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Objective: To compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group., Methods: Using Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation., Results: The event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n = 181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n = 850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62-1.25) and 0.82 (95% CI:0.54-1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66-1.16). Subgroup and sensitivity analyses supported these results., Conclusion: 5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare. SA, KBN, NF, MW and TEM were employees of Acumen, LLC at the time the study was conducted. This study was funded in full by the U.S. Food and Drug Administration, through an interagency agreement with the Centers for Medicare & Medicaid Services, for which Acumen, LLC is a contractor., (Published by Elsevier Inc.)

Background: Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS)., Methods: Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps., Results: Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses., Conclusion: Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

Purpose: In the United States, the National Death Index (NDI) is the most complete source of death information, while epidemiologic studies with mortality outcomes often rely on U.S. Medicare data for outcome ascertainment. The purpose of this study was to assess the agreement of death information between the Centers for Medicare & Medicaid Services (CMS) Medicare enrolment data and NDI., Methods: Using Medicare and NDI data from 1999 through 2016, we identified Medicare beneficiaries who were reported dead in the CMS Medicare enrolment database (EDB) and Common Medicare Environment (CME), linked these beneficiaries to the NDI using CMS Health Insurance Claim number, and compared death dates between the two data sources. To assess agreement between our data sources, we calculated kappa scores; where a kappa of 1 indicates perfect agreement and a kappa of 0 indicates agreement equivalent to chance. We also examined CMS to NDI linkage and death date matching for stability over time., Results: Of the 36 785 640, Medicare beneficiaries reported dead in CMS enrollment data from 1999 to 2016, 97.5% were linked to the NDI. A kappa score of 0.98 showed a near perfect agreement between NDI and CMS reported deaths. The percentage of linked cases exactly matching on death dates increased from 94.8% in 1999 to 99.4% in 2016., Conclusions: Our findings suggest strong concordance between death dates as recorded by CMS enrollment data and the NDI in the entire Medicare population., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

The America's Poison Centres National Poison Data System (NPDS) is set up for the active surveillance of voluntarily reported poisoning cases in near real-time. The Centres for Disease Control and Prevention (CDC)'s Wide-ranging Online Data for Epidemiologic Research (WONDER) database is final national mortality data from state registries. We compared suicide poisoning deaths in both datasets from 2000 to 2020 and tested their relationship using a simple linear regression model. Mean annual suicide poisoning deaths during the review period were 699 (SD 145) in NPDS, and 6150 (SD 577) in WONDER. NPDS annual cases averaged 11% of cases recorded in WONDER (SD 2%; Range 8%-16%). The regression coefficient for the linear relationship between annual deaths recorded in both datasets was 0.18 (p-value<0.001, R 2 =0.51). The rapidly available NPDS data on fatal self-poisoning may provide sentinel surveillance regarding self-poisonings, but do not reliably predict final national data on suicide poisoning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Alpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure., Methods: We performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death)., Results: There were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18)., Conclusions: Prevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19., (Published by Elsevier Inc.)

