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INTRODUCTION: As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. The aim of the study is to determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time, (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on 1-year hospitalization rates. METHODS: We conducted a retrospective single-center study of older adults with IBD from September 1, 2011, to December 31, 2022. Wilcoxon-signed rank and McNemar tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS: Among 512 older adults with IBD, 74.0% experienced polypharmacy at the initial visit, with 42.6% receiving at least one PIM. In addition, severe polypharmacy (≥10 medications) was present among 28.6% individuals at the index visit and increased to 38.6% by the last visit ( P < 0.01). Multivariable analysis revealed that age ≥70 years, body mass index ≥30.0 kg/m 2 , previous IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy ( adj hazard ratio 1.95, 95% confidence interval 1.29-2.92), as well as PIM use ( adj hazard ratio 2.16, 95% confidence interval 1.37-3.43) among those with polypharmacy, was significantly associated with all-cause hospitalization within a year of the index visit. DISCUSSION: Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of the index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at 1 year, highlighting the need for deprescribing efforts in this population.
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OBJECTIVE: The intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS. DESIGN: 39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junction (TJ) proteins, ultrastructural morphology and 16 s sequencing of faecal microbiota rRNA. A casein-based assay was used to measure proteolytic activity (PA) in faecal supernatants (FSNs). Colonic barrier function was determined in mice (ex-germ free) humanised with microbial communities associated with different human PA states. RESULTS: Patients with IBS had higher faecal PA than healthy volunteers. 8/20 postinfection IBS (PI-IBS) and 3/19 constipation- predominant IBS had high PA (>95th percentile). High-PA patients had more and looser bowel movements, greater symptom severity and higher in vivo and ex vivo colonic permeability. High-PA FSNs increased paracellular permeability, decreased occludin and increased phosphorylated myosin light chain (pMLC) expression. Serine but not cysteine protease inhibitor significantly blocked high-PA FSN effects on barrier. The effects on barrier were diminished by pharmacological or siRNA inhibition of protease activated receptor-2 (PAR-2). Patients with high-PA IBS had lower occludin expression, wider TJs on biopsies and reduced microbial diversity than patients with low PA. Mice humanised with high-PA IBS microbiota had greater in vivo permeability than those with low-PA microbiota. CONCLUSION: A subset of patients with IBS, especially in PI-IBS, has substantially high faecal PA, greater symptoms, impaired barrier and reduced microbial diversity. Commensal microbiota affects luminal PA that can influence host barrier function.