State-level factors associated with implementation of prescription drug monitoring program integration and mandatory use policies, United States, 2009-2020.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have been widely adopted as a tool to address the prescription opioid epidemic in the United States. PDMP integration and mandatory use policies are 2 approaches states have implemented to increase use of PDMPs by prescribers. While the effectiveness of these approaches is mixed, it is unclear what factors motivated states to implement them. This study examines whether opioid dispensing, adverse health outcomes, or other non-health-related factors motivated implementation of these PDMP approaches. METHODS: Time-to-event analysis was performed using lagged state-year covariates to reflect values from the year prior. Extended Cox regression estimated the association of states' rates of opioid dispensing, prescription opioid overdose deaths, and neonatal opioid withdrawal syndrome with implementation of PDMP integration and mandatory use policies from 2009 to 2020, controlling for demographic and economic factors, state government and political factors, and prior opioid policies. RESULTS: In our main model, prior opioid dispensing (HR 2.31, 95% CI 1.17, 4.57), neonatal opioid withdrawal syndrome hospitalizations (HR 1.55, 95% CI 1.09, 2.19), and number of prior opioid policies (HR 2.13, 95% CI 1.13, 4.00) were associated with mandatory use policies. Prior prescription opioid overdose deaths (HR 1.21, 95% CI 1.08, 1.35) were also associated with mandatory use policies in a model that did not include opioid dispensing or neonatal opioid withdrawal syndrome. No study variables were associated with implementation of PDMP integration. CONCLUSION: Understanding state-level factors associated with implementing PDMP approaches can provide insights into factors that motivate the adoption of future public health interventions.

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.

Guideline-concordant breast cancer care by patient race and ethnicity accounting for individual-, facility- and area-level characteristics: a SEER-Medicare study.

PURPOSE: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors. METHODS: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties. RESULTS: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: ORBlack 0.83 (0.79-0.88), ORAIAN 0.66 (0.54-0.81); known stage: ORBlack 0.87 (0.80-0.94), ORAIAN 0.63 (0.47-0.85); seeing an oncologist: ORBlack 0.75 (0.71-0.79), ORAIAN 0.60 (0.47-0.72); locoregional treatment: ORBlack 0.80 (0.76-0.84), ORAIAN 0.84 (0.68-1.02); systemic therapies: ORBlack 0.90 (0.83-0.98), ORAIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits. CONCLUSIONS: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care.

The Iowa Health Data Resource (IHDR): an innovative framework for transforming the clinical health data ecosystem.

IMPORTANCE: This manuscript will be of interest to most Clinical and Translational Science Awards (CTSA) as they retool for the increasing emphasis on translational science from translational research. This effort is an extension of the EDW4R work that most CTSAs have done to deploy infrastructure and tools for researchers to access clinical data. OBJECTIVES: The Iowa Health Data Resource (IHDR) is a strategic investment made by the University of Iowa to improve access to real-world health data. The goals of IHDR are to improve the speed of translational health research, to boost interdisciplinary collaboration, and to improve literacy about health data. The first objective toward this larger goal was to address gaps in data access, data literacy, lack of computational environments for processing Personal Health Information (PHI) and the lack of processes and expertise for creating transformative datasets. METHODS: A three-pronged approach was taken to address the objective. The approach involves integration of an intercollegiate team of non-informatics faculty and staff, a data enclave for secure patient data analyses, and novel comprehensive datasets. RESULTS: To date, all five of the health science colleges (dentistry, medicine, nursing, pharmacy, and public health) have had at least one staff and one faculty member complete the two-month experiential learning curriculum. Over the first two years of this project, nine cohorts totaling 36 data liaisons have been trained, including 18 faculty and 18 staff. IHDR data enclave eliminated the need to duplicate computational infrastructure inside the hospital firewall which reduced infrastructure, hardware and human resource costs while leveraging the existing expertise embedded in the university research computing team. The creation of a process to develop and implement transformative datasets has resulted in the creation of seven domain specific datasets to date. CONCLUSION: The combination of people, process, and technology facilitates collaboration and interdisciplinary research in a secure environment using curated data sets. While other organizations have implemented individual components to address EDW4R operational demands, the IHDR combines multiple resources into a novel, comprehensive ecosystem IHDR enables scientists to use analysis tools with electronic patient data to accelerate time to science.

