Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis.

Background And Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).

Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD.

Novel HDAC6 Inhibitors Increase Tubulin Acetylation and Rescue Axonal Transport of Mitochondria in a Model of Charcot-Marie-Tooth Type 2F.

Disruption of axonal transport causes a number of rare, inherited axonopathies and is heavily implicated in a wide range of more common neurodegenerative disorders, many of them age-related. Acetylation of α-tubulin is one important regulatory mechanism, influencing microtubule stability and motor protein attachment. Of several strategies so far used to enhance axonal transport, increasing microtubule acetylation through inhibition of the deacetylase enzyme histone deacetylase 6 (HDAC6) has been one of the most effective.

Vedolizumab use in patients with inflammatory bowel diseases undergoing surgery: clinical trials and post-marketing experience.

Background: Patients with inflammatory bowel diseases frequently require surgery, but immunotherapies used in disease management may increase the risk of post-operative complications. We investigated frequencies of post-operative complications in patients who received vedolizumab-a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn's disease-in clinical-trial and post-marketing settings.

Methods: This post hoc analysis of safety data from GEMINI 1, GEMINI 2, and long-term safety studies included patients who had had colectomy or bowel surgery/resection.

Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease.

Background & Aims: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy.

Methods: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017.

A retrospective observational study of early experiences of vedolizumab treatment for inflammatory bowel disease in the UK: The REVIVE study.

Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK.To describe real-world early experiences of vedolizumab to treat CD and UC in the UK.

Neurological Manifestations of Neuropathy and Ataxia in Celiac Disease: A Systematic Review.

Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed.

Population pharmacokinetic-pharmacodynamic modelling of the relationship between testosterone and prostate specific antigen in patients with prostate cancer during treatment with leuprorelin.

Aims: This investigation aimed to quantitatively characterize the relationship between the gonadotropin-releasing hormone agonist leuprorelin, testosterone (T) and prostate specific antigen (PSA) concentrations over time, to aid identification of a target T concentration that optimises the balance of the benefits of T suppression whilst reducing the risk of side effects related to futile over-suppression.

Methods: Data from a single dose study to investigate the effect of leuprorelin in a 6-month depot formulation on T and PSA in prostate cancer patients were analysed using a population pharmacokinetic-pharmacodynamic modelling approach. The developed model was qualified using external data from 3 studies, in which the effect of different formulations of leuprorelin on T and PSA was evaluated in prostate cancer patients.

The number needed to treat and relevant between-trial comparisons of competing interventions.

The number needed to treat (NNT) is considered an intuitive as well as popular effect measure. The aims of this review were to 1) explain why we cannot compare trial-specific NNT estimates for the competing treatments evaluated in different randomized controlled trials (RCTs) and 2) outline the principles of how relative treatment effects of different trials can be compared and results can be presented as NNT, without violating the principles of valid between-trial comparisons. Our premise is that ratio measures for relative treatment effects of response outcomes are less prone to effect modification than absolute difference measures of response outcomes.

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review.

Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD.

A phase 2, randomized, placebo-controlled study of the efficacy and safety of TAK-063 in subjects with an acute exacerbation of schizophrenia.

Introduction: TAK-063 is a potent, selective inhibitor of phosphodiesterase 10A, an enzyme selectively expressed in medium spiny neurons of the striatum. This randomized, parallel-group study evaluated the efficacy and safety of 20-mg daily TAK-063 versus placebo in subjects with acutely exacerbated symptoms of schizophrenia (NCT02477020).

Methods: Adults aged 18 to 65 with diagnosed schizophrenia and psychotic symptoms that exacerbated within 60 days before screening were included.

Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials.

Rationale: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted.

Objectives: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast.

Treatment choice, medication adherence and glycemic efficacy in people with type 2 diabetes: a UK clinical practice database study.

Objective: Using primary care data obtained from the UK Clinical Practice Research Datalink, this retrospective cohort study examined the relationships between medication adherence and clinical outcomes in patients with type 2 diabetes.

Research Design And Methods: Data were extracted for patients treated between 2008 and 2016, and stratified by oral antihyperglycemic agent (OHA) line of therapy (mono, dual or triple therapy). Patients were monitored for up to 365 days; associations between medication possession ratio (MPR) and outcomes at 1 year (glycated hemoglobin A1c (HbA1c), weight and hypoglycemia incidence) were assessed using linear regression modeling and descriptive analyses.

What Is the Risk of Progressive Multifocal Leukoencephalopathy in Patients With Ulcerative Colitis or Crohn's Disease Treated With Vedolizumab?

Background: Progressive multifocal leukoencephalopathy is a serious condition linked to certain diseases and immunosuppressant therapies, including the α4 integrin antagonist natalizumab. No cases have been reported to date with vedolizumab, a selective antagonist of the α4β7 integrin expressed on gut-homing lymphocytes. This analysis aimed to describe the current and future expected occurrence of progressive multifocal leukoencephalopathy with vedolizumab use, were the risk the same as in other populations in which this disease has been studied.

A Randomized Multiple Dose Pharmacokinetic Study of a Novel PDE10A Inhibitor TAK-063 in Subjects with Stable Schizophrenia and Japanese Subjects and Modeling of Exposure Relationships to Adverse Events.

Background: Phosphodiesterase 10A (PDE10A) is selectively expressed in medium spiny neurons of the striatum. TAK-063 is a selective inhibitor of PDE10A in clinical development for the treatment of schizophrenia.

Objectives: Safety, tolerability, and pharmacokinetics (PK) of TAK-063 were evaluated following multiple rising oral doses, and PK/adverse event (AE) models were developed to characterize the relationship between TAK-063 exposure and incidence of specific AEs.

Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients.

Aims: To evaluate the occurrence of suboptimal therapy among patients with IBD treated with tumor necrosis factor antagonists (anti-TNFs).

Methods: A multinational chart review in Europe and Canada was conducted among IBD patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who initiated anti-TNF therapy between 2009 and 2013.

Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom.

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD).Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data.

Series: Pragmatic trials and real world evidence: Paper 6. Outcome measures in the real world.

Results from pragmatic trials should reflect the comparative treatment effects encountered in patients in real-life clinical practice to guide treatment decisions. Therefore, pragmatic trials should focus on outcomes that are relevant to patients, clinical practice, and treatment choices. This sixth article in the series (see Box) discusses different types of outcomes and their suitability for pragmatic trials, design choices for measuring these outcomes, and their implications and challenges.

Comparison of TachoSil and TachoComb in patients undergoing liver resection-a randomized, double-blind, non-inferiority trial.

Background: This study aimed to demonstrate the noninferior efficacy of TachoSil vs. TachoComb in Japanese patients undergoing liver resection and to assess the safety of TachoSil vs. TachoComb in these patients.

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma.

Background: Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre-post historical database study to investigate asthma-related outcomes by treatment.

Methods: We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]).

Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

Background And Aims: A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data.

Methods: Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated.

Cost-effectiveness of vedolizumab compared with infliximab, adalimumab, and golimumab in patients with ulcerative colitis in the United Kingdom.

Objective: To examine the clinical and economic impact of vedolizumab compared with infliximab, adalimumab, and golimumab in the treatment of moderately to severely active ulcerative colitis (UC) in the United Kingdom (UK).

Methods: A decision analytic model in Microsoft Excel was used to compare vedolizumab with other biologic treatments (infliximab, adalimumab, and golimumab) for the treatment of biologic-naïve patients with UC in the UK. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator.