Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations.

Among patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality.

Objective To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes.Design Retrospective cohort study using propensity score matched cohorts.Settings Healthcare databases from Finland, the Netherlands, Sweden, and the United Kingdom. Data comprised country specific datasets of linked records on prescriptions, hospitals, general practitioners, cancer, and deaths.Participants Patients with type 2 diabetes who initiated pioglitazone (n=56 337) matched with patients with type 2 diabetes in the same country exposed to diabetes drug treatments other than pioglitazone (n=317 109). Two matched cohorts were created, using a 1:1 fixed ratio (nearest match cohort) and a 1:10 variable ratio (multiple match cohort). Patients were matched on treatment history and propensity scores accounting for several variables associated with pioglitazone initiation.Main outcome measures Hazard ratios and 95% confidence intervals were estimated by Cox’s proportional hazards model with adjustments for relevant confounders. To assess the robustness of the findings, several sensitivity and stratified analyses were performed.Results In the cohort exposed to pioglitazone treatment, 130 bladder cancers occurred over a mean follow-up time of 2.9 years. In the nearest match and multiple match cohorts not exposed to pioglitazone treatment, 153 and 970 bladder cancers were recorded, with a mean follow‑up time of 2.8 and 2.9 years, respectively. With regards to bladder cancer risk, the adjusted hazard ratio for patients ever exposed versus never exposed to pioglitazone was 0.99 (95% confidence interval 0.75 to 1.30) and 1.00 (0.83 to 1.21) in the nearest and multiple match cohorts, respectively. Increasing duration of pioglitazone use and increasing cumulative dose were not associated with risk of bladder cancer (>48 months of pioglitazone use, adjusted hazard ratio 0.86 (0.44 to 1.66); >40 000 mg cumulative dose, 0.65 (0.33 to 1.26) in the nearest match cohort).Conclusions This study shows no evidence of an association between ever use of pioglitzone and risk of bladder cancer compared with never use, which is consistent with results from other recent studies that also included a long follow-up period.Trial registration Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626).

Parents of patients with schizophrenia have a considerably higher risk of psychiatric health care and social welfare benefit receipt than other parents. Psychiatric health care use worsens over time and with increasing disease severity of the offspring.

ObjectivesDescribe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.Research design and methodsThis exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models.ResultsThe crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes.ConclusionsThis analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested.Study registration numberEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).

ObjectivesEstimate and compare the risk of mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.DesignRetrospective cohort study.SettingPooled analysis of clinical data collected from primary and/or secondary care settings in four European countries: Finland, The Netherlands, Sweden and the UK .Participants56 337 patients with type 2 diabetes mellitus first prescribed pioglitazone between 2000 and 2011, and 56 337 patients never prescribed pioglitazone matched by treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry using exact and propensity score matching. Patients were followed-up for a mean of 2.90 (SD 2.21) and 2.83 (SD 2.37) years in the pioglitazone-exposed and non-pioglitazone-exposed groups, respectively.OutcomesAll-cause mortality ascertained from clinical or registry data. Mortality was a planned secondary outcome in a study primarily studying the association of pioglitazone use with bladder cancer risk.ResultsThe crude overall mortality rate per 10 000 patient years was 206 (95% CI 199 to 213) in the pioglitazone-exposed group and 448 (95% CI 438 to 458) in the non-pioglitazone-exposed group. The crude HR comparing pioglitazone to alternative antidiabetic exposure was 0.46 (95% CI 0.45 to 0.48). This reduced in magnitude to 0.67 (95% CI 0.64 to 0.70) following further adjustment for matching variables, propensity scores, age, gender and time-dependent variables representing use of alternative antidiabetic drugs.ConclusionsIn this large observational cohort study of patients with type 2 diabetes, pioglitazone exposure was associated with a statistically significant decrease in the risk of all-cause mortality across four European countries. Results should be interpreted with caution due to the potential for residual confounding.Protocol registrationEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance.

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ArtikkelitTerveystieteiden tiedekunta 2018Antipsychotics and mortality in a Introduction: It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. Methods: We linked prospectively gathered nationwide register-based data during 2006-2013 to study all-cause mortality among all patients aged 16-64 years with schizophrenia in Sweden (N = 29,823 in total; N = 4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. Results: During the mean follow-up of 5.7 years, 2515 patients (8.4%) died. During the maximum follow-up (7.5 years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01-1.86) for first generation (FG) LAIs, 1.52 (1.13-2.05) for SG orals, 1.83 (1.33-2.50) for FG orals, and 3.39 (2.53-4.56) for nonuse of antipsychotics. Concerning specific agents, the lowest mortality was observed for once-monthly paliperidone LAI (0.11, 0.03-0.43), oral aripiprazole (0.22, 0.15-0.34), and risperidone LAI (0.31, 0.23-0.43). In pairwise comparison, LAIs were associated with 33% lower mortality than equivalent orals (0.67, 0.56-0.80). The results with incident cohort were consistent with the primary analyses. Conclusions: Among patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality.