Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents.

OBJECTIVES: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens/options in nursing home residents. DESIGN: A retrospective observational cohort analysis of US long-stay nursing home residents. SETTING AND PARTICIPANTS: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016. METHODS: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. RESULTS: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. CONCLUSIONS AND IMPLICATIONS: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.

Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin.

Background: Little to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease. Objectives: To assess the effectiveness and safety of direct oral anticoagulants (DOACs)-individually and as a class-vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease. Methods: We conducted a retrospective, US claims-based, propensity score-matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding. Results: The cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02). Conclusion: While the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.

Comparative safety of adding serotonin and norepinephrine reuptake inhibitors (SNRIs) versus nonsteroidal anti-inflammatory drugs (NSAIDs) to short-acting opioids for non-malignant pain in nursing homes.

BACKGROUND: The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids. METHODS: Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (nSNRIs = 5350; nNSAIDs = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death. RESULTS: Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage. CONCLUSIONS: Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research.

Utilization of Antiseizure Medications in Women of Childbearing Age With Epilepsy and Nonepilepsy Indications: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across different indications for therapy and for the newer-generation ASMs in this population. Thus, we assessed the pattern of ASM use in women of childbearing age with epilepsy and nonepilepsy indications (pain and psychiatric disorders). METHODS: We conducted a retrospective analysis of deidentified administrative data submitted to the Optum Clinformatics database. Eligible participants included women aged 12-50 years who filled ASMs between year 2011 and 2017. Participants were followed from date of index prescription filled to study end or insurance disenrollment, whichever came first. For the overall cohort and potential therapy indications, we assessed the type and frequency of ASMs filled; proportion of participants on monotherapy, polytherapy, or treatment switching; and duration of continuous use. Trends were characterized using annual percent change from study start to study end. RESULTS: Our analysis included 465,131 participants who filled 603,916 distinct ASM prescriptions. At baseline, most of the participants had chronic pain (51.0%) and psychiatric disorders (32.7%), with epilepsy the least common (0.9%). The most frequently dispensed were diazepam (24.3%), lorazepam (20.1%), gabapentin (17.4%), clonazepam (12.7%), topiramate (11.3%), and lamotrigine (4.6%). Significant linear increase in trends were observed with gabapentin (annual percent change [95% CI]: 8.4 [7.3-9.4]; p < 0.001) and levetiracetam (3.4 [0.7-6.2]; p = 0.022) and decreasing trends for diazepam (-3.5 [-2.4 to 4.5]; p < 0.001) and clonazepam (-3.4 [-2.3 to 4.5]; p = 0.001). No significant change in trend was observed with valproate (-0.4 [-2.7 to 1.9]; p = 0.651), while nonlinear changes in trends were observed with lorazepam, topiramate, lamotrigine, and pregabalin. DISCUSSION: Decreasing trends were observed with older ASMs in the overall cohort and across the potential indications for therapy. Conversely, increasing trends were seen with the newer ASMs. Considering the risk of teratogenicity associated with the newer medications largely unknown, counseling and education in addition to a careful consideration of the benefits vs potential risks should remain pivotal when prescribing ASMs for women of childbearing age.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort Study.

BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear. METHODS: We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders. RESULTS: Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46-0.90]) or apixaban (HR, 0.40 [95% CI, 0.19-0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47-1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91-3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58-0.82]), apixaban (HR, 0.60 [95% CI, 0.46-0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62-1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18-2.14]). CONCLUSIONS: Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

Antihyperglycemic Drug Use in Long-Stay Nursing Home Residents with Diabetes Mellitus.

Background: About 29.2% of American adults ≥ 65 years of age have diabetes mellitus, but details regarding diabetes management especially among nursing home residents are dated. Objectives: Evaluate the prevalence of antihyperglycemic agents in residents with diabetes mellitus and describe resident characteristics using major drug classes. Design: cross-sectional study. Setting: virtually all United States nursing homes. Participants: 141,636 residents with diabetes mellitus. Measurements: Minimum Data Set (2016) and Medicare Part D claims determined use of metformin, sulfonylureas, meglitinide analogs, alpha-glucosidase inhibitors, TZDs, DPP4 inhibitors, SGLT2 inhibitors, GLP1 agonists, as monotherapy and with basal insulin. Results: Seventy-two percent received antihyperglycemic drugs [most common: basal insulins (53.9% total; 46.9% with other non-insulin agents), metformin (35.5% total; 14.2% monotherapy), sulfonylureas (19.6% total; 6.3% monotherapy), and DPP4 inhibitors (12.2% total; 2.2% monotherapy)]. Sixty-three percent of meglitinide monotherapy versus 34.1% of metformin monotherapy users; and 38.3% meglitinide-basal insulin versus 22.2% metformin-basal insulin users were ≥85 years. Obesity was greater among users of GLP1 agonists compared to those receiving other agents (monotherapy: 60.5% versus 33-42%; with basal insulin: 76.2% versus 50-58%). End-stage renal disease was least prevalent among metformin users (monotherapy: 6.6%; with basal insulin: 8.8%) and most common among meglitinide monotherapy (19.6%) and GLP1 agonists with basal insulin (22%) users. Conclusions: There is heterogeneity of diabetes treatment in nursing homes. Use of antihyperglycemic drugs with a higher risk of hypoglycemia, such as insulin with sulfonylureas or meglitinides, continue in nursing home residents.

Incorporating a learning unit on vaccine hesitancy into a first-year doctor of pharmacy immunization course.

INTRODUCTION: Vaccine hesitancy is a growing threat to public health. The objective of this research was to investigate the effect of incorporating a learning unit on addressing vaccine hesitancy into a doctor of pharmacy immunization delivery course. METHODS: The learning unit, implemented fall 2019 at the University of Rhode Island, involved two interactive lectures and an at-home assignment. A family medicine physician spoke about her experiences with vaccine-hesitant families, and students viewed video scenarios depicting a pharmacist talking with vaccine-hesitant patients followed by an in-class discussion. Data was collected using pre- and post-surveys and a one-year follow-up survey. RESULTS: Out of 125 students enrolled in the course, 121 completed the pre-survey, 113 the post-survey, and 120 the follow-up survey. For pre-/post-survey comparison questions, statistically significant improvements were seen in 9 of 13 items. The follow-up survey showed 83.4% of students had applied knowledge and 85.7% had applied skills gained from the learning unit. CONCLUSION: Incorporating a learning unit on addressing vaccine hesitancy into a pharmacy immunization class resulted in improvements in student self-reported knowledge and comfort in talking with patients who are vaccine hesitant. Long-term use of self-reported knowledge and skills gained was seen one-year post-implementation.

Geographic Variation in the Use of Gabapentinoids and Opioids for Pain in a Commercially Insured Adult Population in the United States.

BACKGROUND: Gabapentinoids have been prescribed off-label for almost all types of pain. The geographic variation in the use of gabapentinoids as analgesics remains unknown. OBJECTIVE: To describe the geographic variation in gabapentinoids, opioids and concurrent use of both for pain by US state and metropolitan statistical area (MSA). METHODS: We conducted a cross-sectional study on December 1, 2018, among commercially insured adults aged 18-64 years without epilepsy or opioid use disorders using IBM® MarketScan® Research Databases. We described the geographic variation in the analgesic regimens (gabapentinoids, opioids and concurrent use of both) by state and MSA, and assessed factors associated with the geographic variation using multilevel logistic regression. RESULTS: We included 9,314,197 beneficiaries; 1.4% had gabapentinoids, 1.5% had opioids and 0.3% had concurrent use of both. The majority of gabapentinoid use lacked an FDA-approved indication. Use of the analgesic regimens varied across states (gabapentinoids (median (interquartile range)): 1.4% (1.2-1.7%); opioids: 1.5% (1.2-1.9%); both: 0.3% (0.2-0.4%)) and MSAs (gabapentinoids: 1.6% (1.3-2.0%); opioids: 1.8% (1.3-2.3%); both: 0.3% (0.2-0.5%)). Demographics explained the largest proportion of the between-state and between-MSA variation. The pattern of the geographic variation in gabapentinoids was similar to that of opioids across states and MSAs. CONCLUSION: Gabapentinoids were as commonly used as opioids for pain in a commercially insured population (mostly off-label). The geographic variation in gabapentinoids was similar to that of opioids, which suggests that gabapentinoids may be widely used as alternatives or adjuvants to opioids across the US.

