Athos Bousvaros

University of Massachusetts Boston, Boston, Massachusetts, United States

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Publications (167)866.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn's disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD. 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and 'doubly robust' weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups. 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test). In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 11/2014; · 10.73 Impact Factor
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    ABSTRACT: Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression.
    Journal of the American Academy of Child and Adolescent Psychiatry 07/2014; 53(7):726-35. · 6.97 Impact Factor
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    ABSTRACT: Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD and (2) determine predictors of abdominal pain in Crohn's disease (CD) and ulcerative colitis (UC).
    Inflammatory Bowel Diseases 06/2014; · 5.12 Impact Factor
  • Athos Bousvaros
    Gastroenterology 06/2014; · 12.82 Impact Factor
  • Ying Lu, Athos Bousvaros
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    ABSTRACT: The vast majority of patients with inflammatory bowel disease (IBD) will receive immunosuppressive therapy at some point for their disease, whether for the short term (such as a course of corticosteroids) or long term (such as maintenance therapy with immunomodulators or biologics). The systemic immunosuppression places patients at increased risk for infections. Therefore, it is important that patients are up-to-date with immunizations to minimize vaccine-preventable infections. However, the literature shows that the rate of immunization in patients with IBD is low. Ideally, the vaccination status is checked at diagnosis, and patients are immunized with the vaccines they need. Drawing titers is helpful in cases in which vaccination history is unclear or to confirm that titers are at an adequate level in cases in which patients have been vaccinated. Current guidelines recommend that patients with IBD follow the same routine immunization schedule as healthy children, but patients should not be administered live vaccines if they are receiving immunosuppressive therapy. Therefore, it is ideal to administer any necessary vaccinations as early as possible, prior to starting immunosuppressive therapy. Patients may receive inactivated vaccines regardless of immunosuppressive status. The IBD literature suggests that inactivated vaccines are safe and do not worsen disease activity. In general, patients with IBD mount an immune response to vaccines, but the response may be lower if patients are receiving immunosuppressive therapy, especially tumor necrosis factor inhibitors.
    Gastroenterology & hepatology. 06/2014; 10(6):355-63.
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    ABSTRACT: Despite advances in medical therapies, many children with Crohn's disease (CD) will require bowel resection. Although previous registry studies have attempted to identify risk factors for surgery, the effect of immunomodulators and biologics (IMB) on surgical indications has not been well characterized. We reviewed a series of 125 children with CD who underwent bowel resection with reanastomosis between 1977 and 2011 and were followed up for at least 6 months. We compared patients who underwent surgery for perforating disease (abscess or internal fistula) and patients who were operated on for medically refractory or fibrostenosing disease. Between these 2 groups, we examined medications received before surgery. Other demographic and disease-specific covariates were examined. Of the 82 patients who received IMB before surgery, only 19 patients (23%) required surgery for a perforating complication of CD, whereas 63 patients (77%) required surgery for strictures or medically refractory disease. In contrast, of the 43 patients who did not receive IMB preoperatively, 20 patients (45%) developed a perforating complication and 23 patients (53%) required surgery for strictures or refractory disease. These differences across groups were significant, with a lower rate of operation for perforating disease among patients receiving preoperative IMB therapy (P = 0.007). In our surgical cohort, children with CD who were treated with IMB were less likely to have surgery for perforating disease. This finding raises the possibility that the administration of IMB in children who require surgery may be associated with a difference in disease behavior.
    Inflammatory Bowel Diseases 04/2014; · 5.12 Impact Factor
  • Brian P Regan, Athos Bousvaros
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    ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology that frequently presents in the pediatric population. The evaluation of pediatric UC involves excluding infection, and a colonoscopy that documents the clinical and histologic features of chronic colitis. Initial management of mild UC is typically with mesalamine therapy for induction and maintenance. Moderate UC is often initially treated with oral prednisone. Depending on disease severity and response to prednisone, maintenance options include mesalamine, mercaptopurine, azathioprine, infliximab, or adalimumab. Severe UC is typically treated with intravenous corticosteroids. Corticosteroid nonresponders should either undergo a colectomy or be treated with second-line medical rescue therapy (infliximab or calcineurin inhibitors). The severe UC patients who respond to medical rescue therapy can be maintained on infliximab or thiopurine, but 1-year remission rates for such patients are under 50 %. These medications are discussed in detail along with the initial work-up and a treatment algorithm.