Objectives: To examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled., Design: Retrospective cohort study., Setting: USA, Canadian administrative healthcare data, Danish National Prescription Registry and UK primary care electronic health records., Participants: Patients aged 18 years and older between January 2014 and December 2020., Intervention: Valsartan, losartan and irbesartan., Main Outcome: Monthly percentages of individual ARB episodes, new users and switches to another ARB, ACE inhibitors (ACEI) or calcium channel blockers containing products., Results: We identified 10.8, 3.2, 1.8 and 1.2 million ARB users in the USA, UK, Canada and Denmark, respectively. Overall proportions of valsartan, losartan and irbesartan use were 18.4%, 67.9% and 5.2% in the USA; 3.1%, 48.3% and 10.2% in the UK, 16.3%, 11.4% and 18.3% in Canada, 1%, 93.5% and 0.6% in Denmark. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the USA and Canada. A similar trend was observed in Denmark; however, the decline was only minimal. We observed no change in trends of ARB use in the UK. Accompanying the valsartan decline was an increase in switching to other ARBs in the USA, Canada and Denmark. There was a small increase in switching to ACEI relative to the valsartan-to-other-ARBs switch. We also observed increased switching from other affected ARBs, losartan and irbesartan, to other ARBs throughout 2019, in the USA and Canada, although the usage trends in the USA remained unchanged., Conclusion: The first recall notice for valsartan resulted in substantial decline in usage due to increased switching to other ARBs. Subsequent notices for losartan and irbesartan were also associated with increased switching around the time of the recall, however, overall usage trends remained unchanged., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There have been conflicting results from observational studies regarding the risk of psychiatric adverse events (PAEs) with montelukast use., Objective: To determine whether there are associations of depressive disorders, self-harm, and suicide with use of montelukast compared with inhaled corticosteroid (ICS) use., Methods: Using data from the Sentinel Distributed Database from January 1, 2000, to September 30, 2015, patients (n = 457,377) exposed to montelukast or ICS, aged 6 years and older with a diagnosis of asthma, were matched 1:1 on propensity scores. Hazard ratios (HRs) and 95% CIs were estimated for each study outcome overall and by age, sex, psychiatric history, and pre-/post-2008 labeling updates using Cox proportional hazards regression models., Results: Exposure to montelukast was associated with a lower risk of treated outpatient depressive disorder (HR, 0.91; 95% CI, 0.89-0.93). No increased risks of inpatient depressive disorder (HR, 1.06; 95% CI, 0.90-1.24), self-harm (HR, 0.92; 95% CI, 0.69-1.21), or self-harm using a modified algorithm (HR, 0.81; 95% CI, 0.63-1.05) were observed with montelukast use compared with ICS use. Most PAEs occurred in the roughly one-third of patients having a past psychiatric history., Conclusions: When compared with use of ICS, we did not find associations between montelukast use and hospitalizations for depression or self-harm events. Our findings should be interpreted considering the study's limitations. Psychiatric comorbidity was common, and most PAEs occurred in patients with a past psychiatric history., (Published by Elsevier Inc.)

Background: Detailed research on long-term antidepressant (AD) trends within a single large US Medicaid population of youth has not heretofore been reported., Methods: Administrative claims data for eight annual timepoints across 28 years (1987-2014) were organized for youth (<20 years old) who were continuously enrolled during each study year in a mid-Atlantic state Medicaid program. Total annual AD prevalence and age-, gender-, race-, eligibility group-, and diagnosis-specific prevalence were formed from bivariate analyses; logistic regression assessed the change in use (2007-2014) adjusted for covariates. AD-polypharmacy data were assessed in 2014., Results: The major findings are: 1) AD use in state Medicaid enrollees grew 14-fold between 1987 and 2014. Data from 2014 revealed significantly increased odds of youth with SSRI/SNRI dispensings compared to 2007 (AOR=1.15 95% CI 1.11-1.19), representing 78% of total AD users. 2) Recent AD increases were greatest for 15-19-year olds. 3) AD use in girls passed up AD use in boys for the first time in 2014. 4) In 2014, ADs for foster care (12.7%) were 6 times greater than for their income-eligible Medicaid-counterparts. 5) In 2014, a quarter of AD-medicated youth were diagnosed with a behavior disorder. 6) More than 40 percent of AD medicated youth had >=1 other concomitant psychotropic classes for 60 or more days., Conclusions: Second-generation antidepressant use in Medicaid-insured youth has increased despite growing questions that pediatric AD benefits may not outweigh harms. These patterns support the call for publicly funded, independent investigator-conducted post-marketing outcomes research., (Copyright © 2020 Zito, Pennap and Safer.)

Background: Recent reports of increased national estimates of pediatric psychiatric emergency department (ED) visits and psychiatric hospitalizations emphasize the need to research these utilization patterns., Objectives: To assess the patient-provider continuity of care (CoC) and compare the risk of psychiatric ED visits or hospitalization according to the CoC level., Research Design: A cohort design was applied to Medicaid administrative claims data (2007-2014) for 3-16-year olds with a first psychiatric diagnosis between 2009 and 2013 (n=38,825)., Subjects: Continuously enrolled youths with (1) ≥1 outpatient psychiatric visits and (2) ≥4 pediatric outpatient visits in the prior 24 months., Measures: The authors assessed CoC in the 24 months before the first psychiatric outpatient visit and quantified CoC using the Alpha Index. The authors assessed patient-provider CoC before first psychiatric diagnosis and the odds of psychiatric ED visits or psychiatric hospitalizations in the year after diagnosis., Results: Of the 38,825 youths, 88.9% received a first psychiatric diagnosis by age 14. The odds of ED visits were significantly higher among youths with low CoC [6.63%, adjusted odds ratio (AOR), 1.27; 95% confidence interval (CI), 1.13-1.41] or moderate CoC (5.76%; AOR, 1.14; 95% CI, 1.02-1.27) compared with those with high CoC (4.96%). Greater odds of psychiatric hospitalization related to low (7.53%; AOR, 1.17; 95% CI, 1.06-1.29) or moderate CoC (7.01%; AOR, 1.15; 95% CI, 1.03-1.27) compared with high CoC (6.06%)., Conclusions: The odds of potentially disruptive clinical management and costly psychiatric ED visits or hospitalizations were lower for youths with high CoC. The findings support the need to research the impact of CoC on long-term pediatric mental health service use.

Importance: The increased use of psychiatric services in the US pediatric population raises concerns about the appropriate use of psychotropic medications for very young children., Objective: To assess the longitudinal patterns of psychotropic medication use in association with diagnosis and duration of use in a Medicaid-insured birth cohort., Design, Setting, and Participants: A cohort design was applied to computerized Medicaid administrative claims data for 35 244 children born in a mid-Atlantic state in 2007 and followed up for up to 96 months through December 31, 2014. Children were included in the birth cohort if they had an enrollment record at birth or within 3 months of birth and at least 6 months of continuous enrollment from birth. The cohort represents 92.2% of 38 225 Medicaid-insured newborns in 2007., Exposures: Mental health treatments from birth through age 7 years., Main Outcomes and Measures: Cumulative incidence of first psychiatric diagnosis and psychotropic medication use (monotherapy or concomitant use of psychotropic medications) from birth through age 7 years, total and by sex, and the cumulative incidence of the use of psychosocial services (age, 0-7 years) as well as the annual duration of medication use (ie, number of days of psychotropic medication use among children 3-7 years of age)., Results: Of the 35 244 children in the cohort, 17 267 were girls and 17 977 were boys. By age 8 years, 4550 children in the birth cohort (19.7% [percentage adjusted for right censoring]) had received a psychiatric diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290-319); 2624 of these diagnoses (57.7%) were behavioral (codes 312, 313, or 314). Girls were more likely than boys to receive an incident psychiatric diagnosis of adjustment disorder (355 of 1598 [22.2%] vs 427 of 2952 [14.5%]; P < .001) or anxiety disorder (114 of 1598 [7.1%] vs 120 of 2952 [4.1%]; P < .001). By age 8 years, 2196 children in the cohort (10.2% [percentage adjusted for right censoring]) had received a psychotropic medication. Among medication users, 1763 of 2196 (80.5% [percentage adjusted for right censoring]) received monotherapy, 343 of 2196 (16.4% [percentage adjusted for right censoring]) received 2 medication classes concomitantly, and 90 of 2196 (4.3% [percentage adjusted for right censoring]) received 3 or more medication classes concomitantly for 60 days or more (range, 78-180 days). The annual median number of days of psychotropic medication use among medicated children increased with age, reaching 210 of 365 days for children 7 years of age. Among children 7 years of age, the median number of days of use of an antipsychotic (193 days [interquartile range, 60-266 days]), stimulant (183 days [interquartile range, 86-295 days]), or α-agonist (199 days [interquartile range, 85-305 days]) exceeded half of the year., Conclusions and Relevance: Medicaid-insured children received substantial mental health services and had prolonged exposure to psychotropic medications in the early years of life. These findings highlight the need for outcomes research in pediatric populations.

