Prevalence and outcomes of prenatal recreational cannabis use in high-income countries: a scoping review.

BACKGROUND: With expanding recreational cannabis legalisation, pregnant women and their offspring are at risk of potentially harmful consequences. OBJECTIVES: To assess the prevalence of recreational cannabis use among pregnant women, health outcomes associated with prenatal recreational cannabis use, and the potential impact of recreational cannabis legalisation on this population. SEARCH STRATEGY: Five databases and the grey literature were systematically searched (2000-2019). SELECTION CRITERIA: Human studies published in English or French reporting on the prevalence of prenatal recreational cannabis use in high-income countries. DATA COLLECTION AND ANALYSIS: Data on study characteristics, prenatal substance use, and health outcomes were extracted and qualitatively synthesised. MAIN RESULTS: Forty-one publications met our inclusion criteria. The overall prevalence of prenatal cannabis use varied substantially (min-max: 0.24-22.6%), with the greatest use in the first trimester. In the three studies with temporal data available, rates of prenatal cannabis use increased across years. Only 7/41 and 5/41 studies provided information on gestational age of exposure and frequency of use, respectively. The concomitant use of alcohol, illicit drugs, and tobacco was higher among cannabis users than nonusers. Prenatal cannabis use was associated with select neonatal, but not maternal, health outcomes. There were insufficient data to compare prenatal cannabis use between the pre- and post-legalisation periods. CONCLUSION: Cannabis use among pregnant women is prevalent and may be associated with adverse neonatal outcomes. Future studies should assess the gestational age and frequency of cannabis exposure, and usage patterns prior to and following legalisation. TWEETABLE ABSTRACT: Women who consume cannabis during pregnancy could risk predisposing their newborns to poor birth outcomes.

Non-medical cannabis in North America: an overview of regulatory approaches.

OBJECTIVES: The objective of this study was to describe existing regulations of non-medical cannabis legalization in North America to inform recommendations for future health policy. These regulations are among the first in the world and will set a precedent for other jurisdictions globally who legalize cannabis. STUDY DESIGN: This was a review of online grey literature on regulatory approaches to non-medical cannabis legalization in North American jurisdictions. METHODS: We conducted an internet search in June 2019 to identify government and public health resources published after January 1, 2012. We were able to achieve data saturation using a limited number of resources. Data extraction was conducted by two independent reviewers, with disagreements resolved by consensus. RESULTS: Eleven US states, the District of Columbia, and Canada have enacted legal recreational cannabis regulations. The legal age of cannabis possession matches the legal drinking age in all jurisdictions except one. Most consumption is in private residences only, with some provinces/territories permitting public consumption where tobacco is permitted. Most jurisdictions allow for home growing of up to 6 (US) or 4 (Canada) plants and a maximum possession of 1 oz. (US) or 1.06 oz. (Canada). Cannabis is available for purchase only in private retail stores in US states, while Canada has also legalized online sales. Impaired driving assessment is not cannabis-specific in most US states, while Canada has federal driving limits. CONCLUSIONS: Although North American approaches to regulating recreational cannabis use are consistent in many aspects, some exceptions exist (e.g., home growing, personal possession). More research is needed to assess the impact of variations in regulatory policies on potential harms from legalization to inform future policy decisions in North America and abroad. Complementary public health interventions will be crucial in ensuring public health and safety.

Prediction model and web-based risk calculator for postoperative ileus after loop ileostomy closure.

BACKGROUND: Postoperative ileus (POI) is a significant complication after loop ileostomy closure given both its frequency and impact on the patient. The purpose of this study was to develop and externally validate a prediction model for POI after loop ileostomy closure. METHODS: The model was developed and validated according to the TRIPOD checklist for prediction model development and validation. The development cohort included consecutive patients who underwent loop ileostomy closure in two teaching hospitals in Montreal, Canada. Candidate variables considered for inclusion in the model were chosen a priori based on subject knowledge. The final prediction model, which modelled the 30-day cumulative incidence of POI using logistic regression, was selected using the highest area under the receiver operating characteristic curve (AUC) criterion. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. The model was then validated externally in an independent cohort of similar patients from the University of British Columbia. RESULTS: The development cohort included 531 patients, in whom the incidence of POI was 16·8 per cent. The final model included five variables: age, ASA fitness grade, underlying pathology/treatment, interval between ileostomy creation and closure, and duration of surgery for ileostomy closure (AUC 0·68, 95 per cent c.i. 0·61 to 0·74). The model demonstrated good calibration (P = 0·142). The validation cohort consisted of 216 patients, and the incidence of POI was 15·7 per cent. On external validation, the model maintained good discrimination (AUC 0·72, 0·63 to 0·81) and calibration (P = 0·538). CONCLUSION: A prediction model was developed for POI after loop ileostomy closure and included five variables. The model maintained good performance on external validation.

ANTECEDENTES: El íleo postoperatorio (postoperative ileus, POI) es una complicación importante tras el cierre de la ileostomía en asa, dada su frecuencia e impacto en el paciente. El propósito de este estudio fue desarrollar y validar externamente un modelo de predicción para el POI después del cierre de la ileostomía en asa. MÉTODOS: El modelo fue desarrollado y validado de acuerdo con la lista de verificación TRIPOD para el desarrollo y validación de un modelo de predicción. La cohorte de desarrollo incluyó pacientes consecutivos en los que se realizó el cierre de la ileostomía en asa en dos hospitales universitarios en Montreal, Canadá. Las variables candidatas consideradas para su inclusión en el modelo se seleccionaron a priori en función del conocimiento del problema. El modelo de predicción final, que modeló la incidencia acumulada a 30 días de POI mediante regresión logística, se seleccionó según el criterio del área más alta bajo la curva operativa del receptor (area under the receiver operating curve, AUC). La calibración del modelo se evaluó utilizando la prueba de bondad de ajuste de Hosmer-Lemeshow. El modelo fue posteriormente validado externamente en una cohorte independiente de pacientes similares de la Universidad de British Columbia. RESULTADOS: La cohorte de desarrollo incluyó a 531 pacientes, y la incidencia de POI fue de 16,7%. El modelo final incluyó cinco variables: edad, clasificación ASA (American Society of Anaesthesiologists), patología inicial y tratamiento, tiempo entre las dos intervenciones quirúrgicas y tiempo operatorio del cierre de ileostomía (AUC = 0,68; i.c. del 95%: 0,61 a 0,74). El modelo demostró buena calibración (P = 0,142). La cohorte de validación consistió en 216 pacientes, y la incidencia de POI fue de 15,7%. En la validación externa, el modelo mantuvo una buena discriminación (AUC = 0,72; i.c. del 95%: 0,63 a 0,81) y calibración (P = 0,538). CONCLUSIÓN: Se ha desarrollado un modelo de predicción de POI después del cierre de la ileostomía en asa que incluía cinco variables. El modelo mantuvo un buen funcionamiento en la validación externa.

Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

BACKGROUND: The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. OBJECTIVES: To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. SEARCH STRATEGY: We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. SELECTION CRITERIA: Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. DATA COLLECTION AND ANALYSIS: We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. MAIN RESULTS: Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. AUTHOR'S CONCLUSIONS: As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. TWEETABLE ABSTRACT: Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel).

Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting. Patients and methods: We searched PubMed, Embase (OVID), Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to June 2016 for all RCTs comparing cardiovascular and cerebrovascular safety of AIs to tamoxifen, AIs to placebo or no-treatment, or tamoxifen to placebo or no-treatment in the adjuvant or extended adjuvant setting. Relative risks (RRs) were pooled using DerSimonian and Laird random-effects models with analyses stratified by RCT design. Results: A total of 19 RCTs were included in the meta-analysis (n = 62 345). In the adjuvant setting, AIs were associated with a 19% (RR: 1.19, 95% confidence interval [CI]: 1.07-1.34) increased risk of cardiovascular events compared with tamoxifen. AIs were not associated with an increased risk compared with placebo in the extended-adjuvant setting (RR: 1.01, 95% CI: 0.85-1.20). In the adjuvant setting, tamoxifen was associated with a 33% (RR: 0.67, 95% CI: 0.45-0.98) decreased risk compared with placebo or no-treatment. The results from extended adjuvant RCTs comparing tamoxifen to placebo were inconclusive but suggestive of a small protective effect (RR: 0.91, 95% CI: 0.77-1.07). Conclusions: The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.

Drospirenone-containing combined oral contraceptives and the risk of arterial thrombosis: a population-based nested case-control study.

OBJECTIVE: To compare the rate of arterial thromboembolism (ATE) of drospirenone-containing COCs to that of levonorgestrel-containing COCs. DESIGN: Population-based cohort study. SETTING: United Kingdom's Clinical Practice Research Datalink (CPRD), which contains clinical records for >11 million patients. POPULATION: Women aged 16-45 years prescribed a drospirenone- or levonorgestrel-containing COC between May 2002 and June 2012. METHODS: We conducted nested case-control analyses using risk set sampling to randomly select up to 10 controls for each ATE case, matched on age, cohort entry year, CPRD registration year, COC user type (first-time ever, new, switcher, or prevalent users), duration of COC use, duration of progestin-only or implantable contraceptive use, pre-cohort entry duration of drospirenone and levonorgestrel use, and duration of follow up. MAIN OUTCOME MEASURES: We used conditional logistic regression to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for high-dimensional propensity scores. RESULTS: Our cohort included 339 743 women followed over a mean 4.4 years, during which 228 ATE cases occurred: 37 myocardial infarctions, 170 strokes, and 21 other ATEs; overall rate: 1.5 events per 10 000 person-years (PYs). After adjusting for potential confounders, the hazard ratio for ATE with current use of drospirenone-containing COCs versus current use of levonorgestrel-containing COCs was 0.89 (95% CI 0.35, 2.28), corresponding to a rate difference of -0.16 events per 10 000 PYs. CONCLUSIONS: The overall rate of ATE in this population is low regardless of which COC was taken. We found little evidence of a difference in the rate of ATE with drospirenone- versus levonorgestrel-containing COCs. TWEETABLE ABSTRACT: Little evidence was found of a greater incidence of arterial thrombosis with drospirenone versus levonorgestrel contraceptives.

Dipeptidyl peptidase-4 inhibitors and the risk of community-acquired pneumonia in patients with type 2 diabetes.

AIMS: To determine whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with an increased risk of community-acquired pneumonia. METHODS: The UK Clinical Practice Research Datalink and the Hospital Episodes Statistics database were used to conduct a nested case-control analysis within a cohort of new users of antidiabetic drugs between 2007 and 2012. Incident cases of hospitalization for community-acquired pneumonia were matched with up to 20 controls on age, duration of treated diabetes, calendar year and duration of follow-up. Conditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization for community-acquired pneumonia associated with current use of DPP-4 inhibitors compared with current use of two or more oral antidiabetic drugs. RESULTS: The cohort included 49,653 patients, of whom 562 were hospitalized for community-acquired pneumonia during follow-up (incidence rate 5.2/1000 person-years). Compared with current use of two or more oral antidiabetic drugs, current use of DPP-4 inhibitors was not associated with an increased risk of hospitalized community-acquired pneumonia overall (adjusted OR 0.80, 95% CI 0.50-1.29) or according to duration of use (p for trend = 0.57). CONCLUSIONS: The use of DPP-4 inhibitors was not associated with an increased risk of hospitalization for community-acquired pneumonia. Additional research is needed to assess the association between these drugs and other serious infections.

Drospirenone-containing oral contraceptive pills and the risk of venous and arterial thrombosis: a systematic review.

BACKGROUND: Previous studies have provided conflicting results regarding the effect of drospirenone-containing oral contraceptive pills (OCPs) on the risk of venous and arterial thrombosis. OBJECTIVES: To conduct a systematic review to assess the risk of venous thromboembolism (VTE), myocardial infarction (MI), and stroke in individuals taking drospirenone-containing OCPs. SEARCH STRATEGY: We systematically searched CINAHL, the Cochrane Library, Dissertation & Abstracts, EMBASE, HealthStar, Medline, and the Science Citation Index from inception to November 2012. SELECTION CRITERIA: We included all case reports, observational studies, and experimental studies assessing the risk of venous and arterial thrombosis of drospirenone-containing OCPs. DATA COLLECTION AND ANALYSIS: Data were collected independently by two reviewers. MAIN RESULTS: A total of 22 studies [six case reports, three case series (including 26 cases), and 13 comparative studies] were included in our systematic review. The 32 identified cases suggest a possible link between drospirenone-containing OCPs and venous and arterial thrombosis. Incidence rates of VTE among drospirenone-containing OCP users ranged from 23.0 to 136.7 per 100 000 woman-years, whereas those among levonorgestrel-containing OCP users ranged from 6.64 to 92.1 per 100 000 woman-years. The rate ratio for VTE among drospirenone-containing OCP users ranged from 4.0 to 6.3 compared with non-users of OCPs, and from 1.0 to 3.3 compared with levonorgestrel-containing OCP users. The arterial effects of drospirenone-containing OCPs were inconclusive. AUTHOR'S CONCLUSIONS: Our systematic review suggests that drospirenone-containing OCP use is associated with a higher risk for VTE than both no OCP use and levonorgestrel-containing OCP use.

The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials.

BACKGROUND: Pregnant smokers are often prescribed counselling as part of multicomponent cessation interventions. However, the isolated effect of counselling in this population remains unclear, and individual randomised controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION CRITERIA: We included RCTs conducted in pregnant women in which the effect of counselling could be isolated and those that reported biochemically validated abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND ANALYSIS: Overall estimates were derived using random effects meta-analysis models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of which examined abstinence at 6 months. The proportion of women that remained abstinent at the end of follow up was modest, ranging from 4 to 24% among those randomised to counselling and from 2 to 21% among control women. The absolute difference in abstinence reached a maximum of only 4%. Summary estimates are inconclusive because of wide confidence intervals, albeit with little evidence to suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08, 95% confidence interval 0.84-1.40). There was no evidence to suggest that efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs examining the isolated effect of smoking cessation counselling in pregnant women are limited but sufficient to rule out large treatment effects. Future RCTs should examine pharmacological therapies in this population.