Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

ABSTRACT: No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Signal detection of adverse events associated with gabapentinoid use for chronic pain.

INTRODUCTION: Gabapentinoids (GABA) prescribing as a potential and conceivably safer substitute for opioids has substantially increased. Understanding all potential adverse drug events (ADEs) associated with GABA will guide clinical decision-making for pain management. METHODS: A 20% sample of Medicare enrollees with new chronic pain diagnoses in 2017-2018 was selected. GABA users were those with >=30 consecutive days prescription in a year without opioid prescription. Opioid users were similarly defined. The control group used neither of these drugs. Propensity score match across three groups based on demographics and comorbidity was performed. We used proportional reporting ratio (PRR), Gamma Poisson Shrinker, and tree-based scan statistic (TBSS) to detect ADEs within 3, 6, and 12 months of follow-up. RESULTS: Immunity disorder was detected within 3 months of follow-up by PRR compared to opioid use (PRR:2.33), and by all three methods compared to controls. Complications of transplanted organs/tissues and schizophrenia spectrum/other psychotic disorders were consistently detected by PRR and TBSS within 3 months. Skin disorders were detected by TBSS; and stroke was detected by PRR within 3 months compared to opioid use (PRR:4.74). Some malignancies were detected by PRR within 12 months. Other signals detected in GABA users were neuropathy and nerve disorders. CONCLUSIONS: Our study identified expected and unexpected ADE signals in GABA users. Neurological signals likely related to indications for GABA use. Signals for immunity, mental/behavior, and skin disorders were found in the FDA adverse event reporting system database. Unexpected signals of stroke and cancer require further confirmatory analyses to verify.

Inequitable access to nonpharmacologic pain treatment providers among cancer-free U.S. adults.

OBJECTIVE: Using evidence-based nonpharmacologic pain treatments may prevent opioid overuse and associated adverse outcomes. There is limited data on the impact of access-promoting social determinants of health (SDoH: education, income, transportation) on use of nonpharmacologic pain treatments. Our objective was to examine the relationship between SDoH and use of nonpharmacologic pain treatment providers. Our goal was to understand policy-actionable factors contributing to inequity in pain treatment. METHODS: Based on Andersen's Health Utilization Model, this cross-sectional analysis of 2016-2019 Medical Expenditure Panel Survey data evaluated whether use of outpatient nonpharmacologic pain treatment providers is driven by enabling (i.e., advantageous socioeconomic resources) or need (i.e., perceived disability and diagnosed disease) factors. The study sample (unweighted n = 28,188) represented a weighted N = 81,912,730 noninstitutionalized, cancer-free, U.S. adults with pain interference. The primary outcome measured use of nonpharmacologic providers relative to exclusive prescription opioid use or no treatment (i.e., neither opioids nor nonpharmacologic). To quantify equitable access, we compared the variance-between access-promoting enabling factors versus medical need factors-that explained utilization. RESULTS: Compared to enabling factors, need factors explained twice the variance predicting pain treatment utilization. Still, the adjusted odds of using nonpharmacologic providers instead of opioids alone were 39% lower among respondents identifying as Black (95% Confidence Interval [CI], 0.49-0.76) and respondents residing in the U.S. South (95% CI, 0.51-0.74). Higher education (95% CI, 1.72-2.79) and income (95% CI, 1.68-2.42) both facilitated using nonpharmacologic providers instead of opioids. CONCLUSIONS: These findings highlight the substantial influence access-promoting SDoH have on pain treatment utilization.

Pain Control Associated With Gabapentinoid Prescription After Elective Total Knee Arthroplasty.

BACKGROUND: Gabapentinoid (GABA) prescribing has substantially increased as a nonopioid analgesics for surgical conditions. We examined the effectiveness of GABA use for postoperative pain control among patients receiving total knee arthroplasty (TKA). METHODS: This retrospective cohort study using 2016 to 2019 data from a 20% national sample of Medicare enrollees included patients aged 66 and over years who received an elective TKA, were discharged to home, received home health care, and had both admission and discharge assessments of pain (n = 35,186). Study outcomes were pain score difference between admission and discharge and less-than-daily pain interfering with activity at discharge. Opioid and GABA prescriptions after surgery and receipt of nerve block within 3 days of surgery were also assessed. RESULTS: There were 30% of patients who had a pain score decrease of 3 to 4 levels and 55.8% had pain score decreases of 1 to 2 levels. In multivariable analyses, receiving a nerve block was significantly associated with pain score reduction. A GABA prescription increased the magnitude of pain score reduction among those receiving a nerve block. Results from inverse probability weighted analysis with propensity score showed that coprescribing of GABA and low-dose opioid was associated with significantly lower pain scores. CONCLUSIONS: Post-TKA opioid use was not associated with pain score reduction. Receiving a nerve block was associated with a modest pain score reduction. Co-prescribing GABA with low-dose opioid or receiving a nerve block was associated with increasing magnitudes of pain reduction. Further research should identify alternatives to opioid use for managing postoperative TKA pain.

Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis.

BACKGROUND/OBJECTIVES: The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA. METHODS: This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed. RESULTS: Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83-0.95). All regimens except non-tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use. CONCLUSION: Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.

Disparities in Late-Stage Breast and Colorectal Cancer Diagnosis Among Hispanic, Non-Hispanic White, and Non-Hispanic Black Patients: a Retrospective Cohort Study of Texas Medicare Beneficiaries.

BACKGROUND: Disparities in late-stage breast or colorectal cancer diagnosis in younger populations are associated with social determinants of health (SDOH; education, poverty, housing, employment). We hypothesized that, in older Medicare beneficiaries, disparities in late-stage cancer diagnosis between Hispanic, non-Hispanic Black (NHB), and non-Hispanic White (NHW) patients would be associated with SDOH, comorbidities, and primary care physician (PCP) access. METHODS: We analyzed 2005-2017 Texas Cancer Registry data linked with Medicare data for patients aged ≥ 66 (n = 86,501). Variables included age at diagnosis, sex, comorbidities, poverty level, education, PCP, and relevant cancer screening within 1 year. RESULTS: For breast cancer in women (Hispanic, n = 6380; NHW, n = 39,225; NHB, n = 4055), a fully adjusted model showed significantly higher odds of late-stage cancer diagnosis only in NHB patients (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.01-1.22) compared with NHW; adjustment for comorbidities and SDOH partially decreased the odds of late-stage diagnosis relative to NHWs. Interaction terms between race-ethnicity and poverty were not significant. For colorectal cancer, a fully adjusted multivariate model showed significantly higher odds of late-stage diagnosis only among NHBs (n = 3318, OR 1.29, 95% CI 1.19-1.40) relative to NHWs (n = 27,470); adjustment for SDOH partially decreased the odds of late-stage diagnosis in NHB patients. Interaction terms between race-ethnicity and poverty were not significant. CONCLUSION: Racial disparities in late-stage breast and colorectal cancer diagnoses remain after adjustment for SDOH and clinically relevant factors, underscoring the need to optimize access to screening and timely cancer treatment in racial/ethnic minorities.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation.

BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Trends in the Use of Opioids vs Nonpharmacologic Treatments in Adults With Pain, 2011-2019.

Importance: Chronic pain prevalence among US adults increased between 2010 and 2019. Yet little is known about trends in the use of prescription opioids and nonpharmacologic alternatives in treating pain. Objectives: To compare annual trends in the use of prescription opioids, nonpharmacologic alternatives, both treatments, and neither treatment; compare estimates for the annual use of acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy; and estimate the association between calendar year and pain treatment based on the severity of pain interference. Design, Setting, and Participants: A serial cross-sectional analysis was conducted using the nationally representative Medical Expenditure Panel Survey to estimate the use of outpatient services by cancer-free adults with chronic or surgical pain between calendar years 2011 and 2019. Data analysis was performed from December 29, 2021, to August 5, 2022. Exposures: Calendar year (2011-2019) was the primary exposure. Main Outcomes and Measures: The association between calendar year and mutually exclusive pain treatments (opioid vs nonpharmacologic vs both vs neither treatment) was examined. A secondary outcome was the prevalence of nonpharmacologic treatments (acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy). All analyses were stratified by pain type. Results: Among the unweighted 46 420 respondents, 9643 (20.4% weighted) received surgery and 36 777 (79.6% weighted) did not. Weighted percentages indicated that 41.7% of the respondents were aged 45 to 64 years and 55.0% were women. There were significant trends in the use of pain treatments after adjusting for demographic factors, socioeconomic status, health conditions, and pain severity. For example, exclusive use of nonpharmacologic treatments increased in 2019 for both cohorts (chronic pain: adjusted odds ratio [aOR], 2.72; 95% CI, 2.30-3.21; surgical pain: aOR, 1.53; 95% CI, 1.13-2.08) compared with 2011. The use of neither treatment decreased in 2019 for both cohorts (chronic pain: aOR, 0.43; 95% CI, 0.37-0.49; surgical pain: aOR, 0.59; 95% CI, 0.46-0.75) compared with 2011. Among nonpharmacologic treatments, chiropractors and physical therapists were the most common licensed healthcare professionals. Conclusions and Relevance: Among cancer-free adults with pain, the annual prevalence of nonpharmacologic pain treatments increased and the prevalent use of neither opioids nor nonpharmacologic therapy decreased for both chronic and surgical pain cohorts. These findings suggest that, although access to outpatient nonpharmacologic treatments is increasing, more severe pain interference may inhibit this access.

The Case for Early Use of Glucagon-like Peptide-1 Receptor Agonists in Obstructive Sleep Apnea Patients with Comorbid Diabetes and Metabolic Syndrome.

Patients with obstructive sleep apnea (OSA) have high rates of co-occurring type 2 diabetes, hypertension, obesity, stroke, congestive heart failure, and accelerated atherosclerotic cardiovascular diseases. These conditions frequently require multiple medications, raising the risk of polypharmacy, adverse drug-drug and drug-disease interactions, decreased quality of life, and increased healthcare cost in these patients. The current review of extant literature presents evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RA) as one pharmacologic intervention that provides a "one-stop shop" for OSA patients because of the multiple effects GLP-1RA has on comorbidities (e.g., hypertension, diabetes, obesity, metabolic syndrome, and atherosclerotic cardiovascular diseases) that commonly co-occur with OSA. Examples of glucagon-like peptide-1 receptor agonists approved by the FDA for diabetes (some of which are also approved for obesity) are liraglutide, exenatide, lixisenatide, dulaglutide, semaglutide, and albiglutide. Prescribing of GLP-1RAs to address these multiple co-occurring conditions has enormous potential to reduce polypharmacy, cost, and adverse drug events, and to improve quality of life for patients living with OSA and diabetes. We thus strongly advocate for increased and early use of GLP-1RA in OSA patients with co-occurring diabetes and other cardiometabolic conditions common in OSA.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

BACKGROUND: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF). METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. RESULTS: Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA2DS2-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA2DS2-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1). CONCLUSIONS: Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Risk of an Opioid-Related Emergency Department Visit or Hospitalization Among Older Breast, Colorectal, Lung, and Prostate Cancer Survivors.

OBJECTIVE: To assess whether long-term cancer survivors (≥5 years after diagnosis) are at an increased risk of experiencing an opioid-related emergency department (ED) visit or hospitalization compared with persons without cancer. METHODS: A 1:1 matched retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results-Medicare linked data sets. The analysis was conducted from October 2020 to December 2020 in persons who lived 5 years or more after a breast, colorectal, lung, or prostate cancer diagnosis matched to noncancer controls on the basis of age, sex, race, pain conditions, and previous opioid use. Fine-Gray regression models were used to assess the relationship between cancer survivorship status and opioid-related ED visit or hospitalization. RESULTS: The incidence of opioid-related ED visits and hospitalizations was 51.2 (95% CI, 43.5 to 59.8) and 62.2 (95% CI, 53.4 to 72.1) per 100,000 person-years among cancer survivors and matched noncancer controls, respectively. No significant association was observed between survivorship and opioid-related adverse event among opioid naive (hazard ratio, 0.79; 95% CI, 0.61 to 1.02) and non-naive (hazard ratio, 1.26; 95% CI, 0.84 to 1.89) cohorts. CONCLUSION: Cancer survivors and noncancer controls had a similar risk of an ED visit or inpatient admission. Guidelines and policies should promote nonopioid pain management approaches especially to opioid non-naive older adults, a population at high risk for an opioid-related ED visit or hospitalization.

US national trends in prescription opioid use after burn injury, 2007 to 2017.

BACKGROUND: Opioid misuse and overdose in the United States remain a public health emergency. Overprescribing has been recognized as a significant contributor to the epidemic. Opioids are the mainstay for pain management after burn; however, to date, no large-scale nationally representative study has evaluated outpatient opioid prescribing practices in this population. METHODS: A retrospective study was conducted of patients up to 65 years old with burn injuries between 2007 and 2017 using national commercial insurance data. The primary outcome was initial opioid prescribing after burn injury. Secondary outcomes were total days' supply, oral daily morphine milligram equivalents, and number of refills. RESULTS: Of the 140,753 patients with burns, 34,685 (24.6%) received an opioid prescription. The odds of prescription opioid use were lower in 2015, 2016, and 2017 compared with 2007. Interactions with age, severity (P < .0001), and region (P = .003) showed significant variation in rates of decline from 2007 to 2017, with the steepest decline in those aged <20 and in residents of Northeast United States. Prescribing rates remained stable over time among those with more severe burn injuries. The significant decline in daily opioid morphine milligram equivalents after 2013 was paralleled by an increase in days of supply (P values <.005). The odds of refill declined in 2016 and 2017. CONCLUSION: While opioid prescribing after burn has declined in the past decade, significant variation remains among regions and age groups, suggesting a need to develop uniform guidelines to improve the quality of opioid prescribing and pain management protocols in burn patients.

Regional and temporal variation in receipt of long-term opioid therapy among older breast, colorectal, lung, and prostate cancer survivors in the United States.

BACKGROUND: Older cancer survivors have high rates of long-term opioid therapy (≥90 days/year). However, the geographical and temporal variation in long-term opioid therapy rates for older cancer survivors is not known. METHODS: A retrospective cohort study was conducted using SEER-Medicare data. Persons aged ≥66 years, diagnosed with breast, colorectal, lung, or prostate cancer from 1991 to 2011, and alive ≥5 years after diagnosis were included. Persons were followed from 1/1/2008 until 12/31/2016. Persons were assigned to a census region in their state of residence each year. Individuals who were covered by an opioid prescription for at least 90 days in a calendar year were classified as having received long-term opioid therapy. Multivariable analysis was conducted using generalized estimating equations. RESULTS: Temporal trends significantly varied by region (p < 0.0001) and opioid-naïve status (p < 0.0001). Compared to 2013, opioid-naïve cancer survivors in the south and non-naïve survivors in the south and west experienced significant declines in long-term opioid therapy in 2015 and 2016. Significant declines were observed in 2016 for opioid-naïve and non-naïve cancer survivors residing in the northeast and among opioid-naïve cancer survivors living in the Midwest. CONCLUSION: The annual trends in the receipt of long-term opioid therapy significantly varied by region among older cancer survivors. Variation in a clinical practice suggests the need for more research and interventions to improve efficiency, process, cost, and quality of care.

Cognitive impairment in elderly patients with rheumatic disease and the effect of disease-modifying anti-rheumatic drugs.

Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.

Trends in Urine Drug Testing Among Long-term Opioid Users, 2012-2018.

INTRODUCTION: Long-term opioid therapy increases the risk of opioid overdose death. Government agencies and medical societies, including the Center for Disease Control and Prevention and the American Society for Clinical Oncology, emphasized risk mitigation strategies, including urine drug testing, in published guidelines. Urine drug testing rates, time trends, and covariates among long-term opioid therapy users were examined to gauge guideline adherence. METHODS: Using Optum's De-identified Clinformatics DataMart, an incidence cohort (n=28,790) and prevalence cohort (n=621,449) were created to measure baseline and annual urine drug testing, respectively, from 2012 to 2018. Urine drug testing time trends were evaluated by demographics, pain conditions, and Elixhauser comorbidity index. A multivariable generalized estimating model was developed in 2020 to examine the factors associated with urine drug testing. RESULTS: Annual urine drug testing rates doubled from 25.6% in 2012 to 52.2% in 2018, whereas baseline urine drug testing also increased from 3.75% to 11.1%. Annual urine drug testing increased within each age group over time; however, older patients (OR=0.21, 95% CI=0.21, 0.22, aged >79 years) and patients with cancer (OR=0.82, 95% CI=0.80, 0.84) were less likely to receive urine drug testing. Patients residing in the South (OR=1.99, 95% CI=1.96, 2.01) and those with back pain (OR=2.04, 95% CI=2.02, 2.06) or with other chronic pain (OR=1.64, 95% CI=1.62, 1.66) were significantly more likely to be tested. Independent predictors of baseline urine drug testing were similar to predictors of annual urine drug testing. CONCLUSIONS: Despite increasing urine drug testing trends from 2012 to 2018, annual and baseline urine drug testing remained low in 2018, relative to numerous guideline recommendations. Findings suggest a need for research on better guideline implementation strategies and the effectiveness of urine drug testing on patient outcomes.

Impact of Alzheimer's disease and related dementia diagnosis following treatment for bladder cancer.

OBJECTIVES: Our objective was to assess the incidence of Alzheimer's Disease and related dementia diagnosis following treatment for muscle-invasive bladder cancer and impact on survival outcomes. MATERIALS AND METHODS: A total of 4814 patients diagnosed with clinical stage T2-T4a, N0, M0 bladder cancer between January 1, 2002 to December 31, 2011 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were identified. Alzheimer's disease and related dementia diagnosis was identified using International Statistical Classification of Disease-Ninth Edition outpatient and inpatient codes. Incidence of dementia following treatment were calculated and reported as dementia cases per 10,000 person-years. Cox proportional hazards models were used to assess the impact of dementia on survival outcomes. RESULTS: Of the 4814 patients, 2403 (49.9%) underwent radical cystectomy (RC) and 2411 (50.1%) underwent radiotherapy (RTX) and/or chemotherapy (CTX). Overall, 837 (17.4%) patients developed Alzheimer's disease and related dementia following bladder cancer treatment. There was no significant difference in the incidence of Alzheimer's disease and related dementia following either treatment. Patients diagnosed with Alzheimer's disease and related dementia had worse overall (Hazard Ratio (HR), 2.64; 95% Confidence Interval (CI), 2.41-2.89) and cancer-specific (HR, 2.45; 95% CI, 2.18-2.76) survival than those without a dementia diagnosis following treatment. CONCLUSION: While we observed no difference in new-onset Alzheimer's disease and related dementia diagnosis following RC or RTX and/or CTX, patients with a Alzheimer's and related dementia diagnosis was associated with worse overall and cancer-specific survival. These findings have important implications for screening and the development of targeted interventions for improving outcomes in older adults following complex cancer treatments, as observed in this bladder cancer population.

Opioid Prescribing Trends in Women Following Mastectomy or Breast-Conserving Surgery Before and After the 2014 Federal Reclassification of Hydrocodone.

BACKGROUND: Given concerns about suboptimal pain management for actively treated cancer patients following the 2014 federal reclassification of hydrocodone, we examined changes in patterns of opioid prescribing among surgical breast cancer patients. MATERIALS AND METHODS: Data from a large nationally representative commercial health insurance program from 2009 to 2017 were used to identify women aged 18 years and older who were diagnosed with carcinoma in-situ or malignant breast cancer and received breast-conserving surgery or mastectomy from 2010 to 2016. Generalized linear mixed models were used to estimate the adjusted odds ratio (aOR) for receipt of ≥1-day, >30-day, or ≥ 90-day supply of opioids in the 12 months following surgery adjusting for demographics, cancer treatment-related characteristics, and preoperative opioid use. RESULTS: A total of 60,080 patients were included in the study. Surgically treated breast cancer patients in 2015 (aOR = 0.90, 0.84-0.97) and 2016 (aOR = 0.80, 0.74-0.86) were less likely to receive ≥1-day supply of opioid prescriptions when compared with patients in 2013. Patients who had surgery in 2015 (aOR = 0.89, 0.81-0.98) and 2016 (aOR = 0.80, 0.73-0.87) were also less likely to receive >30-day supply of prescription opioids in the 12 months following surgery. However, only surgical breast cancer patients in 2016 were less likely to receive ≥90-day supply (aOR = 0.86, 0.76-0.98). CONCLUSION: Surgically treated breast cancer patients are less likely to receive short- and long-term opioid prescriptions following the implementation of hydrocodone rescheduling. Further studies on the potential impact of federal policy on cancer patient pain management are needed. IMPLICATIONS FOR PRACTICE: Clinicians and researchers with diverse perspectives should be included as stakeholders during policy development for restricting opioid prescriptions. Stakeholders can identify potential unintended consequences early and help identify methods to mitigate concerns, specifically as it relates to policy that influences how providers manage pain for actively treated cancer patients. This work shows how federal policy may have led to declines in opioid prescribing for breast cancer patients who underwent mastectomy or breast-conserving surgery.

Effects of glucagon-like peptide 1 receptor agonists on comorbidities in older patients with diabetes mellitus.

