Mona Akbari

Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease

Background:Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD. Methods:A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities. Results:In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25). Conclusions:Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

The Crohn's disease activity index (CDAI) is similarly elevated in patients with Crohn's disease and in patients with irritable bowel syndrome

While the Crohns disease activity index (CDAI) is the gold standard for defining clinical endpoints in Crohns disease (Crohns) clinical trials, its ability to distinguish symptoms due to inflammation from those that are non‐inflammatory has been questioned.

Patient Perception of Treatment Burden Is High in Celiac Disease Compared With Other Common Conditions

OBJECTIVES:The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of CD, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares with other medical treatments, and there are limited data on the socioeconomic factors influencing treatment adherence. In this study, we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence.METHODS:Survey was mailed to participants with CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome, inflammatory bowel disease, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, and end-stage renal disease (ESRD) on dialysis. Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific health status, and overall health status.RESULTS:We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education, and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment.CONCLUSIONS:Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for CD argues for the need for safe adjuvant treatment, as well as interventions designed to lower the perceived burden of the GFD.

Systematic review: the quality of the scientific evidence and conflicts of interest in international inflammatory bowel disease practice guidelines.

Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes.

Systematic Analysis Underlying the Quality of the Scientific Evidence and Conflicts of Interest in Interventional Medicine Subspecialty Guidelines

OBJECTIVE To determine the validity of guidelines published by interventional medical societies. METHODS We reviewed the interventional medicine subspecialty society websites of the American Association for Bronchology and Interventional Pulmonology (AABIP), American Society of Diagnostic and Interventional Nephrology (ASDIN), American Society for Gastrointestinal Endoscopy (ASGE), and Society for Cardiovascular Angiography and Interventions (SCAI) as of November 15, 2012, for published interventional guidelines. The study was performed between November 15, 2012, and January 1, 2013. The AABIP did not publish guidelines, so American Thoracic Society and American College of Chest Physicians guidelines were reviewed. All the guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest (COIs). RESULTS Of 153 interventional guidelines evaluated, 4 were duplicates. Forty-six percent of guidelines (69 of 149) graded the quality of evidence using 7 different methods. The ASGE graded 71% of guidelines (46 of 65) compared with 29% (23 of 78) by the SCAI and 0 by the ASDIN (n=4) and the pulmonary societies (n=2). Of the 3425 recommendations reviewed, 11% (n=364) were supported by level A, 42% (n=1432) by level B, and 48% (n=1629) by level C. The mean age of the guidelines was 5.2 years. Additionally, 62% of the guidelines (92 of 149) failed to comment on COIs; when disclosed, 91% of guidelines (52 of 57) reported COIs. In total, 1827 COIs were reported by 45% of the authors (317 of 697), averaging 5.8 COIs per author. CONCLUSION Most of the interventional guidelines failed to grade the evidence. When present, most guidelines used lower-quality evidence. Furthermore, most guidelines failed to disclose COIs. When commented on, numerous COIs were present. Future guidelines should clearly state the quality of evidence, use a standard grading system, be transparent regarding potential biases, and provide frequent updates.

Systematic Analysis Underlying the Quality of the Scientific Evidence and Conflicts of Interest in Gastroenterology Practice Guidelines

OBJECTIVES:The practice guidelines published by the American Gastroenterological Association (AGA) and the American College of Gastroenterology (ACG) are used to establish standards of care and improve patient outcomes. We examined the guidelines for quality of evidence, methods of grading evidence, and conflicts of interest (COIs).METHODS:All 81 (AGA and ACG) guidelines available online on 26 July 2012 were reviewed for the presence of grading of evidence and COIs. In total, 570 recommendations were evaluated for level of evidence and methods used to grade the evidence. The data were evaluated in aggregate and by society.RESULTS:Only 31% (n=25) of the guidelines graded the levels of evidence. A total of 12 systems were used to grade the quality of evidence in these 25 guidelines. Of the 570 recommendations reviewed, only 29% (n=165) were supported by the highest quality of evidence, level A; 37% (n=210) level B, 29% (n=165) level C, and 5% (n=30) level D. Since 2007, 87% (n=13/15) of the ACG guidelines graded the evidence compared with only 33% of the AGA guidelines (n=4/12). Furthermore, 70% (n=57/81) of the guidelines failed to disclose any information regarding COIs. Of the 24 articles commenting on COIs, 67% reported COIs.CONCLUSIONS:Although the majority of the gastroenterology guidelines fail to grade the quality of evidence, more recent ACG guidelines grade majority of their recommendations. When the evidence is graded, most of the supporting evidence is based on lower-quality evidence. In addition, most of the guidelines fail to comment on COIs, and when disclosed, numerous COIs were present. This study highlights the critical need to revise the guideline development process. Future guidelines should clearly state the quality of evidence for their recommendations, utilize a standard grading system, and be transparent regarding all COIs.

Systematic review and meta-analysis of third-line salvage therapy with infliximab or cyclosporine in severe ulcerative colitis

Background In patients with ulcerative colitis who fail corticosteroids and are treated with rescue therapy (e.g. infliximab or cyclosporine) but fail to respond, salvage therapy with infliximab or cyclosporine can be considered. We sought to assess the efficacy and safety of this third-line salvage therapy. Methods We performed a meta-analysis of trials published in PubMed up to January 2015 relating to the use of third-line salvage therapy following failure of intravenous corticosteroids and infliximab or cyclosporine. Pooled outcome rates for each salvage strategy and pooled odds ratio comparing the two strategies were calculated using the random effects model. Heterogeneity was assessed by the Q and I2 statistics. Results The search strategy yielded 40 articles of which 4 were eligible for inclusion. Four articles assessed patients who were treated with infliximab after failure of cyclosporine and 2 articles assessed the use of cyclosporine after failure of infliximab. There were 138 patients using infliximab as a third-line salvage therapy and 30 patients using cyclosporine. When comparing these two strategies, there was no significant difference in clinical response (RR 1.03, 95%CI 0.7-1.46 P=0.87), clinical remission (RR 0.69, 95%CI 0.30-1.57 P=0.37), or colectomy at 12 months (RR 1.14, 95%CI 0.79-1.67 P=0.48). Similarly, there was no significant difference in total (RR 1.91, 95% CI0.38-9.64 p=0.43) or serious adverse events (RR 1.18, 95%CI 0.34-4.07 P=0.80). Conclusion While third-line salvage therapy may be efficacious in achieving short-term clinical response/remission, there remains a significant risk of colectomy and adverse events.

Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis

Background:In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined. Methods:We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case–control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies. Results:Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4–0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3–0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5–1.2, P = 0.3), regardless of study setting. Conclusions:Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.

Socioeconomic Risk Factors for Celiac Disease Burden and Symptoms.

Background & Aims: Celiac disease (CD) affects approximately 1% of the population and negatively affects aspects of life including physical and social function. The relationship between socioeconomic (SE) factors, symptom severity, and perceived burden of living with CD is not well understood. The objective of this study was to assess the relationships between income, symptoms, and perceived burden of CD. Methods: In this survey study conducted at a tertiary care center, 773 patients 18 years of age or more with biopsy confirmed CD were eligible to participate. Patients completed a survey with information on SE data, the validated Celiac Symptom Index (CSI), and visual analog scales (VAS) assessing overall health, CD-related health, difficulty in following a gluten-free diet (GFD), and importance of following a GFD. Results: Three hundred forty one patients completed the survey. Higher income predicted better overall health, better CD related health, and fewer symptoms. In the logistic regression model, low income was associated with greater CD symptoms (odds ratio=6.04, P=0.002). Other factors associated with greater symptoms were younger age, poor overall health state, and more physician visits. Factors associated with increased burden of CD included hospitalizations, more symptoms, poor overall health state, and burden of following a GFD. Conclusions: Patients with lower incomes have worse CD-related health and greater symptoms. Those with low income had 6 times the odds of greater symptoms compared with those with high income. Our data suggest that income is associated with perceived overall health, CD-related health, and CD symptoms.

Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality

Objectives The objective of this study was to determine our institutions compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. Methods We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. Results We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). Conclusions Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.