Continuation of Buprenorphine During Hospitalization and Subsequent Retention in Therapy: an Observational Study in Veterans Administration Hospitals.

BACKGROUND: Inpatient hospitalization has the potential to disrupt buprenorphine therapy. OBJECTIVE: Among patients receiving outpatient buprenorphine prior to admission, we determined the rate of discontinuation during medical and surgical admissions to VA hospitals and its association with subsequent post-discharge continuation of buprenorphine therapy. DESIGN AND MAIN MEASURES: We conducted an observational study using Veterans Administration data from 10/1/2018 to 3/31/2020 for all medical and surgical admissions where Veterans had active buprenorphine prescriptions at the time of admission. Pre-admission buprenorphine prescriptions were categorized as either sublingual (presumed indication for opioid use disorder (OUD)) or buccal/topical (presumed indication for pain). The primary measure of post-discharge buprenorphine receipt was any outpatient buprenorphine prescription dispensed between 1 day prior to discharge and 60 days following discharge. KEY RESULTS: A total of 830 unique inpatient hospitalizations to medical or surgical services occurred among Veterans receiving sublingual (48.3%) or buccal/topical (51.7%) buprenorphine prior to admission. Fewer than half (43.9%) of these patients received buprenorphine at some point during the medical or surgical portion of their hospital stay. Among the 766 patients discharged from a medical or surgical unit, 74.3% received an outpatient buprenorphine prescription within the 60 days following discharge (80.2% sublingual and 69.1% buccal/topical). Among patients who had received buprenorphine during the final 36 h prior to discharge, subsequent outpatient buprenorphine receipt was observed in 94.0%, compared to only 63.7% among those not receiving buprenorphine during the final 36 h (χ2 = 83.5, p < 0.001). CONCLUSION: Inpatient buprenorphine administrations near the time of discharge were highly predictive of continued outpatient therapy and a significant subset of patients did not continue or reinitiate buprenorphine therapy following discharge. As recommendations for perioperative and inpatient management of buprenorphine coalescence around continuation, efforts are needed to optimize hospital-based buprenorphine practices.

Incidence of immune-related adverse events in U.S. veterans treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are associated with potentially severe immune-related adverse events (irAEs). Emerging clinical practice reports have suggested higher incidence of irAEs in real-world settings than initially observed in phase III clinical trials. Objectives were to determine the incidence of irAEs associated with ICIs in a clinical population, the Veterans Health Administration, characterize their time to onset, and explore potential risk factors. METHODS: This retrospective observational study included patients from eight Midwest VA medical centers who initiated an ICI between January 1, 2014, and June 30, 2022. Courses of incident prednisone therapy lasting at least seven days at a dose ≥ 20 mg/day were used to identify irAEs, within two years following ICI initiation. A multivariate Cox proportional hazards regression model was used to explore potential irAE risk factors. RESULTS: Of 1314 patients, the incidence of irAEs was 19.8%, with most (86.5%) occurring within one year of ICI initiation. Monthly incidence rates peaked three months following ICI initiation at 3.0% and decreased thereafter. Female gender (hazard ratio [HR] = 2.01, 95% confidence interval [CI]: 1.01-4.00) and combination therapy with ipilimumab and nivolumab (HR = 2.46, 95% CI: 1.44-4.21) were significantly associated with irAE incidence. CONCLUSIONS: These findings are consistent with recent studies in clinical populations that demonstrate higher irAE incidence rates than originally reported in clinical trials. Our findings may enhance prompt recognition and treatment of irAEs for VA patients.

A Nationwide Emergency Department Data Analysis to Predict Beers List Medications Use Among Older Adults.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is considered an important quality indicator for older adults seen in the ambulatory care setting. STUDY OBJECTIVES: To evaluate the pattern of potentially inappropriate medication (PIMs) use as specified in the Beers Criteria, for older adults during emergency department (ED) visits in the United States. METHODS: Using data from the National Hospital Ambulatory Care Survey (NHAMCS) we identified older adults (age 65 or older) discharged home from an ED visit in 2019. We defined PIMs as those with an 'avoid' recommendation under the American Geriatrics Society (AGS) 2019 Beers Criteria in older adults. Logistic regression models were used to assess demographic, clinical, and hospital factors associated with the use of any PIMs upon ED discharge. RESULTS: Overall, 5.9% of visits by older adults discharged from the ED included administration or prescriptions for PIMs. Among those who received any PIMs, 25.5% received benzodiazepines, 42.5 % received anticholinergics, 1.4% received nonbenzodiazepine hypnotics, and 0.5% received barbiturates. A multivariable model showed statistically significant associations for age 65 to 74 (OR 1.91, 95% CI 1.39-2.62 vs. age >=75), dementia (OR 0.45, 95% CI 0.21-0.95), lower immediacy (OR 2.45, 95% CI 1.56-3.84 vs. higher immediacy), and Northeastern rural region (OR 0.34, 95% CI 0.21-0.55 vs. Midwestern rural). CONCLUSION: We found that younger age and lower immediacy were associated with increased prescriptions of PIMs for older adults seen, while dementia and Northeastern rural region was associated with reduced use of PIMs seen and discharged from EDs in United States.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Telehealth Utilization Is Associated with Lower Risk of Discontinuation of Buprenorphine: a Retrospective Cohort Study of US Veterans.

OBJECTIVE: Treatment for opioid use disorder (OUD) may include a combination of pharmacotherapies (such as buprenorphine) with counseling services if clinically indicated. Medication management or engagement with in-person counseling services may be hindered by logistical and financial barriers. Telehealth may provide an alternative mechanism for continued engagement. This study aimed to evaluate the association between telehealth encounters and time to discontinuation of buprenorphine treatment when compared to traditional in-person visits and to evaluate potential effect modification by rural-urban designation and in-person and telehealth combination treatment. METHODS: A retrospective cohort study of Veterans diagnosed with OUD and treated with buprenorphine across all facilities within the Veterans Health Administration (VHA) between 2008 and 2017. Exposures were telehealth and in-person encounters for substance use disorder (SUD) and mental health, treated as time-varying covariates. The primary outcome was treatment discontinuation, evaluated as 14 days of absence of medication from initiation through 1 year. RESULTS: Compared to in-person encounters, treatment discontinuation was lower for telehealth for SUD (aHR: 0.69; 95%CI: 0.60, 0.78) and mental health (aHR: 0.69; 95%CI: 0.62, 0.76). There was no evidence of effect modification by rural-urban designation. Risk of treatment discontinuation appeared to be lower among those with telehealth only compared to in-person only for both SUD (aHR: 0.48, 95%CI: 0.37, 0.62) and for mental health (aHR: 0.46; 95%CI: 0.33, 0.65). CONCLUSIONS: As telehealth demonstrated improved treatment retention compared to in-person visits, it may be a suitable option for engagement for patients in OUD management. Efforts to expand services may improve treatment retention and health outcomes for VHA and other health care systems.

Montelukast and neuropsychiatric events - a sequence symmetry analysis.

OBJECTIVES: Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis. METHODS: National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs. RESULTS: Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80-0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk. CONCLUSIONS: Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation.

Gender differences in medication prescribing patterns for veterans with posttraumatic stress disorder: A 10-year follow-up study.

Women veterans with posttraumatic stress disorder (PTSD) have historically received more psychiatric medications than men. The current analysis identified prescribing trends of medications recommended for (i.e., select antidepressants) and against (i.e., benzodiazepines, select antidepressants, antipsychotics, and select anticonvulsants) use in PTSD treatment among women and men in 2010-2019. All veterans receiving care for PTSD in 2019 were identified using national U.S. Department of Veterans Affairs (VA) administrative data. Multivariable logistic regression analyses, adjusted for demographic characteristics and psychiatric comorbidities, were used to contrast the likelihood of receiving a medication class across genders. Sensitivity analyses using identical selection methods were conducted for the calendar years 2010, 2013, and 2016. In 2019, 877,785 veterans received treatment for PTSD within the VA, 13.5% of whom were women. Across medication classes and years, women were more likely to receive all psychiatric medications of interest. Relative to men, women were slightly more likely to receive antidepressants recommended for PTSD in 2019, adjusted odds ratio (aOR) = 1.07, 95% CI [1.06, 1.09]. However, gender differences for medications recommended against use for PTSD were notably larger, including benzodiazepines, aOR = 1.62, 95% CI [1.59, 1.65]; anticonvulsants. aOR = 1.41, 95% CI [1.38, 1.44]; and antidepressants recommended against use for PTSD, aOR = 1.26, 95% CI [1.19, 1.33]. To inform tailored intervention strategies, future work is needed to fully understand why women receive more medications recommended against use for PTSD.

Risk of Acute Kidney Injury and Clostridioides difficile Infection With Piperacillin/Tazobactam, Cefepime, and Meropenem With or Without Vancomycin.

BACKGROUND: Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostrioides difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to evaluate AKI and CDI risks simultaneously with AP-BL in the same patient cohort. METHODS: This retrospective cohort study included 789 200 Veterans Health Administration medical admissions from 1 July 2010 through 30 June 2016. The antimicrobials examined were vancomycin, cefepime, piperacillin/tazobactam, and meropenem. Cox proportional hazards regression was used to contrast risks for AKI and CDI across individual target antimicrobials and vancomycin combination therapies, including adjustment for known confounders. RESULTS: With respect to the base rate of AKI among patients who did not receive a target antibiotic (4.6%), the adjusted hazards ratios for piperacillin/tazobactam, cefepime, and meropenem were 1.50 (95% CI: 1.43-1.54), 1.00 (.95-1.05), 0.92 (.83-1.01), respectively. Co-administration of vancomycin increased AKI rates (data not shown). Similarly, against the base rate of CDI (0.7%), these ratios were 1.21 (1.07-1.36), 1.89 (1.62-2.20), and 1.99 (1.55-2.56), respectively. Addition of vancomycin had minimal impact on CDI rates (data not shown). CONCLUSIONS: Piperacillin/tazobactam increased AKI risk, which was exacerbated by concurrent vancomycin. Cefepime and meropenem increased CDI risk relative to piperacillin/tazobactam. Clinicians should consider the risks and benefits of AP-BL when selecting empiric regimens. Further well-designed studies evaluating the global risks of AP-BL and patient specific characteristics that can guide empiric selection are needed.

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

BACKGROUND: Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. METHODS: This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. RESULTS: Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum ß-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99). CONCLUSIONS: Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

Inpatient Fluoroquinolone Stewardship Improves the Quantity and Quality of Fluoroquinolone Prescribing at Hospital Discharge: A Retrospective Analysis Among 122 Veterans Health Administration Hospitals.

BACKGROUND: Despite increasing awareness of harms, fluoroquinolones are still frequently prescribed to inpatients and at hospital discharge. Our goal was to describe fluoroquinolone prescribing at hospital discharge across the Veterans Health Administration (VHA) and to contrast the volume and appropriateness of fluoroquinolone prescribing across 3 antimicrobial stewardship strategy types. METHODS: We analyzed a retrospective cohort of patients hospitalized at 122 VHA acute-care hospitals during 2014-2016. Data from a mandatory VHA survey were used to identify 9 hospitals that self-reported 1 of 3 strategies for optimizing fluoroquinolone prescribing: prospective audit and feedback (PAF), restrictive policies (RP), and no strategy. Manual chart reviews to assess fluoroquinolone appropriateness at hospital discharge (ie, postdischarge) were performed across the 9 hospitals (3 hospitals and 125 cases per strategy type). RESULTS: There were 1.7 million patient admissions. Overall, there were 1 727 478 fluoroquinolone days of therapy (DOTs), with 674 918 (39.1%) DOTs prescribed for inpatients and 1 052 560 (60.9%) DOTs prescribed postdischarge. Among the 9 reviewed hospitals, postdischarge fluoroquinolone exposure was lower at hospitals using RP, compared to no strategy (3.8% vs 9.3%, respectively; P = .012). Postdischarge fluoroquinolones were deemed inappropriate in 154 of 375 (41.1%) patients. Fluoroquinolones were more likely to be inappropriate at hospitals without a strategy (52.8%) versus those using either RP or PAF (35.2%; P = .001). CONCLUSIONS: In this retrospective cohort, the majority of fluoroquinolone DOTs occurred after hospital discharge. A large proportion of postdischarge fluoroquinolone prescriptions were inappropriate, especially in hospitals without a strategy to manage fluoroquinolone prescribing. Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial prescribing at hospital discharge.

Lack of Association between 5α-Reductase Inhibitors and Depression.

PURPOSE: Depressed mood and suicidality reported with 5α-reductase inhibitors (finasteride and dutasteride) during post-marketing surveillance resulted in the addition of depression risk to finasteride labeling. As peer reviewed studies are limited and have reported mixed findings, we further evaluated 5α-reductase inhibitor exposure and depression risk using sequence symmetry analysis. MATERIALS AND METHODS: National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5α-reductase inhibitor therapy during fiscal year 2014. Incident depression events were assessed separately using the 2 measures of antidepressant prescription and depression diagnosis. Symmetry ratios were calculated as the ratio of patients with an incident depression event in the year following 5α-reductase inhibitor initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α1-adrenergic receptor antagonists. RESULTS: Incident antidepressant prescribing was observed in 2,563 patients following 5α-reductase inhibitor initiation and 3,051 patients preceding 5α-reductase inhibitor initiation (SR 0.84, 95% CI 0.80-0.89). Similar findings were observed for incident depression diagnosis (SR 0.83, 95% CI 0.79-0.86). Stratification by age group, 5α-reductase inhibitor agent, antidepressant class, prior α1-adrenergic receptor antagonist exposure and depression diagnosis type failed to demonstrate any positive association between 5α-reductase inhibitor and depression. Nearly identical results were observed in the α1-adrenergic receptor antagonist analysis (SR 0.87, 95% CI 0.84-0.90). CONCLUSIONS: Initiation of a 5α-reductase inhibitor was not associated with increased risk of depression. Our findings support the hypothesis that depression is more likely attributable to underlying benign prostatic hyperplasia and associated lower urinary tract symptoms than 5α-reductase inhibitor exposure.

A Typology of New Long-term Opioid Prescribing in the Veterans Health Administration.

BACKGROUND: Narrow definitions of long-term opioid (LTO) use result in limited knowledge of the full range of LTO prescribing patterns and the rates of these patterns. OBJECTIVE: To investigate a model of new LTO prescribing typologies using latent class analysis. DESIGN: National administrative data from the VA Corporate Data Warehouse were accessed using the VA Informatics and Computing Infrastructure. Characterization of the typology of initial LTO prescribing was explored using latent class analysis. PARTICIPANTS: Veterans initiating LTO during 2016 through the Veteran's Administration Healthcare System (N = 42,230). MAIN MEASURES: Opioid receipt as determined by VA prescription data, using the cabinet supply methodology. KEY RESULTS: Over one-quarter (27.7%) of the sample fell into the fragmented new long-term prescribing category, 39.8% were characterized by uniform daily new LTO, and the remaining 32.7% were characterized by uniform episodic LTO. Each of these three broad sub-groups also included two additional sub-groups (6 classes total in the model), characterized by the presence or absence of prior opioid prescriptions. CONCLUSIONS: New LTO prescribing in the VA includes uniform daily prescribing, uniform episodic prescribing, and fragmented prescribing. Future work is needed to elucidate the safety and efficacy of these prescribing patterns.

Associations between initial opioid exposure and the likelihood for long-term use.

OBJECTIVES: This study examined the association between initial opioid exposure and subsequent long-term use in 2 national Veterans Administration (VA) cohorts from 2011 and 2016, a period during which opioid prescribing declined. DESIGN: Two methodologies were used to determine the relationship between initial exposure and subsequent long-term use. SETTING AND PARTICIPANTS: Incident opioid users during 2016 were identified using national VA administrative data. OUTCOME MEASURES: Relationships between days' supply, daily dose, and number of fills within the first 30 days and subsequent long-term opioid use were also examined. All analyses were repeated for an identically derived cohort during 2011. RESULTS: In 2016, 6.2% (method 1: Deyo replication) or 16.8% (method 2: Shah replication) of incident opioid users progressed to long-term opioid use. In 2011, 14.3% (method 1) or 29.2% (method 2) of incident users progressed to long-term use. Cumulative days' supply emerged as the strongest predictor in a multivariable model of long-term opioid use, which occurred in 1.5% of patients dispensed 7 days' supply or less and in 27.7% of patients dispensed greater than 30 days' supply. Results were similar in the 2011 cohort. Although the relationship between days' supply of incident opioid exposure and long-term opioid use remained consistent over time (in both 2011 and 2016), the overall rate of becoming a long-term opioid user decreased over time across levels of initial exposure. CONCLUSION: The findings confirm existing literature demonstrating a strong relationship between initial opioid exposure and future likelihood for long-term use. This valuable prognostic information could potentially be leveraged for intervention, including pharmacist-based approaches to prevent progression to long-term opioid use when it is unintended or clinically inappropriate.

Decline in Prescription Opioids Attributable to Decreases in Long-Term Use: A Retrospective Study in the Veterans Health Administration 2010-2016.

BACKGROUND: Improved understanding of temporal trends in short- and long-term opioid prescribing may inform efforts to curb the opioid epidemic. OBJECTIVE: To characterize the prevalence of short- and long-term opioid prescribing in the Veterans Health Administration (VHA) from 2010 to 2016. DESIGN: Observational cohort study using VHA databases. PARTICIPANTS: All patients receiving at least one outpatient prescription through the VHA during calendar years 2010 through 2016. MAIN MEASURES: Prevalence of opioid use from 2010 through 2016, stratified by short-term, intermediate-term, and long-term use. Temporal trends in discontinuation among existing long-term users and initiation of new long-term use and the net impact on rates of long-term opioid use. Relative likelihood of transitioning to long-term opioid use contrasted with use patterns in the prior year. KEY RESULTS: The prevalence of opioid prescribing was 20.8% in 2010, peaked at 21.2% in 2012, and declined annually to 16.1% in 2016. Between 2010 and 2016, reductions in long-term opioid prescribing accounted for 83% of the overall decline in opioid prescription fills. Comparing data from 2010-2011 to data from 2015-2016, declining rates in new long-term use accounted for more than 90% of the decreasing prevalence of long-term opioid use in the VHA, whereas increases in cessation among existing long-term users accounted for less than 10%. The relative risk of transitioning to long-term use during 2016 was 6.5 (95% CI: 6.4, 6.7) among short-term users and 35.5 (95% CI: 34.8, 36.3) among intermediate users, relative to patients with no opioid prescriptions filled during 2015. CONCLUSIONS: Opioid prescribing trends followed similar trajectories in VHA and non-VHA settings, peaking around 2012 and subsequently declining. However, changes in long-term opioid prescribing accounted for most of the decline in the VHA. Recent VA opioid initiatives may be preventing patients from initiating long-term use. This may offer valuable lessons generalizable to other healthcare systems.

Sedative Prescriptions Are Common at Opioid Initiation: An Observational Study in the Veterans Health Administration.

