Ashwin N Ananthakrishnan

Harvard Medical School, Boston, Massachusetts, United States

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Publications (173)1394.45 Total impact

  • Ashwin N Ananthakrishnan
    The Lancet 12/2014; · 39.21 Impact Factor
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    ABSTRACT: Background Early life exposures may modify risk of inflammatory bowel diseases (IBD; Crohn¿s disease (CD), ulcerative colitis (UC)). However, the relationship between early life exposures and natural history of IBD has not been previously examined.Methods This single center study included patients with CD or UC recruited in a prospective IBD registry. Enrolled patients completed a detailed environmental questionnaire that assessed various early life environmental exposures. Our primary outcome was requirement for disease-related surgery in CD and UC. Logistic regression models defined independent effect of early life exposures, adjusting for potential confounders.ResultsOur study included 333 CD and 270 UC patients. Just over half were female with a median age at diagnosis of 25 years. One-third of the cohort had history of bowel surgery (31%) and nearly half had used at least one biologic agent (47%). Among those with CD, being breastfed was associated with reduced risk of CD-related surgery (34% vs. 55%), while childhood cigarette smoke exposure was associated with increased risk. On multivariate analysis, history of being breastfed (odds ratio (OR) 0.21, 95% confidence interval [CI] 0.09¿0.46) and cigarette smoke exposure as a child (OR 2.17, 95% CI 1.10¿4.29) remained independently associated with surgery. None of the early life variables influenced disease phenotype or outcome in UC.ConclusionA history of being breastfed was associated with a decreased risk while childhood cigarette smoke exposure was associated with an increased risk of surgery in patients with CD. Further investigation to examine biological mechanisms is warranted.
    BMC Gastroenterology 12/2014; 14(1):216. · 2.11 Impact Factor
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    Tanya Sahay, Ashwin N Ananthakrishnan
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    ABSTRACT: Background Clostridium difficile infection (CDI) is increasingly recognized as an important community acquired pathogen causing disease (CA-CDI). Vitamin D [25(OH)D] has immune modulatory effects and plays an important role in intestinal immunity. The role of vitamin D in CA-CDI has not been examined previously.Methods This was a single referral center case¿control study. Cases comprised of all patients with CA-CDI who had a serum 25(OH)D measured within 12 months prior to infection. Controls were drawn from patients who had 25(OH)D checked and matched based on age, gender, race and health status. Serum 25(OH)D was stratified as¿<¿15 ng/mL, 15-30 ng/mL or¿>¿30 ng/mL. Regression models adjusting for potential confounders were used to define independent association between vitamin D and CA-CDI.ResultsWe identified 58 matched case¿control pairs (66% women; 85% Caucasian). The mean age was 62 years. The mean serum 25(OH)D level was significantly lower in CA-CDI cases compared to controls (28.5 ng/mL vs. 33.8 ng/mL, p¿=¿0.046). Cases had higher rate of antibiotic exposure and more comorbidity. Serum 25(OH)D¿<¿15 ng/mL was associated with an increased risk of CA-CDI on univariate (Odds ratio (OR) 5.10, 95% confidence interval (CI) 1.51 ¿ 17.24) and multivariate analysis (OR 3.84, 95% CI 1.10 ¿ 13.42). Vitamin D levels between 15-30 ng/mL did not modify disease risk.Conclusions Low serum 25(OH)D¿<¿15 ng/mL was associated with increased risk of CA-CDI. This suggests vitamin D may have a role in determining susceptibility to CA-CDI.
    BMC Infectious Diseases 12/2014; 14(1):661. · 2.56 Impact Factor
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    ABSTRACT: The success of many population studies is determined by proper matching of cases to controls. Some of the confounding and bias that afflict Electronic Health Record (EHR)-based observational studies may be reduced by creating effective methods for finding adequate controls. We implemented a method to match case and control populations to compensate for sparse and unequal data collection practices common in EHR data. We did this by matching the healthcare utilization of patients after observing that more complete data was collected on high healthcare utilization patients vs. low healthcare utilization patients. In our results, we show that many of the anomalous differences in population comparisons are mitigated using this matching method compared to other traditional age and gender-based matching. As an example, the comparison of the disease associations of Ulcerative Colitis and Crohn's Disease show differences that are not present when the controls are chosen in a random or even a matched age/gender/race algorithm. In conclusion, the use of healthcare utilization-based matching algorithms to find adequate controls greatly enhanced the accuracy of results in EHR studies. Full source code and documentation of the control matching methods is available at https://community.i2b2.org/wiki/display/conmat/.
    Journal of Biomedical Informatics 12/2014; · 2.48 Impact Factor
  • Ashwin N Ananthakrishnan, Stephen B Hanauer
    Gastroenterology 11/2014; · 13.93 Impact Factor
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    ABSTRACT: We performed a prospective study of patients with inflammatory bowel diseases to examine variations in treatment among medical centers. In a prospective cohort study of 1659 patients with CD and 946 patients with UC seen at 7 high-volume referral centers, we collected data on demographics, disease characteristic, and medical and surgical treatments. We used logistic regression to determine differences in treatment among centers, controlling for potential confounders. We found significant variations among centers in treatment of CD with immunomodulators (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.09 - 5.32) but not anti-tumor necrosis factor agents (OR, 1.64; 95% CI, 0.97 - 2.77). There was less variation in treatment of UC; we found no difference in use of immunomodulators (OR,1.83 95% CI, 1.00 - 3.36) or anti-TNF therapy (OR, 0.81; 95% CI, 0.40 - 1.65). Development and implementation of evidence-based standards of care for IBD may help reduce variation and improve outcomes. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical Gastroenterology and Hepatology 11/2014; · 6.53 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 11/2014; · 5.64 Impact Factor
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    ABSTRACT: Background: Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods: We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 - 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 - 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 - 1.61) (p- interaction=0.9). Conclusions: We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC.
    10/2014;
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    ABSTRACT: Temporary fecal diversion has been used to allow severe perianal Crohn's disease (CD) to heal. Most data on intestinal reconnection rates precede the biological era with limited patient follow-up after reconnection. We, therefore, sought to evaluate the natural history of perianal CD after fecal diversion.
    Inflammatory Bowel Diseases 09/2014; · 5.12 Impact Factor
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    ABSTRACT: Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis] often affect women in their reproductive years. Few studies have analyzed the impact of mode of childbirth on long-term IBD outcomes.
    Digestive Diseases and Sciences 09/2014; · 2.26 Impact Factor
  • Ashwin N Ananthakrishnan
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    ABSTRACT: Inflammatory bowel diseases comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases. The key mechanism underlying the pathogenesis of these diseases is a dysregulated immune response to commensal flora in a genetically susceptible host. Thus intestinal microbial dysbiosis, host genetics, and the external environment all play an important role in the development of incident disease and in determining subsequent disease behavior and outcomes. There are several well-defined or putative environmental risk factors including cigarette smoking, appendectomy, diet, stress and depression, vitamin D as well as hormonal influence. The effect of some of the risk factors appears to differ between CD and UC suggesting that despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist. There is a growing body of literature identifying risk factors for incident disease. There is less rigorous literature defining triggers of relapse, and few controlled clinical trials examining if modification of such risk factors results in an improvement in patient outcomes. This is an area of considerable patient, physician, and scientific interest, and there is an important unmet need for rigorous studies of the external environment in disease pathogenesis and subsequent course.
    Digestive Diseases and Sciences 09/2014; · 2.26 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 09/2014; · 3.56 Impact Factor
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    ABSTRACT: To reduce costs and improve clinical relevance of genetic studies, there has been increasing interest in performing such studies in hospital-based cohorts by linking phenotypes extracted from electronic medical records (EMRs) to genotypes assessed in routinely collected medical samples. A fundamental difficulty in implementing such studies is extracting accurate information about disease outcomes and important clinical covariates from large numbers of EMRs. Recently, numerous algorithms have been developed to infer phenotypes by combining information from multiple structured and unstructured variables extracted from EMRs. Although these algorithms are quite accurate, they typically do not provide perfect classification due to the difficulty in inferring meaning from the text. Some algorithms can produce for each patient a probability that the patient is a disease case. This probability can be thresholded to define case-control status, and this estimated case-control status has been used to replicate known genetic associations in EMR-based studies. However, using the estimated disease status in place of true disease status results in outcome misclassification, which can diminish test power and bias odds ratio estimates. We propose to instead directly model the algorithm-derived probability of being a case. We demonstrate how our approach improves test power and effect estimation in simulation studies, and we describe its performance in a study of rheumatoid arthritis. Our work provides an easily implemented solution to a major practical challenge that arises in the use of EMR data, which can facilitate the use of EMR infrastructure for more powerful, cost-effective, and diverse genetic studies.
    Human Genetics 07/2014; · 4.52 Impact Factor
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    ABSTRACT: Background & Aims Crohn’s disease and ulcerative colitis are associated with increased risk of colorectal cancer (CRC). Surveillance colonoscopy is recommended at 2−3 year intervals beginning 8 years after diagnosis of inflammatory bowel disease (IBD). However, there have been no reports of whether colonoscopy examination reduces the risk for CRC in patients with IBD. Methods In a retrospective study, we analyzed data from 6823 patients with IBD (2764 with a recent colonoscopy, 4059 without a recent colonoscopy) seen and followed for at least 3 years at 2 tertiary referral hospitals in Boston. The primary outcome was diagnosis of CRC. We examined the proportion of patients undergoing a colonoscopy within 36 months before a diagnosis of CRC or at the end of the follow-up period, excluding colonoscopies performed within 6 months before a diagnosis of CRC, to avoid inclusion of prevalent cancers. Multivariate logistic regression was performed, adjusting for plausible confounders. Results One hundred fifty-four patients developed CRC. The incidence of CRC among patients without a recent colonoscopy (2.7%) was significantly higher than among patients with a recent colonoscopy (1.6%) (odds ratio [OR], 0.56; 95% confidence interval, 0.39−0.80). This difference persisted in multivariate analysis (OR, 0.65; 95% CI, 0.45−0.93) and was robust when adjusted for a range of assumptions in sensitivity analyses. Among patients with CRC, a colonoscopy within 6−36 months before diagnosis was associated with reduced mortality (OR, 0.34; 95% CI 0.12−0.95). Conclusions Recent colonoscopy (within 36 months) is associated with a reduced incidence of CRC in patients with IBD, and lower mortality in those diagnosed with CRC
    Clinical Gastroenterology and Hepatology 07/2014; · 6.53 Impact Factor
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    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; · 5.48 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; · 5.48 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-177. · 13.93 Impact Factor
  • Ashwin N Ananthakrishnan
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 04/2014; · 5.64 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; · 9.42 Impact Factor

Publication Stats

2k Citations
1,394.45 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
      • • Institute for Technology Assessment
      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
      • • Division of Gastroenterology & Hepatology
      Milwaukee, WI, United States
  • 2011
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2008
    • University of Wisconsin - Milwaukee
      Milwaukee, Wisconsin, United States