Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Prucalopride in diabetic and connective tissue disease-related gastroparesis: Randomized placebo-controlled crossover pilot trial.

BACKGROUND: Gastroparesis, defined by delayed gastric emptying in the absence of mechanical outlet obstruction, is a frequent neuropathic complication of diabetes mellitus, and effective treatments are lacking. Prucalopride is a pan-gut prokinetic with selective agonist effects on serotonin 5-HT4 receptors in the gut. This study aimed to assess the effect of prucalopride 4 mg daily on Gastroparesis Cardinal Symptom Index (GCSI), meal-related symptom score (MRSS), and gastric emptying rate in diabetic or connective tissue disease (CTD)-related gastroparesis patients. METHODS: This was a double-blind crossover trial of four-week treatment periods with prucalopride or placebo divided by two weeks of washout. GSCI, MRSS, gastric emptying scintigraphy, PAGI-SYM, and PAGI-QoL were assessed at baseline and the end of each treatment period. Daily bowel movement (BM) frequency and gastrointestinal symptoms were recorded in each period. KEY RESULTS: Fifteen gastroparesis patients (13 diabetic, 2 CTD) were enrolled. GCSI scores were lower than baseline but not different between treatment arms. MRSS scores over time or cumulative score were not significantly different between groups. Gastric emptying was more rapid in the prucalopride treatment period, with mean four-hour meal retention of 22 ± 6% in PRU period vs 40 ± 9% in the placebo period (P = 0.05). Weekly BM frequency was significantly higher in prucalopride than placebo periods (10.5 ± 1.8 vs 7.5 ± 0.8, P < 0.0001). Perception of weight loss was higher in patients on prucalopride. Analysis of diabetic gastroparesis (n = 13) population did not change the conclusions. CONCLUSION AND INFERENCE: Prucalopride at 4 mg accelerates gastric emptying and bowel movement frequency but does not appear to ameliorate gastroparesis or meal-related symptoms in this study.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Gastroesophageal Reflux Disease Is Not Associated With Jackhammer Esophagus: A Case-control Study.

BACKGROUND/AIMS: The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE. METHODS: High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral. RESULTS: Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (ß = 0.298, P = 0.042), CCB (ß = 0.308, P = 0.035), and inhaled anticholinergics (ß = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003). CONCLUSIONS: Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.

Esophagogastric junction outflow obstruction on manometry: Outcomes and lack of benefit from CT and EUS.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a manometric diagnosis based on the Chicago Classification defined by inadequate relaxation of the gastroesophageal junction (GEJ) with swallowing, but with sufficient peristalsis such that the criteria for achalasia are not met. Possible causes include anatomical and functional etiologies. Further investigations, including computed tomography (CT) of the chest and endoscopic ultrasound (EUS), to help elucidate the etiology of EGJOO have been suggested, but the utility of this approach has not been proven. METHODS: All new diagnoses of EGJOO made in the calendar years 2015-2016 were included. A review was performed for each patient to assess clinical outcomes, diagnostic, and therapeutic interventions after the EGJOO diagnosis. KEY RESULTS: 107 EGJOO patients were included. Their primary complaints were dysphagia (68%), chest pain (12%), reflux (8%), pre-operative assessment (6%), regurgitation (3%), and cough (3%). The mean IRP was 21.8 mm Hg. After a mean follow-up period of 463 days, the etiology of EGJOO remained undetermined in 67% of patients. 48% of patients were investigated with cross-sectional imaging (and 10% with EUS to rule out external compression or malignancy as a cause of EGJOO; none of these tests provided any further useful information). In only two cases did the EGJOO progress to achalasia. CONCLUSIONS & INFERENCES: EGJOO is a manometric diagnosis with unclear clinical significance and outcome. CT and EUS of the GEJ were unhelpful at determining the cause of this entity. In this series, very few appear to progress to achalasia, none were due to malignancy, and many resolved spontaneously.

Prospective evaluation of gastric neurostimulation for diabetic gastroparesis in Canada.

BACKGROUND: The efficacy of gastric neurostimulation therapy for diabetic gastroparesis (GP) in a 'real-life' Canadian setting has not been assessed. AIMS: To assess changes in health-related quality of life (QoL), weekly vomiting frequency (WVF), total symptom score (TSS) and health care utilization 12 months before and after gastric neurostimulator implantation in a diabetic GP cohort. METHODS: Medication-refractory diabetic GP patients (n=7, four female, mean age 42 years) were prospectively recruited from 2008 to 2012. QoL scores were self-administered and obtained at baseline, 24 and 48 weeks postimplantion. WVF and TSS were assessed similarly. Health care usage, measured as hospitalization frequency and medication cost, was obtained six and 12 months before and after implant. Changes from baseline to six and 12 months for all outcomes were compared. RESULTS: The mean ( ± SD) QoL according to EuroQol was significantly better at 24 weeks after the baseline measurement (baseline 29 ± 5, 24 weeks 52 ± 7; P = 0.03). The mean improvement in TSS was significantly better at one year postintervention (baseline score 35 ± 5 versus 12 months 27 ± 3; P = 0.03). Changes in Short-Form 36 Health Survey and WVF were not significant. Days of GP-related hospitalization were highly variable but decreased from a median of 71 days (range 0 to 227 days) to 29 days (range two to 334 days) one year before and after surgery, respectively (P = 0.735). Outpatient medication costs did not decrease to a significant extent. CONCLUSION: Gastric neurostimulation for diabetic GP appeared to show some beneficial palliative effects overall in the present small open-label series, but the effect is highly variable among patients, and placebo effect cannot be ruled out.

Evaluation of endoscopist and pathologist factors affecting the incidence of microscopic colitis.

BACKGROUND: Microscopic colitis (MC) is an umbrella term for collagenous colitis (CC) and lymphocytic colitis (LC). The incidence of these diseases is increasing for unclear reasons. OBJECTIVE: To identify factors that may impact diagnosis rates of MC in a North American population. METHODS: Population-based pathology and endoscopy databases were searched to identify all cases of MC and the number of lower endoscopy (LE) procedures performed over a five-year period (January 2004 to December 2008) in a catchment area of 1.2 million people. Endoscopist characteristics were compared with diagnostic rates. RESULTS: MC incidence increased from 1.68 per 10,000 in 2004, to 2.68 per 10,000 in 2008, with an average annual increase of 12% per year (95% CI 7% to 16%; P<0.0001). The incidence rate of LC increased but the rate of CC remained stable over the study period. Approximately one-half of the cases were probable and one-half were definite based on pathologists' reports - a proportion that remained stable over time. The number of LEs per population increased by 4.6% annually over the study period (95% CI 2.8% to 6.4%; P<0.0001), and biopsy rates in LE for MC indications (eg, unexplained diarrhea, altered bowel habits) increased over time (3.4% annual increase [95% CI 1.8% to 6.0%]; P<0.001). Endoscopists with an academic practice, gastroenterologists and those with lower annual endoscopy volumes were more likely to make a diagnosis of MC. CONCLUSION: The incidence of MC is rising due to increased diagnosis of LC, while CC incidence remains stable. Patients with MC symptoms have stable endoscopy rates but are being biopsied more often. Physician training, practice type and endoscopy volume impact the diagnostic rates of MC.