Association between benzodiazepine use and risks of chronic-onset poststroke pneumonia: a population-based cohort study.
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SUBMITTER: Lin SM
PROVIDER: S-EPMC6347861 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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Project description:ImportanceIncreased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently.ObjectiveTo examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures.Design, setting, and participantsThis cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020.Main outcomes and measuresReceipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively.ResultsAmong 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180-day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50).Conclusions and relevanceIn this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.
| S-EPMC8176328 | biostudies-literature
Project description:BackgroundConcerns were raised about pneumonia development from benzodiazepines (BZDs) and Z-drugs, but direct evidence is limited, conflicting and without examining the highly susceptible patients with chronic kidney disease (CKD) nor specifying the risk for different drug utilizations. This study aimed to investigate whether use of BZDs and Z-drugs was each associated with an increased risk of pneumonia in a CKD population.MethodsWe performed a nested case-control study of 36,880 CKD patients analyzing the Taiwan National Health Insurance Database between 01/1/2000 and 12/31/2011. Among the study cohort, we identified 4,533 cases of pneumonia based on validated disease codes, chest x-ray examination, and prescriptions of respiratory antibiotics, and randomly selected 16,388 controls from risk sets, matched by sex, age, and number of CKD-related hospitalizations. All prescription filling records of BZDs and Z-drugs in the year before the event/index date were analyzed for cases and controls. Conditional logistic regressions were performed to estimate the odds ratios (ORs).ResultsCurrent use of BZDs was associated with a 1.31-fold (95% CI, 1.18-1.26) increased risk of pneumonia compared to nonuse, but not for recent and past use. The risk from current BZD use was confined to new initiation (adjusted OR, 2.47; 95% CI, 2.02-3.03) or use for ≤ 30 days, and elevated to 2.88-fold (95% CI, 1.87-4.42) with parenteral administration. New initiation and current short-term use of Z-drugs was associated with a 2.94-fold (95% CI, 1.65-5.26) and 1.75-fold (95% CI, 1.13-2.72) increased risk of pneumonia, respectively. The findings were robust to adoption of a case-crossover study that analyzed cases only.ConclusionsUse of BZRAs is associated with an increased risk of pneumonia in CKD patients, especially for patients newly initiating BZDs or Z-drugs or those injected with BZDs. Physicians should exercise cautions for signs of pneumonia when prescribing BZDs or Z-drugs to CKD patients.
| S-EPMC5503235 | biostudies-literature
Project description:PurposeStudies have reported mixed results on the association between benzodiazepine use and mortality. Here, we investigated whether benzodiazepine use is associated with a higher risk of 5-year all-cause mortality, and examined the association between benzodiazepine use and 5-year disease-specific mortality.Materials and methodsIn this population-based cohort study, a nationally representative sample cohort in South Korea was examined. In 2010, benzodiazepine users were defined as individuals prescribed benzodiazepine continuously over 30 days for regular administration, and all other subjects were included in the control group. The primary endpoint was 5-year all-cause mortality, evaluated from 2011 to 2015. Propensity score (PS) matching and time-dependent Cox regression were performed for statistical analysis, which included benzodiazepine use during 2011-2015 as a time-dependent variable.ResultsA total of 822414 adult individuals were included in the final analysis, and the all-cause 5-year mortality was recorded in 20991 individuals (2.7%). The benzodiazepine group included 30837 patients and the control group comprised 791377 patients. After PS matching, 61672 individuals (30836 in each group) were included in the final analysis. After PS matching, the 5-year all-cause mortality in the benzodiazepine group was 10.0% (3082/30836), whereas that in the control group was 9.4% (2893/30836). In time-dependent Cox regression analysis of the PS-matched cohort, the benzodiazepine group showed 1.15-fold higher 5-year all-cause mortality (hazard ratio: 1.15, 95% confidence interval: 1.09-1.22; p<0.001) compared to the control group.ConclusionBenzodiazepine use was associated with increased 5-year all-cause mortality in the South Korean adult population. Further studies are needed to confirm these findings.