Elderly patients with diabetes are at high risk of polypharmacy because of multiple coexisting diseases and syndromes. Polypharmacy increases the risk of drug-drug and drug-disease interactions in these patients, who may already have age-related sensory and cognitive deficits; such deficits may delay timely communication of early symptoms of adverse drug events. Several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved for diabetes: liraglutide, exenatide, lixisenatide, dulagluatide, semaglutide, and albiglutide. Some are also approved for treatment of obesity. The current review of literature along with clinical case discussion provides evidence supporting GLP-1 RAs as diabetes medications for polypharmacy reduction in older diabetes patients because of their multiple pleiotropic effects on comorbidities (e.g. hyperlipidemia, hypertension, and fatty liver) and syndromes (e.g. osteoporosis and sleep apnea) that commonly co-occur with diabetes. Using one medication (in this case, GLP-1 RAs) to address multiple conditions may help reduce costs, medication burden, adverse drug events, and medication nonadherence.

Long-Term Opioid Therapy in Older Cancer Survivors: A Retrospective Cohort Study.

OBJECTIVES: To examine the rates and predictors of long-term opioid therapy in older cancer survivors. DESIGN: Retrospective cohort study. SETTING: Texas, United States. PARTICIPANTS: Cancer survivors (5 years or more postcancer diagnosis) diagnosed from 1995 to 2008 and who were also Medicare Parts A, B, and D beneficiaries. MEASUREMENTS: We used Medicare Part D event data to calculate the proportion of cancer survivors with a prolonged opioid prescription (90-day or more supply of opioids/year). Adjusted odds ratios were calculated to identify predictors of prolonged opioid prescribing. All analyses were repeated with a subcohort of opioid-naïve cancer survivors. RESULTS: The rate of prolonged opioid therapy for cancer patients diagnosed in 2008 was 7.1% prior to cancer diagnosis; it rose to 9.8% within a year of cancer treatments, and to 13.3% at 5 years postdiagnosis. The rate at the sixth year varied by cancer sites: 19.4% in lung cancer and 9.6% in prostate cancer. Among opioid-naïve survivors, the rate increased from 1.4% to 7.1%, from 5 to 18 years postcancer diagnosis. Cancer survivors diagnosed in 2004 to 2008 had higher rates of opioid prescribing compared to those diagnosed in 1995 to 1998 and 1999 to 2003. Years since diagnosis, a later year of diagnosis, female sex, urban location, lung cancer diagnosis, disability as reason for Medicare entitlement, Medicaid eligibility, one or more comorbidity, and history of depression or drug abuse were predictors of prolonged opioid therapy. Among opioid-naïve cancer survivors, diagnosis in 2004 to 2008 was the strongest predictor, while a history of drug abuse was the strongest predictor for all the survivors. CONCLUSION: The rates of prolonged opioid prescribing for older cancer survivors remained high at 5 or more years after cancer diagnosis. Our findings have potential to inform the development of clinical guidelines and public policy to ensure safer and more effective pain treatment in older cancer survivors. J Am Geriatr Soc 67:945-952, 2019.

Decline in opioid prescribing after federal rescheduling of hydrocodone products.

PURPOSE: To examine differences in opioid prescribing by patient characteristics and variation in hydrocodone combination product (HCP) prescribing attributed to states, before and after the 2014 Drug Enforcement Administration's reclassification of HCP from schedule III to the more restrictive schedule II. METHODS: We used 2013 to 2015 data for 9 202 958 patients aged 18 to 64 from a large nationally representative commercial health insurance program to assess the temporal trends in the monthly rate of opioid prescribing. RESULTS: HCP prescribing decreased by 26% from June 2013 to June 2015; the rate of prescriptions for any opioid decreased by 11%. Prescribing of non-hydrocodone schedule III opioids increased slightly while prescribing of non-hydrocodone schedule II opioids and tramadol was stable. Absolute decreases in HCP prescribing rates were larger in patients being treated for cancer (-2.26% vs -0.7% for non-cancer patients, P < 0.0001) and in those with high comorbidities (-2.13% vs -0.55% for those with no comorbidity, P < 0.0001). Differences in the absolute and relative changes in HCP prescribing rates among states were large; for example, a relative decrease of 46.7% in Texas and a 12.7% increase in South Dakota. The variation in HCP prescribing attributable to the state of residence increased from 6.6% in 2013 to 8.7% in 2015. CONCLUSIONS: The 2014 federal policy was associated with a decrease in rates of HCP and total opioid prescribing. The large decrease in the rates of HCP prescribing for patients with actively treated cancer may represent an unintended consequence.