depression who began treatment with bupropion XL or SR between September 2003 and February 2004. Persistence of use was higher with once-daily bupropion XL (n = 1074) than with twice-daily bupropion SR (n = 1917) across measures assessed by univariate tests of proportions.

A double-blind, randomized, 26-week study comparing the cognitive and psychomotor effects and efficacy of 75 mg (37.5 mg b.i.d.) venlafaxine and 75 mg (25 mg mane, 50 mg nocte) dothiepin in elderly patients with moderate major depression being treated in general practice.

To investigate the efficacy and cognitive and psychomotor effects of venlafaxine and dothiepin in elderly patients with moderate major depression. A prospective, randomized, double-blind, parallel-group, active comparator controlled study was conducted. Eighty-eight patients (aged > or = 60 years) were enrolled.

Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening.

The objective was to assess residual effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double-blind, placebo-controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg.