Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. METHODS: Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. RESULTS: Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. CONCLUSION: Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

Patients' perspectives on marijuana use for inflammatory bowel disease: a multicenter survey.

Background: As marijuana use is rising among patients with inflammatory bowel disease (IBD), so is interest in its potential use as a therapeutic agent. We sought to survey IBD patients regarding marijuana use, self-reported impact on IBD symptoms, and perceptions of safety. Methods: A multicenter anonymous survey was administered to patients with IBD between October 2020 and June 2021. The 70-question survey collected demographic variables, clinical variables, attitudes about marijuana, and perceptions of its safety and efficacy in IBD. Participants were classified by their marijuana use: "rarely/never," "current," and "former". Percentage and chi-square tests were used to compare categorical variables between the 3 groups, and means and 2-group ANOVA were used for continuous variables. Results: Of 181 patients surveyed, 166 were eligible for the study. Of these, 70 (42.2%) participants were rare/never marijuana users, 44 (26.5%) were current users, and 52 (31.3%) were former users. Fifty-three percent thought marijuana would help with IBD inflammation and 80% thought it would help with IBD pain. Over 70% of patients from all groups thought marijuana had a low-to-moderate risk of harm, and 69.6% of the participants who never or rarely used marijuana thought marijuana was addictive, compared to 20.5% of the current users and 44% of the former marijuana users. Conclusions: While many patients thought marijuana use helps with IBD-related pain and inflammation, many expressed concerns about addiction to marijuana and a possible risk of harm. Further studies are needed to examine the benefit and harm of marijuana in IBD.

Trends in Hospitalizations of Esophageal Varices From 2011 to 2018: A United States Nationwide Study.

Background: Prevalence of gastroesophageal varices is around 50% of patients with cirrhosis. In compensated cirrhosis they are present in 30-40%. Progression from small to large varices occurs at rate of 10-12% annually. That percentage increases significantly in decompensated liver cirrhosis with gastroesophageal varices found in 85% of patients. Variceal hemorrhage occurs at a rate around 10-15% per year. The outcome of variceal hemorrhage depends on the severity of liver disease, size of varices, and presence of stigmata of recent bleeding (red whale sign). Six-week mortality of variceal hemorrhage ranges between 15% and 25%. Without treatment, variceal hemorrhage tends to recur in 60% of patients within 1 - 2 years. The aim of the study was to assess demographics of esophageal varices with and without bleeding, geographic distribution, comorbidities, outcomes, main payers, and cost of hospitalizations. Methods: The National Inpatient Sample (NIS) database from year 2011 to 2018 was used. Patients who had a primary diagnosis of esophageal varices with or without bleeding were identified using the International Classification of Diseases, Ninth Revision (ICD-9) codes (456.0 for esophageal varices with bleeding, and 456.1 for esophageal varices without bleeding), and International Classification of Diseases, 10th Revision (ICD-10) codes (I85.01 for esophageal varices with bleeding, and I85.00 for esophageal varices without bleeding) in the first two discharge diagnoses. The propensity score to calculate the inverse probability treatment weighting (IPTW) to adjust between the differences of the compared groups was implemented. Two groups were compared in terms of their hospitalization outcomes, including LOS, hospital charges, hospital mortality, and disposition. Results: A total of 322,761 patients were admitted with esophageal varices between 2011 and 2018, with 236,802 (73.6%) had bleeding esophageal varices and 85,959 (26.4%) had nonbleeding esophageal varices. The majority of the patients from both groups were white (66%), covered with Medicare (38% in the esophageal varices with bleeding vs. 41% in the nonbleeding group). There was a steady increase of patients admitted with nonbleeding esophageal varices. Most common comorbidities were liver diseases, alcohol abuse, uncomplicated hypertension and depression in both groups. There were no significant changes in OLS over the years in both groups, but there was a significant increase in hospital charges, especially in the patients with bleeding esophageal varices starting in 2015, and no change in mortality throughout the years. Regarding hospital disposition, there was a notable decline in rehab discharge in the bleeding esophageal varices group. Conclusions: Esophageal varices with and without bleeding have been steadily increasing since the beginning of this century. This may result in a substantial impact on increasing health care costs and utilization due to acute variceal hemorrhage. Odds of death, transfer to urban hospital, and transfer to visiting nursing assistance remained unchanged.

WITHDRAWN: Non-Anti-TNF Biologics as Salvage Therapy for Refractory Acute Severe Ulcerative Colitis, A Systematic Review

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Efficacy and safety of biologic therapy in microscopic colitis: systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC). METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs). RESULTS: A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases. CONCLUSION: Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy.

Quality measures in endoscopy: A systematic analysis of the overall scientific level of evidence and conflicts of interest.

Background and study aims Quality measures were established to develop standards to help assess quality of care, yet variation in endoscopy exists. We performed a systematic review to assess the overall quality of evidence cited in formulating quality measures in endoscopy. Methods A systematic search was performed on multiple databases from inception until November 15, 2020, to examine the quality measures proposed by all major societies. Quality measures were assessed for their level of quality evidence and categorized as category A (guideline-based), category B (observational studies) or category C (expert opinion). They were also examined for the type of measure (process, structure, outcome), the quality, measurability, review, existing conflicts of interest (COI), and patient participation of the quality measure. Results An aggregate total of 214 quality measures from nine societies (15 manuscripts) were included and analyzed. Of quality measures in endoscopy, 71.5 %, 23.8 %, and 4.7 % were based on low, moderate, and high quality of evidence, respectively. The proportion of high-quality evidence across societies was significantly different ( P  = 0.028). Of quality measures, 76 % were quantifiable, 18 % contained patient-centric outcomes, and 7 % reported outcome measures. None of the organizations reported on patient involvement or external review, six disclosed existing COI, and 40 % were published more than 5 years ago. Conclusions Quality measures are important to standardize clinical practice. Because over 70 % of quality measures in endoscopy are based on low-quality evidence, further studies are needed to improve the overall quality to effectively set a standard, reduce variation, and improve care in endoscopic practice.

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis.

BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC). METHODS: We searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). RESULTS: A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2 : 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2 : 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2 : 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2 : 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2 : 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2 : 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2 : 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2 : 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2 : 0%), respectively. Higher dose was associated with an increased frequency of AEs. CONCLUSIONS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.

Colorectal Cancer Prevention in Inflammatory Bowel Disease: A Systematic Analysis of the Overall Quality of Guideline Recommendations.

BACKGROUND: Owing to the increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD), numerous societies developed preventative guidelines. We aimed to assess the overall quality of CRC prevention guidelines in IBD. METHODS: A systematic search was performed in multiple databases to identify all guidelines pertaining to CRC prevention in IBD in September 2020. All guidelines were reviewed for conflicts of interest (COIs)/funding, recommendation quality/strength, external guideline review, use of patient representation, and plans for update-as per Institute of Medicine standards. In addition, recommendations were compared amongst societies. RESULTS: One hundred forty-nine recommendations from 14 different guidelines/societies were included. Not all guidelines provided recommendations on key elements surrounding (1) screening initiation and surveillance, (2) screening modality, (3) pharmacological chemoprevention, (4) dysplasia management and follow-up, and (5) molecular marker use. Only 71% of guidelines disclosed COIs, 43% reported industry funding, 14% were externally reviewed, 7% included patient representation, and 36% had plans for update. Of the total recommendations, 7.4%, 23.5%, and 69.1% were based on high,- moderate-, and low-quality evidence, respectively. Additionally, 20.1% of recommendations were strong, 14.1%, were weak/conditional, and 65.8% did not provide a strength. The proportion of high-quality evidence (P = 0.34) and strong recommendations (P = 0.57) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of CRC prevention in IBD. Over 90% of recommendations are based on low- to moderate-quality evidence; therefore, further studies on CRC prevention in IBD are needed to improve the overall quality of evidence.

Pros and Cons of Performing Early Endoscopy in Geriatric Patients Admitted with Non-variceal Upper Gastrointestinal Bleeding: Analysis of the US National Inpatient Database.

BACKGROUND: Age greater than 65 years is a well-defined risk factor for increased mortality in patients with non-variceal upper gastrointestinal bleeding (NVGIB). Endoscopy is indicated in most patients at any age but presents unique risks in the elderly cohort, and ideal timing is unclear. This study examined the association between outcomes and early (within 24 h) esophagogastroduodenoscopy (EGD) among elderly patients with NVGIB. METHODS: All patients over age 65 admitted primarily for NVGIB who underwent EGD were included from the National Inpatient Sample 2016-2017. Clinical outcomes stratified by early EGD versus late EGD were compared after adjustment for comorbidities and bleeding severity using inverse probability of treatment weighting with survey-adjusted linear and logistic regression. RESULTS: Out of estimated 625,530 admissions with a primary diagnosis of NVGIB, 120,835 met eligibility criteria; 24,830 underwent early EGD. Mean length of stay and total charges decreased by 1.17 days (95%CI 1.04-1.30, P < 0.001) and $5717.24 (95%CI 4034.57-7399.91, P < 0.001), respectively, in the early EGD group. Early EGD increased the odds ratio of death 1.32 (95%CI 1.06-1.64, P 0.01) and transfer to other hospitals 1.48 (95%CI 1.22-1.81, P < 0.001). No change was seen in the requirement for surgery or angiography. Rates of discharge to a nursing facility or home health were similar. CONCLUSION: In a comprehensive cohort of geriatric patients with NVGIB, early EGD is associated with decreased hospital stay and charges, but also with increased mortality and inter-hospital transfer. Further research is needed to determine the optimal management of this vulnerable population.

Assessing the repercussions of COVID-19 pandemic on symptoms, disease management, and emotional well-being in patients with inflammatory bowel disease: a multi-site survey study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has created numerous challenges in provision of safe and effective care for patients with Inflammatory Bowel Disease (IBD). In this study, we surveyed patients with IBD to highlight the impact of the pandemic on their IBD symptoms, management, and well-being. METHODS: A multi-site survey was administered to patients with IBD. We evaluated patient's symptoms, medications changes, seeking medical attention, eating behaviors, sleep patterns, stress, self-reported anxiety and depression. The survey also measured emotional impact of the pandemic using the validated Pandemic Emotional Impact Scale (PEIS) and resilience using the Brief Resilience Scale (BRS). Logistic, ordinal, and linear regression models were utilized to perform sensitivity analyses. RESULTS: The response rate to the survey was 61%. Of 391 surveyed patients, 21.1% reported worsened gastrointestinal symptoms, 17.5% reported changing biologic medication infusion schedule, 18.7% reported changing medication regimen, 43.6% attended at least one telemedicine visit with their gastroenterologist, 16.5% reported a less healthy diet, 40.5% reported worsening sleep, 63.7% reported more stress, and 65.3% reported feeling more vulnerable than before the pandemic. Women and participants with self-reported anxiety and depression were more likely to have worse symptoms, psychological well-being and daily functioning. Increased PEIS scores and decreased BRS scores were associated with worse outcomes. CONCLUSIONS: COVID-19 pandemic has impacted symptoms, disease management and well-being for patient with IBD, more prominently in patients who suffer from anxiety and depression. Utilizing PEIS and BRS scores as screening tools could help better tailor outreach and follow-up to support these patients.

Feature selection and predicting chemotherapy-induced ulcerative mucositis using machine learning methods.

OBJECTIVE: Ulcerative mucositis (UM) is a devastating complication of most cancer therapies with less recognized risk factors. Whilst risk predictions are most vital in adverse events, we utilized Machine learning (ML) approaches for predicting chemotherapy-induced UM. METHODS: We utilized 2017 National Inpatient Sample database to identify discharges with antineoplastic chemotherapy-induced UM among those received chemotherapy as part of their cancer treatment. We used forward selection and backward elimination for feature selection; lasso and Gradient Boosting Method were used for building our linear and non-linear models. RESULTS: In 2017, there were 253 (unweighted numbers) chemotherapy-induced UM patient discharges from 21,626 (unweighted numbers) adult patients who received antineoplastic chemotherapy as part of their cancer treatment. Our linear model, lasso showed performance (C-statistics) AUC: 0.75 (test dataset), 0.75 (training dataset); the Gradient Boosting Method (GBM) model showed AUC: 0.76 in the training and 0.79 in the test datasets. The feature selection derived from stepwise forward selection and backward elimination methods showed variables of importance--antineoplastic chemotherapy-induced pancytopenia, agranulocytosis due to cancer chemotherapy, fluid and electrolyte imbalance, age, anemia due to chemotherapy, median household income, and depression. Higher importance variable derived from GBM in the order of importance were antineoplastic chemotherapy-induced pancytopenia > co-morbidity score > agranulocytosis due to cancer chemotherapy > age > and fluid and electrolyte imbalance. Further, when the analysis was stratified to females only, the ML models performed better than the unstratified model. CONCLUSION: Our study showed ML methods performed well in predicting the chemotherapy-induced UM. Predictors identified through ML approach matched to the clinically meaningful and previously discussed predictors of the chemotherapy-induced UM.

Association between palliative care referral and burden of illness among cancers of the lip, oral cavity and pharynx.

PURPOSE: To evaluate the burden of illness--length of stay (LOS), total charges, and discharge disposition--among cancers of the lip, oral cavity and pharynx (CLOP) patients with and without palliative care (PC) referral. METHODS: This cross-sectional study utilized the 2017 National inpatient sample database to identify hospitalizations with a primary diagnosis of CLOP. Generalized linear models were used to assess the association between PC referral status and the outcomes-LOS, total charges, and discharge disposition while controlling for patients' characteristics. RESULTS: There were 4165 PC referral among 52, 524 CLOP patients. The geometric mean of LOS for non-PC referral patients was 3.7 days, and for PC referral was 5.02 days, P < 0.001. In the adjusted analysis, CLOP patients with PC referral were more likely to have a higher LOS (Coefficient:1.16; 95% CI, 1.01-1.25) compared to those without PC referral. The geometric mean of total charge among non-PC referral group was 48,308 USD, and CLOP-PC referral was 48,983 USD, P = 0.72. After adjusting for covariates, there was still no significant difference between the PC and non-PC referral groups. Discharge disposition were considerably different across the non-PC vs. PC referral groups. Compared to non-PC referral patients, PC referral patients were more likely to be discharge to skilled nursing facility, intermediate care, and another type of facility (aOR = 7.10; CIs, 5.51-9.12), or home health care (aOR = 4.13; CIs, 3.31-5.15). CONCLUSION: During primary hospitalization, total charges was not different between patient non-PC and PC referral groups; however, the LOS and discharge dispositions were significantly different.

Patient Perspective on Safety of Elective Gastrointestinal Endoscopy During the COVID-19 Pandemic.

BACKGROUND: Patients' perception regarding the risks of COVID-19 infection with gastrointestinal (GI) and the preventive measures taken in GI endoscopy units to mitigate infection risk remains unclear. We aimed to assess patients' perception regarding risks of COVID-19 with GI endoscopy and the changes in the endoscopy unit as a result of the ongoing pandemic. METHODS: Outpatients undergoing GI endoscopy at our institution were categorized into those scheduled to undergo GI endoscopy (preprocedure) and those who had recently undergone GI endoscopy during the pandemic (postprocedure). Two separate but similar survey instruments were designed. Patients were asked to respond on a 5-point Likert scale. Responses were stratified as "low," "neutral," and "high" for analysis. RESULTS: A total of 150 and 355 respondents completed the preprocedure and postprocedure surveys, with a combined response rate of 82.5%. Non-white ethnicity was associated with reporting a "high" level of concern for endoscopy related COVID-19 exposure in both the preprocedure (OR 4.09, 95% CI 1.54-10.82) and postprocedure cohorts (OR 2.11, 95% CI 1.04-4.29). 42% of patients in the preprocedure cohort and 11.8% in the postprocedure cohort reported their level of concern for COVID exposure as "high." Among the postprocedure cohort, 88% of the patients were likely to undergo repeat endoscopy during the pandemic if recommended. CONCLUSION: Patients are willing to undergo GI endoscopy during the COVID-19 pandemic. Non-white and older patients, and those undergoing screening examinations were more concerned with the GI endoscopy related COVID-19 transmission risk.

The impact of obesity on hospitalized patients with ulcerative colitis.

BACKGROUND: Obesity is the fifth leading risk factor for mortality in the world and it has increased among patients with ulcerative colitis in recent years. We examined the impact of obesity on the hospitalized patients admitted primarily with a diagnosis of ulcerative colitis. METHODS: We used the National Inpatient Sample data for the year 2016 to identify patients with ulcerative colitis and compared obese and non-obese patients in terms of length of hospital stay, total charges, and mortality. We used multiple imputations to estimate missing values and survey analysis to estimate the outcomes, and we adjusted for confounders by implementing the inverse probability of treatment weighting using propensity score. RESULTS: A total of 61,075 admissions with ulcerative colitis were identified. Among these, 6020 were diagnosed with obesity. Baseline hospital and patient characteristics between the 2 groups were notable for differences in age and sex. Patients with obesity were found to have a mean hospital stay longer by 0.57 days (95% confidence interval [CI] 0.22-0.93; P=0.002) and charges $6341.71 higher (95%CI 2499.72-10,183.71; P=0.001) compared to non-obese patients. There was no difference in hospital mortality, with an odds ratio of 0.28 (95%CI 0.04-2.05; P=0.212). CONCLUSION: In a comprehensive review of inpatient admissions in 2016, primarily for ulcerative colitis, obesity was associated with a longer hospital stay and higher total charges per admission after balancing of confounders.

Evidence supporting the benefits of marijuana for Crohn's disease and ulcerative colitis is extremely limited: a meta-analysis of the literature.

BACKGROUND: Medical marijuana is increasingly used to control inflammation and pain in inflammatory bowel disease (IBD). We performed a meta-analysis to investigate the effect of marijuana on the clinical response, induction of clinical remission, and maintenance of clinical remission compared to placebo/standard of care. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science in June 2019, for cannabis/marijuana and IBD, Crohn's disease or ulcerative colitis (UC). The statistical analysis was performed using Revman (version 5.3). GRADE methodology was used to assess the quality of the evidence. RESULTS: Of the 334 studies initially reviewed, 1 trial in UC and 2 trials in Crohn's disease met eligibility. For UC, 29 patients were treated with marijuana and 31 with placebo/standard of care. There was no difference in failure to achieve clinical remission (relative risk [RR] 1.02, 95% confidence interval [CI] 0.76-1.37) or response (RR 0.99, 95%CI 0.65-1.21). Adverse events occurred in all patients receiving marijuana (RR 1.28, 95%CI 1.05-1.56). For Crohn's disease, 21 patients were treated with marijuana and 19 with placebo/standard of care. There was no difference in failure to achieve clinical remission (RR 0.72, 95%CI 0.47-1.12) or failure to achieve clinical response (RR 0.15, 95%CI 0.02-1.05). Adverse events were not reported per patient. The quality of evidence was low to very low using GRADE methodology. CONCLUSIONS: Data supporting the use of marijuana for the management of IBD are extremely limited. Further well-designed studies are needed before any positive conclusions regarding marijuana use can be drawn.

Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults With Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis.

INTRODUCTION: Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions. METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts' definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology. RESULTS: We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88-1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35-1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15-0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77-1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE. CONCLUSIONS: This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.

Meta-analysis of Virtual-based Chromoendoscopy Compared With Dye-spraying Chromoendoscopy Standard and High-definition White Light Endoscopy in Patients With Inflammatory Bowel Disease at Increased Risk of Colon Cancer.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. We sought to assess the comparative efficacy of virtual chromoendoscopy (VCE) vs high definition white light endoscopy (HDWLE) or dye-spraying chromoendoscopy (DCE) through a meta-analysis and rating the quality of evidence. METHODS: A systematic review of the literature was performed through February 15, 2019. Primary outcomes were number of patients in whom dysplasia was identified and number of dysplastic lesions identified in these patients. We included only randomized control trials (RCTs) and performed meta-analysis using RevMan5.3. RESULTS: Of the 3205 studies identified, 11 RCTs were included, with a total of 1328 patients. Per patient analysis, VCE was not statistically different compared with DCE (risk ratio [RR] 0.77; 95% CI, 0.55-1.08) or HDWLE (RR 0.72; 95% CI, 0.45-1.15). However, per dysplasia analysis, VCE was not statistically different compared with DCE (RR 0.72; 95% CI, 0.47-1.11) and inferior compared with HDWLE (RR 0.62; 95% CI, 0.44-0.88). The quality of evidence was moderate in the HDWLE and low to moderate in the DCE studies. CONCLUSION: Based on this meta-analysis, VCE was as good as HDWLE and DCE in identifying dysplasia per patient analysis. However, per dysplasia analysis, VCE was inferior compared with HDWLE and no different from DCE. Further studies need to examine the efficacy of each individual VCE technique.