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1.
Dig Dis Sci ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932198

RESUMO

BACKGROUND: Frailty may be a risk factor for complications in inflammatory bowel diseases (IBD) patients. We examined the impact of treatment on IBD patients who were frail prior to treatment and identified predictors of post-treatment change in frailty. METHODS: In an electronic health record-based cohort of IBD patients initiating anti-tumor necrosis factor (TNF)-α agents, we applied a validated claims-based frailty index to determine frailty in the 1 year prior to and after treatment initiation. We characterized treatment non-response using a composite outcome of IBD-related hospitalization, surgery, change in therapy, or initiation of systemic steroids. We constructed multivariable logistic regression models to identify determinants of post-treatment frailty. RESULTS: The 1210 patients initiating anti-TNF therapy had a median age of 30 years; 20% were ≥ 50 years. In the first year after anti-TNF initiation, 40% were non-responders. Many more treatment non-responders were frail in the year following treatment compared with treatment responders (27% vs 7%, p < 0.001). Pre-treatment frailty (OR 2.01, 95% CI 1.35-3.00) and prior IBD-related hospitalization (OR 1.63, 95% CI 1.15-2.30) were independently predictive of higher likelihood of post-treatment frailty. Therapy response was associated with a lower likelihood (OR 0.24, 95% CI 0.16-0.34) of post-treatment frailty. Nearly 85% of patients who were frail prior to treatment demonstrated improvement in frailty following treatment CONCLUSIONS: Response to anti-TNF therapy is an important determinant of post-treatment frailty in patients with IBD. Our findings suggest that effectively treating inflammatory states in older patients with IBD may improve frailty.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33775898

RESUMO

BACKGROUND & AIMS: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (NHS; 1986-2016), NHSII (1991-2017), and Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semi-quantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over follow-up period. RESULTS: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up. Dietary gluten intake was not associated with risk of IBD. Compared to participants in the lowest quintile of gluten intake, the adjusted hazard-ratios and 95% confidence intervals (CI) for participants in the highest quintile of gluten intake were 1.16 (95% CI: 0.82-1.64; Ptrend = 0.41) for CD and 1.04 (95% CI: 0.75-1.44; Ptrend = 0.64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates. CONCLUSIONS: In three large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.

4.
Gastroenterol Clin North Am ; 50(1): 151-167, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33518162

RESUMO

With the increasing global prevalence of inflammatory bowel diseases, research in this field is expanding to better understand the multifactorial etiologies of this complex disease. Nutrition and diet, as modifiable risk factors, have been shown to play an important role in disease activity and prognosis. This article reviews the role of nutrition in inflammatory bowel disease, including appropriate nutrition screening in this at-risk population, and associated micronutrient deficiencies. We provide recommendations on dosing supplementation. We briefly review diet as a risk factor for inflammatory bowel disease and the currently proposed published dietary intervention studies.

7.
Dig Dis Sci ; 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385264

RESUMO

BACKGROUND: Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age. AIMS: In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients. METHODS: Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality. RESULTS: From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14-1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02-1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission. CONCLUSIONS: Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33280139

RESUMO

BACKGROUND: Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown. AIM: To examine the incidence of IBD in individuals with another IMD. METHODS: We used data from the prospective Nurses' Health Study II cohort (1995-2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders. RESULTS: We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77-3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (Ptrend  < 0.0001). This association was only modestly attenuated by adjustment for environmental risk factors (HR 2.35 and 2.46, respectively). The risk of UC was not increased, with multivariable-adjusted HRs of 1.22 (95% CI 0.85-1.76) and 1.33 (95% CI 0.67-2.65) for those with 1 and ≥ 2 IMDs, respectively, compared to those with none (Ptrend 0.16) (Pheterogeneity comparing CD and UC 0.037). Asthma, atopic dermatitis, psoriasis and rosacea were individually associated with higher risk of CD (HR ranging from 2.15 to 3.39) but not UC. CONCLUSIONS: Individuals with one or more IMDs are at an increased risk for CD but not UC.