Expanding Student Knowledge and Confidence on Dietary Supplements Through Mock Patient Consultations.

INTRODUCTION: As dietary supplements are widely used in the United States, student pharmacists should be prepared to assess their appropriateness for self-care. The purpose of this project was to assess the impact of mock patient consults regarding common dietary supplements on second-year (P2) Doctor of Pharmacy (PharmD) students. METHODS: This activity was part of a required course, Self-Care I. Twenty-four groups of 4 to 5 students were created, with each assigned a unique patient vignette. Students had 10 minutes to speak on the phone with their "patient" to obtain needed information in order to make an appropriate recommendation in the form of a 2 to 3-minute recorded oral response. Anonymous, voluntary pre- and post-project surveys assessing perceived dietary supplement knowledge, patient counseling skills, and attitudes about the activity were conducted during class through Google Forms. The Wilcoxon Signed-Rank Test was used to determine differences in mean 10-point Likert scale score between pre- and post-test for each survey question, with significance if p < 0.05. RESULTS: Significant differences were found between pre- and post-survey Likert scale means. Reported confidence in using the QuEST/SCHOLAR-MAC approaches to self-care counseling increased by 45% from baseline. Perceived student knowledge on dietary supplements increased by 44%. Self-rated counseling abilities of students increased by 87% for glucosamine/chondroitin, 28% for melatonin, 39% for red yeast rice, 38% for fish oil, and 42% for cranberry regarding their use in particular cases. CONCLUSIONS: The activity provided students with realistic exposure to questions about dietary supplements that patients ask community pharmacists.

Prevalence and treatment of neuropathic pain diagnoses among U.S. nursing home residents.

ABSTRACT: Neuropathic pain is a common condition experienced by older adults. Prevalence estimates of neuropathic pain and descriptive data of pharmacologic management among nursing home residents are unavailable. We estimated the prevalence of neuropathic pain diagnoses and described the use of pain medications among nursing home residents with possible neuropathic pain. Using the Minimum Data Set 3.0 linked to Medicare claims for residents living in a nursing home on November 30, 2016, we included 473,815 residents. ICD-10 codes were used to identify neuropathic pain diagnoses. Identification of prescription analgesics/adjuvants was based on claims for the supply of medications that overlapped with the index date over a 3-month look-back period. The prevalence of neuropathic pain was 14.6%. Among those with neuropathic pain, 19.7% had diabetic neuropathy, 27.3% had back and neck pain with neuropathic involvement, and 25.1% had hereditary or idiopathic neuropathy. Among residents with neuropathic pain, 49.9% received anticonvulsants, 28.6% received antidepressants, 19.0% received opioids, and 28.2% had no claims for analgesics or adjuvants. Resident characteristics associated with lack of medications included advanced age, dependency in activities of daily living, cognitive impairment, and diagnoses of comorbid conditions. A diagnosis of neuropathic pain is common among nursing home residents, yet many lack pharmacologic treatment for their pain. Future epidemiologic studies can help develop a more standard approach to identifying and managing neuropathic pain among nursing home residents.

Online Promotion of "Brain Health" Supplements.

Objective: To identify the dietary supplements most commonly promoted online for brain health and to compare their major ingredients over 18 months. Mild cognitive impairment and Alzheimer's disease are increasing globally with few effective treatments available. Dietary supplements are widely promoted in the media and online for brain health and memory improvement despite minimal evidence of an actual effect. Methods: Incognito mode on Google Chrome was used to conduct four separate searches using the terms: memory supplement, brain health supplement, Alzheimer's supplement, and dementia supplement. The four separate searches for products were conducted through CVS, Walgreens, Walmart, GNC, Amazon, Yahoo, and Google. For each website, the top 10 supplement products and their ingredients were documented in August 2017 and again in January 2019. Results: Of the four terms used, "memory supplement" and "brain health supplement" provided the most results. The most common products were Prevagen®, Procera®, and Neuro Health®. Amazon had the most repeated products in 2017 and 2019, while Google and CVS had the least. Focus Factor® appeared 11 times in 2019 compared with once in 2017. At both time points, the most commonly promoted products were proprietary blends of Ginkgo biloba, vitamins, particularly vitamin B12 and folic acid, huperzine-A, Bacopa monnieri, and phosphatidylserine. Conclusions: Though the 2017 and 2019 datasets showed diverse products, the primary ingredients were similar. These supplements have insufficient evidence of efficacy and are expensive. Health professionals must be knowledgeable about dietary supplements for brain health to appropriately counsel individuals.

A systematic review of integrative medicine for opioid withdrawal.

INTRODUCTION: The United States has been battling an opioid epidemic for decades. As substance use disorders have grown, so too has investigation into treatment options, including integrative medicine approaches, for managing opioid withdrawal symptoms (OWS). OBJECTIVES: This systematic review sought to assess the use of integrative medicine approaches for the alleviation of OWS in patients dependent on opioids and to summarize the available data. METHODS: The authors searched using synonyms for opioids, substance use disorder, and integrative medicine and standardized searches in Embase, PubMed, and Cochrane Library. We also hand searched references for systematic reviews. This review did not include articles that could not be obtained as full-text publications via interlibrary loan. The review also excluded studies with interventions involving acupuncture because multiple systematic reviews on this approach already exist. In addition, we also excluded studies of therapy for opioid maintenance. We evaluated studies for inclusion based on the Jadad criteria. We compared opioid withdrawal outcomes of the studies to determine the efficacy of integrative medicine approaches. RESULTS: The authors identified a total of 382 unique publications initially for possible inclusion through systematic searches. After applying inclusion and exclusion criteria, five studies met Jadad criteria. The authors identified an additional two studies for inclusion via hand searching. A total of seven studies included interventions consisting of passionflower, weinicom, fu-yuan pellet, jinniu capsules, tai-kang-ning, dynorphin, and l-tetrahydropalmatine. Analyzing the articles was difficult given the varied scoring methods they used to quantify opioid withdrawal symptoms and the small sample sizes in the trials. Most showed evidence that supported integrative medicine approaches for OWS, although the strength of evidence was limited because of sample sizes. CONCLUSIONS: This review found evidence of multiple integrative medicine approaches for opioid withdrawal symptoms. Well-designed randomized controlled trials should assess the efficacy of integrative medicine for improvement in OWS.

National Trends in Statin Use among the United States Nursing Home Population (2011-2016).

BACKGROUND: Little is known about trends in statin use in United States (US) nursing homes. OBJECTIVES: The aim of this study was to describe national trends in statin use in nursing homes and evaluate the impact of the introduction of generic statins, safety warnings, and guideline recommendations on statin use. METHODS: This study employed a repeated cross-sectional prevalence design to evaluate monthly statin use in long-stay US nursing home residents enrolled in Medicare fee-for-service using the Minimum Data Set 3.0 and Medicare Part D claims between April 2011 and December 2016. Stratified by age (65-75 years, ≥ 76 years), analyses estimated trends and level changes with 95% confidence intervals (CI) following statin-related events (the availability of generic statins, American Heart Association/American College of Cardiology guideline updates, and US FDA safety warnings) through segmented regression models corrected for autocorrelation. RESULTS: Statin use increased from April 2011 to December 2016 (65-75 years: 38.6-43.3%; ≥ 76 years: 26.5% to 30.0%), as did high-intensity statin use (65-75 years: 4.8-9.5%; ≥ 76 years: 2.3-4.5%). The introduction of generic statins yielded little impact on the prevalence of statins in nursing home residents. Positive trend changes in high-intensity statin use occurred following national guideline updates in December 2011 (65-75 years: ß = 0.16, 95% CI 0.09-0.22; ≥ 76 years: ß = 0.09, 95% CI 0.06-0.12) and November 2013 (65-75 years: ß = 0.11, 95% CI 0.09-0.13; ≥ 76 years: ß = 0.04, 95% CI 0.03-0.05). There were negative trend changes for any statin use concurrent with FDA statin safety warnings in March 2012 among both age groups (65-75 years: ß trend change = - 0.06, 95% CI - 0.10 to - 0.02; ≥ 76 years: ß trend change = - 0.05, 95% CI - 0.08 to - 0.01). The publication of the results of a statin deprescribing trial yielded a decrease in any statin use among the ≥ 76 years age group (ß level change = - 0.25, 95% CI - 0.48 to - 0.09; ß trend change = - 0.03, 95% CI - 0.04 to - 0.01), with both age groups observing a positive trend change with high-intensity statins (65-75 years: ß = 0.11, 95% CI 0.02-0.21; ≥ 76 years: ß = 0.05, 95% CI 0.01-0.09). CONCLUSION: Overall, statin use in US nursing homes increased from 2011 to 2016. Guidelines and statin-related events appeared to impact use in the nursing home setting. As such, statin guidelines and messaging should provide special consideration for nursing home populations, who may have more risk than benefit from statin pharmacotherapy.

Priority-Setting to Address the Geriatric Pharmacoparadox for Pain Management: A Nursing Home Stakeholder Delphi Study.

BACKGROUND: Evidence to guide clinical decision making for pain management in nursing home residents is scant. OBJECTIVE: Our objective was to explore the extent of consensus among expert stakeholders regarding what analgesic issues should be prioritized for comparative-effectiveness studies of beneficial and adverse effects of analgesic regimens in nursing home residents. METHODS: Two stakeholder panels (nurses only and a mix of clinicians/researchers) were engaged (n = 83). During a three-round online modified Delphi process, participants rated and commented on the need for new evidence on nonopioid analgesic regimens and opioid regimens, short-term adverse effects, long-term adverse effects, comorbid conditions, and other factors in the nursing home setting (9-point scale; 1 = not essential to 9 = very essential to obtain new evidence). The quantitative data were analyzed to determine the existence of consensus using an approach from the RAND/UCLA Appropriateness Method User's Manual. The qualitative data, consisting of participant explanations of their numeric ratings, were thematically analyzed by an experienced qualitative researcher. RESULTS: For nursing home residents, evidence generation was deemed essential for opioids, gabapentin (alone or with serotonin norepinephrine reuptake inhibitors [SNRIs]), and nonsteroid anti-inflammatory drugs with SNRIs. Experts prioritized the following outcomes as essential: long-term adverse effects, including delirium, cognitive decline, and decline in activities of daily living (ADLs). Kidney disease and depression were deemed essential conditions to consider in studies of pain medications. Coprescribing analgesic regimens with benzodiazepines, sedating medications, serotonergic medications, and non-SNRI antidepressants were considered essential areas of study. Experts noted that additional study was essential in residents with moderate/severe cognitive impairment and limitations in ADLs. CONCLUSIONS: Stakeholder priorities for more evidence reflect concerns related to treating medically complex residents with complex drug regimens and included long-term adverse effects, coprescribing, and sedating medications. Carefully conducted observational studies are needed to address the vast evidence gap for nursing home residents.

Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis.

Importance: Prolonged opioid use after surgery may be associated with opioid dependency and increased health care use. However, published studies have reported varying estimates of the magnitude of prolonged opioid use and risk factors associated with the transition of patients to long-term opioid use. Objectives: To evaluate the rate and characteristics of patient-level risk factors associated with increased risk of prolonged use of opioids after surgery. Data Sources: For this systematic review and meta-analysis, a search of MEDLINE, Embase, and Google Scholar from inception to August 30, 2017, was performed, with an updated search performed on June 30, 2019. Key words may include opioid analgesics, general surgery, surgical procedures, persistent opioid use, and postoperative pain. Study Selection: Of 7534 articles reviewed, 33 studies were included. Studies were included if they involved participants 18 years or older, evaluated opioid use 3 or more months after surgery, and reported the rate and adjusted risk factors associated with prolonged opioid use after surgery. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two reviewers independently assessed and extracted the relevant data. Main Outcomes and Measures: The weighted pooled rate and odds ratios (ORs) of risk factors were calculated using the random-effects model. Results: The 33 studies included 1 922 743 individuals, with 1 854 006 (96.4%) from the US. In studies with available sex and age information, participants were mostly female (1 031 399; 82.7%) and had a mean (SD) age of 59.3 (12.8) years. The pooled rate of prolonged opioid use after surgery was 6.7% (95% CI, 4.5%-9.8%) but decreased to 1.2% (95% CI, 0.4%-3.9%) in restricted analyses involving only opioid-naive participants at baseline. The risk factors with the strongest associations with prolonged opioid use included preoperative use of opioids (OR, 5.32; 95% CI, 2.94-9.64) or illicit cocaine (OR, 4.34; 95% CI, 1.50-12.58) and a preoperative diagnosis of back pain (OR, 2.05; 95% CI, 1.63-2.58). No significant differences were observed with various study-level factors, including a comparison of major vs minor surgical procedures (pooled rate: 7.0%; 95% CI, 4.9%-9.9% vs 11.1%; 95% CI, 6.0%-19.4%; P = .20). Across all of our analyses, there was substantial variability because of heterogeneity instead of sampling error. Conclusions and Relevance: The findings suggest that prolonged opioid use after surgery may be a substantial burden to public health. It appears that strategies, such as proactively screening for at-risk individuals, should be prioritized.

Prescription analgesia and adjuvant use by pain severity at admission among nursing home residents with non-malignant pain.

OBJECTIVE: We estimated the use of prescribed analgesics and adjuvants among nursing home residents without cancer who reported pain at their admission assessment, in relation to resident-reported pain severity. METHODS: Medicare Part D claims were used to define 3 classes of analgesics and 7 classes of potential adjuvants on the 21st day after nursing home admission (or the day of discharge for residents discharged before that date) among 180,780 residents with complete information admitted between January 1, 2011 and December 9, 2016, with no cancer diagnosis. RESULTS: Of these residents, 27.9% reported mild pain, 46.6% moderate pain, and 25.6% reported severe pain. The prevalence of residents in pain without Part D claims for prescribed analgesic and/or adjuvant medications was 47.3% among those reporting mild pain, 35.7% among those with moderate pain, and 24.8% among those in severe pain. Among residents reporting severe pain, 33% of those ≥ 85 years of age and 35% of those moderately cognitively impaired received no prescription analgesics/adjuvants. Use of all classes of prescribed analgesics and adjuvants increased with resident-reported pain severity, and the concomitant use of medications from multiple classes was common. CONCLUSION: Among nursing home residents with recognized pain, opportunities to improve the pharmacologic management of pain, especially among older residents, and those living with cognitive impairments exist.

Comparative Safety and Effectiveness of Direct-Acting Oral Anticoagulants Versus Warfarin: a National Cohort Study of Nursing Home Residents.

BACKGROUND: Research comparing direct-acting oral anticoagulants (DOACs) to warfarin has excluded nursing home residents, a vulnerable and high-risk population. OBJECTIVE: To compare the safety and effectiveness of DOACs versus warfarin. DESIGN: New-user cohort study (2011-2016). PATIENTS: US nursing home residents aged > 65 years with non-valvular atrial fibrillation enrolled in fee-for-service Medicare for > 6 months. EXPOSURES: Initiators of DOACs (2881 apixaban, 1289 dabigatran, 3735 rivaroxaban) were 1:1 propensity matched to warfarin initiators. MAIN MEASURES: Outcomes included ischemic stroke or transient ischemic attack (i.e., ischemic cerebrovascular event), bleeding (extracranial or intracranial), other vascular events, death, and a composite of all outcomes. Absolute rate differences (RD) and cause-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated. Subgroup analyses were performed by alignment of DOAC dosing with labeling. KEY RESULTS: Median age (84 years), CHA2DS2-Vasc (5), and ATRIA risk scores (3) were similar across medications. Clinical outcome rates were similar for dabigatran and rivaroxaban users versus warfarin users. However, ischemic cerebrovascular event rates were higher among dabigatran and rivaroxaban users that received reduced dosages without an indication. Overall, apixaban users had higher ischemic cerebrovascular event rates (HR 1.86; 95% CI 1.00-3.45) and lower bleeding rates (HR 0.66; 95% CI 0.49-0.88), but outcome rates varied by dosing alignment. Mortality rates (per 100 person-years) were lower for apixaban (RDs - 9.30; 95% CI - 13.18 to - 5.42), dabigatran (RDs - 10.79; 95% CI - 14.98 to - 6.60), and rivaroxaban (RDs - 8.92; 95% CI - 12.01 to - 5.83) versus warfarin; composite outcome findings were similar. CONCLUSIONS: Among US nursing home residents, the DOACs were each associated with lower mortality versus warfarin. Misaligned DOAC dosing was common in nursing homes and was associated with clinical and mortality outcomes. Overall, DOAC users had lower rates of adverse outcomes including mortality compared with warfarin users.

Prevalent Statin Use in Long-Stay Nursing Home Residents with Life-Limiting Illness.

OBJECTIVES: To evaluate the prevalence and factors associated with statin pharmacotherapy in long-stay nursing home residents with life-limiting illness. DESIGN: Cross-sectional. SETTING: US Medicare- and Medicaid-certified nursing home facilities. PARTICIPANTS: Long-stay nursing home resident Medicare fee-for-service beneficiaries aged 65 years or older with life-limiting illness (n = 424 212). MEASUREMENTS: Prevalent statin use was estimated as any low-moderate intensity (daily dose low-density lipoprotein-cholesterol [LDL-C] reduction <30%-50%) and high-intensity (daily dose LDL-C reduction >50%) use via Medicare Part D claims for a prescription supply on September 30, 2016, with a 90-day look-back period. Life-limiting illness was operationally defined to capture those near the end of life using evidence-based criteria to identify progressive terminal conditions or limited prognoses (<6 mo). Poisson models provided estimates of adjusted prevalence ratios and 95% confidence intervals for resident factors. RESULTS: A total of 34% of residents with life-limiting illness were prescribed statins (65-75 y = 44.0%, high intensity = 11.1%; >75 y = 31.1%, high intensity = 5.4%). Prevalence of statins varied by life-limiting illness definition. Of those with a prognosis of less than 6 months, 23% of the 65 to 75 and 12% of the older than 75 age groups were on statins. Factors positively associated with statin use included minority race or ethnicity, use of more than five concurrent medications, and atherosclerotic cardiovascular disease or risk factors. CONCLUSION: Despite having a life-limiting illness, more than one-third of clinically compromised long-stay nursing home residents remain on statins. Although recent national guidelines have expanded indications for statins, the benefit of continued therapy in an advanced age population near the end of life is questionable. Efforts to deprescribe statins in the nursing home setting may be warranted. J Am Geriatr Soc 68:708-716, 2020.

The Prevalence and Factors Associated with Antiepileptic Drug Use in US Nursing Home Residents.

