An approach for modelling multiple correlated outcomes in a network of interventions using odds ratios

A multivariate meta‐analysis of two or more correlated outcomes is expected to improve precision compared with a series of independent, univariate meta‐analyses especially when there are studies reporting some but not all outcomes. Multivariate meta‐analysis requires estimates of the within‐study correlations, which are seldom available. Existing methods for analysing multiple outcomes simultaneously are limited to pairwise treatment comparisons. We propose a model for a joint, simultaneous synthesis of multiple dichotomous outcomes in a network of interventions and introduce a simple way to elicit expert opinion for the within‐study correlations by utilizing a set of conditional probability parameters. We implement our multiple‐outcomes network meta‐analysis model within a Bayesian framework, which allows incorporation of expert information. As an example, we analyse two correlated dichotomous outcomes, response to the treatment and dropout rate, in a network of pharmacological interventions for acute mania. The produced estimates have narrower confidence intervals compared with the simple network meta‐analysis. We conclude that the proposed model and the suggested prior elicitation method for correlations constitute a useful framework for performing network meta‐analysis for multiple outcomes. Copyright © 2014 John Wiley & Sons, Ltd.     

The modified Clavien classification system: a standardized platform for reporting complications in transurethral resection of the prostate

Purpose

The aim of the study was to evaluate the applicability of the modified Clavien classification system (CCS) in grading perioperative complications of transurethral resection of the prostate (TURP).

Methods

All patients with benign prostatic hyperplasia submitted to monopolar TURP from January 2006 to February 2008 at a non-academic center were evaluated for complications occurring up to the end of the first postoperative month. All complications were classified according to the modified CCS independently by two urologists, and the final decision was based on consensus. If multiple complications per patient occurred, categorization was done in more than one grade. Results were presented as complication rates per grade.

Results

Forty-four complications were recorded in 31 out of 198 patients (overall perioperative morbidity rate: 15.7%), and their grading was generally easy, non-time-consuming and straightforward. Most of them were classified as grade I (59.1%) and II (29.5%). Higher grade complications were scarce (grade III: 2.3% and grade IV: 6.8%, respectively) There was one death (grade V: 2.3%) due to acute myocardial infarction (overall mortality rate: 0.5%). Negative outcomes such as mild dysuria during this early postoperative period or retrograde ejaculation were considered sequelae and were not recorded. Nobody was complicated with severe dysuria. There was one re-operation due to residual adenoma (0.5%).

Conclusions

The modified CCS represents a straightforward and easily applicable tool that may help urologists to classify the complications of TURP in a more objective and detailed way. It may serve as a standardized platform of communication among clinicians allowing for sound comparisons.     

Colobomata associated with Noonan's syndrome

A patient with Noonan's syndrome and fundal colobomata in both eyes is described. To our knowledge, this is the first report of the association of colobomata with Noonan's syndrome. Although the patient had poor sight since early childhood and dyspnea on exertion as a teenager, the diagnosis of Noonan's syndrome was not made until early adulthood. We hope this report will encourage recognition of this syndrome and its implications at an earlier stage.     

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase

Inflammatory bowel disease (IBD) is associated with mucosal T cell activation and diarrhea. We found that T cell activation with anti-CD3 mAb induces profound diarrhea in mice. Diarrhea was quantified by intestinal weight-to-length (wt/l) ratios, mucosal Na(+)/K(+)-ATPase activity was determined and ion transport changes were measured in Ussing chambers. Anti-CD3 mAb increased jejunal wt/l ratios by more than 50% at 3 hours, returning to base line after 6 hours. Fluid accumulation was significantly reduced in TNF receptor-1 (TNFR-1(-/-)), but not IFN-gamma knockout mice. Anti-CD3 mAb decreased mucosal Na(+)/K(+)-ATPase activity, which was blocked by anti-TNF mAb and occurred to a lesser degree in TNFR-1(-/-) mice. Neither alpha nor beta subunits of Na(+)/K(+)-ATPase decreased in abundance at 3 hours. Intestinal tissue from anti-CD3-treated mice exhibited increased permeability to mannitol at 1 hour and decreases in electroneutral Na(+) absorption, Na(+)-dependent glucose absorption, and cAMP-stimulated anion secretion at 3 hours. Furthermore, enteral fluid accumulation was observed in CFTR(-/-) mice, indicating a minor role of active anion secretion. These data suggest that diarrhea in IBD is due to TNF-mediated malabsorption rather than to secretory processes. T cell activation induces luminal fluid accumulation by increasing mucosal permeability and reducing epithelial Na(+)/K(+)-ATPase activity leading to decreased intestinal Na(+) and water absorption.     

Role of biological agents in immune-mediated inflammatory diseases

A new era in the treatment of immune-mediated inflammatory disorders has begun with the clinical availability of anticytokine therapy. Biological agents that are currently available include 3 agents that decrease the activity of tumor necrosis factor-alpha (infliximab, adalimumab, etanercept) and an interleukin-1 receptor antagonist (anakinra), with many more in development. Those extraordinarily effective medications are an important addition to our therapeutic armamentarium, and, although originally developed for rheumatoid arthritis and Crohn disease, have been found to be efficacious in the treatment of seronegative spondyloarthropathies (psoriatic arthritis, ankylosing spondylitis) and juvenile rheumatoid arthritis. Their role is currently being defined in other autoimmune disorders such as uveitis, sarcoidosis, interstitial lung disease, vasculitis, inflammatory myopathies, graft-versus-host disease, and Sj?gren syndrome.     

Small Bowel Perforation due to Ingested Foreign body

Small bowel perforation due to ingested foreign body is a rare but potentially life-threatening event. We present here 4 cases of small intestinal perforation caused by accidental ingestion of foreign bodies, from a total of 1,100 surgical procedures in one unit over a one-year period (September 2016 -August 2017). All 4 cases occurred in elderly patients who were using an artificial denture. The clinical appearance was that of acute abdomen, and in one case there had been formation of an enterocutaneous fistula a long time after the foreign body was swallowed. Typically, preoperative abdominal computed tomography (CT) showed the possible presence of a foreign body, which was confirmed intraoperatively.All 4 patients underwent surgery. Removal of the foreign body was performed, followed by primary intestinal closure or small bowel resection with a side-to-side anastomosis. Three of the 4 patients had an uneventful postoperative course, but one died on the 10th postoperative day, due to a severe postoperative pulmonary infection.Old age and artificial denture use appear to be strong risk factors, and the time and location of the perforation, and the presence of co-morbidities are prognostic factors for a successful surgical outcome. The choice of the type of surgery is individualized. A high level of clinical suspicion and meticulous investigation of the entire small intestine are required to ensure the correct diagnosis and early intervention for a successful outcome.     

<Emphasis Type="Italic">TNFRSF13B/TACI</Emphasis> Alterations in Greek Patients with Antibody Deficiencies

TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations.