Browsing by Author "Zaidi, Deenaz"
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Item Open Access Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases(2019-01-03) Armstrong, Heather; Alipour, Misagh; Valcheva, Rosica; Bording-Jorgensen, Michael; Jovel, Juan; Zaidi, Deenaz; Shah, Prachi; Lou, Yuefei; Ebeling, Cory; Mason, Andrew L; Lafleur, Dawson; Jerasi, Jeremy; Wong, Gane K; Madsen, Karen; Carroll, Matthew W; Huynh, Hien Q; Dieleman, Levinus A; Wine, EytanAbstract Background Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis. Results IgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not. Conclusion Using IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.Item Open Access Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis(2021-07-04) Okpechi, Ikechi G.; Tinwala, Mohammed M.; Muneer, Shezel; Zaidi, Deenaz; Ye, Feng; Hamonic, Laura N.; Khan, Maryam; Sultana, Naima; Brimble, Scott; Grill, Allan; Klarenbach, Scott; Lindeman, Cliff; Molnar, Amber; Nitsch, Dorothea; Ronksley, Paul; Shojai, Soroush; Soos, Boglarka; Tangri, Navdeep; Thompson, Stephanie; Tuot, Delphine; Drummond, Neil; Mangin, Dee; Bello, Aminu K.Abstract Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ].