Baseline Cannabinoid Use Is Associated with Increased Sedation Requirements for Outpatient Endoscopy.

Background and Aims: Given the underlying properties of cannabinoids, we aimed to assess associations between cannabinoid use and sedation requirements for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods: A prospective cohort study was conducted at three endoscopy units. Adult outpatients undergoing EGD or colonoscopy with endoscopist-directed conscious sedation (EDCS) were given questionnaires on cannabinoid use and relevant parameters. Outcomes included intraprocedural midazolam, fentanyl, and diphenhydramine use, procedural tolerability, and adverse events. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) of outcomes. Results: A total of 419 patients were included. Baseline cannabinoid use was associated with high midazolam use, defined as ≥5 mg, during EGD (AOR 2.89, 95% confidence interval, CI: 1.19-7.50), but not during colonoscopy (AOR 0.89, 95% CI 0.41-1.91). Baseline cannabinoid use was associated with the administration of any diphenhydramine during EGD (AOR 3.04, 95% CI: 1.29-7.30) with a similar nonsignificant trend for colonoscopy (AOR 2.36, 95% CI: 0.81-7.04). Baseline cannabinoid use was associated with increased odds of requiring high total sedation, defined as any of midazolam ≥5 mg, fentanyl ≥100 mcg, or any diphenhydramine during EGD (AOR 3.72, 95% CI: 1.35-11.68). Cannabinoid use was not independently associated with fentanyl use, intraprocedural awareness, discomfort, or adverse events. Conclusions: Baseline cannabinoid use was associated with higher sedation use during endoscopy with EDCS, particularly with midazolam and diphenhydramine. Given increasingly widespread cannabinoid use, endoscopists should be equipped with optimal sedation strategies for this population. As part of the informed consent process, cannabis users should be counseled that they may require higher sedation doses to achieve the same effect.

Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Adverse events associated with endoscopic retrograde cholangiopancreatography: protocol for a systematic review and meta-analysis.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to diagnose and manage conditions of the biliary and pancreatic ducts. Though effective, it is associated with common adverse events (AEs). The purpose of this study is to systematically review ERCP AE rates and report up-to-date pooled estimates. METHODS AND ANALYSIS: A comprehensive electronic search will be conducted of relevant medical databases through 10 November 2020. A study team of eight data abstracters will independently determine study eligibility, assess quality and abstract data in parallel, with any two concordant entries constituting agreement and with discrepancies resolved by consensus. The primary outcome will be the pooled incidence of post-ERCP pancreatitis, with secondary outcomes including post-ERCP bleeding, cholangitis, perforation, cholecystitis, death and unplanned healthcare encounters. Secondary outcomes will also include rates of specific and overall AEs within clinically relevant subgroups determined a priori. DerSimonian and Laird random effects models will be used to perform meta-analyses of these outcomes. Sources of heterogeneity will be explored via meta-regression. Subgroup analyses based on median dates of data collection across studies will be performed to determine whether AE rates have changed over time. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as it is a planned meta-analysis of previously published data. Participant consent is similarly not required. Dissemination is planned via presentation at relevant conferences in addition to publication in peer-reviewed journals.PROSPERO registration numberCRD42020220221.

Lessons learned from descriptions and evaluations of knowledge translation platforms supporting evidence-informed policy-making in low- and middle-income countries: a systematic review.

BACKGROUND: Knowledge translation (KT) platforms are organisations, initiatives and networks that focus on supporting evidence-informed policy-making at least in part about the health-system arrangements that determine whether the right programmes, services and products get to those who need them. Many descriptions and evaluations of KT platforms in low- and middle-income countries have been produced but, to date, they have not been systematically reviewed. METHODS: We identified potentially relevant studies through a search of five electronic databases and a variety of approaches to identify grey literature. We used four criteria to select eligible empirical studies. We extracted data about seven characteristics of included studies and about key findings. We used explicit criteria to assess study quality. In synthesising the findings, we gave greater attention to themes that emerged from multiple studies, higher-quality studies and different contexts. RESULTS: Country was the most common jurisdictional focus of KT platforms, EVIPNet the most common name and high turnover among staff a common infrastructural feature. Evidence briefs and deliberative dialogues were the activities/outputs that were the most extensively studied and viewed as helpful, while rapid evidence services were the next most studied but only in a single jurisdiction. None of the summative evaluations used a pre-post design or a control group and, with the exception of the evaluations of the influence of briefs and dialogues on intentions to act, none of the evaluations achieved a high quality score. CONCLUSIONS: A large and growing volume of research evidence suggests that KT platforms offer promise in supporting evidence-informed policy-making in low- and middle-income countries. KT platforms should consider as next steps expanding their current, relatively limited portfolio of activities and outputs, building bridges to complementary groups, and planning for evaluations that examine 'what works' for 'what types of issues' in 'what types of contexts'.

Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents.

INTRODUCTION:: Many international guidelines for management of psoriasis exist and most have variations in grading evidence quality, strength of recommendations, and dosing. The objective of our review is to compare international guidelines published in the United Kingdom, Canada, Europe, and the United States for the management of moderate-to-severe plaque psoriasis. METHODS:: We conducted a literature review on systemic therapies and phototherapy for moderate-to-severe plaque psoriasis in adult patients. The British, Canadian, European, and American guidelines served as the key comparators in our review. To identify relevant supporting clinical trials not referenced in the guidelines, we conducted literature searches in PubMed and EMBASE. Two authors independently extracted data on indications, dosing, efficacy, evidence grade, and strength of clinical recommendation for each therapy. RESULTS:: Monoclonal antibodies directed toward tumour necrosis factor and interleukin (IL)-12/23 received the strongest recommendations for treatment of moderate-to-severe plaque psoriasis, supported by robust, high-quality randomized controlled trials (RCTs). Newer agents such as IL-17 and IL-23 inhibitors are not referenced in most guidelines. There are fewer RCTs for conventional therapies and few head-to-head comparisons with biologics, making it difficult to draw direct comparisons. Among older agents, methotrexate is most strongly recommended for long-term maintenance and cyclosporine is recommended for short-term control of flares. CONCLUSION:: Physicians should individualize psoriasis-management strategies based on medication tolerance, efficacy, safety, patient comorbidities, availability of the medication, and patient preference.

SGLT2 inhibitors: practical considerations and recommendations for cardiologists.

PURPOSE OF REVIEW: To address common concerns regarding sodium-glucose cotransporter 2 (SGLT2) inhibitor use for patients with type 2 diabetes mellitus (T2DM) in cardiovascular practice. RECENT FINDINGS: SGLT2 inhibitors provide glycemic control and improve cardiovascular and renal endpoints in T2DM. Cardiovascular outcome trials have demonstrated sustained cardiovascular, heart failure and renal benefits independent of glycemic control, which persist down to an eGFR of 30 ml/min/1.73 m. SGLT2 inhibitors can be safely administered alongside common diuretics, and routine monitoring of renal function is advised at initiation of therapy, particularly for patients on loop diuretics. Mild initial reductions in eGFR are expected, usually stabilizing over time. The most common adverse effect noted with SGLT2 inhibitors is genital mycotic infections, primarily in women. Less common, but concerning effects associated with canagliflozin include increased risk of fractures and lower limb amputations, particularly in patients with previous amputation history. Overall, SGLT2 inhibitors are well tolerated and effective adjuncts to diabetic treatment, for which the benefits seem to outweigh the risks. SUMMARY: The care of patients with T2DM requires an interdisciplinary team approach, within which the role of cardiologists is expanding. SGLT2 inhibitors are an encouraging treatment option for achieving glycemic control, whilst also improving cardiovascular and renal outcomes.