A first step towards best practice recommendations for the design and statistical analyses of pragmatic clinical trials: A modified Delphi approach.

Aim: Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs.

Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease.

Background & Aims: Resistance to single cytokine blockade, namely anti-tumor necrosis factor (TNF) therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines interferon (IFN)-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically.

Human Intestinal Barrier Function in Health and Disease.

The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders.

An increased B-type natriuretic peptide in the absence of a cardiac abnormality identifies those whose left ventricular mass will increase over time.

Objectives: The purpose of this study was to identify the relationship of B-type natriuretic peptide (BNP) with evolution of left ventricular mass (LVM) in optimally treated primary prevention patients.

Background: Patients who have an elevated BNP no cardiac abnormality on echocardiography are common and at increased risk of adverse events. One hypothesis is that an elevated BNP is an early sensitive indicator of who will develop future structural abnormalities such as left ventricular (LV) hypertrophy.

The unintended consequences of clinical trials regulations.

Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH) guidance on good clinical practice (GCP), arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe.

How to ascertain drug safety in the context of benefit. Controversies and concerns.

There is great concern about clearly defining benefit and risk in the context of both drug development and clinical practice. In view of this pressure, the OMERACT Executive identified the need to bring together clinical trialists, pharmacoepidemiologists, clinicians, clinical epidemiologists, statistical experts, and regulatory representatives to discuss different approaches to define risk and perhaps improved ways to express it. Each attendee spoke on a given topic and the group was charged to consider the issue of risk in the context of formally posed questions.

Functional effects of genetic variants in the 11beta-hydroxylase (CYP11B1) gene.

Objective: We previously described an association between the -344C/T 5'-untranslated region (UTR) polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with a raised aldosterone to renin ratio (ARR); the same genetic variant is also associated with impaired adrenal 11beta-hydroxylase efficiency. The -344 polymorphism does not seem to be functional, so is likely to be in linkage with variants in CYP11B1 that determine the associated variation in 11beta-hydroxylase efficiency. We therefore aimed to determine whether there is an association between CYP11B1 variants and hypertension and/or an altered ARR.

Organisational factors in relation to control of blood pressure: an observational study.

Background: Studies show that 60-75% of treated patients with hypertension in general practice, still do not reach the recommended blood pressure targets of <150/90 mmHg.

Aim: To investigate aspects of hypertension management in relation to sociodemographic variables, antihypertensive drug treatment, and organisational factors in primary care.

Design Of Study: Observational study over 3 years.