Objective: This cross-sectional study assessed the impact of a peer-review program on the prevalence of pediatric antipsychotic use among Medicaid-insured youths in a Mid-Atlantic state., Methods: Medicaid claims (2010-2014) were assessed among continuously enrolled youths in the 12 months before and after implementation of peer review. The study identified children ages zero to four preimplementation (N=118,815) and postimplementation (N=121,431), ages five to nine preimplementation (N=98,681) and postimplementation (N=107,872), and ages 10 to 17 preimplementation (N=154,696) and postimplementation (N=161,370). (Age ranges are inclusive of the final number). In each age group, multivariable logistic regression models with generalized estimating equations assessed the change in annual prevalence of antipsychotic use pre- to postimplementation. Use of other leading psychotropic classes and antipsychotic prescribing by medical specialty were also examined., Results: The annual pre- to postimplementation prevalence of antipsychotic use decreased significantly, from .07% to .03% (adjusted odds ratio [AOR]=.41) among children ages zero to four, from 1.57% to .86% (AOR=.54) among those ages five to nine, and from 3.28% to 2.40% (AOR=.72) among those ages 10 to 17. With the exception of alpha-agonist use, which increased postimplementation (AOR=1.30) among those ages zero to four, no clinically significant pre-post change was noted in other leading psychotropic classes among children ages zero to four and 10 to 17. By contrast, postimplementation use of other psychotropic medications decreased among those ages five to nine (AOR=.73)., Conclusions: A state Medicaid peer-review program resulted in decreased antipsychotic use across all age groups, particularly among children younger than ten. No notable substitution of other psychotropic classes for antipsychotics was observed.

Objective: This study aimed to evaluate a conceptual framework that assessed the effect of Hispanic residential isolation on Attention Deficit Hyperactivity Disorder (ADHD) health service utilization among 2.2 million publicly insured youth., Design: Cross-sectional., Setting: Medicaid administrative claims data for ambulatory care services from a US Pacific state linked with US census data., Participants: Youth, aged 2-17 years, continuously enrolled in 2009., Main Outcome Measures: The percent annual prevalence and odds of ADHD diagnosis and stimulant use according to two measures of racial/ethnic residential isolation: 1) the county-level Hispanic isolation index (HI) defined as the population density of Hispanic residents in relation to other racial/ethnic groups in a county (<.5; .5-.64; ≥.65); and 2) the proportion of Hispanic residents in a ZIP code tabulation area (<25%; 25%-50%; >50%)., Results: Among the 47,364 youth with a clinician-reported ADHD diagnosis, 60% received a stimulant treatment (N = 28,334). As the county level HI increased, Hispanic residents of ethnically isolated locales were significantly less likely to receive an ADHD diagnosis (adjusted odds ratio [AOR]=.92 [95% CI=.88-.96]) and stimulant use (AOR=.61 [95% CI=.59-.64]) compared with Hispanic youth in less isolated areas. At the ZIP code level, a similar pattern of reduced ADHD diagnosis (AOR=.81 [95% CI=.77-.86]) and reduced stimulant use (AOR=.65 [95% CI=.61-.69]) was observed as Hispanic residential isolation increased from the least isolated to the most isolated ZIP code areas., Conclusions: These findings highlight the opportunity for Big Data to advance mental health research on strategies to reduce racial/ethnic health disparities, particularly for poor and vulnerable youth. Further exploration of racial/ethnic residential isolation in other large data sources is needed to guide future policy development and to target culturally sensitive interventions., Competing Interests: Competing Interests: None declared.

Background: Studies have found an association between the use of estrogen-containing oral contraceptives (OCs) and the risk of gallbladder disease. This study evaluated this relation as well as the role of progestogen on the risk of gallbladder disease among users of drospirenone-containing OCs compared to users of levonorgestrel-containing OCs., Database: The UK General Practice Research DATABASE. We conducted a nested case-control analysis among women aged 14 to 60 years during 2001 through 2008 who had ever received drospirenone- or levonorgestrel-containing OCs. Cases were women with a first diagnosis of gallbladder disease during the study period. Women who received a study OC within 6 months of the index date were exposed. All other women were nonexposed. We matched two controls to each case on year of birth, index date, amount of recorded history and general practice attended., Results: The adjusted odds ratio for gallbladder disease comparing drospirenone and levonorgestrel OCs to nonexposure were 0.9 [95% confidence interval (CI) 0.7-1.1] and 1.0 (95% CI 0.9-1.1), respectively., Conclusions: There is no evidence in these data that drospirenone- or levonorgestrel-containing OC use confers an increased risk of gallbladder disease compared to women not currently exposed to an OC. Nor is use of drospirenone OCs associated with a higher risk of gallbladder disease than use of levonorgestrel-containing OCs., (Copyright © 2012 Elsevier Inc. All rights reserved.)