Turki AlAmeel

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

BACKGROUND AND AIMS Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. RESULTS In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. CONCLUSIONS Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials.

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

Minimising placebo response is essential for drug development.

Clinical application of a single-operator direct visualization system improves the diagnostic and therapeutic yield of endoscopic retrograde cholangiopancreatography

BACKGROUND Single-operator cholangioscopy enables direct diagnostic visualization and therapeutic intervention in the biliary tree. There is increasing evidence of its clinical utility in the assessment of biliary strictures and treatment of difficult stones. OBJECTIVE To describe the first reported Canadian experience with managing biliary disease using single-operator cholangioscopy. METHODS The present study was a retrospective analysis of data collected from all sequential patients undergoing single-operator cholangioscopy for assessment of biliary strictures and treatment of biliary stones. The main outcome measures were the ability to make an overall diagnosis of stricture (based on visual appearances and tissue histology), and to fragment and extract biliary stones. RESULTS Thirty patients (17 women), mean age 66 years (range 41 to 89 years) underwent single-operator cholangioscopy. In biliary strictures (20 patients), overall accuracy for visual and tissue diagnosis was 84% and 81%, respectively. Successful electrohydraulic lithotripsy with stone clearance was achieved in 90% of the 10 patients who failed previous conventional therapy. The mean (± SD) procedure time was 61±21 min (range 20 min to 119 min). One patient developed mild postendoscopic retrograde cholangioscopy pancreatitis. CONCLUSION The results of this experience reaffirms the clinical utility and safety of single-operator cholangioscopy for the management of biliary pathology. Further improvements can be achieved with increasing operator experience and refinements in optical technology.

Advances in the diagnosis and management of inflammatory bowel disease: challenges and uncertainties.

Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohns Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes.

Digestive Symptoms in Older Adults: Prevalence and Associations with Institutionalization and Mortality

BACKGROUND Digestive symptoms are common in adults. However, little is known about their prevalence in older adults and the association of digestive symptoms with institutionalization and mortality in community-dwelling older adults. OBJECTIVE To determine the prevalence of digestive symptoms among older adults in Canada and whether they are associated with increased risk of institutionalization and mortality, independent of the effect of potential confounders. METHODS The present study was a secondary analysis of data collected from community-dwelling participants 65 years of age and older in the Canadian Study of Health and Aging. Measures incuded age, sex, presence of digestive symptoms, cognition, impairment in activities of daily living (ADL) and self-reported health. Outcome measures included death or institutionalization over the 10 years of follow-up. RESULTS Digestive symptoms were found in 2288 (25.6%) of the 8949 subjects. Those with digestive symptoms were older, with a mean difference in age of six months (P=0.007). Digestive symptoms were more common among women (28.4%) than men (20.3%), among individuals with poor self-reported health and those with an increased number of impairments in their ADLs (P<0.001). The presence of digestive symptoms was associated with higher mortality (HR 1.15 [95% CI 1.05 to 1.25] adjusted for age, sex, cognitive function and ADL impairment); however, this association was not statistically significant after adjusting for self-reported health. CONCLUSION Although digestive symptoms were associated with increased mortality independent of age and sex, cognition and function, this association was largely explained by poor self-assessed health. Digestive symptoms were not associated with institutionalization.

Yield of Screening Colonoscopy in Renal Transplant Candidates

BACKGROUND Cardiovascular disease is the most common cause of death among patients with end-stage renal disease undergoing maintenance dialysis. Renal transplantation offers a survival advantage to patients with end-stage renal disease; it is also associated with a three- to fivefold increase in the risk of developing a neoplasm. OBJECTIVE To determine the yield of screening colonoscopy among patients with chronic kidney disease who were considered for renal transplantation. METHODS Patients were included if they were ≥50 years of age, had chronic kidney disease and were being considered for renal transplantation. They underwent a screening colonoscopy that was performed as part of their pretransplant workup. Data from December 2008 to May 2014 were collected retrospectively for all eligible patients. RESULTS During the study period, 433 patients were considered for renal transplantation. Of these, 170 underwent colonoscopies as part of their pretransplant workup. One was excluded because of previous history of colon cancer. Of the 169 procedures performed, ≥1 polyp(s) was diagnosed in 24%. The most common pathological diagnoses were hyperplastic polyp or normal colonic tissue. Fifteen (37%) patients had tubular adenomas and one patient had a sessile serrated adenoma. Advanced adenomas, defined as villous, tubulovillous or high-grade dysplasia, were found in four patients. Adenocarcinoma was diagnosed in one patient. CONCLUSION In a population of asymptomatic potential kidney transplant recipients ≥50 years of age, the prevalence of colorectal adenomatous polyps was 24%. Colonoscopy appeared to be useful as a screening tool in potential transplant recipients.

