The fragility index applied to liver-related trials.

The goal of this manuscript was to apply the fragility index (FI), which is a statistically sound method to evaluate robustness of test results, to liver-related randomized clinical trials. The authors searched the ClinicalTrials.gov database with the following limitations: term "liver," recruitment completed, with results, interventional study type, last updated May 01, 2016, to May 01, 2017. Forty-eight trials were included and four had FI of 0. The median FI for trials moving from significance to non-significance was 6 (IQR 18; 2 to 20), while the median for trials moving from non-significance to significance was 5 (IQR 5; 4 to 9). The median number lost to follow up was 17 (IQR 42; 3 to 45). Of the 21 trials that showed statistical significance, the number lost to follow up was greater than the FI in 13 (61.90%) trials. Investigators of liver-related studies should consider adding the FI to evaluate their work.

Assessing adherence and cost-benefit of colorectal cancer screening for accountable providers.

The objective of this study was to assess adherence and costs-benefits of colorectal cancer (CRC) screenings from an accountable care organization/population health perspective. We performed a retrospective review of 94 patients (50-75 years of age) in an integrated safety net system for whom fecal CRC screening was abnormal for the period of June 1, 2014, to June 1, 2016. A cost-benefit model was constructed using Medicare payment rates and a sensitivity analysis. Most patients included in the study (64/94, 68%) received or were offered a colonoscopy. Of those receiving a colonoscopy, 24 of 45 (53%) had an abnormal finding. Total direct medical costs avoided by screening the patient panel was $32,926 but could have exceeded $63,237 had more patients received follow-up colonoscopies. A sensitivity analysis with 1000 patients demonstrated total monetary benefits between $2.2 million and $8.16 million when follow-up and colonoscopy rates were allowed to vary. Although the resulting rates of follow-up were within the range reported in the literature, there is room for improvement, especially considering the monetary benefit that could be used on other diseases. Health systems and payers should work cooperatively to structure payment models to better incentivize CRC screenings.

From clinical practice guideline development to trial registration: A systematic investigation of research pipeline for inflammatory bowel disease.

BACKGROUND: Clinical practice guidelines help practitioners manage patients in an effective and systematic way, and they assist in making evidence-based decisions related to diagnosis and treatment. Each recommendation is ranked based on evidence. The goal of this study is to determine gaps in research for inflammatory bowel diseases (IBD) by using the low-level evidence recommendations. METHODS: We extracted low-level evidence recommendations set forth by the American College of Gastroenterology in IBD, ulcerative colitis (UC), and Crohn's disease. ClinicalTrials.gov , the World Health Organization's International Clinical Trials Registry Platform and PubMed were then used to locate studies relevant to the recommendations. RESULTS: There were 30 low-level evidence recommendations, and 23 had recent or ongoing studies addressing them. We screened 2938 trials and 4321 published articles, 221 of which addressed low-quality recommendations. There were five recommendations that received the majority of research attention (143/221, 65%). CONCLUSION: This study used clinical practice guidelines to help determine areas of needed research in IBD, UC, and Crohn's disease. By searching trial registries and articles indexed on PubMed, we identified the extent to which studies were being conducted to address research gaps. Of the gaps identified, five recommendations received most of the attention. While most of the significant gaps had some recent or ongoing research, our study found several areas where investigation is still needed. Clinical practice guidelines are an effective method to prioritize future research.

Diagnostic Accuracy in Primary Care E-Visits: Evaluation of a Large Integrated Health Care Delivery System's Experience.

OBJECTIVE: To compare diagnostic accuracy between primary care E-Visit and face-to-face (F2F) encounters for low-acuity illnesses. PATIENTS AND METHODS: This cross-sectional retrospective analysis of electronic health records in a large not-for-profit integrated delivery system included patients covered by the health care system's employee health plan with an established affiliated physician-patient relationship and an F2F encounter in the past 12 months who had an E-Visit (n=490) or an F2F (n=2201) primary care encounter for a low-acuity illness from July 1, 2015, through December 22, 2016. Patients with a related follow-up visit within 10 days resulting in a revised diagnosis, as determined by 2 physician reviewers, were compared (1) including only the first encounter for each patient and (2) including all encounters more than 10 days apart for included patients. RESULTS: In both analyses, a follow-up visit occurred within 10 days more than 40% of the time in both groups. However, follow-up visits related to the initial diagnosis occurred only 9% to 12% of the time. Only 2.1% to 2.4% of initial diagnoses were identified by both physician reviewers as revised, whereas 3.8% to 5.5% were so identified by at least 1 reviewer. The only significant difference observed between the E-Visit and F2F groups was in the rate of related follow-up visits when only each patient's first encounter was considered, which was higher for E-Visits (12% vs 9%; P=.04). CONCLUSION: Diagnostic accuracy for low-acuity illnesses in this population was equivalent between E-Visit and F2F encounters.

Testing the ability of the nonalcoholic fatty liver disease fibrosis score to predict 1-year all-cause hospital admission.

The nonalcoholic fatty liver disease fibrosis score (NFS) has been shown to be a cost-effective screening strategy in the primary care setting to determine when gastroenterology referral is needed, but NFS as a predictor of hospitalization within 1 year is uncertain. This retrospective observational cohort study involved 1803 patients with a diagnosis of nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. The NFS was categorized into the following: low (less than -1.455), moderate (between -1.455 and 0.676), and high (>0.676). The average NFS score by hospital admission was -0.760, the average number of admissions was 1.81, and the median number of days to hospital admission was 135.8 days (45.5-363, 25th to 75th percentile). A univariate logistic regression model showed that NFS significantly predicted hospital admission (P = 0.007); however, a multivariate logistic regression model, after adjusting for hypertension and tobacco use, indicated that NFS was not significantly associated with hospital admission. Using the logistic regression model, hypertension predicted admission at low (P < 0.0001) and moderate (P = 0.0005) NFS. Using this same model, tobacco use also predicted admission at low (P < 0.0001) and moderate (P = 0.0002) NFS. The NFS should not be used to determine which patients are at increased risk of hospitalization.

Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease.

The Hypothalamic-Pituitary-Adrenal (HPA) axis has an important role in maintaining the physiological homeostasis in relation to external and internal stimuli. The HPA axis dysfunctions were extensively studied in neuroendocrine disorders such as depression and chronic fatigue syndrome but less so in hepatic cholestasis, cirrhosis or other liver diseases. The HPA axis controls many functions of the liver through neuroendocrine forward signaling pathways as well as negative feedback mechanisms, in health and disease. This review describes cell and molecular mechanisms of liver and HPA axis physiology and pathology. Evidence is presented from clinical and experimental model studies, demonstrating that dysfunctions of HPA axis are correlated with liver cholestatic disorders. The functional interactions of HPA axis with the liver and immune system in cases of bacterial and viral infections are also discussed. Proinflammatory cytokines stimulate glucocorticoid (GC) release by adrenals but they also inhibit bile acid (BA) efflux from liver. Chronic hepatic inflammation leads to cholestasis and impaired GC metabolism in the liver, so that HPA axis becomes depressed. Recently discovered interactions of GC with self-oscillating transcription factors that generate circadian rhythms of gene expression in brain and liver, in the context of GC replacement therapies, are also outlined.

A review of publication bias in the gastroenterology literature.

In systematic reviews and meta-analyses, publication bias is particularly problematic, given that combining only statistically significant outcomes is likely to overestimate the true effect of an intervention since non-significant findings have been omitted. We examined practices for evaluating publication bias from gastroenterology literature. We performed a PubMed search to identify systematic reviews published in American Journal of Gastroenterology, Gut, and Gastroenterology from 2005 to 2015. Of the 304 found, 215 studies were eligible for inclusion based on relevant study characteristics. There were 190 systematic reviews which used at least one method to evaluate publication bias and/or included ten or more primary studies. There were 115/190 (60.53%) systematic reviews which used at least one method to evaluate publication bias. Most (105/115, 91.27%) qualified reviews used at least one method to evaluate publication bias and 78/115 (67.83%) used a combination of methods. The most common methods were funnel plot (100/115, 86.96%), Egger's regression (67/115, 58.26%), and Begg's (28/115, 24.35%). Of the 115 reviews that performed evaluations, 26 (22.61%) conducted these analyses with fewer than ten primary studies, and a minority (24/115, 20.87%) reached the conclusion that publication bias was present in their work. While methods to assess publication bias were frequently noted among qualified systematic reviews, these methods are limited in value and could be improved by incorporating approaches that assess the degree of publication bias severity.

Reporting guideline and clinical trial registration requirements in gastroenterology and hepatology journals.

AIM: The objective of this study was to evaluate the current recommendations and requirements of gastroenterology and hepatology journals concerning reporting guidelines and clinical trial registration. Current research on the topic is sparse and in need of further research in both clinical trial registration and guideline adherence. METHODS: The authors performed a review of journal protocols and 'Instructions for Authors' regarding guideline adherence and trial registration requirements within 30 gastroenterology and hepatology journals. We searched the Expanded Science Citation Index of the 2015 Journal Citation Reports to determine if each journal required, recommended, or made no mention of 17 guidelines and clinical trial registration. RESULTS: A majority (23/30; 76.7%) of the journals either required or recommended reporting guideline usage, whereas the remainder (7/30; 23.3%) had no such policy. In addition, 14 (14/30; 46.7%) require or recommend trial registration. Journals with a higher impact factor were associated with greater reporting guideline adherence (rpb = 0.43, P < 0.05). There was not a significant relationship between journal impact factor and trial registration requirements (rpb = 0.16, P > 0.05). Consolidated Standards of Reporting Trials was the most often required guideline (9/30; 30%), whereas Animal Research: Reporting of In Vivo Experiments and Preferred Reporting Items for Systematic Reviews and Meta-Analyses were tied for second most often required (6/30 each; 20% each). Clinical trial registration was most common via ClinicalTrials.gov (9/30; 30%). CONCLUSION: A majority of gastroenterology or hepatology journals either require or recommend reporting guideline usage, but just less than one-half of the journals did the same for trial registration.

Heterogeneity assessment in gastroenterology systematic reviews: an analysis of current practices.

AIM: In systematic reviews and meta-analyses, variation (heterogeneity) in the primary studies is often a concern resulting from factors such as study design, data analysis methods, study quality, settings and interventions and/or patient characteristics. After determining the extent of heterogeneity, authors examine the causes of heterogeneity via sensitivity analysis, subgroup analysis and/or meta-regression analysis. There is no assessment of heterogeneity practices in gastroenterological literature; thus, we present this assessment. METHODS: We performed a PubMed search to identify systematic reviews published from 2011 to 2016 in the top 10 gastroenterology journals, as well as gastrointestinal topics in general medical journals and the PROSPERO trial registry. The first and second authors independently abstracted data elements, such as levels of inconsistency, sensitivity analysis, subgroup analysis and meta-regression analysis. RESULTS: The search identified 3154 studies; of these, 337 were eligible for inclusion. Included studies consisted of 306 from the gastroenterology literature, 19 studies from PROSPERO and 12 studies from the general internal medicine journals. A significant number of reviews in gastroenterology journals (31.05%, 95/306), internal medicine journals (16.67%, 2/12) and PROSPERO (52.63%, 10/19) conducted a meta-analysis despite having fewer than 10 primary studies. Most of the reviews in gastroenterology journals (81.05%, 248/306), general internal medicine journals (75%, 9/12) and PROSPERO results (73.68%, 14/19) used a combination of methods to assess heterogeneity. There were 20 various definitions of levels of inconsistency (I) throughout all the results. Random effects was the most common model choice in gastroenterology journals reviews (57.84%; 177/306), internal medicine journals (75%, 9/12) and for PROSPERO results (41.11%, 8/19). The majority of reviews did not discuss the impact of heterogeneity on results in the gastroenterology journals (62.09%, 190/306), only one study in the general internal medicine journals and only one study in the PROSPERO results. CONCLUSION: In gastroenterology journals and other journals printing gastrointestinal topic systematic reviews, most conducted statistical tests for heterogeneity; however, the statistical methods could be more robust and the impact of heterogeneity discussed more often in the article.

An unusual presentation of Tropheryma whipplei infection.

Whipple's disease is an infection caused by the Gram-positive bacillus Tropheryma whipplei. Invasion or uptake of the bacteria can occur in various parts of the body. The differential diagnoses are broad due to the wide spectrum of infection, and the disease is diagnosed based on biopsy of suspected lesions, usually in the small intestine. We present the case of a 56-year-old man with no significant prior medical history who presented with swelling and pain in the left eye. Review of systems revealed 6 months of persistent diarrhea, and intestinal biopsy revealed periodic acid-Schiff-positive macrophages.