    Paediatric Drugs 04/2014; · 1.72 Impact Factor
  • Journal of pediatric gastroenterology and nutrition 02/2014; · 2.18 Impact Factor
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    ABSTRACT: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.
    Clinical Infectious Diseases 02/2014; 58(3):309-18. · 9.37 Impact Factor
  • The Journal of pediatrics 01/2014; 164(1):4-5.e1. · 4.02 Impact Factor
  • Journal of pediatric gastroenterology and nutrition 01/2014; 58(1):130-8. · 2.18 Impact Factor
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    ABSTRACT: The association between Inflammatory bowel disease (IBD) and depression provides a unique opportunity to understand the relationship between systemic inflammation and depressive symptom profiles. Youth (n = 226) ages 9-17 years with co-morbid IBD and depression underwent psychiatric assessment and evaluation of IBD activity. Latent profile analysis (LPA) identified depressive subgroups based on similar responses to the Children's Depression Rating Scale-Revised (CDRS-R). Demographic factors, depression severity, anxiety, IBD activity, inflammatory markers, IBD-related medications, and illness perception were evaluated as predictors of profile membership. Mean age was 14.3 years; 75% had Crohn's disease; 31% were on systemic corticosteroids. Mean depressive severity was moderate whereas IBD activity, which reflects inflammation, was mild. LPA identified three subgroups: Profile-1 mild (75%) had diverse low-grade depressive symptoms and highest quality of life; Profile-2 somatic (19%) had severe fatigue, appetite change, anhedonia, decreased motor activity, and depressed mood with concurrent high dose steroid therapy and the highest IBD activity; and Profile-3 cognitive (6%) had the highest rates of self-reported depressive symptoms, ostomy placements, and anxiety with IBD symptoms in the relative absence of inflammation. Evidence was found for three depression profiles in youth with IBD and depression. Our analyses determined that patients with predominantly somatic or cognitive symptoms of depression comprised 25% of our cohort. These findings may be used to design subgroup-specific interventions for depression in adolescents with IBD and potentially other physical illnesses associated with systemic inflammation.
    Journal of pediatric gastroenterology and nutrition 12/2013; · 2.18 Impact Factor
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    ABSTRACT: Determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn's disease (CD). Five hundred and fifty (n = 550) youth aged 9-17 with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized-controlled trial. 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children's Depression Inventory (CDI). A child or parent CDI ≥ 12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn's Disease Activity Index (PCDAI) were collected as potential predictors of depression. Univariate regression models were constructed to determine relationships between predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relationship between infliximab use and depression while controlling for other predictors of depression. Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (p < 0.01) and negatively associated with socioeconomic status (p < 0.001). In multivariate models, PCDAI and socioeconomic status (SES), were the strongest predictors of depression. Disease activity and socioeconomic status are significant predictors of depression in youth with Crohn's disease.
    Journal of pediatric gastroenterology and nutrition 12/2013; · 2.18 Impact Factor
  • 60th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2013
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    ABSTRACT: The primary purpose of this study was to investigate the relationship between Pediatric Ulcerative Colitis Activity Index (PUCAI) and operative management. We also specifically evaluated those patients receiving tacrolimus for their disease. A retrospective review (1/06-1/11) identified ulcerative colitis patients (≤21 years old) undergoing restorative proctocolectomy with rectal mucosectomy and ileal pouch-anal anastomosis. Main outcomes included pre-operative PUCAI, combined versus staged procedure, and postoperative complications. Patients receiving tacrolimus within 3 months of surgical intervention were identified. PUCAI at tacrolimus induction and medication side effects were also noted. Sixty patients were identified. Forty-two (70%) underwent combined and 18 (30%) had staged procedures. Pre-operative PUCAI was lower for combined versus staged patients (p=<0.001). Furthermore, a higher pre-operative PUCAI strongly correlated with the likelihood of undergoing a staged procedure (p<0.001). Forty-four patients (73%) received tacrolimus. Significant improvement in their PUCAI was noted from induction to pre-operative evaluation (p<0.001). Minor and reversible side effects occurred in 46% of patients receiving tacrolimus, but complication rates were not significantly different. There is a very strong correlation between the PUCAI and the likelihood of undergoing a staged procedure. A significant improvement in PUCAI occurs following preoperative tacrolimus therapy.
