Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.

BackgroundPregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis.MethodsMEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes).ResultsAfter screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23–7.07), valproate (OR, 2.93; 95% CrI, 2.36–3.69), topiramate (OR, 1.90; 95% CrI, 1.17–2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35–2.47), phenytoin (OR, 1.67; 95% CrI, 1.30–2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10–1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72–1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43–1.16) were not.ConclusionThe newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control.Systematic Review RegistrationPROSPERO CRD42014008925Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0845-1) contains supplementary material, which is available to authorized users.

Many unhealthy behaviors often begin during adolescence and represent major public health challenges. Substance abuse has a major impact on individuals, families, and communities, as its effects are cumulative, contributing to costly social, physical, and mental health problems. We conducted an overview of systematic reviews to evaluate the effectiveness of interventions to prevent substance abuse among adolescents. We report findings from a total of 46 systematic reviews focusing on interventions for smoking/tobacco use, alcohol use, drug use, and combined substance abuse. Our overview findings suggest that among smoking/tobacco interventions, school-based prevention programs and family-based intensive interventions typically addressing family functioning are effective in reducing smoking. Mass media campaigns are also effective given that these were of reasonable intensity over extensive periods of time. Among interventions for alcohol use, school-based alcohol prevention interventions have been associated with reduced frequency of drinking, while family-based interventions have a small but persistent effect on alcohol misuse among adolescents. For drug abuse, school-based interventions based on a combination of social competence and social influence approaches have shown protective effects against drugs and cannabis use. Among the interventions targeting combined substance abuse, school-based primary prevention programs are effective. Evidence from Internet-based interventions, policy initiatives, and incentives appears to be mixed and needs further research. Future research should focus on evaluating the effectiveness of specific interventions components with standardized intervention and outcome measures. Various delivery platforms, including digital platforms and policy initiative, have the potential to improve substance abuse outcomes among adolescents; however, these require further research.

MD; for the COPPS-2 Investigators IMPORTANCE Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postop-erative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients 70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, −2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, −8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastro-intestinal adverse effects reduced the potential benefits of colchicine in this setting.