| S-EPMC8149930 | biostudies-literature
Project description:BackgroundThe association between long-term benzodiazepine use and risk of dementia remains controversial. Therefore, current study aimed to quantify this association, and to explore a potential dose-response pattern.MethodsWe searched PubMed, Embase and the Cochrane Library through August 17, 2014. We included nested case-control or prospective cohort studies that provided risk estimates on the association of benzodiazepine use with risk of dementia, and a clear definition of status of benzodiazepine use. Overall effect size was calculated using a random-effects model.FindingsSix studies were eligible for inclusion, involving 11,891 dementia cases and 45,391 participants. Compared with never users, pooled adjusted risk ratios (RRs) for dementia were 1.49 (95% confidence interval (CI) 1.30-1.72) for ever users, 1.55 (95% CI 1.31-1.83) for recent users, and 1.55 (95% CI 1.17-2.03) for past users. The risk of dementia increased by 22% for every additional 20 defined daily dose per year (RR, 1.22, 95%CI 1.18-1.25). When we restricted our meta-analyses to unadjusted RRs, all initial significant associations persisted.ConclusionsLong-term benzodiazepine users have an increased risk of dementia compared with never users. However, findings from our study should be treated with caution due to limited studies and potential reverse causation. Large prospective cohort studies with long follow-up duration are warranted to confirm these findings.
| S-EPMC4446315 | biostudies-literature
Project description:ObjectiveTo evaluate the association between use of benzodiazepines and incident dementia.DesignProspective, population based study.SettingPAQUID study, France.Participants1063 men and women (mean age 78.2 years) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up.Main outcome measuresIncident dementia, confirmed by a neurologist.ResultsDuring a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10 to 1.94). Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users.ConclusionsIn this prospective population based study, new use of benzodiazepines was associated with increased risk of dementia. The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study. Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population, indiscriminate widespread use should be cautioned against.
| S-EPMC3460255 | biostudies-literature
Project description:Rationale: Older adults with chronic obstructive pulmonary disease (COPD) are at substantially increased risk for medication-related adverse events. Two frequently prescribed classes of drugs that pose a particular risk to this patient group are opioids and benzodiazepines. Research on this topic has yielded conflicting findings.Objectives: The purpose of this study was to examine, among older adults with COPD, whether: 1) independent or concurrent use of opioid and benzodiazepine medications was associated with hospitalizations for respiratory events, and 2) this association was exacerbated by the presence of obstructive sleep apnea (OSA).Methods: We conducted a case-control study of Medicare beneficiaries aged ≥66 years, who were diagnosed with COPD in 2013, using the 5% national Medicare database. Cases (n = 3,232) were defined as patients hospitalized for a primary COPD-related respiratory diagnosis in 2014 and were matched with up to two control subjects (n = 6,247) on index date, age, sex, socioeconomic status, comorbidity, presence of OSA, COPD medication, and COPD complexity.Results: In comparison to the referent (no opioid or benzodiazepine use), opioid use alone (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.52-1.97), benzodiazepine use alone (aOR, 1.42; 95% CI, 1.21-1.66), and concurrent opioid/ benzodiazepine use (aOR, 2.32; 95% CI, 1.94-2.77) in the 30 days before the event/index date were all associated with an increased risk of hospitalization for a respiratory condition. Risk of hospitalization was higher with concurrent opioid and benzodiazepine use when compared with use of either medication alone. There was no statistically significant interaction between OSA and either of the drugs, alone or in combination. However, the adverse respiratory effects of concurrent opioid and benzodiazepine use were increased in patients with a high degree of COPD complexity. All of the above findings persisted using exposure windows that extended to 60 and 90 days before the event/index date.Conclusions: Among older adults with COPD, use of opioid and benzodiazepine medications alone or in combination were associated with increased adverse respiratory events. The adverse effects of these medications were not exacerbated in patients with COPD-OSA overlap syndrome. However, the adverse impact of dual opioid and benzodiazepine was greater in patients with high-complexity COPD.
| S-EPMC6812171 | biostudies-literature
Project description:The relationship between chronic obstructive pulmonary disease (COPD) and diabetes remains incompletely understood. This study evaluated diabetes risk and post-diabetes outcomes in COPD patients with and without exacerbations.We identified 4671 adults newly diagnosed with COPD exacerbations and 9342 adults newly diagnosed with COPD without exacerbations during 2000-2008 using Taiwan's National Health Insurance Research Database. A comparison cohort of 18684 adults without COPD, matched by age and sex, was randomly selected from the same dataset for the control group. Diabetes events during 2000-2013 were ascertained from medical claims during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with COPD with or without exacerbations were calculated. We conducted another nested cohort study of 395516 patients with diabetes hospitalization during 2002-2013 and calculated adjusted odds ratios (ORs) and 95% CIs of histories of COPD and COPD exacerbations associated with adverse events after diabetes admission.During the follow-up period, the incidences of diabetes for patients without COPD and for patients with COPD without or with exacerbations were 3.4, 4.1 and 7.4 per 1000 person-years, respectively (P < 0.0001). Increased risk of diabetes for patients with COPD without exacerbations (HR 1.09, 95% CI 1.02-1.17) and COPD with exacerbations (HR 2.18, 95% CI 1.88-2.52) was noted. Post-diabetes pneumonia (OR 3.28, 95% CI 3.13-3.43), intensive care admission (OR 1.32, 95% CI 1.26-1.39) and mortality (OR 2.06, 95% CI 1.88-2.25) were associated with COPD exacerbations.Prevention and intervention strategies for diabetes and post-diabetes outcomes are needed for this susceptible population.
| S-EPMC5558949 | biostudies-other
Project description:BackgroundGuidelines recommend most benzodiazepine (BZD) treatment be short-term, though chronic BZD use is increasing.ObjectiveDetermine the rate of BZD discontinuation among chronic users and identify patient- and provider-level factors associated with discontinuation.Design, setting, and participantsA retrospective cohort study using nationwide insurance claims data from 2014 to 2016 of US adults ≥ 18 years old with chronic BZD use (i.e., > 120 days) during the baseline year.Main outcomes and measuresThe primary outcome was BZD discontinuation among chronic users after 1 year of follow-up. A series of multilevel logistic regression models examined the association of BZD discontinuation with patient and provider characteristics. Covariates included patient sociodemographics, medical and psychiatric comorbidity, co-prescribed opioids and other psychotropics, and characteristics of the prescribed BZD.Key resultsOf 141,008 chronic BZD users, 13.4% discontinued use after 1 year. Females had lower odds of discontinuation (AOR 0.83, 99% CI 0.79-0.87), while African-American patients had higher odds (AOR 1.12, 99% CI 1.03-1.22). Those prescribed a high-potency BZD had lower odds of discontinuation (AOR 0.51, 99% CI 0.47-0.54), as did those prescribed an opioid (AOR 0.94, 99% CI 0.89-0.99). After adjusting for patient- and provider-level factors, differences between providers accounted for 5.8% of variation in BZD discontinuation (p < 0.001). The median odds ratio for provider was 1.54, an association with discontinuation larger than almost all patient-level clinical variables.ConclusionsA small minority of patients prescribed chronic BZD in a given year are no longer prescribed BZDs 1 year later. There is significant variation in the likelihood of discontinuation accounted for by non-clinical factors such as race, geography, and a patient's provider, which had a stronger association with the odds of discontinuation than almost every other patient-level variable. Provider-facing elements of interventions to reduce BZD prescribing may be critical.
