Valentino Conti

Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case–control study

BackgroundOnly three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs.MethodsWe identified 84,253 adult individuals who began antipsychotic treatment in a large Italian health care system. Cases were all cohort members who were hospitalized for non-fatal or fatal pulmonary embolism during follow-up. Up to 20 controls for each case were extracted from the study cohort using incidence density sampling and matched by age at cohort entry and gender. Each individual was classified as current, recent or past antipsychotic user. The occurrence non-fatal or fatal pulmonary embolism was the outcome of interest.ResultsCompared to past use, current antipsychotic use more than double the risk of pulmonary embolism (odds ratio 2.31, 95% confidence interval 1.16 to 4.59), while recent use did not increase the risk. Both conventional and atypical antipsychotic exposure was associated with an increase in risk, and the concomitant use of both classes increased the risk of four times (odds ratio 4.21, 95% confidence interval 1.53 to 11.59).ConclusionsAdding the results of this case–control study to a recent meta-analysis of three observational studies substantially changed the overall estimate, which now indicates that antipsychotic exposure significantly increases the risk of pulmonary embolism.

Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Clinical Factors and Acute Pharmacological Management.

Objective:Paroxysmal sympathetic hyperactivity (PSH) is widely described as occurring during intensive care, but in a number of patients it may last longer into the rehabilitation phase. Furthermore, drug therapy has been based on isolated observations. In this study, our aims are to describe a group of 26 pediatric rehabilitation patients with PSH and to quantify the effect of several drugs used to suppress PSH episodes. Setting:Neurorehabilitation unit of IRCCS Eugenio Medea, Bosisio Parini (LC), Italy. Participants:A total of 407 pediatric patients with postacute acquired brain injury, 26 of which had PSH. Design:Retrospective cohort study. Main Measures:Descriptive demographic and clinical data. Odds ratios quantification of the efficacy of drug therapies administered acutely to suppress PSH episodes. Results:PSH was associated with a longer duration of coma and a greater incidence of death. When administered acutely to suppress PSH episodes, the best drugs were clonazepam, hydroxyzine, and delorazepam, while analgesic drugs showed little efficacy. Conclusions:PSH, whether causative or not, is associated with a worse long-term course in rehabilitation. Clinical management of PSH may be helped by a number of acutely administered drug therapies.

Seriousness, preventability, and burden impact of reported adverse drug reactions in Lombardy emergency departments: a retrospective 2-year characterization

Objective The purpose of this study was to determine the prevalence of adverse drug reactions (ADRs) reported in emergency departments (EDs) and carry out a thorough characterization of these to assess preventability, seriousness that required hospitalization, subsequent 30-day mortality, and economic burden. Methods This was a retrospective cohort study of data from an active pharmacovigilance project at 32 EDs in the Lombardy region collected between January 1, 2010 and December 31, 2011. Demographic, clinical, and pharmacological data on patients admitted to EDs were collected by trained and qualified monitors, and deterministic record linkage was performed to estimate hospitalizations. Pharmacoeconomic analyses were based on Diagnosis-Related Group reimbursement. Results 8,862 ADRs collected with an overall prevalence rate of 3.5 per 1,000 visits. Of all ADRs, 42% were probably/definitely preventable and 46.4% were serious, 15% required hospitalization, and 1.5% resulted in death. The System Organ Classes most frequently associated with ADRs were: skin and subcutaneous tissue, gastrointestinal, respiratory thoracic and mediastinal, and nervous system disorders. The most common Anatomical Therapeutic Chemical classes involved in admissions were J (anti-infectives and immunomodulating agents), B (blood and blood-forming organs), and N (nervous system). Older age, yellow and red triage, higher number of concomitantly taken drugs, and previous attendance in ED for the same ADR were significantly associated with an increased risk of hospitalization. The total cost associated with ADR management was €5,184,270, with a mean cost per patient of €585. Fifty-eight percent of the economic burden was defined as probably/definitely preventable. Conclusion ADRs are a serious health/economic issue in EDs. This assessment provides a thorough estimation of their seriousness, preventability, and burden impact in a large population from a representative European region.

Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Pathological Features and Scheduled Pharmacological Therapies.

Objective: Information on course and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation and in pediatric patients is lacking. To increase knowledge on the course and treatment of PSH in pediatric patients during rehabilitation, we retrospectively analyzed 23 pediatric patients with PSH, describing the course of PSH and administered drugs, and explored the association of PSH remission with drug doses. Setting: Neurorehabilitation unit of IRCCS Eugenio Medea, Bosisio Parini (LC), Italy. Participants: Twenty-three pediatric patients with postacute acquired brain injury, who remitted from PSH. Design: Retrospective cohort study. Main Measures: Description of features and course of PSH, description of drug therapies, and analysis of covariance of their doses. Correlations between remission and drug doses/clinical variables. Estimation of the odds ratios of remission. Results: At admittance patients displayed at least 3 features of PSH with an overall score of 9, which diminished progressively during remission. Therapies with propranolol, baclofen, niaprazine, and diazepam were progressively uptitrated, indicating potential usefulness. When testing possible predictors of remission, we found positive effects of propranolol and diazepam and of traumatic etiology and a negative effect of maximum PSH severity. Conclusions: Results should be interpreted carefully regarding causal relationships and drug doses and combinations, but they encourage further studies on the use of propranolol and diazepam to favor PSH remission.

Cardiovascular safety of tiotropium Respimat vs HandiHaler in the routine clinical practice: A population-based cohort study

The cardiovascular safety of tiotropium Respimat formulation in the routine clinical practice is still an open issue. Our aim was to compare the risk of acute myocardial infarction and heart rhythm disorders in incident users of either tiotropium Respimat or HandiHaler. The study population comprises patients aged ≥45 years, resident in two Italian regions with a first prescription of tiotropium (HandiHaler or Respimat) between 01/07/2011-30/11/2013. The cohort was identified through the database of prescriptions reimbursed by the Italian National Health Service. Comorbidities and clinical outcomes were obtained from hospital records. The primary outcome was the first hospitalization for acute myocardial infarction and/or for heart rhythm disorders during the exposure period. Hazard ratios were estimated in the propensity score-matched groups through Cox regression. After matching, 31,334 patients with incident prescription of tiotropium were included. The two groups were balanced with regard to baseline characteristics. Similar incidence rates of the primary outcome between Respimat and HandiHaler users were identified (adjusted hazard ratio 1.02, 95% CI 0.82–1.28). No risk difference between Respimat and HandiHaler emerged when considering clinical events separately. This large cohort study showed a comparable acute cardiovascular safety profile of the two tiotropium formulations.

When important steps for a reliable meta-analysis are missing: the bevacizumab versus ranibizumab case.

Dear Sir,W e have read with attention and interest the systematic review on the effectiveness and safety of bevacizumab and ranibizumab in the treatment of age-related macular degeneration(AMD)written by Zhang et al[1]and published on number of April 2014 of International Journal of Ophthalmology.The authors,who collected data from 4randomized clinical trials(RCTs)and 11 observational