Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease.

BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

[Atypical scurvy associated with anorexia nervosa]. / Scorbut atypique associé à une anorexie mentale.

INTRODUCTION: Scurvy, or "Barlow's disease", is a widely described disease involving cutaneous and mucosal lesions resulting from vitamin C deficiency. Herein, we report a case of scurvy in a 48-year-old woman that was unusual in its atypical cutaneous-mucosal presentation as well as its association with anorexia nervosa. PATIENTS AND METHODS: A 48-year-old woman treated for depression for several years was admitted to hospital for her impaired general state of health. Over the last year, she had presented palmoplantar rash and episodes of perimalleolar oedema. The clinical examination showed the patient to have wasting syndrome, with a BMI of 11.9kg/m2, lower-limb oedema, palmoplantar fissures, geographic tongue, telogen effluvium and purpuric petechiae on her right knee. However, no gingival bleeding was noted and there was no loss of tooth enamel. The remainder of the clinical examination was normal. Blood tests revealed extremely low vitamin C levels without any other associated deficiencies, as well as laboratory signs of cytolysis and anicteric cholestasis without inflammatory syndrome. The diagnosis of anorexia nervosa was made by psychiatrists, despite the unusual age of onset. Favorable clinical outcome was rapidly achieved via a one-month course of vitamin C supplements at a daily dose of 1g. DISCUSSION: The absence of classical buccal-dental symptoms and the presence of keratotic dermatosis with fissures and ulcers on the hands and feet are atypical in scurvy; however, this diagnosis was confirmed by the existence of purpura evoking capillary fragility, the patient's drastically low vitamin C level and the rapid subsidence of symptoms following treatment with oral vitamin C alone. Anorexia nervosa was doubtless the cause of deficiency. This situation is rare and a systematic review of the literature in Medline via PubMed showed that only three reports of scurvy associated with mental anorexia have been published since 1975.

Comparison of arthroscopic and open Latarjet with a learning curve analysis.

PURPOSE: To compare arthroscopic and open Latarjet performed by a single shoulder surgeon with learning curve analysis METHODS: A comparative and learning curve analysis was carried out on a prospectively gathered database of 2 consecutive series of patients treated with arthroscopic and open Latarjet procedures performed by a single shoulder surgeon between 2008 and 2014. The database included patient characteristics, ISIS scores, operative time, intra- and postoperative complications, graft and screws positioning, as well as pre- and postoperative Walch-Duplay scores. RESULTS: Sixty-four patients were included in the study, 28 in the arthroscopic group and 36 in the open group with similar age, sex ratio and preoperative ISIS score. Operative time was significantly higher in the arthroscopic group (146 versus 81 min, p = 0.001), and although no intra-operative complications were recorded in either group, there were significantly more postoperative complications in the arthroscopic group (29 vs. 11 %, p = 0.03). Screw placement was more accurate in the open group, and postoperative Walch-Duplay score did not show any significant difference between the groups (88 points in the arthroscopic group and 91 points in the open group). The arthroscopic Latarjet learning curve analysis showed that the need for conversion ceased after the first 10 patients and that surgical time came close to that of open procedure after 20 procedures. CONCLUSIONS: In this study, 10 arthroscopic Latarjet procedures were needed to overcome the need for conversion, and 20 procedures to achieve equal operating time to the open technique. Even though functional outcome and patient satisfaction were similar in both techniques, complications, screw placement inaccuracy, persistent apprehension and recurrences still remain higher with the arthroscopic technique. LEVEL OF EVIDENCE: Retrospective comparative analysis, Level III.

Reverse shoulder arthroplasty in patients with pre-operative impairment of the deltoid muscle.

The indications for reverse shoulder arthroplasty (RSA) continue to be expanded. Associated impairment of the deltoid muscle has been considered a contraindication to its use, as function of the RSA depends on the deltoid and impairment of the deltoid may increase the risk of dislocation. The aim of this retrospective study was to determine the functional outcome and risk of dislocation following the use of an RSA in patients with impaired deltoid function. Between 1999 and 2010, 49 patients (49 shoulders) with impairment of the deltoid underwent RSA and were reviewed at a mean of 38 months (12 to 142) post-operatively. There were nine post-operative complications (18%), including two dislocations. The mean forward elevation improved from 50° (sd 38; 0° to 150°) pre-operatively to 121° (sd 40; 0° to 170°) at final follow-up (p < 0.001). The mean Constant score improved from 24 (sd 12; 2 to 51) to 58 (sd 17; 16 to 83) (p < 0.001). The mean Single Assessment Numeric Evaluation score was 71 (sd 17; 10 to 95) and the rate of patient satisfaction was 98% (48 of 49) at final follow-up. These results suggest that pre-operative deltoid impairment, in certain circumstances, is not an absolute contraindication to RSA. This form of treatment can yield reliable improvement in function without excessive risk of post-operative dislocation.

Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes. AIM: To characterise any possible clinically-relevant association between RBC transfusion following NVUGIB with rebleeding and mortality. METHODS: Observational study utilising the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE). Multivariable logistic regression models were used to examine and quantify independent associations between RBC transfusion and clinical outcomes. RESULTS: Overall, 1677 patients were included (66.2 ± 16.8 years, 61.7% male, 2.5 ± 1.7 comorbid conditions, initial haemoglobin, 96.8 ± 27.2 g/L); 53.7% received RBC transfusions (2.9 ± 1.6 units of blood), 31.6% had haemodynamic instability, 5.1% fresh blood on rectal examination and 8.6% in the nasogastric tube aspirate. Endoscopic haemostasis was performed in 35.2%. Overall rebleeding (defined as continuous bleeding, rebleeding or surgery) and mortality rates were 17.9% and 5.4%, respectively. After adjusting for potential confounders, transfusion of RBC within 24 h of presentation was significantly and independently associated with an increased risk of rebleeding (OR: 1.0, 95% CI: 0.6-1.8), but not death (OR: 1.5, 95% CI: 0.94-2.23). CONCLUSIONS: This study suggests an association between RBC transfusion following NVUGIB and subsequent rebleeding, after appropriate and extensive adjustment for confounding. Prospective randomised trial evidence is needed to identify the most efficacious and cost-effective transfusional strategies in these patients.