BACKGROUND: Antiepileptic drugs (AEDs) are commonly used by nursing home residents, both on- and off-label. The landscape of AED use has changed over the past two decades; however, despite this, contemporaneous research on AED use in US nursing home residents is scant. OBJECTIVE: The aim of this study was to estimate the prevalence of AED use, describe prescribing patterns, identify factors associated with AED use, and assess whether these factors differ among AEDs with expanded indications in older adults (i.e. gabapentin, pregabalin, topiramate, and lamotrigine). METHODS: We conducted a cross-sectional study among 549,240 long-stay older residents who enrolled in fee-for-service Medicare and lived in 15,111 US nursing homes on 1 September 2016. Demographics and conditions associated with AED indications, epilepsy comorbidities, and safety data came from the Minimum Data Set Version 3.0 (MDS 3.0). Medicare Part D claims were used to identify AED use. Robust Poisson models and multinomial logistic models for clustered data estimated adjusted prevalence ratios (aPR), adjusted odds ratios (aOR), and 95% confidence intervals (CIs). RESULTS: Overall, 24.0% used AEDs (gabapentin [13.3%], levetiracetam [4.7%], phenytoin [1.9%], pregabalin [1.8%], and lamotrigine [1.2%]). AED use was associated with epilepsy (aPR 3.73, 95% CI 3.69-3.77), bipolar disorder (aPR 1.20, 95% CI 1.18-1.22), pain (aPRmoderate/severe vs. no pain 1.42, 95% CI 1.40-1.44), diabetes (aPR 1.27, 95% CI 1.26-1.28), anxiety (aPR 1.12, 95% CI 1.11-1.13), depression (aPR 1.17, 95% CI 1.15-1.18), or stroke (aPR 1.08, 95% CI 1.06-1.09). Residents with advancing age (aPR85+ vs. 65-74 years 0.73, 95% CI 0.73-0.74), Alzheimer's disease/dementia (aPR 0.87, 95% CI 0.86-0.88), or cognitive impairment (aPRsevere vs. no impairment 0.62, 95% CI 0.61-0.63) had decreased AED use. Gabapentinoid use was highly associated with pain (aORmoderate/severe vs. no pain 2.07, 95% CI 2.01-2.12) and diabetes (aOR 1.79, 95% CI 1.76-1.82), but not with an epilepsy indication. CONCLUSIONS: AED use was common in nursing homes, with gabapentin most commonly used (presumably for pain). That multiple comorbidities were associated with AED use underscores the need for future studies to investigate the safety and effectiveness of AED use in nursing home residents.

Changes in Anticoagulant Utilization Among United States Nursing Home Residents With Atrial Fibrillation From 2011 to 2016.

Background Nursing home residents with atrial fibrillation are at high risk for ischemic stroke and bleeding events. The most recent national estimate (2004) indicated less than one third of this high-risk population was anticoagulated. Whether direct-acting oral anticoagulant ( DOAC ) use has disseminated into nursing homes and increased anticoagulant use is unknown. Methods and Results A repeated cross-sectional design was used to estimate the point prevalence of oral anticoagulant use on July 1 and December 31 of calendar years 2011 to 2016 among Medicare fee-for-service beneficiaries with atrial fibrillation residing in long-stay nursing homes. Nursing home residence was determined using Minimum Data Set 3.0 records. Medicare Part D claims for apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin were identified and point prevalence was estimated by determining if the supply from the most recent dispensing covered each point prevalence date. A Cochran-Armitage test was performed for linear trend in prevalence. On December 31, 2011, 42.3% of 33 959 residents (median age: 85; Q1 79, Q3 90) were treated with an oral anticoagulant, of whom 8.6% used DOAC s. The proportion receiving treatment increased to 47.8% of 37 787 residents as of December 31, 2016 ( P<0.01); 48.2% of 18 054 treated residents received DOAC s. Demographic and clinical characteristics of residents using DOAC s and warfarin were similar in 2016. Half of the 8734 DOAC users received standard dosages and most were treated with apixaban (54.4%) or rivaroxaban (35.8%) in 2016. Conclusions Increases in anticoagulant use among US nursing home residents with atrial fibrillation coincided with declining warfarin use and increasing DOAC use.