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.

An Electronic Clinical Decision-Making Tool for Patients with Suspected Colorectal Cancer-Preliminary Evaluation in Patients Presenting with Rectal Bleeding.

BACKGROUND AND OBJECTIVES: The CarePath-CRC electronic clinical decision-making application was designed to assist physicians with evaluation of patients with suspected colorectal cancer (CRC). The physician completes an interactive checklist of evidence-based clinical parameters, and a recommended referral urgency is generated based on the post-test probability of CRC. This study aimed toward validation of the tool in symptomatic patients presenting with rectal bleeding. METHODS: The medical records of a sample of patients with histologically confirmed CRC from 2010 to 2014 were reviewed. The CarePath-CRC tool was applied retrospectively to all patients who initially presented with rectal bleeding, to determine its sensitivity for detecting CRC in this population. A generated recommendation of 'immediate referral' (referral ≤24 hours, expected endoscopy ≤2 weeks) or 'urgent referral' (expected consultation and endoscopy ≤4 and ≤8 weeks) was considered a positive test result. An a priori sensitivity of 90% was deemed adequate, based on test characteristics of the tool's individual clinical criteria. RESULTS: The tool was applied to 281 patients. A total of 69 (24.6%) and 211 (75.1%) patients met criteria for immediate and urgent referral, respectively. The remaining patient (0.4%) met criteria for 'possible priority referral', while none met criteria for 'no specific action recommended'. This resulted in a calculated sensitivity of 99.6% (95% confidence interval 98.0 to 99.9%). CONCLUSIONS: The CarePath-CRC tool is sensitive in the prediction of CRC in patients presenting with rectal bleeding. A prospective cohort study is being designed to allow for acquisition of comprehensive test performance characteristics and full validation of the instrument.

Accuracy of endoscopic ultrasound-fine needle aspiration of solid lesions over time: Experience from a new endoscopic ultrasound program at a Canadian community hospital.

BACKGROUND AND OBJECTIVES: A Canadian Community Hospital launched a new Endoscopic Ultrasound (EUS) Program in 2011. The aim of this study was to report the accuracy of EUS-fine needle aspiration (EUS-FNA) of solid lesions over time as it pertains to cytotechnologists' involvement and learning curves. METHODS: The electronic medical records of patients that had a EUS from July 2011 to January 2014 were retrospectively reviewed. Only solid lesions with FNA sampling were included in the study. The primary outcome assessed was the accuracy of specimen acquisition for pathological review. The secondary outcome was diagnostic accuracy. Cases were separated by chronological order into thirds for the assessment of learning curves. Cytotechnologists' involvement was correlated to determine its impact on accuracy. RESULTS: Two hundred and seventy-one EUS-FNA procedures were completed for solid lesions. Cytotechnologists' involvement resulted in a specimen acquisition accuracy of 82.6%, compared with 68.8% without a cytotechnologist (P = 0.009; 95% confidence interval [CI] 3.2%-25.0%). Diagnostic accuracy was 74.2% with a cytotechnologist while 62.4% without a cytotechnologist (P = 0.038; 95% CI 0.3%-23.7%). The specimen acquisition accuracy increased from 73.2% from the first third of cases to 92.3% for the last third with a cytotechnologist (P = 0.004; 95% CI 6%-33.0%). Without a cytotechnologist, the specimen accuracy was 67.6% for the first third while 57.7% for the last third of cases (P = 0.434; 95% CI - 33.9-14.4%). In the multivariable regression analysis, after adjusting for other predictors, a present cytotechnologist (P = 0.022) and lesion size 21 mm-30 mm (P = 0.039) and >30 mm (P = 0.001) were significantly associated with increased specimen acquisition accuracy. Only a present cytotechnologist (P = 0.046) was significantly associated with increased diagnostic accuracy. INTERPRETATION: Cytotechnologists' involvement significantly improved the accuracy of specimen acquisition. Although accuracy was impacted by a cytotechnologist learning curve, our results highlight the importance of a cytotechnologist being present for EUS-FNA sampling of solid lesions.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

AIM: To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). METHODS: This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. RESULTS: High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. CONCLUSIONS: Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. GOV REGISTRATION NO: NCT02615288.

Domperidone Prescribing Practices Exposed Patients to Cardiac Risk despite a "Black Box" Warning: A Canadian Tertiary Care Center Study.

Background. In 2012, Health Canada released a warning regarding domperidone use, based on associations with life-threatening arrhythmias and death. Objective. This study aimed to compare the appropriateness of domperidone prescribing patterns before the advisory to those afterward. Methods. Two retrospective reviews were conducted for patients prescribed domperidone during quarters in 2005 and 2012. Outcomes included appropriateness of indication, dosing regimens, monitoring of electrolytes, baseline electrocardiogram performance and characteristics, presence of left ventricular dysfunction, and coprescription of QT-prolonging medications. Univariable and multivariable logistic regression analyses were performed. p values < 0.05 were considered significant. Results. 290 and 287 patients were analyzed in 2005 and 2012, respectively. Domperidone initiation in hospital decreased from 2005 to 2012 (71.4% versus 39.4%, p < 0.0001) as did prescriptions for nonapproved indications (84.8% versus 58.2%, p < 0.0001). In-hospital initiation predicted prescription for nonapproved indications (OR = 7.01, 95% CI 4.52-10.87, p < 0.0001). Use of domperidone as the sole GI drug predicted nonapproved indications (OR = 2.51, 95% CI 1.38-4.55, p = 0.002). Conclusions. The advisory was associated with more appropriate domperidone initiation and compliance with recommended dosages. Our study suggests the need for increased awareness of the dosing and monitoring of domperidone to ensure patient safety.

To thin or not to thin: a case of peripartum cardiomyopathy.

We describe the case of a 29-year-old woman with peripartum cardiomyopathy (PPCM) complicated by multiple cerebral infarcts. Current treatment of PPCM is reviewed with a focus on the role of anticoagulation in PPCM.

Bats, fever and adenopathy - what is the link?

A case of travel-related, subacute, progressive disseminated histoplasmosis in a nonimmunocompromised individual is described. The present case highlights the environmental exposure to Histoplasma capsulatum in Costa Rica, the diagnostic approach and treatment options, as well as new alternatives for salvage therapy for histoplasmosis infection.

Les chercheurs décrivent un cas d'histoplasmose disséminée subaiguë progressive liée à un voyage chez une personne non immunocompromise. Le présent cas fait ressortir l'exposition environnementale à l'Histoplasma capsulatum au Costa Rica, la démarche diagnostique et les possibilités thérapeutiques, ainsi que de nouvelles possibilités de thérapie de rattrapage de l'infection par l'histoplasmose.

Mitochondrial ATP-sensitive K+ channels regulate NMDAR activity in the cortex of the anoxic western painted turtle.

Hypoxic mammalian neurons undergo excitotoxic cell death, whereas painted turtle neurons survive prolonged anoxia without apparent injury. Anoxic survival is possibly mediated by a decrease in N-methyl-d-aspartate receptor (NMDAR) activity and maintenance of cellular calcium concentrations ([Ca(2+)](c)) within a narrow range during anoxia. In mammalian ischaemic models, activation of mitochondrial ATP-sensitive K(+) (mK(ATP)) channels partially uncouples mitochondria resulting in a moderate increase in [Ca(2+)](c) and neuroprotection. The aim of this study was to determine the role of mK(ATP) channels in anoxic turtle NMDAR regulation and if mitochondrial uncoupling and [Ca(2+)](c) changes underlie this regulation. In isolated mitochondria, the K(ATP) channel activators diazoxide and levcromakalim increased mitochondrial respiration and decreased ATP production rates, indicating mitochondria were 'mildly' uncoupled by 10-20%. These changes were blocked by the mK(ATP) antagonist 5-hydroxydecanoic acid (5HD). During anoxia, [Ca(2+)](c) increased 9.3 +/- 0.3% and NMDAR currents decreased 48.9 +/- 4.1%. These changes were abolished by K(ATP) channel blockade with 5HD or glibenclamide, Ca(2+)(c) chelation with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or by activation of the mitochondrial Ca(2+) uniporter with spermine. Similar to anoxia, diazoxide or levcromakalim increased [Ca(2+)](c) 8.9 +/- 0.7% and 3.8 +/- 0.3%, while decreasing normoxic whole-cell NMDAR currents by 41.1 +/- 6.7% and 55.4 +/- 10.2%, respectively. These changes were also blocked by 5HD or glibenclamide, BAPTA, or spermine. Blockade of mitochondrial Ca(2+)-uptake decreased normoxic NMDAR currents 47.0 +/- 3.1% and this change was blocked by BAPTA but not by 5HD. Taken together, these data suggest mK(ATP) channel activation in the anoxic turtle cortex uncouples mitochondria and reduces mitochondrial Ca(2+) uptake via the uniporter, subsequently increasing [Ca(2+)](c) and decreasing NMDAR activity.