Ashwin N Ananthakrishnan

Harvard Medical School, Boston, Massachusetts, United States

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Publications (159)1250.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Crohn's disease (CD) often affects women during the reproductive years. Although several studies have examined the impact of pregnancy on luminal disease, limited literature exists in those with perianal CD. Decision regarding mode of delivery is a unique challenge in such patients due to concerns regarding the effect of pelvic floor trauma during delivery on preexisting perianal involvement.
    Inflammatory Bowel Diseases 06/2014; · 5.12 Impact Factor
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    ABSTRACT: Crohn's disease (CD) requires surgical management in up to two-thirds of patients. Few studies have addressed the issue of ileal recurrence after colectomy and permanent ileostomy. The aims of our study were to assess the rate and predictors of postoperative recurrence of CD in patients with permanent ileostomy.
    Inflammatory Bowel Diseases 05/2014; · 5.12 Impact Factor
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    ABSTRACT: Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with > 90% follow up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Among 151,871 women, we confirmed 191 cases of CD (incidence 8/100,000 person-years [p-y]) and 230 cases of UC (incidence 10/100,000 p-y) over 2,292,849 p-y. Compared to women with reported usual sleep durations of 7-8 hrs/day (incidence 8/100,000 p-y), women with reported sleep duration < 6 hrs/day (11/100,000 p-y) or > 9 hrs/day (20/100,000 p-y) had a higher incidence of UC (P<.05).The multivariate HRs for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations < 6 hrs/day and 2.05 (95% CI, 1.44-2.92) for sleep durations > 9 hrs/day, compared to sleep durations of 7-8 hrs/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. Based on data from the NHS I and II, less than 6 hrs sleep/day and more than 9 hrs sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 04/2014; · 5.64 Impact Factor
  • Gauree G Konijeti, Jenny Sauk, Mark G Shrime, Meera Gupta, Ashwin N Ananthakrishnan
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    ABSTRACT: Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.
    Clinical Infectious Diseases 03/2014; · 9.37 Impact Factor
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    ABSTRACT: Cigarette smoking is a well-established environmental risk factor for Crohn's disease (CD) and ulcerative colitis (UC). The exact mechanism of its effect remains unexplained. Genetic polymorphisms in metabolizing enzymes may influence susceptibility to the effect of smoking and shed light on its mechanism of action. We used a prospective cohort of patients with CD, UC, and healthy controls. Smoking status was defined as current, former, or never smoking. Patients were genotyped for polymorphisms in CYP2A6, glutathione transferase enzymes (GSTP1 and GSTM1), NAD(P)H quinone oxidoreductase (NQO), and heme oxygenase 1 using a Sequenom platform. Multivariate logistic regression models with CD or UC as the outcome, stratified by genotype, were developed and interaction P-values calculated. Our study included 634 patients with CD, 401 with UC, and 337 healthy controls. Ever smokers had an increased risk of CD (odds ratio = 3.88, 95% confidence interval = 2.35-6.39) compared with nonsmokers among patients with AG/AA genotypes at CYP2A6. However, ever smoking was not associated with CD among patients with the AA genotype (Pinteraction = 0.001). Former smoking was associated with an increased risk for UC only in the presence of GG/AG genotypes for GSTP1 but not in those with the AA genotype (Pinteraction = 0.012). Polymorphisms at the NQO and HMOX loci did not demonstrate a statistically significant interaction with smoking and risk of CD or UC. Genetic polymorphisms in metabolizing enzymes may influence the association between smoking and CD and UC. Further studies of gene-environment interaction in inflammatory bowel disease are warranted.
    Inflammatory Bowel Diseases 03/2014; · 5.12 Impact Factor
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    ABSTRACT: Background Patients with inflammatory bowel diseases (IBD) have an increased risk of clostridium difficile infection (CDI). Cathelicidins are anti-microbial peptides that attenuate colitis and inhibit the effect of clostridial toxins. Plasma calcifediol [25(OH)D] stimulates production of cathelicidins.AimTo examine the association between plasma 25(OH)D and CDI in patients with IBD.Methods From a multi-institutional IBD cohort, we identified patients with at least one measured plasma 25(OH)D. Our primary outcome was development of CDI. Multivariate logistic regression models adjusting for potential confounders were used to identify independent effect of plasma 25(OH)D on risk of CDI.ResultsWe studied 3188 IBD patients of whom 35 patients developed CDI. Patients with CDI-IBD were older and had greater co-morbidity. The mean plasma 25(OH)D level was significantly lower in patients who developed CDI (20.4 ng/mL) compared to non-CDI-IBD patients (27.1 ng/mL) (P = 0.002). On multivariate analysis, each 1 ng/mL increase in plasma 25(OH)D was associated with a 4% reduction in risk of CDI (OR 0.96, 95% CI 0.93–0.99, P = 0.046). Compared to individuals with vitamin D >20 ng/mL, patients with levels <20 ng/mL were more likely to develop CDI (OR 2.27, 95% CI 1.16–4.44). The mean plasma 25(OH)D in patients with CDI who subsequently died was significantly lower (12.8 ± 8.1 ng/mL) compared to those who were alive at the end of follow-up (24.3 ± 13.2 ng/mL) (P = 0.01).Conclusions Higher plasma calcifediol [25(OH)D] is associated with reduced risk of C. difficile infection in patients with IBD. Further studies of therapeutic supplementation of vitamin D in patients with inflammatory bowel disease and C. difficile infection may be warranted.
    Alimentary Pharmacology & Therapeutics 03/2014; · 4.55 Impact Factor
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    ABSTRACT: Inflammatory bowel disease (IBD) is a well-known risk factor for venous thromboembolism (VTE). Existing guidelines for thromboprophylaxis in hospitalized patients do not extend to other clinical scenarios that may also be associated with VTE risk. Our aim was to estimate the fraction of VTE events in patients with IBD that could be prevented. A retrospective analysis assessed all patients with IBD diagnosed with VTE at a single academic medical center from 2002 to 2012. Confirmed cases were analyzed for VTE risk factors, inpatient status, the use of deep venous thrombosis prophylaxis, and when applicable the reason for omission of prophylaxis. IBD VTE cases were compared with age- and sex-matched non-IBD VTE controls with regards to risk factors and potential opportunities for VTE prevention. There were 204 patients with IBD (108 ulcerative colitis, 96 Crohn's disease) diagnosed with VTE (110 deep venous thrombosis, 66 pulmonary embolism, 27 intra-abdominal thromboses, and 1 other). One-third of the VTE events occurred in hospitalized patients. Two-third of the medical inpatients and 44% of surgical inpatients who developed VTE did not receive prophylaxis. Importantly, 129 VTE events occurred in outpatients. The proportion of outpatients hospitalized within 4 weeks of developing venous thrombosis was higher in patients with IBD than non-IBD controls (33% versus 15%, P = 0.0003). One-third (36%) of patients were experiencing ambulatory disease flares at the time of VTE diagnosis. A substantial portion of VTE events in patients with IBD occurred in clinical scenarios is not routinely recommended for thromboprophylaxis. Further investigation of primary prophylaxis for patients with IBD in high-risk outpatients may be warranted.
    Inflammatory Bowel Diseases 02/2014; · 5.12 Impact Factor
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    ABSTRACT: More than 80% of Crohn's disease (CD) patients will require surgery. Surgery is not curative and rates of re-operation are high. Identification of genetic variants associated with repeat surgery would allow risk stratification of patients who may benefit from early aggressive therapy and/or post-operative prophylactic treatment. CD patients who had at least one CD-related bowel resection were identified from the Prospective Registry in IBD Study at Massachusetts General Hospital (PRISM). The primary outcome was surgical recurrence. Covariates and potential interactions were assessed using the Cox proportional hazard model. Kaplan-Meier curves for time to surgical recurrence were developed for each genetic variant and analyzed with the log-rank test. 194 patients were identified who had at least 1 resection. Of these, 69 had two or more resections. Clinical predictors for repeat surgery were stricturing (HR 4.18, p=0.022) and penetrating behavior (HR 3.97, p=0.024). Smoking cessation was protective for repeat surgery (HR 0.45, p=0.018). SMAD3 homozygosity for the risk allele was also independently associated with increased risk of repeat surgery (HR 4.04, p=0.001). NOD2 was not associated with increased risk of surgical recurrence. Stricturing and penetrating behavior were associated with increased risk of surgical recurrence, while smoking cessation was associated with a decreased risk. A novel association between SMAD3 and increased risk of repeat operation and shorter time to repeat surgery was observed. This finding is of particular interest as SMAD3 may represent a new therapeutic target specifically for prevention of post-surgical disease recurrence.
    Journal of Crohn s and Colitis 01/2014; · 3.39 Impact Factor
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    ABSTRACT: OBJECTIVES:Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases with a progressive relapsing remitting course. There is considerable heterogeneity in disease course and accurate prediction of natural history has been challenging. The phenotypic implication of increasing genetic predisposition to CD or UC is unknown.METHODS:The data source for our study was a prospective cohort of CD and UC patients recruited from a tertiary referral center. All patients underwent genotyping on the Illumina Immunochip. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for each of the 163 inflammatory bowel disease (IBD) risk loci was calculated and phenotypic associations examined across GRS quartiles.RESULTS:Our study cohort included 1,105 patients (697 CD, 408 UC). Increasing genetic burden was associated with earlier age of diagnosis of CD (Ptrend=0.008). Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile. Increasing genetic burden was also associated with ileal involvement in CD (Ptrend <0.0001). The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers. UC patients with an involved first-degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in UC.CONCLUSIONS:Increasing genetic burden is associated with early age of diagnosis in CD, but not UC. The expanded panel of IBD risk loci explains only a fraction of variance of disease phenotype, suggesting limited clinical utility of genetics in predicting natural history.Am J Gastroenterol advance online publication, 14 January 2014; doi:10.1038/ajg.2013.464.
    The American Journal of Gastroenterology 01/2014; · 7.55 Impact Factor
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    ABSTRACT: Patients with inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC)) are at increased risk of colorectal cancer (CRC). Persistent inflammation is hypothesized to increase risk of CRC in patients with IBD; however the few studies in this area have been restricted to cross-sectional assessments of histologic severity. No prior studies have examined association between C-reactive protein or erythrocyte sedimentation rate (ESR) elevation and risk of CRC in an IBD cohort. From a multi-institutional validated IBD cohort, we identified all patients with at least one measured CRP or ESR value. Patients were stratified into quartiles of severity of inflammation based on their median CRP or ESR, and subsequent diagnosis of CRC was ascertained. Logistic regression adjusting for potential confounders was used to identify the independent association between CRP or ESR elevation and risk of CRC. Our study included 3,145 patients with at least 1 CRP (CRP cohort) and 4,008 with at least 1 ESR (ESR cohort). Thirty-three patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer during a median follow-up of 5 years, at a median age of 55 years. On multivariate analysis, there was a significant increase in risk of CRC across quartiles of CRP elevation (Ptrend 0.017, Odds ratio for Q4 vs. Q1: 2.72, 95% CI 0.95 - 7.76). Similarly higher median ESR was also independently associated with risk of CRC across the quartiles (OR 2.06, 95% CI 1.14 - 3.74) (Ptrend=0.007). An elevated CRP or ESR is associated with increased risk of CRC in patients with IBD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; · 5.64 Impact Factor
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    ABSTRACT: Background & Aims Patients with inflammatory bowel diseases (IBD) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE following IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. Methods In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn’s disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE following discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22–0.97). Increased numbers of co-morbidities (HR, 1.30; 95% CI, 1.16–1.47) and need for corticosteroids before hospitalization (HR 1.71, 95% CI 1.02 –2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. Conclusions Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; · 5.64 Impact Factor
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    ABSTRACT: Introduction Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) frequently co-occur. PSC is associated with increased risk for colorectal cancer (CRC). However, whether PSC is associated with increased risk of extraintestinal cancers or affects mortality in an IBD cohort has not been examined previously. Methods In a multi-institutional IBD cohort of IBD, we established a diagnosis of PSC using a novel algorithm incorporating narrative and codified data with high positive and negative predictive value. Our primary outcome was occurrence of extraintestinal and digestive tract cancers. Mortality was determined through monthly linkage to the social security master death index. Results In our cohort of 5506 patients with CD and 5522 patients with UC, a diagnosis of PSC was established in 224 patients (2%). Patients with IBD–PSC were younger and more likely to be male compared to IBD patients without PSC; three-quarters had UC. IBD–PSC patients had significantly increased overall risk of cancers compared to patients without PSC (OR 4.36, 95% CI 2.99–6.37). Analysis of specific cancer types revealed that a statistically significant excess risk for digestive tract cancer (OR 10.40, 95% CI 6.86–15.76), pancreatic cancer (OR 11.22, 95% CI 4.11–30.62), colorectal cancer (OR 5.00, 95% CI 2.80–8.95), and cholangiocarcinoma (OR 55.31, 95% CI 22.20–137.80) but not for other solid organ or hematologic malignancies. Conclusions PSC is associated with increased risk of colorectal and pancreatobiliary cancer but not with excess risk of other solid organ cancers.
    Journal of Crohn s and Colitis 01/2014; · 3.39 Impact Factor
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    ABSTRACT: Background & Aims Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn’s disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. Methods We conducted a prospective study of women who were enrolled in the Nurses’ Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with > 90% follow up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results Among 151,871 women, we confirmed 191 cases of CD (incidence 8/100,000 person-years [p-y]) and 230 cases of UC (incidence 10/100,000 p-y) over 2,292,849 p-y. Compared to women with reported usual sleep durations of 7–8 hrs/day (incidence 8/100,000 p-y), women with reported sleep duration < 6 hrs/day (11/100,000 p-y) or > 9 hrs/day (20/100,000 p-y) had a higher incidence of UC (P<.05).The multivariate HRs for UC were 1.51 (95% CI, 1.10–2.09) for sleep durations < 6 hrs/day and 2.05 (95% CI, 1.44–2.92) for sleep durations > 9 hrs/day, compared to sleep durations of 7–8 hrs/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. Conclusions Based on data from the NHS I and II, less than 6 hrs sleep/day and more than 9 hrs sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.
    Clinical Gastroenterology and Hepatology. 01/2014;
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    ABSTRACT: : This review describes the history of U.S. government funding for surveillance programs in inflammatory bowel diseases (IBD), provides current estimates of the incidence and prevalence of IBD in the United States, and enumerates a number of challenges faced by current and future IBD surveillance programs. A rationale for expanding the focus of IBD surveillance beyond counts of incidence and prevalence, to provide a greater understanding of the burden of IBD, disease etiology, and pathogenesis, is provided. Lessons learned from other countries are summarized, in addition to potential resources that may be used to optimize a new form of IBD surveillance in the United States. A consensus recommendation on the goals and available resources for a new model for disease surveillance are provided. This new model should focus on "surveillance of the burden of disease," including (1) natural history of disease and (2) outcomes and complications of the disease and/or treatments.
    Inflammatory Bowel Diseases 11/2013; · 5.12 Impact Factor
  • Gauree Gupta Konijeti, Mark G Shrime, Ashwin N Ananthakrishnan, Andrew T Chan
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    ABSTRACT: Recent studies report that the risk of colorectal cancer (CRC) among patients with ulcerative colitis (UC) may be lower than previously estimated. Although white-light endoscopy (WLE) with random biopsies is recommended for dysplasia detection in patients with UC, several studies reported increased detection of dysplasia by chromoendoscopy. To analyze the cost effectiveness of chromoendoscopy relative to WLE or no endoscopy for CRC surveillance in patients with UC. Decision-analytic state-transition (Markov) model with Monte Carlo simulation. To simulate the clinical course of chronic UC, we estimated dysplasia and CRC incidence and progression, endoscopic test characteristics, stage-specific mortality rates, and costs from published literature and Medicare reimbursement data. Patients from a population-based age distribution with ulcerative colitis for ≥8 years. We compared 3 different strategies at various surveillance intervals: chromoendoscopy with targeted biopsies, WLE with random biopsies, and no surveillance. The robustness of the model was assessed by using probabilistic sensitivity analysis. One-way sensitivity analyses were performed to evaluate individual variables, and 3-dimensional analysis was used to examine the effects of varying screening intervals. Incremental cost-effectiveness ratio (ICER). Chromoendoscopy was found to be more effective and less costly than WLE at all surveillance intervals. However, compared with no surveillance, chromoendoscopy was cost effective only at surveillance intervals of at least 7 years, with an ICER of $77,176. Chromoendoscopy was the most cost effective strategy at sensitivity levels >0.23 for dysplasia detection and cost <$2200, regardless of the level of sensitivity of WLE for dysplasia detection. The estimated population lifetime risk of developing CRC ranged from 2.5% (annual chromoendoscopy) to 5.9% (chromoendoscopy every 10 years). Estimates used for the model are based on best available data in the literature. Chromoendoscopy is both more effective and less costly than WLE and becomes cost effective relative to no surveillance when performed at intervals of ≥7 years.
    Gastrointestinal endoscopy 11/2013; · 6.71 Impact Factor
  • V P Mouli, A N Ananthakrishnan
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    ABSTRACT: Vitamin D is traditionally associated with bone metabolism. The immunological effects of vitamin D have increasingly come into focus. To review the evidence supporting a role of vitamin D in inflammatory bowel diseases. A comprehensive search was performed on PubMed using the terms 'crohn's disease' 'ulcerative colitis' and 'vitamin D'. Vitamin D deficiency is common in patients with inflammatory bowel diseases (IBD) (16-95%) including those with recently diagnosed disease. Evidence supports immunological role of vitamin D in IBD. In animal models, deficiency of vitamin D increases susceptibility to dextran sodium sulphate colitis, while 1,25(OH)2 D3 ameliorates such colitis. One prospective cohort study found low predicted vitamin D levels to be associated with an increased risk of Crohn's disease (CD). Limited data also suggest an association between low vitamin D levels and increased disease activity, particularly in CD. In a large cohort, vitamin D deficiency (<20 ng/mL) was associated with increased risk of surgery (OR 1.8, 95% CI 1.2-2.5) in CD and hospitalisations in both CD (OR 2.1, 95% CI 1.6-2.7) and UC (OR 2.3, 95% CI 1.7-3.1). A single randomised controlled trial demonstrated that vitamin D supplementation may be associated with reduced frequency of relapses in patients with CD compared with placebo (13% vs. 29%, P = 0.06). There is growing epidemiological evidence to suggest a role for vitamin D deficiency in the development of IBD and also its influence on disease severity. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.
    Alimentary Pharmacology & Therapeutics 11/2013; · 4.55 Impact Factor
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    ABSTRACT: Vitamin D deficiency is common among patients with inflammatory bowel diseases (IBD) (Crohn's disease or ulcerative colitis). The effects of low plasma 25-hydroxy vitamin D (25[OH]D) on outcomes other than bone health are understudied in patients with IBD. We examined the association between plasma level of 25(OH)D and risk of cancers in patients with IBD. From a multi-institutional cohort of patients with IBD, we identified those with at least 1 measurement of plasma 25(OH)D. The primary outcome was development of any cancer. We examined the association between plasma 25(OH)D and risk of specific subtypes of cancer, adjusting for potential confounders in a multivariate regression model. We analyzed data from 2809 patients with IBD and a median plasma level of 25(OH)D of 26 ng/mL. Nearly one-third had deficient levels of vitamin D (<20 ng/mL). During a median follow-up period of 11 y, 196 patients (7%) developed cancer, excluding non-melanoma skin cancer (41 cases of colorectal cancer). Patients with vitamin D deficiency had an increased risk of cancer (adjusted odds ratio=1.82; 95% CI, 1.25-2.65) compared to those with sufficient levels. Each 1 ng/mL increase in plasma 25(OH)D was associated with an 8% reduction in risk of colorectal cancer (odds ratio=0.92; 95% CI, 0.88-0.96). A weaker inverse association was also identified for lung cancer. In a study of from 2809 patients with IBD, low plasma level of 25(OH)D was associated with an increased risk of cancer-especially colorectal cancer.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2013; · 5.64 Impact Factor
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    ABSTRACT: Introduction: Emerging evidence supports an immunologic role for 25-hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti-tumor necrosis factor (TNF)-α therapy in patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: All IBD patients who had plasma 25(OH)D level checked <3 months prior to initiating anti-TNF-α therapy were included in this retrospective single-center cohort study. Our main predictor variable was insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting for potential confounders was used to identify the independent effect of pretreatment vitamin D on biologic treatment cessation. Results: Our study included 101 IBD patients (74 CD; median disease duration 9 years). The median index 25(OH)D level was 27 ng/mL (interquartile range, 20-33 ng/mL). One-third of the patients had prior exposure to anti-TNF-α therapy. On multivariate analysis, patients with insufficient vitamin D demonstrated earlier cessation of anti-TNF-α therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.39; P = .04). This effect was significant in patients who stopped treatment for loss of response (HR, 3.49; 95% CI, 1.34-9.09) and stronger for CD (HR, 2.38; 95% CI, 0.95-5.99) than UC (P = NS). Conclusions: Our findings suggest that vitamin D levels may influence durability of anti-TNF-α induction and maintenance therapy. Larger cohort studies and clinical trials of supplemental vitamin D use with disease activity as an end point may be warranted.
    Journal of Parenteral and Enteral Nutrition 10/2013; · 2.49 Impact Factor
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    ABSTRACT: Introduction of biologic agents in inflammatory bowel disease (IBD) has increased the likelihood of disease remission. Despite resolution of active inflammation, a subset of IBD patients report persistent defecatory symptoms. To evaluate a group of patients with inflammatory bowel disease with suspected functional defecatory disorders, by use of anorectal manometric testing and subsequent biofeedback therapy. A group of IBD patients with persistent defecatory problems despite clinical improvement were included in this study. These patients had no evidence of left-sided disease. Endoscopic and radiographic study findings and timing in relation to the manometry study were recorded. Anorectal manometry was performed by the standard protocol and included rectal sensory assessment, ability to expel a balloon, and pressure dynamics with simulated defecation. Thirty IBD patients (Crohn's 23 patients; ulcerative colitis six patients) presented with defecatory disorders including constipation (67 %) increased stooling (10 %), and rectal urgency and/or incontinence and rectal pain (6 %). All but one patient had anorectal manometric criteria of dyssynergia (presence of anismus motor pattern and inability to expel the balloon). Of the patients who completed biofeedback therapy, 30 % had a clinically significant (≥7-point) improvement in SIBDQ score, with a reduction in health-care utilization after a six-month period (p = 0.02). Despite remission, some inflammatory bowel disease patients have persistent defecatory symptoms. Defecatory symptoms may not be predictive of an underlying inflammatory disorder. Lack of inflammatory activity and absence of left-sided disease should prompt investigation of functional disorders. Anorectal manometric testing and biofeedback therapy for patients with a diagnosis of dyssynergia may be a useful therapy.
    Digestive Diseases and Sciences 09/2013; · 2.26 Impact Factor
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    ABSTRACT: & Aims: Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn's disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses' Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39-0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58-1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Based on data from the Nurses' Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.
    Gastroenterology 08/2013; · 12.82 Impact Factor

Publication Stats

2k Citations
1,250.45 Total Impact Points

Institutions

  • 2012–2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, Massachusetts, United States
  • 2010–2014
    • Massachusetts General Hospital
      • Division of Gastroenterology
      Boston, Massachusetts, United States
  • 2013
    • All India Institute of Medical Sciences
      New Dilli, NCT, India
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 2006–2012
    • Medical College of Wisconsin
      • • Department of Medicine
      • • Gastroenterology & Hepatology
      Milwaukee, WI, United States
  • 2011
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2008
    • University of Wisconsin - Milwaukee
      Milwaukee, Wisconsin, United States