Patterns of Evidence-Based Care for the Diagnosis, Staging, and First-line Treatment of Breast Cancer by Race-Ethnicity: A SEER-Medicare Study.

BACKGROUND: Racial and ethnic disparities in guideline-recommended breast cancer treatment are well documented, however studies including diagnostic and staging procedures necessary to determine treatment indications are lacking. The purpose of this study was to characterize patterns in delivery of evidence-based services for the diagnosis, clinical workup, and first-line treatment of breast cancer by race-ethnicity. METHODS: SEER-Medicare data were used to identify women diagnosed with invasive breast cancer between 2000 and 2017 at age 66 or older (n = 2,15,605). Evidence-based services included diagnostic procedures (diagnostic mammography and breast biopsy), clinical workup (stage and grade determination, lymph node biopsy, and HR and HER2 status determination), and treatment initiation (surgery, radiation, chemotherapy, hormone therapy, and HER2-targeted therapy). Poisson regression was used to estimate rate ratios (RR) and 95% confidence intervals (CI) for each service. RESULTS: Black and American Indian/Alaska Native (AIAN) women had significantly lower rates of evidence-based care across the continuum from diagnostics through first-line treatment compared to non-Hispanic White (NHW) women. AIAN women had the lowest rates of HER2-targeted therapy and hormone therapy initiation. While Black women also had lower initiation of HER2-targeted therapy than NHW, differences in hormone therapy were not observed. CONCLUSIONS: Our findings suggest patterns along the continuum of care from diagnostic procedures to treatment initiation may differ across race-ethnicity groups. IMPACT: Efforts to improve delivery of guideline-concordant treatment and mitigate racial-ethnic disparities in healthcare and survival should include procedures performed as part of the diagnosis, clinical workup, and staging processes.

Factors Associated With Receipt of Molecular Testing and its Impact on Time to Initial Systemic Therapy in Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: Despite recommendations for molecular testing irrespective of patient characteristics, differences exist in receipt of molecular testing for oncogenic drivers amongst metastatic non-small cell lung cancer (mNSCLC) patients. Exploration into these differences and their effects on treatment is needed to identify opportunities for improvement. PATIENTS AND METHODS: We conducted a retrospective cohort study of adult patients diagnosed with mNSCLC between 2011 and 2018 using PCORnet's Rapid Cycle Research Project dataset (n = 3600). Log-binomial, Cox proportional hazards (PH), and time-varying Cox regression models were used to ascertain whether molecular testing was received, and time from diagnosis to molecular testing and/or initial systemic treatment in the context of patient age, sex, race/ethnicity, and multiple comorbidities status. RESULTS: The majority of patients in this cohort were ≤ 65 years of age (median [25th, 75th]: 64 [57, 71]), male (54.3%), non-Hispanic white individuals (81.6%), with > 2 comorbidities in addition to mNSCLC (54.1%). About half the cohort received molecular testing (49.9%). Patients who received molecular testing had a 59% higher probability of initial systemic treatment than patients who were yet to receive testing. Multiple comorbidity status was positively associated with receipt of molecular testing (RR, 1.27; 95% CI 1.08, 1.49). CONCLUSION: Receipt of molecular testing in academic centers was associated with earlier initiation of systemic treatment. This finding underscores the need to increase molecular testing rates amongst mNSCLC patients during a clinically relevant period. Further studies to validate these findings in community centers are warranted.

Evaluating the performance of machine learning methods for risk estimation of delirium in patients hospitalized from the emergency department.

INTRODUCTION: Delirium is a cerebral dysfunction seen commonly in the acute care setting. It is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) and inpatient care by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions in the hospital setting. OBJECTIVE: Our objective was to leverage electronic health records to identify a clinically valuable risk estimation model for prevalent delirium in patients being transferred from the ED to inpatient units. METHODS: This was a retrospective cohort study to develop and validate a risk model to detect delirium using patient data available from prior visits and ED encounter. Electronic health records were extracted for patients hospitalized from the ED between January 1, 2014, and December 31, 2020. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM-ICU recorded within 72 h of hospitalization. Six machine learning models were developed to estimate the risk of delirium using clinical variables including demographic features, physiological measurements, medications administered, lab results, and diagnoses. RESULTS: A total of 28,531 patients met the inclusion criteria with 8057 (28.4%) having a positive delirium screening within the outcome observation period. Machine learning models were compared using the area under the receiver operating curve (AUC). The gradient boosted machine achieved the best performance with an AUC of 0.839 (95% CI, 0.837-0.841). At a 90% sensitivity threshold, this model achieved a specificity of 53.5% (95% CI 53.0%-54.0%) a positive predictive value of 43.5% (95% CI 43.2%-43.9%), and a negative predictive value of 93.1% (95% CI 93.1%-93.2%). A random forest model and L1-penalized logistic regression also demonstrated notable performance with AUCs of 0.837 (95% CI, 0.835-0.838) and 0.831 (95% CI, 0.830-0.833) respectively. CONCLUSION: This study demonstrated the use of machine learning algorithms to identify a combination of variables that enables an estimation of risk of positive delirium screens early in hospitalization to develop prevention or management protocols.

Postoperative Use of the Muscle Relaxants Baclofen and/or Cyclobenzaprine Associated With an Increased Risk of Delirium Following Lumbar Fusion.

STUDY DESIGN: Retrospective, single-center, cohort study. OBJECTIVE: Investigate whether the incidence of postoperative delirium in older adults undergoing spinal fusion surgery is associated with postoperative muscle relaxant administration. SUMMARY OF BACKGROUND DATA: Baclofen and cyclobenzaprine are muscle relaxants frequently used for pain management following spine surgery. Muscle relaxants are known to cause central nervous system side effects in the outpatient setting and are relatively contraindicated in individuals at high risk for delirium. However, there are no known studies investigating their side effects in the postoperative setting. METHODS: Patients over 65 years of age who underwent elective posterior lumbar fusion for degenerative spine disease were stratified into two treatment groups based on whether postoperative muscle relaxants were administered on postoperative day one as part of a multimodal analgesia regimen. Doubly robust inverse probability weighting with cox regression for time-dependent covariates was used to examine the association between postoperative muscle relaxant use and the risk of delirium while controlling for variation in baseline characteristics. RESULTS: The incidence of delirium was 17.6% in the 250 patients who received postoperative muscle relaxants compared with 7.9% in the 280 patients who did not receive muscle relaxants ( P=0.001 ). Multivariate analysis to control for variation in baseline characteristics between treatment groups found that patients who received muscle relaxants had a 2.00 (95% CI: 1.14-3.49) times higher risk of delirium compared with controls ( P=0.015 ). CONCLUSION: Postoperative use of muscle relaxants as part of a multimodal analgesia regimen was associated with an increased risk of delirium in older adults after lumber fusion surgery. Although muscle relaxants may be beneficial in select patients, they should be used with caution in individuals at high risk for postoperative delirium.

Challenges and opportunities in creating a deprescribing program in the emergency department: A qualitative study.

BACKGROUND: As the population of older adults increases, appropriate deprescribing becomes increasingly important for emergency geriatric care. Older adults represent the sickest patients with chronic medical conditions, and they are often exposed to high-risk medications. We need to provide an evidence-based, standardized deprescribing program in the acute care setting, yet the evidence base is lacking and standardized medication programs are needed. METHODS: We conducted a qualitative study with the goal to understand the perspective of healthcare workers, patients, and caregivers on deprescribing high-risk medications in the context of emergency care practices, provider preferences, and practice variability, along with the facilitators and barriers to an effective deprescribing program in the emergency department (ED). To ensure rich, contextual data, the study utilized two qualitative methods: (1) a focus group with physicians, advanced practice providers, nurses, pharmacists, and geriatricians involved in care of older adults and their prescriptions in the acute care setting; (2) semi-structured interviews with patients and caregivers involved in treatment and emergency care. Transcriptions were coded using thematic content analysis, and the principal investigator (S.L.) and trained research staff categorized each code into themes. RESULTS: Data collection from a focus group with healthcare workers (n = 8) and semi-structured interviews with patients and caregivers (n = 20) provided evidence of a potentially promising ED medication program, aligned with the vision of comprehensive care of older adults, that can be used to evaluate practices and develop interventions. We identified four themes: (1) Challenges in medication history taking, (2) missed opportunities in identifying high-risk medications, (3) facilitators and barriers to deprescribing recommendations, and (4) how to coordinate deprescribing recommendations. CONCLUSIONS: Our focus group and semi-structured interviews resulted in a framework for an ED medication program to screen, identify, and deprescribe high-risk medications for older adults and coordinate their care with primary care providers.

Cardiac Adverse Events Associated With Chemo-Radiation Versus Chemotherapy for Resectable Stage III Non-Small-Cell Lung Cancer: A Surveillance, Epidemiology and End Results-Medicare Study.

Background We compared cardiac outcomes for surgery-eligible patients with stage III non-small-cell lung cancer treated adjuvantly or neoadjuvantly with chemotherapy versus chemo-radiation therapy in the Surveillance, Epidemiology and End Results-Medicare database. Methods and Results Patients were age 66+, had stage IIIA/B resectable non-small-cell lung cancer diagnosed between 2007 and 2015, and received adjuvant or neoadjuvant chemotherapy or chemo-radiation within 121 days of diagnosis. Patients having chemo-radiation and chemotherapy only were propensity-score matched and followed from day 121 to first cardiac outcome, noncardiac death, radiation initiation by patients who received chemotherapy only, fee-for-service enrollment interruption, or December 31, 2016. Cause-specific hazard ratios (HRs) and competing risks subdistribution HRs were estimated. The primary outcome was the first of these severe cardiac events: acute myocardial infarction, other hospitalized ischemic heart disease, hospitalized heart failure, percutaneous coronary intervention/coronary artery bypass graft, cardiac death, or urgent/inpatient care for pericardial disease, conduction abnormality, valve disorder, or ischemic heart disease. With median follow-up of 13 months, 70 of 682 patients who received chemo-radiation (10.26%) and 43 of 682 matched patients who received chemotherapy only (6.30%) developed a severe cardiac event (P=0.008) with median time to first event 5.45 months. Chemo-radiation increased the rate of severe cardiac events (cause-specific HR: 1.62 [95% CI, 1.11-2.37] and subdistribution HR: 1.41 [95% CI, 0.97-2.04]). Cancer severity appeared greater among patients who received chemo-radiation (noncardiac death cause-specific HR, 2.53 [95% CI, 1.93-3.33] and subdistribution HR, 2.52 [95% CI, 1.90-3.33]). Conclusions Adding radiation therapy to chemotherapy is associated with an increased risk of severe cardiac events among patients with resectable stage III non-small-cell lung cancer for whom survival benefit of radiation therapy is unclear.

Role of Changing Procedural Characteristics Versus Changing Risk Profile in Age-Based Trends of Outcomes in Patients With Transfemoral Transcatheter Aortic Valve Replacement From 2012 to 2018: A Nationwide Analysis.

Background The trends in outcomes in patients who undergo transcatheter aortic valve replacement are well described in the literature. Some of these trends are driven by the decreasing risk profile of patients because of changing indications for transcatheter aortic valve replacement. We aimed to evaluate these trends in different age groups and quantify how much of these trends are driven by changes in procedural characteristics. Methods and Results Using the National Inpatient Sample from 2012 to 2018, we identified 204 230 adult patients who underwent transfemoral aortic valve replacement. The study's primary objective was to evaluate the changes in age-based trends in in-hospital mortality driven by changes in procedural characteristics over time. The secondary objectives were to evaluate similar trends in cardiac and noncardiac complications and resource use. Univariate and multivariate linear and logistic regression were used to obtain effect sizes. From 2012 to 2018, in-hospital mortality decreased from 1.8% to 0.79% in the age group 18 to 64 years, from 3.8% to 1.6% in the age group 65 to 80 years, and from 5.3% to 1.5% in the age group >80 years (P trend<0.01 for all age groups); these trends remained statistically significant on adjusted analysis except in patients aged 18 to 64 years. The other outcomes also showed variable trends over time. Length of stay, cost, and early discharge rates improved even after adjusting for comorbidities, which is likely attributable to improvement in procedural characteristics. Conclusions The changes in outcomes related to transcatheter aortic valve replacement are partly driven by changing patient risk profiles over time, but procedural characteristics have likely contributed to these trends in all age groups.

The effects of antidepressants on depressive symptoms in manifest Huntington's disease.

OBJECTIVE: Currently there is little evidence to guide the treatment of depression in Huntington's disease (HD). The primary objective was to determine the effectiveness of antidepressant medications on lowering depressive symptom scores in patients with manifest HD. The secondary objective was to determine the effect of antidepressant use on measures of disease progression. METHODS: After retrospectively identifying motor-manifest HD participants with at least borderline depressive symptoms from the Enroll-HD database, 86 new users of antidepressant medication were exact matched with non-users on depression score, and matched on propensity scores developed using age, sex, CAG repeat length, anxiety scores, and disease progression measures. Linear mixed effect models were used to assess the change in depression scores, anxiety scores, and disease progression measures based on antidepressant use between two visits approximately one-year apart. RESULTS: There was no significant difference in the change in depression score between antidepressant users and non-users (p = 0.46). There were also no significant differences in the change in total motor score (p = 0.88), total functional capacity score (p = 0.16), number correct on the symbol digit modality test (p = 0.49), or anxiety score (p = 0.68). CONCLUSIONS: Initiation of antidepressant medication was not associated with a greater reduction in depressive symptoms or changes in other symptoms when compared to non-use. The findings of this study support further research on the effectiveness of antidepressants in Huntington's disease patients. Clinical trials or studies with a larger sample of new antidepressant users should be used to assess the causal effects of antidepressant medications on depressive symptoms.

Emergency Department Communication in Persons Living With Dementia and Care Partners: A Scoping Review.

OBJECTIVES: To synthesize published research exploring emergency department (ED) communication strategies and decision-making with persons living with dementia (PLWD) and their care partners as the basis for a multistakeholder consensus conference to prioritize future research. DESIGN: Systematic scoping review. SETTINGS AND PARTICIPANTS: PLWD and their care partners in the ED setting. METHODS: Informed by 2 Patient-Intervention-Comparison-Outcome (PICO) questions, we conducted systematic electronic searches of medical research databases for relevant publications following standardized methodological guidelines. The results were presented to interdisciplinary stakeholders, including dementia researchers, clinicians, PLWD, care partners, and advocacy organizations. The PICO questions included: How does communication differ for PLWD compared with persons without dementia? Are there specific communication strategies that improve the outcomes of ED care? Future research areas were prioritized. RESULTS: From 5451 studies identified for PICO-1, 21 were abstracted. From 2687 studies identified for PICO-2, 3 were abstracted. None of the included studies directly evaluated communication differences between PLWD and other populations, nor the effectiveness of specific communication strategies. General themes emerging from the scoping review included perceptions by PLWD/care partners of rushed ED communication, often exacerbated by inconsistent messages between providers. Care partners consistently reported limited engagement in medical decision-making. In order, the research priorities identified included: (1) Barriers/facilitators of effective communication; (2) valid outcome measures of effective communication; (3) best practices for care partner engagement; (4) defining how individual-, provider-, and system-level factors influence communication; and (5) understanding how each member of ED team can ensure high-quality communication. CONCLUSIONS AND IMPLICATIONS: Research exploring ED communication with PLWD is sparse and does not directly evaluate specific communication strategies. Defining barriers and facilitators of effective communication was the highest-ranked research priority, followed by validating outcome measures associated with improved information exchange.

Therapeutic relationships between Veterans and buprenorphine providers and effects on treatment retention.

OBJECTIVE: To examine the extent to which there was any therapeutic relationship between Veterans and their initial buprenorphine provider and whether the presence of this relationship influenced treatment retention. DATA SOURCES: National, secondary administrative data used from the Veterans Health Administration (VHA), 2008-2017. STUDY DESIGN: Retrospective cohort study. The primary exposure was a therapeutic relationship between the Veteran and buprenorphine provider, defined as the presence of a previous visit or medication prescribed by the provider in the 2 years preceding buprenorphine treatment initiation. The primary outcome was treatment discontinuation, evaluated as 14 days of absence of medication from initiation through 1 year. DATA COLLECTION/EXTRACTION METHODS: Adult Veterans (age ≥ 18 years) diagnosed with opioid use disorder and treated with buprenorphine or buprenorphine/naloxone within the VHA system were included in this study. We excluded those receiving buprenorphine patches, those with documentation of a metastatic tumor diagnosis within 2 years prior to buprenorphine initiation, and those without geographical information on rurality. PRINCIPAL FINDINGS: A total of 28,791 Veterans were included in the study. Within the overall study sample, 56.3% (n = 16,206) of Veterans previously had at least one outpatient encounter with their initial buprenorphine provider, and 24.9% (n = 7174) of Veterans previously had at least one prescription from that provider in the 2 years preceding buprenorphine initiation. There was no significant or clinically meaningful association between therapeutic relationship history and treatment retention when defined as visit history (aHR: 0.99; 95% CI: 0.96, 1.02) or medication history (aHR: 1.03; 95% CI: 1.00, 1.07). CONCLUSIONS: Veterans initiating buprenorphine frequently did not have a therapeutic history with their initial buprenorphine provider, but this relationship was not associated with treatment retention. Future work should investigate how the quality of Veteran-provider therapeutic relationships influences opioid use dependence management and whether eliminating training requirements for providers might affect access to buprenorphine, and subsequently, treatment initiation and retention.

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.

Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012).

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.

Impact of Surgeon Type and Rurality on Treatment and Survival of Ovarian Cancer Patients.

BACKGROUND: National Comprehensive Cancer Network guidelines recommend ovarian cancer patients receive cancer-directed surgery from a gynecologic oncologist surgeon. We aimed to determine if rurality impacts type of surgeon and estimate if the interaction between rurality and type of surgeon impacts cytoreductive surgery, chemotherapy initiation, and survival. METHODS: Our population-based cohort of Iowan (N=675) ovarian cancer patients included women diagnosed with histologically confirmed stages IB-IV cancer in 2010 to 2016 at the ages of 18 to 89 years old and who received cancer-directed surgery in Iowa. Multivariable logistic regression analysis and Cox proportional hazards models were used. RESULTS: Rural (vs. urban) patients were less likely to receive surgery from a gynecologic oncologist (adjusted odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.30-0.78). Rural patients with a gynecologic oncologist (vs. nongynecologic oncologist) surgeon were more likely to receive cytoreduction (OR: 2.84; 95% CI: 1.31-6.14) and chemotherapy (OR: 4.22; 95% CI: 1.82-9.78). Gynecologic oncologist-provided surgery conferred a 3-year cause-specific survival advantage among rural patients (adjusted hazard ratio: 0.57; 95% CI: 0.33-0.97) and disadvantage among urban patients (hazard ratio: 1.77; 95% CI: 1.02-3.06) in the model without treatment covariates. Significance dissipated in models with treatment variables. DISCUSSION: The variation in the gynecologic oncologist survival advantage may be because of treatment, referral, volume, or nongynecologic oncologist surgeons' specialty difference by rurality. This is the first study to investigate the ovarian cancer survival advantage of having a gynecologic oncologist surgeon by rurality.

Association Between Buprenorphine for Opioid Use Disorder and Mortality Risk.