Background: Concurrent use of sedatives, especially anxiolytics, and opioids is associated with increased risk of medication-related harms. To the extent that multiple prescribers are involved, approaches to influence patterns of coprescribing will differ from those to influence prescribing within a single drug class. Objectives: Describe the proportion of new opioid recipients with concurrent sedative medications at opioid initiation and determine whether these medications were prescribed by the same prescriber. Methods: We used national Department of Veterans Affairs (VA) outpatient pharmacy administration data to identify veterans who received a new opioid prescription between October 20, 2010, and September 1, 2011 (FY 2011), preceded by a 365-day opioid-free period. Concurrent sedative use was defined as a skeletal muscle relaxant, benzodiazepine, atypical antipsychotic, or hypnotic filled on the opioid start date or before and after the opioid start date with a gap of less than twice the day supply of the prior fill. Results: Concurrent sedative use at opioid initiation was 21.4% (112,408/526,499) in FY 2011. The proportion of concurrent recipients who received at least one concurrent sedative prescribed by a provider other than the opioid prescriber was 61.4% (69,002/112,408). The proportion of recipients who received a sedative concurrent with opioid initiation from the same prescriber varied across sedative class. Benzodiazepines and opioids were prescribed by the same provider in 41.1% (15,520/37,750) of concurrent users. Conclusion: One in five patients newly prescribed opioids also had a sedative prescription. Less than half of patients with concurrent opioid and benzodiazepine prescriptions received these from the same provider. Efforts to reduce concurrent opioid and sedative prescribing will require addressing care coordination.

Risk for Prolonged Opioid Use Following Total Knee Arthroplasty in Veterans.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) may be at risk for prolonged postsurgical opioid use due to a high prevalence of persistent postsurgical pain (20%) and high rates of presurgical opioid use. METHODS: The current study uses a Veterans Health Administration sample of 6653 Veterans who underwent TKA in the fiscal year 2014 that did not require surgical revision during the subsequent year. RESULTS: Sixty percent of the sample had used an opioid in the year prior to surgery, including 20% who were on long-term opioid use at the time of surgery (defined as 90+ days of continuous use) and 40% with any other opioid use in the year prior to surgery. In patients on long-term opioids at the time of surgery, 69% received opioids for at least 6 months and 57% for at least 12 months after TKA. In patients not on long-term opioids at the time of TKA, only 4% received opioids for at least 6 months and 2% for at least 12 months after TKA. Differing risk factors for prolonged opioid use 12 months after TKA were identified in these 2 cohorts (ie, those who were and were not receiving long-term opioids at TKA). CONCLUSION: These findings suggest that the greatest risk for prolonged opioid use after TKA is preoperative opioid use.

Association between polypharmacy and death: A systematic review and meta-analysis.

OBJECTIVE: Polypharmacy has been linked to a myriad of adverse consequences, and escalating rates of polypharmacy present an emerging concern, particularly among older adults. This systematic review and meta-analysis summarizes the existing literature concerning the association between polypharmacy and mortality. DATA SOURCES: A systematic literature review was done by searching the EMBASE, PubMed, Scopus, and International Pharmaceutical Abstract databases to identify studies assessing the association between polypharmacy and death published until June 2016. STUDY SELECTION: Studies that investigated the association between polypharmacy and mortality were eligible for this systematic review and meta-analysis. DATA EXTRACTION: Data were extracted by the first and second authors independently using a data extraction form. Disagreement was resolved by consensus. A meta-analysis was performed using random effect models. Heterogeneity was assessed using the I2 statistic. RESULTS: Forty-seven studies were included in this meta-analysis. The underlying populations were heterogeneous (I2= 91.5%). When defined as a discrete variable, pooled risk estimates demonstrated a significant association between polypharmacy and death (pooled-adjusted odds ratio [aOR] 1.08 [95% CI 1.04-1.12]). When defined categorically, a dose-response relationship was observed across escalating thresholds for defining polypharmacy. Categorical thresholds for polypharmacy using values of 1-4 medications, 5 medications, and 6-9 medications were significantly associated with death (P <0.05; aOR 1.24 [1.10-1.39], aOR 1.31 [1.17, 1.47], and aOR 1.59 [1.36-1.87], respectively). Excessive polypharmacy (ie, the use of 10 or more medications) was also associated with death (aOR 1.96 [1.42-2.71]). CONCLUSIONS: Pooled risk estimates from this meta-analysis reveal that polypharmacy is associated with increased mortality risk, using both discrete and categorical definitions. The causality of this relationship remains unclear, but it emphasizes the need for approaches to health care delivery that achieve an optimal balance of risk and benefit in medication prescribing.

The 1-Year Treatment Course of New Opioid Recipients in Veterans Health Administration.

BACKGROUND: Understanding opioid prescribing trends requires differentiating clinically distinct short- and long-term receipt patterns. OBJECTIVES: Describe the one-year course of opioid receipt among new opioid recipients and determine the proportion with subsequent long-term opioid therapy. Discern variation in proportion with long-term therapy initiation by geographic region and across Veterans Health Administration (VHA) medical centers. METHODS: Longitudinal course of opioid receipt was analyzed using a cabinet supply approach. Short-term receipt was defined as index treatment episode lasting no longer than 30 days; long-term therapy as treatment episode of >90 days that began within the first 30 days following opioid index date. PATIENTS: All VHA pharmacy users in 2004 and to 2011 who received a new prescription for an opioid (incident opioid recipients) preceded by 365 days with no opioid prescribed. RESULTS: The proportion of all incident recipients who met the definition for long-term therapy within the first year decreased from 20.4% (N = 76,280) in 2004 to 18.3% (N = 96,166) in 2011. The proportion of incident recipients with chronic pain was unchanged between 2004 and 2011. Hydrocodone and tramadol increased as a proportion of initial opioids prescribed. Median days initially supplied decreased from 30 to 20 days. A greater percentage of new opioid prescriptions were for 7 days or fewer (20.9% in 2004; 27.9% in 2011). The proportion of new recipients who initiated long-term opioid therapy varied widely by medical center. Medical centers with higher proportions of new long-term recipients in 2004 saw greater decreases in this metric by 2011. CONCLUSION: The proportion of new opioid recipients who initiated long-term opioid therapy declined between 2004 and 2011.

Pharmacy use by dual-eligible non-elderly veterans with private healthcare insurance.

BACKGROUND: Utilization of private sector healthcare services among dual enrolled veterans with private healthcare insurance plans (PHIP) has not been well-characterized. Concurrent use of Veterans Health Administration (VHA) and non-VHA pharmacies may increase risk for adverse outcomes. Thus, the objectives of this study were to determine the extent to which dual VHA-PHIP enrollees obtain medications through VHA and non-VHA pharmacies and to characterize medications obtained through non-VHA pharmacies. METHODS: This observational study used merged administrative data from VHA and a predominant regional PHIP to select veterans < 65 years of age, residing in two Midwestern US states, and simultaneously enrolled in both VHA and the PHIP during fiscal years (FY) 2001-2010. Primary outcome measures included counts of prescriptions dispensed from VHA and non-VHA pharmacies, and frequencies of medications dispensed by non-VHA pharmacies based on PHIP claims. RESULTS: Of 5783 veterans who filled ≥ 1 prescription in FY10, 2935 (50.8 %) used non-VHA pharmacies exclusively, 1165 (20.2 %) used VHA pharmacies exclusively and 1683 (29.1 %) were dual users. Health services utilization was higher for dual users compared to exclusive users of either VHA or non-VHA pharmacies across multiple measures, including total prescriptions, outpatient encounters, and inpatient admissions. The most common medications dispensed by non-VHA pharmacies, by proportion of veterans treated, were hydrocodone (20.9 %), amoxicillin (18.5 %), simvastatin (17.5 %), azithromycin (17.4 %), and lisinopril (15.1 %). Antidepressants comprised 3 of 10 most common medications dispensed by VHA, but none of the most common medications dispensed to exclusive non-VHA pharmacy users. CONCLUSIONS: Our findings align with VHA-Medicare dual enrolled veterans where only a minority of veterans used VHA services exclusively. Younger veterans relied disproportionately on VHA for mental health medications.