Dataset Information

Pioglitazone use and risk of bladder cancer: population based cohort study.

ABSTRACT:

Objective

To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.

Design

Population based cohort study.

Setting

General practices contributing data to the United Kingdom Clinical Practice Research Datalink.

Participants

A cohort of 145,806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.

Main outcome measures

The use of pioglitazone was treated as a time varying variable, with use lagged by one year for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident bladder cancer associated with pioglitazone overall and by both cumulative duration of use and cumulative dose. Similar analyses were conducted for rosiglitazone, a thiazolidinedione not previously associated with an increased risk of bladder cancer.

Results

The cohort generated 689,616 person years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence 90.2 per 100,000 person years). Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100,000 person years; hazard ratio 1.63, 95% confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 v 88.9 per 100,000 person years; 1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed for pioglitazone but not for rosiglitazone.

Conclusion

The results of this large population based study indicate that pioglitazone is associated with an increased risk of bladder cancer. The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.

SUBMITTER: Tuccori M

PROVIDER: S-EPMC4816602 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

Pioglitazone use and risk of bladder cancer: population based cohort study.

Tuccori Marco M Filion Kristian B KB Yin Hui H Yu Oriana H OH Platt Robert W RW Azoulay Laurent L

BMJ (Clinical research ed.) 20160330

<h4>Objective</h4>To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.<h4>Design</h4>Population based cohort study.<h4>Setting</h4>General practices contributing data to the United Kingdom Clinical Practice Research Datalink.<h4>Participants</h4>A cohort of 145,806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.<h4>M ...[more]

PMID: 27029385

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Project description: To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes. Retrospective cohort study using propensity score matched cohorts. 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. 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. 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. 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). 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. Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626).

Project description:BackgroundAlthough radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes.MethodsThis large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray's competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC.ResultsOf 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P<0.05), and decreased with increasing age at diagnosis, and increased with time since diagnosis. In competing risk regression analysis, undergoing RT was associated with a higher risk of SBC (hazard ratio [HR], 1.443, 95% confidence interval [CI], 1.209-1.720; P<0.001). The results of the dynamic SIR for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency, and was significantly related to the variations of age at RC diagnosis and decreased with time progress. The 10-year OS and CSS among SBC patients after RT were comparable to SBC patients after NRT.ConclusionRadiation was associated with an increased risk of developing SBC in RC patients, and special attention should be paid to the surveillance of these patients.

Project description:BACKGROUND:In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice. METHODS AND FINDINGS:The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ?50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding. CONCLUSIONS:In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.

Dataset Information

Pioglitazone use and risk of bladder cancer: population based cohort study.

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusion

Publications

Pioglitazone use and risk of bladder cancer: population based cohort study.

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