9.
Inflamm Bowel Dis ; 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33367749

RESUMO

BACKGROUND: Fatigue is a disabling symptom in patients with inflammatory bowel disease (IBD). Its prevalence, mechanism, and impact remain poorly understood. We determined changes in fatigue status over time and identified predictors of incident or resolving fatigue. METHODS: This was a prospective study nested within the IBD Partners cohort. Participants prospectively completed the Multidimensional Fatigue Inventory and the Functional Assessment of Chronic Illness Therapy-Fatigue at baseline, 6 months, and 12 months. A Functional Assessment of Chronic Illness Therapy-Fatigue score ≤43 defined significant fatigue. Multivariable regression models using baseline covariates were used to identify risk factors for incident fatigue at 6 months and to predict the resolution of fatigue. RESULTS: A total of 2429 patients (1605 with Crohn disease, 824 with ulcerative colitis) completed a baseline assessment, and 1057 completed a second assessment at 6 months. Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients. One-sixth (15.7%) of patients had fatigue at 1 timepoint, whereas fewer than one-fifth (18.5%) of patients never reported fatigue. Among patients not fatigued at baseline, 26% developed fatigue at 6 months. The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91; 95% confidence interval, 1.48-5.72). In contrast, only 12.3% of those with fatigue at baseline had symptom resolution by month 6. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity. CONCLUSIONS: Fatigue is common in patients with IBD. However, only a few fatigued patients experience symptom resolution at 6 or 12 months, suggesting the need for novel interventions to ameliorate its impact.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33010406

RESUMO

BACKGROUND: Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies. METHODS: We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined. FINDINGS: Our meta-analysis included 28 studies contributing 2,806 patients (2,677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR 2.41, 95% CI 1.91 - 3.04), with a similar effect noted in the subgroup with endoscopic Mayo score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates - Geboes <3.1 (OR 2.40, 95% CI 1.57 - 3.65), Geboes < 2.1 (OR 3.91, 95% CI 2.21 - 6.91) and Geboes 0 (OR 7.40, 95% CI 2.00 - 18.27). Among individual histologic features, basal plasmacytosis (OR 1.94), neutrophilic infiltrations (OR 2.30), mucin depletion (OR 2.05), and crypt architectural irregularities (OR 2.22) predicted relapse. There was no association between histologic activity and relapse in CD. CONCLUSIONS: In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact.

12.
Dig Dis Sci ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037969

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) is important in optimizing use of biologics in inflammatory bowel diseases (IBD). However, the role of proactive TDM during remission remains uncertain. METHODS: This retrospective study included patients receiving infliximab (IFX) therapy at Massachusetts General Hospital or Erasmus University Medical Center. All eligible patients had completed induction phase of IFX and were in clinical and endoscopic remission. Our primary outcome was clinical relapse within 2 years after baseline. Multivariable regression models examined the association between infliximab trough levels during remission and relapse, need for IBD-related surgery or hospitalization. RESULTS: Our study cohort included 110 patients with IBD (72 CD, 38 UC) on IFX maintenance therapy. In total, 12 patients (10.9%) experienced relapse of disease over 2 years. The mean IFX trough level at baseline was 8.0 µg/mL (± 8.6) and did not differ between the institutions. 49.1% of patients had levels < 5 µg/mL and 2.7% had antibodies to infliximab at baseline. There was no difference in the mean IFX trough levels between patients who relapsed (7.5 µg/mL ± 3.7 µg/mL) over 24 months compared to those who did not (8.1 µg/mL ± 7.9 µg/mL, p = 0.815). On multivariable logistic regression analysis, IFX trough levels at baseline were not associated with relapse of disease over 24 months (OR 1.01, 95% CI 0.93-1.09, p = 0.856). CONCLUSION: This retrospective multicenter study provides evidence that IFX trough levels during quiescent disease do not predict relapse over 2 years, suggestive that proactive TDM in this setting is not warranted.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33065312

RESUMO

BACKGROUND: Treatment of patients with inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC) who have a prior history of cancer pose a unique challenge. The impact of Vedolizumab (VDZ) on the risk of new or recurrent cancers in patients with a previous malignancy is unknown. METHODS: This was a retrospective study of patients with IBD with a history of current or prior cancer who were subsequently initiated on VDZ, tumor necrosis factor α antagonists (anti-TNF), or had no immunosuppressive therapy after the index cancer diagnosis. The occurrence of a new primary cancer or recurrent cancer was ascertained on follow-up. Multivariable Cox-proportional hazard models were used to determine the independent effect of post-cancer treatment on new/recurrent cancer. RESULTS: The study included 96 patients exposed to VDZ after a prior diagnosis of cancer who were compared to 184 and 183 patients exposed to anti-TNF or no immunosuppressive therapy, respectively. The most common primary cancer were solid tumors (50%). Over a median of 6.2 person-years of follow-up, 18 patients on VDZ developed new (7) or recurrent (11) cancer corresponding to a rate of 22 per 1000 person-years after cancer diagnosis. In a multivariable Cox-model, after adjusting for confounders, there was no increase in the risk of new or recurrent cancer with VDZ (HR 1.38 95% CI 0.38 - 1.36) or anti-TNF therapy (HR 1.03, 95% CI 0.65 - 1.64), when compared to no IS. CONCLUSIONS: Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy.

14.
Inflamm Bowel Dis ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089863

RESUMO

BACKGROUND: The effect of immunosuppressive treatment for immune-mediated diseases on risk of the novel coronavirus disease 2019 (COVID-19) has not been established. We aimed to define the effect of targeted biologic and immunomodulator therapy on risk of COVID-19 in a multi-institutional cohort of patients with inflammatory bowel disease (IBD). METHODS: We identified patients 18 years and older who received care for IBD at Partners Healthcare between January 2019 and April 2020. The primary outcome was development of COVID-19 defined as a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Multivariable regression models were used to examine the effect of immunosuppression on risk of COVID-19 and its outcomes. RESULTS: In a cohort of 5302 IBD patients, 39 (0.7%) developed COVID-19. There was no difference in age, sex, or race between IBD patients with and without COVID-19. The rate of COVID-19 was similar between patients treated with immunosuppression (0.8%) compared with those who were not (0.64%; P = 0.55). After adjusting for age, sex, race, and comorbidities, use of immunosuppressive therapy was not associated with an increased risk of COVID-19 (odds ratio, 1.73; 95% confidence interval, 0.82-3.63). The presence of obesity was associated with a higher risk of COVID-19 (odds ratio, 8.29; 95% confidence interval, 3.72-18.47). There were 7 hospitalizations, 3 intensive care unit stays, and 1 death. Older age and obesity but not immunosuppressive treatment were associated with severe COVID-19 infection. CONCLUSIONS: The use of systemic immunosuppression was not associated with an increased risk of COVID-19 in a multi-institutional cohort of patients with IBD.

16.
Gastroenterology ; 159(5): 1993-1994, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32946899
17.
Inflamm Bowel Dis ; 26(10): 1524-1532, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32766830

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease. METHODS: This prospective study enrolled patients with quiescent Crohn disease and ulcerative colitis, defined as the absence of clinical symptoms (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) and endoscopic remission within the prior year. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy or IBD-related hospitalization or surgery. Biomarkers were tested in a derivation cohort, and their performance was examined in an independent validation cohort. RESULTS: Our prospective cohort study included 164 patients with IBD (108 with Crohn disease, 56 with ulcerative colitis). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (interleukin-10, glial cell line-derived neurotrophic factor, and T-cell surface glycoprotein CD8 alpha chain) and 4 metabolomic markers (propionyl-L-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models. Proteomic and metabolomic risk scores independently predicted relapse with a combined area under the curve of 0.83. A high proteomic risk score (odds ratio = 9.11; 95% confidence interval, 1.90-43.61) or metabolomic risk score (odds ratio = 5.79; 95% confidence interval, 1.24-27.11) independently predicted a higher risk of relapse over 2 years. Fecal metagenomics showed an increased abundance of Proteobacteria (P = 0.0019, q = 0.019) and Fusobacteria (P = 0.0040, q = 0.020) and at the species level Lachnospiraceae_bacterium_2_1_58FAA (P = 0.000008, q = 0.0009) among the relapses. CONCLUSIONS: Proteomic, metabolomic, and microbial biomarkers identify a proinflammatory state in quiescent IBD that predisposes to clinical relapse.

