Dataset Information

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

ABSTRACT:

Background

Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality.

Methods

We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations.

Results

Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78-1.85) and mixed users (HR = 1.44; 95% CI = 1.42-1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71-0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk.

Conclusions

The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.

SUBMITTER: Lan TY

PROVIDER: S-EPMC4692546 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

Lan Tzuo-Yun TY Zeng Ya-Fang YF Tang Gau-Jun GJ Kao Hui-Chuan HC Chiu Hsien-Jane HJ Lan Tsuo-Hung TH Ho Hsiao-Feng HF

PloS one 20151228 12

<h4>Background</h4>Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality.<h4>Methods</h4>We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data ...[more]

PMID: 26709926

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Project description:BackgroundBenzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.Methods and findingsThe retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.ConclusionsIn US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

Project description:An estimated 6%-10% of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality.A large integrated health system in the USA.Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis.Subjects (mean age 54?years) were 10?529 patients who received hypnotic prescriptions and 23?676 matched controls with no hypnotic prescriptions, followed for an average of 2.5?years between January 2002 and January 2007.Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards models controlled for risk factors and using up to 116 strata, which exactly matched cases and controls by 12 classes of comorbidity.As predicted, patients prescribed any hypnotic had substantially elevated hazards of dying compared to those prescribed no hypnotics. For groups prescribed 0.4-18, 18-132 and >132 doses/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36) and 5.32 (4.50 to 6.30), respectively, demonstrating a dose-response association. HRs were elevated in separate analyses for several common hypnotics, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates and sedative antihistamines. Hypnotic use in the upper third was associated with a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55). Results were robust within groups suffering each comorbidity, indicating that the death and cancer hazards associated with hypnotic drugs were not attributable to pre-existing disease.Receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death even when prescribed <18 pills/year. This association held in separate analyses for several commonly used hypnotics and for newer shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality.

Project description:BACKGROUND:Risk factors for cause-specific mortality have not been widely studied among people with HIV infection. Our objectives were to estimate rates of and risk factors for all-cause and cause-specific mortality from 1995 to 2014 among HIV-infected people in Ontario. METHODS:We conducted a population-based retrospective cohort study using provincial health databases of people with HIV infection who were aged 16 years or more, were residents of Ontario between 1995 and 2014, and had HIV infection according to a previously validated algorithm. We used International Classification of Diseases codes to classify the underlying cause of death and estimated age-adjusted mortality rates per 100 person-years for 1995 to 2014. We used descriptive statistics to characterize the cohort at baseline and calculated adjusted mortality rate ratios (RRs) using generalized estimating equations. RESULTS:Among 23 043 people, the all-cause mortality rate declined from 6.69 to 1.53 per 100 person-years over the study period, and the rate of death from HIV/AIDS declined from 4.75 to 0.46 per 100 person-years. Concomitantly, the proportions of deaths due to cancer, cardiovascular disease and other noncommunicable diseases rose; however, rates remained constant or declined. Compared to males, females had higher mortality due to cardiovascular disease (adjusted RR 1.36, 95% confidence interval [CI] 1.04-1.77), noncommunicable causes (adjusted RR 1.75, 95% CI 1.39-2.20) and, by 2010-2014, any cause (adjusted RR 1.19, 95% CI 1.02-1.38). Residing in a low-income neighbourhood was associated with increased risk for most causes, including HIV/AIDS (adjusted RR in 2010-2014 1.86, 95% CI 1.49-2.31). Rural residence was associated with increased mortality due to malignant disease (adjusted RR 1.60, 95% CI 1.10-2.34) and noncommunicable disease (adjusted RR 1.86, 95% CI 1.25-2.77). Being an immigrant was associated with lower risk of death from all causes. INTERPRETATION:Over the study period, death was increasingly due to common chronic conditions rather than to HIV infection itself. Care should incorporate the prevention and management of these conditions, especially among females and those residing in rural and low-income areas.

Project description:BackgroundMany antipsychotics elevate prolactin, a hormone implicated in breast cancer aetiology however no studies have investigated antipsychotic use in patients with breast cancer. This study investigated if antipsychotic use is associated with an increased risk of cancer-specific mortality among breast cancer patients.MethodsA cohort of 23,695 women newly diagnosed with a primary breast cancer between 1st January 1998 and 31st December 2012 was identified from the UK Clinical Practice Research Datalink linked to English cancer-registries and followed for until 30th September 2015. Time-dependent Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific mortality comparing use of antipsychotics with non-use, overall, and by prolactin elevating activitiy. Analyses were repeated restricting to patients with a history of severe mental illness to control for potential confounding by indication.ResultsIn total 848 patients were prescribed an antipsychotic and of which 162 died due to their breast cancer. Compared with non-use, antipsychotic use was associated with an increased risk of breast-cancer specific mortality (HR 2.25, 95%CI 1.90-2.67), but this did not follow a dose response relation. Restricting the cohort to patients with severe mental illness attenuated the association between antipsychotic use and breast cancer-specific mortality (HR 1.11, 95%CI 0.58-2.14).ConclusionsIn this population-based cohort of breast cancer patients, while the use of antipsychotics was associated with increased breast cancer-specific mortality, there was a lack of a dose response, and importantly null associations were observed in patients with severe mental illness, suggesting the observed association is likely a result of confounding by indication. This study provides an exemplar of confounding by indication, highlighting the importance of consideration of this important bias in studies of drug effects in cancer patients.

Dataset Information

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

Background

Methods

Results

Conclusions

Publications

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

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