Browsing by Author "Panaccione, Remo"
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- ItemOpen AccessAnti-Indigenous bias of medical school applicants: a cross-sectional study(2022-09-19) Roach, Pamela; Hernandez, Santanna; Carbert, Amanda; Jalil, Rabiya; Panaccione, Remo; Ruzycki, Shannon M.Abstract Background Structural and interpersonal anti-Indigenous racism is prevalent in Canadian healthcare. The Truth and Reconciliation Commission calls on medical schools to address anti-Indigenous bias in students. We measured the prevalence of interpersonal anti-Indigenous bias among medical school applicants to understand how the medical school selection process selects for or against students with high levels of bias. Methods All applicants to a single university in the 2020–2021 admissions cycle were invited to participate. Explicit anti-Indigenous bias was measured using two sliding scale thermometers. The first asked how participants felt about Indigenous people (from 0, indicating ‘cold/unfavourable’ to 100, indicating ‘warm/favourable’) and the second asked whether participants preferred white (scored 100) or Indigenous people (scored 0). Participants then completed an implicit association test examining preferences for European or Indigenous faces (negative time latencies suggest preference for European faces). Explicit and implicit anti-Indigenous biases were compared by applicant demographics (including gender and racial identity), application status (offered an interview, offered admission, accepted a position), and compared to undergraduate medical and mathematics students. Results There were 595 applicant respondents (32.4% response rate, 64.2% cisgender women, 55.3% white). Applicants felt warmly toward Indigenous people (median 96 (IQR 80–100)), had no explicit preference for white or Indigenous people (median 50 (IQR 37–55), and had mild implicit preference for European faces (− 0.22 ms (IQR -0.54, 0.08 ms)). There were demographic differences associated with measures of explicit and implicit bias. Applicants who were offered admission had warmer feelings toward Indigenous people and greater preference for Indigenous people compared to those were not successful. Conclusions Medical school applicants did not have strong interpersonal explicit and implicit anti-Indigenous biases. Outlier participants with strong biases were not offered interviews or admission to medical school.
- ItemOpen AccessAssociations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn’s disease subjects(2020-10-15) Turpin, Williams; Bedrani, Larbi; Espin-Garcia, Osvaldo; Xu, Wei; Silverberg, Mark S; Smith, Michelle I; Garay, Juan A R; Lee, Sun-Ho; Guttman, David S; Griffiths, Anne; Moayyedi, Paul; Panaccione, Remo; Huynh, Hien; Steinhart, Hillary A; Aumais, Guy; Dieleman, Levinus A; Turner, Dan; Paterson, Andrew D; Croitoru, KennethAbstract Background Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn’s disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset. Methods Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15–40-fold increased risk of developing CD in homozygous or compound heterozygous individuals. Results Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae. Conclusions This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.
- ItemOpen AccessCrohn’s-like disease in a patient exposed to anti-Interleukin-17 blockade (Ixekizumab) for the treatment of chronic plaque psoriasis: a case report(2019-09-05) Smith, Matthew K; Pai, Jay; Panaccione, Remo; Beck, Paul; Ferraz, Jose G; Jijon, HumbertoAbstract Background Plaque psoriasis and inflammatory bowel disease (IBD) are both chronic immune-mediated inflammatory diseases with an overlapping genetic profile and have been linked in epidemiological studies. Psoriasis and IBD share similar components in their inflammatory pathways and animal and human studies have suggested a potential role for targeting interleukin (IL)-17 with novel antibody therapies in the treatment of these diseases. These studies, while promising for psoriasis, have been associated with deterioration in patients with IBD. Post-hoc analyses of clinical trials involving Ixekizumab revealed adverse outcomes in a small cluster of patients with IBD, prompting recommendations to monitor this population with the use of this drug. Case presentation Forty-two year old Caucasian male with treatment-refractory chronic plaque psoriasis who developed new onset diarrheal illness and rectal bleeding following a 12 week induction period with Ixekizumab (anti-IL-17 neutralizing antibody). Colonoscopy revealed severe ulceration throughout the ascending and transcending colon. Histopathology, combined with endoscopic findings, led to a diagnosis of Crohn’s-like colitis. The patient’s anti-IL-17 medication was discontinued and endoscopic remission was induced with the use of corticosteroids, escalated anti-TNF therapy and eventually anti IL-12/23 neutralizing antibody (ustekinumab). Conclusion Murine studies implicate IL-17 and the downstream effects of its inhibition, in the breakdown of the gut epithelial layer, the disruption of normal host immune responses and the propagation of intestinal inflammation. The increasing use of IL-17 inhibitors has led to reports of exacerbation and potential development of inflammatory bowel disease. While clinical trials have revealed clusters of new inflammatory bowel disease cases amongst psoriasis patients using an IL-17 inhibitor, there remains a lack of evidence to suggest a causal relationship. This is the first case report of de-novo severe Crohn’s-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.
- ItemOpen AccessIncorporating patient experience into drug development for ulcerative colitis: development of the Urgency Numeric Rating Scale, a patient-reported outcome measure to assess bowel urgency in adults(2022-04-01) Dubinsky, Marla C.; Irving, Peter M.; Panaccione, Remo; Naegeli, April N.; Potts-Bleakman, Alison; Arora, Vipin; Shan, Mingyang; Travis, SimonAbstract Background Bowel urgency, the sudden or immediate need to have a bowel movement, is a common, bothersome and disruptive symptom of ulcerative colitis (UC). UC treatment goals include control of urgency; however, it is not consistently assessed in UC clinical trials. The Urgency Numeric Rating Scale (NRS) is a new patient-reported measure to assess severity of bowel urgency in adults with UC developed in accordance with Food and Drug Administration guidelines. Methods Qualitative interviews were used to develop Urgency NRS. The scale asks patients to report the immediacy status of their UC symptom over the past 24 h on an 11-point horizontal numeric rating scale [0 (No urgency) to 10 (Worst possible urgency)]. Higher scores indicate worse urgency severity. A 2-week diary study assessed floor and ceiling effects, test–retest reliability (intraclass correlation coefficient (ICC) (2,1) between Week 1 and 2), and construct validity (Spearman correlation using Week 1 scores). Weekly scores were calculated as mean score over each 7-day period. Results Qualitative interviews with 16 UC patients (mean age 37.9 ± 11.6 years; 50% female; 56% White) confirmed relevance, content, and comprehensiveness. The 2-week diary study included 41 UC patients (mean age 44.2 ± 14.6 years; 51% female; 56% White). No ceiling or floor effects were identified. Test–retest reliability was high (ICC = 0.877). Average Urgency NRS and patient global rating of severity scores were highly correlated, with a moderate correlation between average Urgency NRS and stool frequency, demonstrating construct validity. Conclusions Bowel urgency is a distinct symptom of UC. The Urgency NRS is a well-defined, content-valid, and reliable measurement of bowel urgency in adults with UC.
- ItemOpen AccessPostoperative complications following colectomy for ulcerative colitis: A validation study(BioMed Central, 2012) Kaplan, Gilaad G.; Ma, Christopher; Crespin, Marcelo; Proulx, Marie-Claude; DeSilva, Shanika; Hubbard, James; Prusinkiewicz, Martin; Nguyen, Geoffrey C; Panaccione, Remo; Ghosh, Subrata; Myers, Robert P; Quan, Hude