Aasma Shaukat

Long-Term Mortality after Screening for Colorectal Cancer

BACKGROUND In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex. METHODS In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. RESULTS Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). CONCLUSIONS The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

CIMP Status of Interval Colon Cancers: Another Piece to the Puzzle

OBJECTIVES:Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers.METHODS:We searched our institutions cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patients first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI.RESULTS:There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.01–3.8), MSI (OR 2.7; 95% CI 1.1–6.8) and CIMP (OR 2.41; 95% CI 1.2–4.9) were independently associated with interval cancers. CIMP was associated with interval cancers independent of MSI status. There was no difference in 5-year survival between the two groups.CONCLUSIONS:Interval cancers are more likely to arise in the proximal colon and demonstrate CIMP, which suggests there may be differences in biology between these and non-interval CRC. Additional studies are needed to determine whether interval cancers arise as a result of missed lesions or accelerated neoplastic progression.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review

Key Summary Points Fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is increasingly used, primarily for recurrent CDI but also for refractory CDI and treatment of the initial CDI episode. Although 35 studies of FMT for CDI were identified, only 2 were randomized, controlled trials (RCTs), with only 1 RCT having a non-FMT comparator group. Among the 36 patients who received FMT for recurrent CDI in the 2 RCTs, 27 (75%) had resolution of symptoms without recurrence. Among the 480 patients in 21 case-series studies who received FMT for recurrent CDI, 85% had resolution of symptoms without recurrence. Few studies reported on FMT for refractory CDI or for treatment of the initial CDI episode; among these, success rates were highly variable. Since its discovery as the cause of pseudomembranous colitis in 1978 (1, 2), Clostridium difficile has become an increasingly important pathogen. Initially largely confined to patients with health care exposure, C. difficile infection (CDI) now also affects persons with no or limited contact with the health care system (3). In 2013, the Centers for Disease Control and Prevention placed C. difficile into the top threat category (urgent) in its threat report on antimicrobial resistance (4). The high rate of recurrence15% to 30% of patients after their initial CDI episode and increasing thereafteris a major challenge (5, 6). Several treatment or recurrence episodes may result in repeated hospitalizations, clinic visits, deconditioning, malnourishment, and fecal incontinence. Antimicrobial treatment of recurrent disease yields success rates between 30% and 80%, depending on the number of recurrences and the agent and treatment duration selected (58). These suboptimal response rates have spurred investigation of additional treatment options, including fecal microbiota transplantation (FMT). Severe colonic microbiome (normal colonic bacteria) alterations are characteristic of CDI. Restoring the microbiome has been proposed to prevent recurrence, and probiotics are the most widely used intervention. However, probiotic microorganisms are less diverse than those of the organisms that characterize the colonic microbiome in healthy persons (9). Fecal microbiota transplantation is increasingly used as a treatment of recurrent CDI on the basis of the idea that importing the colonic microbiome of a healthy person is a simple method of reconstituting the normal colonic flora. Most FMT cases in the medical literature are from noncontrolled case-series studies (10). Reported success rates of up to 100% and the publication of a randomized, controlled trial (RCT) comparing FMT with antimicrobial treatment (11) have increased interest in FMT, even as regulations have evolved. The U.S. Food and Drug Administration currently requires an investigational new drug application for human studies of FMT but not for clinical use in treating CDI. The first reported use of FMT (delivered via enema) in medical literature was a small case-series study of hospitalized patients. Since then, various reports have described performing the procedure outside of the hospital, including at home by means of self-administered enema (12). Timing and frequency of FMT has also varied; most are administered in a single session, whereas others have relied on serial administration over several days. Several guidelines and reviews are available to help providers select appropriate patients for FMT, guide the selection and screening of stool donors, and choose from among the delivery methods (1315). The 2 most recent guidelines differ about the strength of evidence supporting FMTa European guideline stated that FMT is strongly recommended (A-I) after a second recurrence of CDI (13), whereas a guideline from the American College of Gastroenterology offered a more cautious recommendation, stating that if there is a third recurrence after a pulsed vancomycin regimen, fecal microbiota transplant (FMT) should be considered. (Conditional recommendation, moderate-quality evidence) (14). We did a systematic review of the evidence about the effectiveness of FMT for recurrent, refractory, and initial CDI and looked for evidence that effectiveness varied by method of transplantation. We also assessed harms of FMT and procedure acceptability. This report is derived from work done for a larger U.S. Department of Veterans Affairs Evidence-based Synthesis Program review. Methods Search Strategy We searched MEDLINE for articles published in English from 1980 to January 2015 that enrolled human participants and described FMT for known or suspected CDI (Appendix Table). We also searched the Cochrane Library and ClinialTrials.gov through January 2015. Our search included studies of any design, although we excluded case reports unless they reported harms. Additional articles, including some predating our search period or using nonstandard descriptors for CDI or FMT, were identified from hand-searching reference lists of existing systematic reviews and included studies as well as from suggestions by a technical expert panel. Appendix Table. Search Strategy Study Selection and Definitions Titles, abstracts, and articles were independently reviewed by 2 investigators, and disagreements were resolved by discussion and involvement of a third investigator, if needed. We considered initial CDI to be the first occurrence of CDI in a particular patient, recurrent CDI to be an episode occurring after previous treatment and favorable response for at least 1 previous episode, and refractory CDI to be an episode that did not respond to antimicrobial treatment. Data Abstraction and Quality Assessment Study characteristics, patient characteristics, and outcomes data were abstracted from included articles. Because all but 2 of the included studies were case-series studies, we did not formally assess quality but rather noted that conventional methods for rating strength of evidence would classify even well-conducted and reported case-series studies as high risk of bias (16). Therefore, strength of evidence would typically be considered insufficient or low. For the 2 RCTs, quality was assessed on the following criteria: allocation concealment, blinding, analysis approach, and description of withdrawalsa modification of the Cochrane approach to determining risk of bias (17). Our key outcomes included resolution of symptoms (primary outcome), time to resolution of symptoms, recurrence, all-cause mortality, and adverse events. We report results after a single administration of FMT or, in the case of studies that specified serial administration of FMT on successive days, a single prespecified series of administrations. In several studies, patients having recurrence were offered repeated FMT; these patients were categorized as having unsuccessful FMT because they met the recurrence outcome. Data Synthesis and Analysis Most findings are summarized narratively. Because the included studies report outcomes on small numbers of patients derived largely from case-series studies, any pooled estimate of the effect size and a surrounding CI was considered to be of questionable validity. Therefore, we report descriptive summaries of each included study and an overall percentage of patients remaining free of recurrent CDI. Role of the Funding Source This review was funded by the U.S. Department of Veterans Affairs. The funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Members of a technical expert panel and peer reviewers of the evidence report provided advice and feedback. Technical expert panel members and peer reviewers were not compensated for their contributions. Results Our literature search yielded 190 abstracts or titles. We excluded 129 articles after abstract review and performed full-text reviews of 61 articles; of those, we excluded 51, leaving 10 articles. From hand-searching reference lists of systematic reviews and included studies and suggestions from technical expert panel members, we identified another 25 articles for a total of 35 included studies: 2 RCTs, 28 case-series studies, and 5 case reports (Figure). Figure. Summary of evidence search and selection. CDI = Clostridium difficile infection; FMT = fecal microbiota transplantation; RCT = randomized, controlled trial. * Included 1 RCT. FMT for Recurrent CDI Data From RCTs Two small RCTs with moderate risk of bias (11, 18) reported use of FMT for patients with recurrent CDI. The first compared FMT using a nasoduodenal tube with 2 control groups (43 patients; 1 withdrew after random assignment); 81% of FMT patients achieved resolution of symptoms within 3 months compared with 31% and 23% for the vancomycin and vancomycin-plus-bowel lavage control groups, respectively (P < 0.001 for FMT vs. both control groups) (11). The study, which we rated as moderate quality, was unblinded and done in the Netherlands. It was terminated after the investigators saw extremely low response rates in the control groups, which differed substantially from the 60% rate used for calculations of sample sizes. Patients had a mean age of 70 years, and 58% were men. Previous CDI episodes were numbered from 1 to 9. Administration of FMT was done after 4 to 5 days of oral vancomycin (500 mg 4 times daily), whereas the control groups received the same dose of vancomycin for 14 days. The second RCT compared 2 FMT treatment approaches, nasogastric tube and colonoscopy, in 20 patients. Overall, 70% of patients had resolution of symptoms; the difference between treatment approaches was not significant (60% in the nasogastric tube group and 80% in the colonoscopy group; P= 0.63) (18). This moderate-quality study was unblinded, did not include a non-FMT control group, and was done in the United States. The patients in this trial were

Systematic Review: Effective Management Strategies for Lactose Intolerance

BACKGROUND Lactose intolerance resulting in gastrointestinal symptoms is a common health concern. Diagnosis and management of this condition remain unclear. PURPOSE To assess the maximum tolerable dose of lactose and interventions for reducing symptoms of lactose intolerance among persons with lactose intolerance and malabsorption. DATA SOURCES Multiple electronic databases, including MEDLINE and the Cochrane Library, for trials published in English from 1967 through November 2009. STUDY SELECTION Randomized, controlled trials of individuals with lactose intolerance or malabsorption. DATA EXTRACTION Three investigators independently reviewed articles, extracted data, and assessed study quality. DATA SYNTHESIS 36 unique randomized studies (26 on lactase- or lactose-hydrolyzed milk supplements, lactose-reduced milk, or tolerable doses of lactose; 7 on probiotics; 2 on incremental lactose administration for colonic adaptation; and 1 on another agent) met inclusion criteria. Moderate-quality evidence indicated that 12 to 15 g of lactose (approximately 1 cup of milk) is well tolerated by most adults. Evidence was insufficient that lactose-reduced solution or milk with a lactose content of 0 to 2 g, compared with greater than 12 g, is effective in reducing symptoms of lactose intolerance. Evidence for probiotics, colonic adaptation, and other agents was also insufficient. LIMITATIONS Most studies evaluated persons with lactose malabsorption rather than lactose intolerance. Variation in enrollment criteria, outcome reporting, and the composition and dosing of studied agents precluded pooling of results and limited interpretation. CONCLUSION Most individuals with presumed lactose intolerance or malabsorption can tolerate 12 to 15 g of lactose. Additional studies are needed to determine the effectiveness of lactose intolerance treatment.

The management of antithrombotic agents for patients undergoing GI endoscopy.

Ruben D. Acosta, MD, Neena S. Abraham, MD, MSCE, FASGE (invited content expert, ad-hoc member), Vinay Chandrasekhara, MD, Krishnavel V. Chathadi, MD, Dayna S. Early, MD, FASGE, Mohamad A. Eloubeidi, MD, MHS, FASGE, John A. Evans, MD, Ashley L. Faulx, MD, FASGE, Deborah A. Fisher, MD, MHS, FASGE, Lisa Fonkalsrud, BSN, RN, CGRN, Joo Ha Hwang, MD, PhD, FASGE, Mouen A. Khashab, MD, Jenifer R. Lightdale, MD, MPH, FASGE, V. Raman Muthusamy, MD, FASGE, Shabana F. Pasha, MD, John R. Saltzman, MD, FASGE, Aasma Shaukat, MD, MPH, FASGE, Amandeep K. Shergill, MD, Amy Wang, MD, Brooks D. Cash, MD, FASGE, previous Committee Chair, John M. DeWitt, MD, FASGE, Chair

Effects of Vitamin D and Calcium Supplementation on Markers of Apoptosis in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop “treatable” biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis, in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D3, alone or in combination, versus placebo over 6 months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter) in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, Bax expression along the full lengths of crypts increased 56% (P = 0.02) in the vitamin D group and 33% in both the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; P = 0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.

Variation in Detection of Adenomas and Polyps by Colonoscopy and Change Over Time With a Performance Improvement Program

BACKGROUND & AIMS There has been no prospective, community-based study to track changes in adenoma detection by individual physicians over time and to determine the effectiveness of targeted educational interventions. METHODS We prospectively collected information on 47,253 screening colonoscopies in average-risk individuals 50 years and older performed by a community-based practice in the Twin Cities of Minnesota. During a period of 3 years, 5 specific interventions were implemented; each was designed to improve adenoma detection rates. Controlling for patient-related and procedure-related factors, rates of adenoma detection and 3-year trends for individual physicians were plotted, and intraclass correlation coefficients were calculated. Generalized estimating equations were used to identify factors associated with detection of adenomas and polyps. RESULTS At least 1 polyp and 1 adenoma were found in 36% and 22% of examinations, respectively. Adenoma detection rates by endoscopists ranged from 10%-39%. There was no significant improvement during the study period despite planned, systematic interventions. Factors associated with adenoma detection included age of the patient (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.02), male sex (OR, 1.53; 95% CI, 1.34-1.74), and adequate preparation quality (OR, 2.26; 95% CI, 1.64-3.12). CONCLUSIONS The detection of adenomas by individual physicians during a 3-year period varied and did not appear to change between individual endoscopists, despite planned, systematic interventions. This indicates that other targeted interventions might be required to improve adenoma detection rates among experienced, community gastroenterologists.

Antiviral Therapy for Adults With Chronic Hepatitis B: A Systematic Review for a National Institutes of Health Consensus Development Conference

Hepatitis B is highly prevalent, with 350 million chronic cases worldwide (1). Despite immunization efforts, 4713 incident cases of hepatitis B were diagnosed in the United States in 2006 (2). An estimated 2000 to 4000 deaths per year in the United States are related to chronic hepatitis B liver diseases (3), including liver cirrhosis and hepatocellular carcinoma (4). Because most patients are asymptomatic, treatment goals of antiviral therapy include long-term prevention of progression, development of cirrhosis and liver failure, and hepatocellular carcinoma. Short-term intermediate laboratory responses have been proposed as potential surrogate measures of treatment effects on clinical outcomes (1). Normalization of liver enzyme levels, viral suppression and clearance, reduction in histologic scores of liver inflammation or fibrosis, and combinations of these outcomes have been used to measure response to antiviral drugs or development of antiviral resistance (1, 5). Seven antiviral agents are approved to treat hepatitis B in the United States, including oral medications (lamivudine, telbuvidine, adefovir, tenofovir, and entecavir) and injected interferons (standard interferon-2b and pegylated interferon-2a). Other agents are under investigation. The U.S. Food and Drug Administration approved tenofovir for adults in August 2008 on the basis of ongoing, unpublished trials that compared tenofovir with adefovir on intermediate outcomes, the results of which were not available for our review (6). This review was commissioned as background material for the National Institutes of Health Consensus Development Conference on Management of Chronic Hepatitis B in Adults to synthesize the published evidence about the effectiveness of interferon therapy, oral therapy, and various combinations with defined or continuous courses of treatment. The full report, including a detailed description of our methods, is available at www.ahrq.gov/downloads/pub/evidence/pdf/hepb/hepb.pdf (7). Methods Data Sources and Study Selection We searched MEDLINE, PubMed, the Cochrane Library (8), and other databases (911). We included randomized, controlled clinical trials (RCTs) of adults with chronic hepatitis B published in English after 1989 that reported death; incidence of hepatocellular carcinoma or liver failure; prevalence and incidence of cirrhosis; presence or seroconversion of hepatitis B e antigen (HBeAg) or surface antigen (HBsAg); viral load of hepatitis B virus (HBV) DNA; aspartate aminotransferase and alanine aminotransferase (ALT) levels; and histologic necroinflammatory or fibrosis scores after therapy with interferon-2b, pegylated interferon-2a, lamivudine, adefovir, entecavir, and telbivudine (12). Studies that enrolled at least 50 adults and provided treatment for 24 weeks or more were eligible for this review. Interferon studies of any size were eligible if participants were given treatment for at least 12 weeks. We excluded studies evaluating pregnant women, patients with hepatocellular carcinoma or HIV infection at baseline, patients undergoing chemotherapy or liver transplantation, or patients with several causes of hepatitis, unless outcomes for participants meeting our eligibility criteria were reported separately. The full report describes the search strategies (7). We included publications from the multinational HBV 99-01 Study Group assessing pegylated interferon-2b, a treatment that has been intensively examined in patients with chronic hepatitis B but is not yet approved in the United States (13). Three investigators independently measured study eligibility (14). Data Extraction and Quality Assessment Three researchers independently evaluated the studies and extracted data to detect errors and discrepancies (14). We abstracted the number of events among treatment groups to calculate rates, relative risks (RRs), and absolute risk differences (15). We abstracted the number of patients randomly assigned to each treatment group as the denominator to calculate estimates, applying the intention-to-treat principle. We recorded intervals for outcome assessments in weeks from randomization for the active-treatment period and from the end of treatment for follow-up assessments. We prioritized clinical outcomes in the assessment of treatment benefits and harms. Sustained HBsAg loss or seroconversion was considered the criterion for resolution of hepatitis B viral infection and a major goal of antiviral therapy (1). Liver histologic outcomes included improved necroinflammatory and fibrosis scores. Sustained ALT normalization as diagnostic criteria of hepatocyte injury and sustained clearance of HBV DNA were assigned as secondary outcomes. Although positive associations with better clinical outcomes exist in observational studies, both outcomes may reverse after treatment. Because low levels of evidence from observational studies suggested that HBeAg-negative status was associated with worse clinical outcomes, we defined sustained HBeAg seroconversion as a desirable intermediate outcome. We analyzed RCTs for participant selection, duration of and loss to follow-up, intention-to-treat principle, masking of treatment status, randomization scheme and its adequacy, allocation concealment, and justification of sample sizes (16). We assessed the level of evidence on the basis of the Grading of Recommendations Assessment, Development and Evaluation Working Group criteria (17, 18). We assigned a low level of evidence when data were from small RCTs or RCTs with flaws in design or analysis or were from post hoc subgroup analysis. We assigned a moderate level of evidence when a single, large multinational study or several small RCTs reported consistent associations between antiviral agents and outcomes and a high level of evidence when several high-quality studies in applicable patients reported consistent sustained effects at least 6 months after therapy. Data Synthesis and Analysis The full report includes evidence tables that summarize results of individual studies (7). We compared baseline data across the studies to test for differences in the target sample and to detect unusual patterns in the data (1921). Analyses were conducted separately for clinical, biochemical, virologic, and histologic outcomes and for RRs and absolute risk differences. The protocol for meta-analyses was created according to recommendations (22, 23) to assess the consistency of the association between treatments and outcomes with random-effects models (24). Pooling criteria included the same operational definitions of outcomes and drug interventions (23). We used chi-square tests to assess heterogeneity (25, 26). Calculations used Stata statistical software, version 9.2 (StataCorp, College Station, Texas) (27). We assumed the presence of publication bias and did not use statistical tests for bias caused by sparse and heterogeneous data (14, 2830). Role of the Funding Source The Agency for Healthcare Research and Quality suggested the initial questions and provided copyright release for this manuscript. The funding source had no role in the literature search, data analysis, conduct of the study, preparation of the review, or interpretation of the results. The funding source reviewed and approved the submitted manuscript without revisions. Results Ninety-three articles represented 60 unique RCTs (31102). The full report contains the study flow diagram and the appendix with excluded studies (7). Studies enrolled 20 to 1367 patients who were predominately HBeAg-positive. Men constituted 78% of enrollees. Most enrollees were Asian (64%) or white (30%). The estimated duration of infection, reported in 8 studies, ranged from approximately 2 to 6 years. However, individual patient duration of infection ranged from 6 months to 20 years (3140). Clinical Outcomes Studies that reported death, liver-related death, hepatocellular carcinoma, hepatic decompensation, or cirrhosis (Table) were not designed and did not have sufficient power to reliably assess drug effects on these clinical outcomes. Table. Effects of Drug Therapies for Chronic Hepatitis B on Clinical Outcomes Death was assessed in 13 studies, with very few deaths reported (36, 3950). Low-level evidence suggested that lamivudine (41), entecavir (4347), interferon-2b (36, 39, 48), pegylated interferon-2a (49), pegylated interferon-2b (50), and adefovir (42) did not decrease mortality. Two studies assessed cirrhosis with small sample size and relatively short-term treatment with interferon-2b. Reduction in cirrhosis incidence (40) or prevalence (51) was not observed. Few events occurred, and the studies were not sufficiently powered to detect differences in cirrhosis (52). Three studies reported hepatic decompensation with very few events (44, 47, 53). There was no significant difference in hepatic decompensation after administration of lamivudine versus placebo (55) or entecavir versus lamivudine (44, 47). A multicenter study involving 651 Asian patients (58% were HBeAg-positive) with confirmed cirrhosis (61%) or advanced fibrosis (41) reported a decrease in disease progression (7.8% vs. 17.7% [hazard ratio, 0.45; P= 0.001]) for lamivudine versus placebo. Disease progression was the first occurrence of an increase of at least 2 points in the ChildPugh score, hepatic decompensation, bleeding varices, renal insufficiency, bleeding gastric or esophageal varices, spontaneous bacterial peritonitis with proven sepsis, hepatocellular carcinoma, or death related to liver disease. Four studies reported hepatocellular carcinoma. None demonstrated a statistically significant difference compared with no treatment after lamivudine (41), interferon-2b (54), prolonged adefovir therapy (42), or interferon monotherapy with and without corticosteroids (51). Incidence of hepatocellular carcinoma did not differ between lamivudine and placebo in the multicenter study of patients with confirmed cirrhosis or advanced fibrosis mention

Bowel preparation before colonoscopy

This is one of a series of documents discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this document that updates a previously issued consensus statement and a technology status evaluation report on this topic. In preparing this guideline, a search of the medical literature was performed by using PubMed between January 1975 and March 2014 by using the search terms “colonoscopy,” “bowel preparation,” “intestines,” and “preparation.” Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When limited or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Recommendations for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the documents are drafted. Further controlled clinical studies may be needed to clarify aspects of recommendations contained in this document. This document may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence (Table 1). The strength of individual recommendations is based both on the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as “we suggest,” whereas stronger recommendations are typically stated as “we recommend.” This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. It is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient’s condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these recommendations and suggestions.

A trial of calcium and Vitamin D for the prevention of colorectal adenomas

BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopists recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).