Summary The growing obesity epidemic requires an evidence‐based approach to management of patients with obesity. Two systematic reviews on obesity‐management interventions in undergraduate medical education, both published in 2012, reported discrepant findings. This study aimed to build on previous research by identifying, systematically reviewing, and synthesizing current literature on the effectiveness of educational interventions aimed at teaching management of patients with obesity to medical students. A comprehensive search of seven databases was performed with no date or language restrictions. Database search identified 6462 studies; 5373 were screened against title and abstract, 156 full‐text articles were retrieved, 31 met eligibility criteria, and 17 were included after critical appraisal of study methodology. Nine cohort‐studies, three qualitative, two case–controls, two mixed‐methods, and one randomized controlled trial were included. Findings supported the educational effectiveness of brief (<3 h) educational interventions, the value of video‐clips to deliver content, and the importance of in‐person teaching. Findings also demonstrated an increase in the number of studies describing educational interventions aimed at teaching management of patients with obesity to medical students. These results can be used by medical educators to inform the design of educationally effective curricula focused on the management of patients with obesity in undergraduate medical education.
Opioid tolerance (OT) leads to dose escalation and serious side effects, including opioid-induced hyperalgesia (OIH). We sought to better understand the mechanisms underlying this event in the gastrointestinal tract. Chronicin vivoadministration of morphine by intraperitoneal injection in male C57BL/6 mice evoked tolerance and evidence of OIH in an assay of colonic afferent nerve mechanosensitivity; this was inhibited by the δ-opioid receptor (DOPr) antagonist naltrindole when intraperitoneally injected in previous morphine administration. Patch-clamp studies of DRG neurons following overnight incubation with high concentrations of morphine, the µ-opioid receptors (MOPr) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or the DOPr agonist [D-Ala2, D-Leu5]-Enkephalin evoked hyperexcitability. The pronociceptive actions of these opioids were blocked by the DOPr antagonist SDM25N but not the MOPr antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. The hyperexcitability induced by DAMGO was reversed after a 1 h washout, but reapplication of low concentrations of DAMGO or [D-Ala2, D-Leu5]-Enkephalin restored the hyperexcitability, an effect mediated by protein kinase C. DOPr-dependent DRG neuron hyperexcitability was blocked by the endocytosis inhibitor Pitstop 2, and the weakly internalizing DOPr agonist ARM390 did not cause hyperexcitability. Bioluminescence resonance energy transfer studies in HEK cells showed no evidence of switching of G-protein signaling from Gito a Gspathway in response to either high concentrations or overnight incubation of opioids. Thus, chronic high-dose opioid exposure leads to opioid tolerance and features of OIH in the colon. This action is mediated by DOPr signaling and is dependent on receptor endocytosis and downstream protein kinase C signaling.SIGNIFICANCE STATEMENTOpioids are effective in the treatment of abdominal pain, but escalating doses can lead to opioid tolerance and potentially opioid-induced hyperalgesia. We found that δ-opioid receptor (DOPr) plays a central role in the development of opioid tolerance and opioid-induced hyperalgesia in colonic afferent nociceptors following prolonged exposure to high concentrations of MOPr or DOPr agonists. Furthermore, the role of DOPr was dependent on OPr internalization and activation of a protein kinase C signaling pathway. Thus, targeting DOPr or key components of the downstream signaling pathway could mitigate adverse side effects by opioids.
Background Over the past 10 years, interest in patient and public involvement (PPIn) in research has grown. Several arguments support the engagement of patients as partners in the research process. Patients with lived experience of a condition can offer their knowledge to study design as experience-based experts, helping researchers incorporate patient-pertinent outcomes. PPIn has also been shown to boost patient enrolment and retention in clinical trials. Benefits, challenges, and best practices of PPIn have been examined in other fields. However, to date, no study has examined PPIn in inflammatory bowel disease (IBD) research. Many factors amenable to research involvement may impact IBD patients’ quality of life, including disease morbidity, complications, and efficacy/side effects of therapy. Aims This review aims to characterize methods of PPIn in IBD research and highlight themes relating to best practices, benefits, and challenges. Methods We ran a systematic search on MEDLINE, EMBASE, and Cochrane for all IBD research studies in which IBD patients were involved in the research process. PPIn included but was not limited to patient input in one of the following 3 stages: Study Design (prioritization of research topics, outcome selection, study tool development), Study Execution (recruitment, data collection & analysis), and Dissemination of Research. After abstract and full-text screening, 14 studies were selected. Results Patients were recruited for PPIn through IBD and patient organizations (7/14), outpatient clinics (4/14), tertiary care sites (2/14), and pre-existing patient advisory groups (1/14). The majority of studies (11/14) engaged patients in the development of study materials, which included a physical activity intervention for stoma patients, an IBD pregnancy decision aid, and a quality of life questionnaire. Two studies interviewed patients to determine comprehensibility of survey items and guide revisions. One study involved patients in data analysis and manuscript development. Most consultations were open-ended, including focus groups (8/14) and semi-structured interviews (3/14). According to study authors, PPIn helps guide IBD research priorities by focusing on patient-relevant issues. Authors also cited the role of PPIn in designing patient-friendly study tools. One challenge reported by 2 studies was that PPIn requires patients to have access to high-quality information and requires a significant time commitment, which may contribute to demographic biases. Conclusions The majority of IBD studies engaged patients in an open-ended format and were engaged in study design, particularly in developing study materials. Authors recommend continuous involvement of patients throughout the research process to address their research priorities. Funding Agencies None
Background We have shown that Irritable Bowel Syndrome diarrhea-predominant (IBS-D) patients with a history of a dysbiotic-like onset have distinct stool metabolomic profiles versus those with a non-dysbiotic-like onset. IBS stool supernatants can sensitize mouse colonic afferent nerves via both histamine and proteases. However, it is unknown if stool supernatants from the two IBS-D subgroups modulate the excitability of nociceptive neurons via different neuroactive mediators Aims To evaluate whether there are differences in neuroactive mediators within stool supernatants from subgroups of IBS-D patients that can modulate the excitability of nociceptive neurons. Methods Stool samples from healthy control (HC) (N=5) and IBS-D patients with a dysbiotic (N=7) or non-dysbiotic-like (N=7) onset, was homogenized with Krebs solution and filtered. Proteolytic activity was assessed using casein as a substrate with and without protease inhibitors. Histamine was quantified by ELISA. DRG neurons from C57BL/6 mice were incubated overnight or acutely (30 min) with stool supernatants. Some neurons were pre-incubated with PAR2 (GB83, 10 μM) or H1R (pyrilamine, 1μM) antagonists prior to supernatant incubation. Changes in neuronal excitability were assessed with perforated patch-clamp by measuring the rheobase (current that elicits an action potential). Results Proteolytic activity in dysbiotic-like (57.9 U/μg, p<0.05) but not non-dysbiotic like (37.4 U/μg) stool supernatant was increased compared to HC (25.2 U/μg). Serine inhibitor decreased proteolytic activity of dysbiotic (46.6%, p<0.05) and non-dysbiotic (34.2%, p<0.01) supernatant whereas cysteine, aspartic and metalloproteases inhibitors had no effect. Histamine was increased 78% (p<0.05) in IBS-D compared to HC. No differences in proteolytic activity and histamine concentration between IBS-D subtypes were found. In patch-clamp recordings, overnight incubation with dysbiotic (19%, p<0.05) and non-dysbiotic (22%, p< 0.01) stool supernatant decreased rheobase of DRG neurons compared to HC. No difference in rheobase was observed between IBS-D subtypes. GB83 blocked the overnight actions of supernatants from both subgroups, but pyrilamine had no effect. In contrast, following acute incubation, pyrilamine blocked the hyperexcitability evoked by dysbiotic like supernatant (60pA vs 48pA, p<0.001) but had no effect on non-dysbiotic like supernatants. Conclusions Proteases in stool supernatants from IBS-D patients increase neuronal excitability but only those with a history of dysbiotic like onset acutely increase neuronal excitability through H1 receptors. These findings suggest that stool supernatants from subgroups of IBS-D may modulate nociceptor excitability via different mechanisms. Funding Agencies CIHRAmerican Neurogastroenterology and Motility Society
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