    Journal of Pediatric Surgery 07/2013; 48(7):1540-5. · 1.38 Impact Factor
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    ABSTRACT: OBJECTIVES:: Pediatric inpatients with IBD are rarely considered for thromboprophylaxis due to concerns about safety and under-appreciation of thrombotic risk. We characterized thromboembolism (TE) in children and young adults with inflammatory bowel disease (IBD) at a single tertiary care hospital. METHODS:: We performed a retrospective review of inpatient billing database for all IBD admissions with colonic involvement and an anticoagulation database for thrombotic complications from 2006 to 2011. RESULTS:: Of 532 patients admitted with IBD with colonic involvement, ten (1.9%) had TE (nine venous, one arterial), two of whom had recurrent thrombosis. Many of the events resulted in considerable morbidity, including four cerebrovascular events and two pulmonary emboli. Established risk factors in IBD colitis inpatients with TE included: indwelling catheter (4/10), first-degree family member with TE (2/10), hereditary thrombophilia (3/10), smoking (1/10), oral contraceptive (1/5 females) and thalidomide (1/10). Additionally most (8/10) patients had acquired thrombophilia, mostly elevation of factor VIII and anticardiolipin antibodies. Patients with IBD and TE received therapeutic anticoagulation without significantly increased bleeding. Thrombus resolution was documented in seven cases, persistence in two cases and recurrence in two cases. CONCLUSIONS:: Pediatric inpatients hospitalized with IBD with colonic involvement have increased risk of TE, including complications of pulmonary embolism, recurrence, persistence, and indefinite long term anticoagulation. Therapeutic anticoagulation in IBD patients with active colitis appears safe. We identified both inherited thrombophilias and acquired risk factors in patients with IBD and TE. We currently use risk stratification and recommend prophylactic anticoagulation in high-risk patients.
    Journal of pediatric gastroenterology and nutrition 06/2013; · 2.18 Impact Factor
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    ABSTRACT: OBJECTIVE:: Clinicians often evaluate for Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) presenting with exacerbations. A highly sensitive polymerase chain reaction (PCR) test for the toxin B gene of C. difficile is increasingly used to diagnose CDI. The aim of this study was to determine the prevalence of positive C. difficile PCR results in children and young adults with and without active IBD compared with patients with non-IBD gastrointestinal disease. METHODS:: Fecal samples were obtained from patients with ulcerative colitis (UC, n = 76) or Crohn's disease (CD, n = 69) and 51 controls followed in our Gastroenterology program. Samples were analyzed for C. difficile using a PCR test for the C. difficile toxin B gene (BD GeneOhm™ Cdiff Real-Time PCR assay). Proportions of positive tests in each group were compared using the Pearson's χ square test. RESULTS:: The prevalence of positive PCR results was 11.6% in patients with CD, 18.4% in patients with UC, and 11.8% in controls (p = 0.25). There were no significant differences in the prevalence of positive C. difficile results among IBD patients with and without active disease or among patients with and without diarrhea. CONCLUSIONS:: Positive C. difficile PCR results occur with similar frequency in IBD patients with and without active disease and in patients with other gastrointestinal diseases. A positive result in a highly sensitive PCR assay that detects low copy numbers of a toxin gene in C. difficile may reflect colonization in a subset of IBD patients, confounding clinical decision-making in managing disease exacerbations.
    Journal of pediatric gastroenterology and nutrition 05/2013; · 2.18 Impact Factor
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    ABSTRACT: OBJECTIVES:: Recent reports demonstrate a link between Inflammatory Bowel Disease (IBD) and sleep disturbance. Increased psychiatric dysfunction is consistently reported in patients with IBD. Our objective is to examine relationships among sleep disturbance, inflammation, and psychiatric dysfunction in a pediatric population with Crohn's disease (CD) and depression. METHODS:: Pediatric CD patients with depression (n = 96) and healthy controls (n = 19) completed measures of sleep (Pittsburgh Sleep Quality Index [PSQI]), depression, anxiety, and abdominal pain, and provided blood for inflammatory markers. CD activity was determined by Pediatric Crohn's Disease Activity Index (PCDAI). Factor analysis was performed on subscales of the PSQI in order to derive measures of sleep disturbance. Univariate and multivariate regression analyses assessed relationships between sleep disturbance, psychosocial, and biological measures of CD and psychiatric dysfunction. RESULTS:: Sleep disturbance in depressed youth with CD was significantly greater than healthy controls, and was significantly related to measures of abdominal pain, depression, and anxiety, but not biomarkers of inflammation. Factor analysis of the PSQI demonstrated a two-factor solution. The first factor, termed 'Qualitative,' included Subjective Sleep Quality, Daytime Dysfunction, Sleep Disturbance, and Sleep Latency, whereas the second, 'Quantitative,' factor consisted of Habitual Sleep Efficiency and Sleep Duration. This factor showed a significant relationship with inflammatory markers. Multivariate modeling suggested Qualitative sleep disturbance was predicted by disease activity, pain, and anxiety whereas Quantitative sleep disturbance was predicted by disease activity. CONCLUSIONS:: These results indicate that sleep disturbance in depressed CD sufferers differs depending upon illness activity. Patients may require different interventions depending upon the sleep disturbance exhibited.