Combination Therapy With Adalimumab and Thiopurines in Inflammatory Bowel Disease: Is It a Case of Nepotism in Pharmacology?

We read with great interest the article published by Hindryckx et al.1 discussing current and future therapeutic options in managing patients with inflammatory bowel disease. The authors argued that the benefit of adding azathioprine to infliximab that was shown in the SONIC and UC-SUCCESS studies can be generalized to other anti-tumour necrosis factor [anti-TNF] agents, including adalimumab. The three potential benefits of co-administration of azathioprine with anti-TNF agents should be relevant as a class effect for the TNF antagonists according to the authors. We respectfully disagree. To our knowledge, the DIAMOND study is the only randomized controlled trial that has attempted to answer this question.2 The study did not meet its primary end point. Clinical remission rates were similar between the two groups. However, the rate of endoscopic improvement was higher in the combination group than in those who received adalimumab monotherapy. We are sceptical about the latter finding. Despite it being a randomized controlled trial, it had several limitations. It was an open label study with no placebo arm. The endoscopists who assessed the simple endoscopic score for Crohn’s disease [SES-CD] were aware of the treatment assignment. It would have been better if the investigators had their readings made centrally with the reading endoscopist blinded to treatment allocation. On the other hand, other studies have shown no benefits to combination treatment. In a post-hoc analysis of randomized trials for the induction or maintenance of remission or mucosal healing [CLASSIC-I, GAIN, CHARM, EXTEND, ULTRA 1 and ULTRA 2], the efficacy of combination therapy was compared with adalimumab monotherapy. It showed no added benefit in Crohn’s disease or ulcerative colitis patients who failed conventional treatment.3 Moreover, it appears that combination therapy of adalimumab and thiopurine may cause more harm than either therapy alone. A pooled analysis of 1500 patients with Crohn’s disease who took part in placebo-controlled trials of adalimumab [CLASSIC I and II, CHARM, GAIN, EXTEND and ADHERE studies] was published in 2014. It showed the risk of non-melanoma skin cancer [NMSC] in patients receiving adalimumab monotherapy to be similar to the general population. However, those receiving combination therapy had a greater than expected incidence of NMSC [standardized incidence ratio, 4.59; 95% confidence interval, 2.51–7.70].4 A recently published French population-based study looked at the incidence of lymphoma among IBD patients. It included more than 90 000 patients with IBD who were exposed to thiopurines or anti-TNF agents. The risk of lymphoma was higher among patients who were exposed to combination therapy than in those treated with either therapy alone.5 In our opinion, the combination of immunomodulator and adalimumab adds no clinical benefits and may increase the risk of adverse events over adalimumab monotherapy.

Is Anesthetist-Directed Sedation Better for Advanced Endoscopic Procedures?

To the Editor: Advanced endoscopic procedures are technically demanding and require a longer time than conventional endoscopic tests. Adequate sedation is a crucial part to achieve the desired outcomes from such procedures. We read with great interest the study by Buxbaum et al. ( 1 ) looking at the impact of sedation strategy (gastroenterologist-directed sedation (GDS) vs. anesthesia-directed sedation (ADS)) on the success of advanced endoscopy procedures. Th ey concluded that ADS improves the success of advanced endoscopic procedures and attributed this to reduced sedation failure In our opinion, the authors did not take into account other factors that may have led to their fi ndings. One such factor is the diff erence in timing between the two groups. Most gastroenterologist-directed sedation sessions were aft ernoon sessions, as opposed to anesthesia-directed sedation sessions, which were held in the morning. Previous studies have shown declined sensitivity and diagnostic accuracy of endoscopic ultrasound and colonoscopy procedures done later in the day compared to morning procedures ( 2,3 ). Another factor that may have aff ected the outcome of the study is the experience of the endoscopists involved. In most North American centers, each physician has an assigned day of the week when they book their endoscopic procedures. If junior physicians were performing most of their procedures with GDS, this may have played a role in the lower success rate compared to anesthesia-provided sedation. We realize that most of the failure in the GDS group could be attributed to the type of sedation To the Editors: In their recent Letter to the Editor ( 1 ), Dr. AlAmeel and Dr. Bseiso raise valuable points. Although prior studies have reported an increased risk of technical failure rather than sedation failure for aft ernoon and evening endoscopic procedures, the potential impact of procedure timing is worth further examination ( 2,3 ). In our study, we indeed found that a smaller proportion of advanced endoscopic procedures performed in the aft ernoon were supported by anesthetist-directed sedation (ADS) compared to morning procedures (31.1 vs. 49.6%, P <0.001). However, procedure timing did not confound our observed association between sedation strategy and the risk of procedure failure. In order to address this question, we repeated our multivariate analysis among 1,171 unique patients while including procedure timing (morning vs. aft ernoon) as a covariate in addition to the original covariates of age, sex, ethnicity, ASA score, and procedure indication. Aft er further adjustment for procedure timing, the risk of overall procedure failure remained higher for procedures with gastroenterologist-directed sedation (GDS) than for those supported by ADS (odds ratio (OR) 2.3 (95% confi dence interval (CI): 1.5–3.6), P <0.001). Similarly, the risk of sedation failure remained higher for procedures with GDS than for those with ADS (OR 7.6 (95% CI: 3.1–18.6), P <0.001). Inclusion of procedure timing as a covariate also did not alter our fi nding of no diff erence in the risk of technical failure between the ADS and GDS groups (OR 1.1 (95% CI 0.7–1.9)). For further evaluation, we also added procedure timing to our sensitivity analysis using propensity score matching. We were able to match 353 GDS cases to 353 ADS cases based on their propensity score (a regression-based estimate of a patient’s probability of receiving ADS based on his or her age, sex, ethnicity, and ASA score), procedure type, procedure indication, and procedure timing. In a multivariate conditional logistic regression model, we again confi rmed that overall procedure failure remained more likely for cases with GDS than those supported by ADS (OR 2.0 (95 CI: 1.2–3.4), P =0.009). Th us, used rather than technical factors. Nonetheless, an experienced endoscopist might be able to complete a procedure in a shorter time and may therefore require less sedation than a junior physician. In a study looking at the eff ect of simulator training in endoscopic retrograde cholangiopancreatography, participants in the intervention group not only had a higher success rate but also shorter time to cannulation ( 4 ). In conclusion, we agree that anesthesiadirected sedation is an important factor in the success of the technically demanding advanced endoscopic procedure. However, we believe that other important factors, including endoscopy session time and provider experience, should be taken into account when interpreting such results.

Is solitary rectal ulcer syndrome uncommon in Saudi Arabia

In our opinion, the study did not reflect the true picture of SRUS in Saudi Arabia. The authors used pathology specimens for case identification. Depending only on histopathology will not provide the whole picture of the disease and might lead to missing some cases. An accurate diagnosis of SRUS is more commonly made based on a combination of symptoms, endoscopic findings, and histological appearances.[3]

Extrahepatic cholangiocarcinoma with prolonged survival: a case report

BackgroundCholangiocarcinoma has poor prognosis and short term-survival. Here, we report the case of a patient with unusually prolonged survival.Case presentationOur patient was a 56-year-old Arab man with a 6-month history of obstructive jaundice. A computed tomography scan of his abdomen revealed a mass at the confluence of the hepatic ducts with suspected malignant strictures on endoscopy. A positive tissue diagnosis was achieved more than 18 months after commencement of his symptoms. He remained functional throughout this period despite recurrent episodes of cholangitis.ConclusionsCholangiocarcinoma is a presumably fatal disease, especially because patients tend to present late with unresectable disease. Many patient-related and disease-related factors may alter survival.