Objectives To evaluate the cardiac safety of central nervous system stimulants in children and adolescents.Design Population based retrospective cohort study.Setting Automated healthcare claims data from 1 219 847 children and young people eligible for 28 state Medicaid programmes from 1999 to 2006 linked to the Social Security Death Master File and the National Death Index.Participants Children and young people age 3-18 entered the cohort at the first diagnosis of a mental health condition commonly treated with stimulants (such as attention-deficit/hyperactivity disorder) after a minimum period of six months' eligibility and were followed until loss of eligibility, their 19th birthday, admission to hospital for longer than 30 days, or death. Exclusion criteria included transplant recipients, receipt of dialysis, or claims indicating substance misuse. We retained high risk groups with similar use of stimulants as low risk children (such as children with congenital heart disease). Sociodemographic characteristics, cardiac risk factors, and psychiatric diagnoses obtained from before the index period were summarised with a propensity score. We used discrete survival analysis to estimate the relative risk for periods of stimulant use and non-use, adjusted for propensity score and antipsychotic use for the full cohort and the high risk and low risk groups. Main outcome measuresComposite endpoint of stroke, acute myocardial infarction, or sudden cardiac death; a secondary composite endpoint added ventricular arrhythmia Results A total of 66 (95 including ventricular arrhythmia) events occurred during 2 321 311 years of follow-up. The odds ratio adjusted for propensity score and antipsychotic use for current versus no stimulant use was 0.62 (95% confidence interval 0.27 to 1.44), with a corresponding adjusted incidence rate of 2.2 and 3.5 per 100 000 patient years for current stimulant and non-use, respectively. Twenty six events occurred in high risk patients (incidence rate 63 per 100 000 patient years) with an odds ratio of 1.02 (0.28 to 3.69). Odds ratios for the secondary endpoint were similar to those for the primary endpoint (0.74, 0.38 to 1.46). ConclusionsTreatment of children with central nervous stimulants is not significantly associated with an increase in the short term risk of severe cardiac events. Analyses cannot be generalised to children with long term use of stimulants. Furthermore, long term effects of slight increases in heart rate or blood pressure are unknown. IntroductionThe past decade has seen clinical and policy debates over the potential cardiac risk of central nervous system stimulants approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). The paucity of conclusive evidence regarding safety of stimulants has resulted in recommendations in favour of and against a black box warning, 1 2 withdrawal and reintroduction of Adderall (mixed amphetamine salts) by the Canadian regulatory agency, and controversy regarding the need for electrocardiography before the star...

The continuous infusions of MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and ionized magnesium levels similar to levels required to produce smooth muscle relaxation in other clinical settings. Further studies are needed to investigate the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment for severe asthma treatment and determine the SrMg level required to maintain airway smooth muscle relaxation.

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Aim:A global afatinib named patient use program in non-small-cell lung carcinoma (NSCLC) commenced in 2010. Materials & methods: Eligible NSCLC patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had activating EGFR/HER2 mutations, exhausted all other treatments, and were ineligible for afatinib trials. Results: Data, as of January 2016, were reported on 3966 heavily pretreated NSCLC patients (41 countries; 6 continents). Among 2595/3966 (65.4%) patients with tumor EGFR status, 2407 (92.8%) were EGFR mutation positive. Median time to treatment failure (2862/3966 [72.2%] patients with available data) was 4.4 months. Among 1141/2862 (39.9%) patients with response reported, objective response rate was 23.4% (267/1141). Safety findings were as expected. Conclusion: Time to treatment failure durations and objective response rates were encouraging. Afatinib is an orally available, irreversible ErbB family (EGFR/ErbB1; HER2/ErbB2; and HER4/ErbB4) blocker approved in the European Union, USA, Canada, Switzerland and several Asian, Latin American and Middle East countries for non-small-cell lung carcinoma (NSCLC) patients with certain sensitizing EGFR mutations [1,2]. In contrast to the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, afatinib covalently binds to the ErbB receptor in vitro, irreversibly blocking signaling with sustained inhibition of mitogenic activity [3]. The global, Phase III LUX-Lung 3 (LL3) trial in metastatic EGFR mutation-positive NSCLC demonstrated a significant improvement in the primary end point of progression-free survival (PFS) with first-line afatinib 40 mg/day versus pemetrexed/cisplatin (11.1 vs 6.9 months; hazard ratio [HR]: 0.58; p = 0.001) for all patients with EGFR mutations [4]. A larger median PFS difference was noted for patients with common mutations of Del19 and Future Oncol. (Epub ahead of print)