    Journal of pediatric gastroenterology and nutrition 04/2013; · 2.18 Impact Factor
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    ABSTRACT: BACKGROUND:: Female patients receiving immunosuppressive therapy may be at increased risk for human papillomavirus (HPV) infection and cervical neoplasia. METHODS:: We administered the 3-dose HPV vaccine Gardasil to 37 females aged 9 to 26 years with inflammatory bowel disease (IBD) prescribed immunosuppressive therapy (prospective cohort). Geometric mean titers (GMT) in milli-Merck (mMu/mL) units were determined before dose 1 and 1 month after dose 3 by competitive Luminex immunoassay (cLIA) and qualitatively compared with healthy females of similar age from Merck's database. Side effects and adverse events were evaluated. Concurrently, in 15 similar patients with inflammatory bowel disease previously vaccinated by their primary care provider, we assessed antibody titers by competitive Luminex immunoassay and total immunoglobulin G LIA after dose 3 of vaccine (range, 0.5-27 months). RESULTS:: Mean age of prospective patients was 15 years with 51% on anti-tumor necrosis factor therapy and 49% on immunomodulators: 33 of 37 completed all 3 doses. Seropositivity after dose 3 was 100% for types 6, 11 and 16 and 96% for type 18. Geometric mean titers for HPV-6, HPV-11, HPV-16 and HPV-18 was 1080, 1682, 3975 and 858, respectively and did not qualitatively differ from healthy females. No serious adverse events were attributable to the vaccine. In the previously vaccinated cohort, seropositivity was 100% for types 6, 11, and 16, and 40% for type 18 by competitive Luminex immunoassay (93% for HPV-18 by immunoglobulin G LIA). Titers decreased with time since dose 3. CONCLUSIONS:: In this small study of patients with inflammatory bowel disease prescribed immunosuppressive therapy, Gardasil was immunogenic and there were no clinically significant vaccine-associated adverse events.
    Inflammatory Bowel Diseases 04/2013; · 5.12 Impact Factor
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Publication Stats

3k Citations
866.58 Total Impact Points

Institutions

  • 2014
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1996–2014
    • Boston Children's Hospital
      • • Center for Inflammatory Bowel Disease
      • • Division of Gastroenterology, Hepatology and Nutrition
      Boston, Massachusetts, United States
  • 2012
    • University of Pittsburgh
      • Division of Pediatric Pathology at Children's Hospital of Pittsburgh of UPMC
      Pittsburgh, PA, United States
  • 2006–2012
    • IWK Health Centre
      Halifax, Nova Scotia, Canada
    • Mayo Foundation for Medical Education and Research
      • Division of Gastroenterology and Hepatology
      Scottsdale, AZ, United States
    • The Children’s Hospital of Eastern Ontario
      Ottawa, Ontario, Canada
  • 2008–2011
    • Connecticut Children's Medical Center
      Hartford, Connecticut, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 1996–2011
    • Harvard Medical School
      • Division of Immunology
      Boston, Massachusetts, United States
  • 2010
    • Nationwide Children's Hospital
      Columbus, Ohio, United States
  • 2009
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
    • Albany Medical College
      Albany, New York, United States
  • 2007
    • Medical College of Wisconsin
      • Department of Pediatrics
      Milwaukee, WI, United States
    • Children's Hospital of Eastern Ontario
      • Department of Pediatrics
      Ottawa, Ontario, Canada
  • 2001–2007
    • Harvard University
      Cambridge, Massachusetts, United States