INTRODUCTION: Veterans with opioid use disorder have an increased risk of suicide and overdose compared with the general population. Buprenorphine, a U.S. Food and Drug Administration-approved medication to treat opioid use disorder, has shown benefits, including decreased risk of illicit drug use and overdose. This study assesses the mortality outcomes with buprenorphine pharmacotherapy among Veterans up to 5 years from treatment initiation. METHODS: This was a retrospective cohort study of Veterans receiving buprenorphine (2008-2017) across any Veterans Health Administration facility. Buprenorphine pharmacotherapy was evaluated as a time-varying covariate. The primary outcome was death up to 5 years from treatment initiation by suicide and overdose combined; secondary outcomes included suicide, overdose, opioid-specific overdose, and all-cause death. Secondary analyses included evaluating the risk of mortality in recent discontinuation and effect modification by select characteristics. All analyses were conducted in 2020. RESULTS: Veterans who were not receiving buprenorphine were 4.33 (adjusted hazard ratio; 95% CI=3.60, 5.21) times more likely to die by suicide/overdose than those receiving buprenorphine pharmacotherapy on any given day, with similar protective associations with treatment across secondary outcomes. The risk of suicide/overdose was highest 8-14 days from treatment discontinuation (adjusted hazard ratio=6.54, 95% CI=4.32, 9.91) than in currently receiving buprenorphine pharmacotherapy. There was no evidence of effect modification by the selected covariates. CONCLUSIONS: Mortality risk was greater among Veterans who were not receiving buprenorphine pharmacotherapy than among those who were. Providers should consider whether buprenorphine pharmacotherapy, either intermittent or continuous, may provide health benefits for their patients and prevent mortality.

Antipsychotic Initiation Among Older Dementia Patients Using Cholinesterase Inhibitors: A National Retrospective Cohort Study.

BACKGROUND: Evidence regarding the initiation of antipsychotic medications across individual cholinesterase inhibitors (ChEIs) to manage the behavioral symptoms of dementia is lacking. OBJECTIVES: This study compared the risk of initiation of antipsychotic medications among older adults with dementia treated with the ChEIs donepezil, rivastigmine, or galantamine. METHODS: This retrospective cohort study used multiyear (2013-2015) Medicare claims data involving Parts A, B, and D. The study sample included community-dwelling older adults (aged ≥ 65 years) with a diagnosis of dementia. The study identified new users of ChEIs and followed them for up to 180 days for antipsychotic initiation. The ChEIs included donepezil, rivastigmine, and galantamine, whereas antipsychotics included typical and atypical agents. Donepezil was used as the reference category as it is the most commonly used ChEI and only acts on acetylcholinesterase, whereas both rivastigmine and galantamine have dual mechanisms of action. Multivariable Cox proportional hazards regression compared the risk of and time to antipsychotic initiation among the three ChEIs, adjusting for other risk factors. RESULTS: The study cohort consisted of 178,441 older adults with dementia who were new users of ChEIs. A total of 23,433 (15.14%) donepezil users, 4114 (19.04%) rivastigmine users, and 324 (15.77%) galantamine users initiated antipsychotics. The mean time to antipsychotic initiation among patients who received antipsychotics was 109.29 ± 69.72 days for donepezil users, 96.70 ± 71.60 days for rivastigmine users, and 104.15 ± 72.53 days for galantamine users. The Cox regression analysis showed that rivastigmine (adjusted hazard ratio [aHR] = 1.27; 95% confidence interval [CI], 1.20-1.34) was significantly associated with antipsychotic initiation compared with donepezil, whereas no significant difference was observed between galantamine and donepezil (aHR = 0.98; 95% CI, 0.81-1.20). CONCLUSION: The study found a 27% increased risk of antipsychotic initiation among users of rivastigmine compared with donepezil users. There was no difference between galantamine and donepezil for antipsychotic initiation. Although the limitations of the study should be considered, the results suggest that donepezil or galantamine may be more appropriate treatments for older patients with dementia, to minimize antipsychotic use.