| S-EPMC6712149 | biostudies-literature
Project description:ImportanceThe association between preoperative benzodiazepine use and long-term postoperative outcomes is not well understood.ObjectiveTo characterize the association between preoperative benzodiazepine use and postoperative opioid use and health care costs.Design, setting, and participantsIn this cohort study, retrospective analysis of private health insurance claims data on 946 561 opioid-naive patients (no opioid prescriptions filled in the year before surgery) throughout the US was conducted. Patients underwent 1 of 11 common surgical procedures between January 1, 2004, and December 31, 2016; data analysis was performed January 9, 2020.ExposuresBenzodiazepine use, defined as long term (≥10 prescriptions filled or ≥120 days supplied in the year before surgery) or intermittent (any use not meeting the criteria for long term).Main outcomes and measuresThe primary outcome was opioid use 91 to 365 days after surgery. Secondary outcomes included opioid use 0 to 90 days after surgery and health care costs 0 to 30 days after surgery.ResultsIn this sample of 946 561 patients, the mean age was 59.8 years (range, 18-89 years); 615 065 were women (65.0%). Of these, 23 484 patients (2.5%) met the criteria for long-term preoperative benzodiazepine use and 47 669 patients (5.0%) met the criteria for intermittent use. After adjusting for confounders, long-term (odds ratio [OR], 1.59; 95% CI, 1.54-1.65; P < .001) and intermittent (OR, 1.47; 95% CI, 1.44-1.51; P < .001) benzodiazepine use were associated with an increased probability of any opioid use during postoperative days 91 to 365. For patients who used opioids in postoperative days 91 to 365, long-term benzodiazepine use was associated with a 44% increase in opioid dose (additional 0.6 mean daily morphine milligram equivalents [MMEs]; 95% CI, 0.3-0.8 MMEs; P < .001), although intermittent benzodiazepine use was not significantly different (0.0 average daily MMEs; 95% CI, -0.2 to 0.2 MMEs; P = .65). Preoperative benzodiazepine use was also associated with increased opioid use in postoperative days 0 to 90 for both long-term (32% increase, additional 1.9 average daily MMEs; 95% CI, 1.6-2.1 MMEs; P < .001) and intermittent (9% increase, additional 0.5 average daily MMEs; 95% CI, 0.4-0.6 MMEs; P < .001) users. Intermittent benzodiazepine use was associated with an increase in 30-day health care costs ($1155; 95% CI, $938-$1372; P < .001), while no significant difference was observed for long-term benzodiazepine use.Conclusions and relevanceThe findings of this study suggest that, among opioid-naive patients, preoperative benzodiazepine use may be associated with an increased risk of developing long-term opioid use and increased opioid dosages postoperatively, and also may be associated with increased health care costs.
| S-EPMC7592026 | biostudies-literature
Project description:Dipeptidyl-peptidase-4 inhibitors (DPP4Is) are drugs for the treatment of type 2 diabetes mellitus (T2DM). There is increasing evidence that DPP4Is may result in suppression of the immune system and may increase the risk of infections such as pneumonia. Aim of this study was to evaluate the association between the use of DPP4Is and the risk of pneumonia in a population-based study.We conducted a population-based cohort study using data from the world's largest primary care database, the UK Clinical Practice Research Datalink (CPRD). We selected all users of non-insulin antidiabetic drugs (NIADs), including DPP4Is, between 2007 and 2012. To each NIAD user, we matched randomly selected non-users. The NIAD user's first prescription defined the index date, which was then assigned to the matched non-users. Patients were followed from their first prescription until end of data collection or the first event of pneumonia, whichever came first. Cox regression analysis estimated the association between pneumonia and current use of DPP4Is versus 1) current use of other NIADs and 2) non-users. DPP4I use was then stratified to daily and cumulative dose. Analyses were statistically adjusted for age, sex, lifestyle factors and comorbidities and concomitant use of various other drugs.Risk of pneumonia was not increased with current DPP4I use versus use of other NIADs, adjusted Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.55-0.91. Also higher cumulative doses or daily doses did not further increase risk of pneumonia.We found no increased risk of pneumonia in T2DM patients using DPP4Is compared to T2DM patients using other NIADs. Our finding is in line with direct and indirect evidence from observational studies and RCTs. There is probably no need to avoid prescribing of DPP4Is to elderly patients who are at risk of pneumonia.
| S-EPMC4607497 | biostudies-other