18.
Inflamm Bowel Dis ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812048

RESUMO

BACKGROUND: The development of chromoendoscopy (CE) and high definition endoscopy (HDE) has improved detection of subtle colonic dysplasia in patients with inflammatory bowel diseases (IBDs). The role of random biopsies for dysplasia surveillance is unclear. METHODS: We reviewed patients with IBD who underwent a CE or HDE colonoscopy and had colonic dysplasia detected. Detection of dysplasia was classified as either visible or random and graded as low grade dysplasia (LGD), high grade dysplasia (HGD), or indefinite for dysplasia. Multivariable regression adjusted for relevant confounders examined the predictors of dysplasia detectable on random biopsies alone. RESULTS: The study included 300 patients (203 ulcerative colitis, 97 Crohn's disease with colonic involvement) contributing 442 colonoscopies; the mean disease duration was 24.5 years; 7.2% had primary sclerosing cholangitis (PSC). Three hundred sixty-two colonoscopies (82%) had only visible dysplasia, 52 (12%) had only random dysplasia, and 28 (6%) had both visible and random dysplasia. Longer disease duration (odds ratio, 1.04; 95% CI, 1.01-1.07), active inflammation (odds ratio, 2.89; 95% CI, 1.26-6.67), and concomitant PSC (odds ratio, 3.66; 95% CI, 1.21-11.08) were associated with detecting dysplasia on random biopsies compared with visible lesions. Patients with random dysplasia (21%) or both random and visible dysplasia (21%) were more likely to undergo surgical resection compared with those with only visible dysplasia (5%; P < 0.001) and have subsequent development of colorectal cancer (15%, 7%, 1%, respectively; P < 0.0001). CONCLUSION: Nearly one fifth of dysplasia detected in patients with IBD was found on random biopsies. Patients with high risk characteristics may benefit from continuing the practice of random biopsies during surveillance examinations.

19.
Dig Dis Sci ; 65(12): 3672-3678, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32617768

RESUMO

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32683099

RESUMO

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently experience chronic pain. Patients will often seek out care in the emergency department (ED) where short-term opioid use may be associated with potential treatment-related complications. We aimed to assess the rate and factors associated with opioid prescription in IBD patients discharged from the ED. METHODS: We conducted a cross-sectional analysis of data collected in the US National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2006-2017. We determined the proportion of adult patients (≥18 years) with IBD prescribed an opioid in ED or at ED discharge. Logistic regression was used to evaluate predictors of opioid prescription. Time-trend analysis was performed to evaluate temporal patterns in opioid use. All analyses were adjusted for complex survey design. RESULTS: We identified ∼965,000 weighted discharges from the ED for patients with IBD. In total, 51.9% [95% CI: 42.2% -61.6%] of visits resulted in opioid administration in ED and 35.3% [95% CI: 26.5% -45.2%] of IBD-related ED discharges were associated with an opioid prescription. IBD patients with moderate/severe pain (adjusted odds ratio aOR 5.06 [95% CI: 1.72 -14.90], p < 0.01) were more likely to receive opioids whereas older age (aOR 0.73 per decade [95% CI: 0.55 -0.98], p = 0.04) were less likely. In temporal analysis, a trend towards decreasing opioid use in ED and opioid prescriptions at discharge was observed in 2015-2017. CONCLUSIONS: More than one third of IBD patients are prescribed an opioid at discharge from ED, highlighting a potential gap in care for accessing effective pain management solutions in this population.

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