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.

Sex Differences in Time to Initiate Nonsteroidal Anti-Inflammatory Drugs or Biologic Disease-Modifying Antirheumatic Drugs Among Patients With Axial Spondyloarthritis.

OBJECTIVE: We evaluated sex differences in time to initiation of receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with axial spondyloarthritis (axSpA). METHODS: Using the 2013 to 2018 IBM MarketScan Database, we identified 174,632 patients with axSpA aged ≥18 years. We evaluated the time between axSpA diagnosis and the first prescription NSAID dispensing (among those with no baseline NSAIDs reception) or bDMARDs infusion/procedure claim (among those who were dispensed two or more different prescription NSAIDs in the baseline period). Adjusted hazard ratios (aHRs) for time to initiation of patients receiving NSAIDs or bDMARDs were computed using survival analyses. Cox proportional hazard models estimated associations between sex and predictors of treatment initiation. RESULTS: Average age at diagnosis was 48.2 years, 65.7% were female, and 37.8% were dispensed one or more NSAIDs before axSpA diagnosis. Of those who did not receive two or more different prescription NSAIDs before diagnosis, NSAID reception was initiated earlier in female patients than in male patients (NSAID reception initiators: female patients (32.9%), male patients (29.3%); aHR 1.14, 95% confidence interval [CI] 1.11-1.16). Among those who received two or more different prescription NSAIDs in the baseline period, 4.2% received a bDMARD, whereas 77.9% continued receiving NSAIDs after diagnosis. Time to bDMARD reception initiation was longer for female patients than for male patients (aHR 0.61, 95% CI 0.52-0.72), but bDMARDs were received sooner among those who received NSAIDs in the baseline period. CONCLUSION: Prescription NSAID reception was more common than initiation of receiving bDMARDs among patients newly diagnosed with axSpA. Female patients appeared more likely to continue receiving NSAIDs after diagnosis, and the time to initiation of receiving bDMARDs was longer for female patients than for male patients.

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.

Understanding Perinatal Depression Care Gaps by Examining Care Access and Barriers in Perinatal Individuals With and Without Psychiatric History.

Background: Depression affects one in seven perinatal individuals and remains underdiagnosed and undertreated. Individuals with a psychiatric history are at an even greater risk of perinatal depression, but it is unclear how their experiences with the depression care pathway may differ from individuals without a psychiatric history. Methods: We conducted a secondary analysis evaluating care access and barriers to care in perinatal individuals who screened positive for depression using the Edinburgh Postnatal Depression Scale (N = 280). Data were analyzed from the PRogram in Support of Moms (PRISM) study, a cluster randomized controlled trial of two interventions for perinatal depression. Results: Individuals with no prepregnancy psychiatric history (N = 113), compared with those with a history (N = 167), were less likely to be screened for perinatal depression, and less likely to be offered a therapy referral, although equally likely to attend if referred. When examining how these differences affected outcomes, those without a psychiatric history had 46% lower odds of attending therapy (95% confidence interval [CI]: 0.19-1.55), 79% lower odds of taking medication (95% CI: 0.08-0.54), and 80% lower odds of receiving any depression care (95% CI: 0.08-0.47). Barriers were similar across groups, except for concerns regarding available treatments and beliefs about self-resolution of symptoms, which were more prevalent in individuals without a psychiatric history. Conclusions: Perinatal individuals without a prepregnancy psychiatric history were less likely to be screened, referred, and treated for depression. Differences in screening and referrals resulted in missed opportunities for care, reinforcing the urgent need for universal mental health screening and psychoeducation during the perinatal period. Clinical Trial Registration No.: NCT02935504.

Postpartum Depression in Reproductive-Age Women With and Without Rheumatic Disease: A Population-Based Matched Cohort Study.

OBJECTIVE: To examine postpartum depression (PPD) among women with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) in comparison with a matched population without rheumatic disease (RD). METHODS: A retrospective analysis using the 2013-2018 IBM MarketScan Commercial Claims and Encounters Database was conducted. Pregnant women with axSpA, PsA, or RA were identified, and the delivery date was used as the index date. We restricted the sample to women ≤ 55 years with continuous enrollment ≥ 6 months before date of last menstrual period and throughout pregnancy. Each patient was matched with 4 individuals without RD on: (1) maternal age at delivery, (2) prior history of depression, and (3) duration of depression before delivery. Cox frailty proportional hazards models estimated the crude and adjusted hazard ratios (aHR) and 95% CI of incident postpartum depression within 1 year among women with axSpA, PsA, or RA (axSpA/PsA/RA cohort) compared to the matched non-RD comparison group. RESULTS: Overall, 2667 women with axSpA, PsA, or RA and 10,668 patients without any RD were included. The median follow-up time in days was 256 (IQR 93-366) and 265 (IQR 99-366) for the axSpA/PsA/RA cohort and matched non-RD comparison group, respectively. Development of PPD was more common in the axSpA/PsA/RA cohort relative to the matched non-RD comparison group (axSpA/PsA/RA cohort: 17.2%; matched non-RD comparison group: 12.8%; aHR 1.22, 95% CI 1.09-1.36). CONCLUSION: Postpartum depression is significantly higher in women of reproductive age with axSpA/PsA/RA when compared to those without RD.

Unhealed pressure ulcers among nursing home residents with diabetes.

INTRODUCTION: Nearly a third of US nursing home residents have diabetes mellitus. These residents have an increased risk of pressure ulcer (PU) development and progression; however, little is known about the characteristics of their PUs or the role of other risk factors. This study estimates the prevalence of PUs, describes characteristics of PUs, and quantifies associations between risk factors and PUs in nursing home residents with diabetes. METHODS: We conducted a cross-sectional study of nursing home residents aged ≥50 years with diabetes mellitus using national 2016 Minimum Data Set 3.0 data. Pressure ulcers were defined as the presence of any stage PU and by subgroups of stage and tissue type. Prevalence estimates of PUs were calculated overall and by covariate subgroups. Unadjusted and adjusted odds ratios were calculated using logistic regression. RESULTS: The prevalence of any unhealed PU was 8.1%. Of those with a PU, 19.4% had at least two ulcers and the most common subtypes were identified as unstageable and stage 2 ulcers. These were most often treated by pressure reducing devices. In our fully adjusted model, risk factors that were strongly associated with PUs were related to mobility, nutrition, incontinence, and infections. CONCLUSION: We observed that the prevalence of PUs remains high in nursing home residents with diabetes and that higher stage ulcers were common in this population. Our adjusted model highlights the importance of suspected risk factors in the development of PUs. Further research is needed to understand the unique needs of nursing home residents with diabetes.

Trends in Screening for Diabetes in Early Pregnancy in the United States.

Objective: The aim of this study was to characterize current diabetes screening practices in the first trimester of pregnancy in the United States, evaluate patient characteristics and risk factors associated with early diabetes screening, and compare perinatal outcomes by early diabetes screening. Methods: This was a retrospective cohort study of US medical claims data of persons diagnosed with a viable intrauterine pregnancy and who presented for care with private insurance before 14 weeks of gestation, without pre-existing pregestational diabetes, from the IBM MarketScan® database for the period January 1, 2016, to December 31, 2018. Univariate and multivariate analyses were used to evaluate perinatal outcomes. Results: A total of 400,588 pregnancies were identified as eligible for inclusion, with 18.0% of persons receiving early screening for diabetes. Of those with laboratory order claims, 53.1% underwent hemoglobin A1c testing, 30.0% underwent fasting glucose testing, and 16.9% underwent oral glucose tolerance testing. Compared with those who did not undergo early diabetes screening, those who did were more likely to be older; obese; having a history of gestational diabetes, chronic hypertension, polycystic ovarian syndrome, or hyperlipidemia; and having a family history of diabetes. In adjusted logistic regression, history of gestational diabetes (adjusted odds ratio 3.99; 95% confidence interval 3.73-4.26) had the strongest association with early diabetes screening. Adverse perinatal outcomes, including a higher rate of cesarean delivery, preterm delivery, preeclampsia, and gestational diabetes, occurred more frequently among women who underwent early diabetes screening. Conclusions: First-trimester early diabetes screening was mostly commonly performed by hemoglobin A1c evaluation, and persons who underwent early diabetes screening were more likely to experience adverse perinatal outcomes.

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.

An algorithm to identify gabapentin misuse and/or abuse in administrative claims data.

BACKGROUND: Despite gabapentin's misuse and abuse potential and associated adverse events, few algorithms are available to detect gabapentin misuse and/or abuse in claims data. This study aims to develop an algorithm to identify gabapentin misuse and/or abuse in administrative claims data. METHODS: We developed an algorithm to identify gabapentin misuse and/or abuse over a 12-month period based on input from 21 clinical experts. We implemented the algorithm among 334,128 patients with at least one dispensed prescription of gabapentin between December 1, 2017 and December 1, 2018 in the IBM® MarketScan® Research Databases. We described the characteristics of patients who potentially misused and/or abused gabapentin and assessed factors associated with misuse and/or abuse using logistic regression. RESULTS: The algorithm identified 17.6% of patients with gabapentin use who potentially misused and/or abused gabapentin. Factors associated with potential gabapentin misuse and/or abuse included men (adjusted odds ratio (aOR): 1.08; 95% confidence interval (CI): 1.06-1.10), comorbid conditions (e.g., drug and alcohol dependence (aOR: 1.31; 95% CI: 1.24-1.39); bipolar disorder (aOR: 1.34; 95% CI: 1.27-1.41)), and medication use (e.g., opioids (aOR: 1.23; 95% CI: 1.20-1.26), muscle relaxants (aOR: 1.24; 95% CI: 1.21-1.27), or serotonin-norepinephrine reuptake inhibitors (aOR: 1.33; 95% CI: 1.29-1.36)). CONCLUSIONS: Approximately one in six patients with gabapentin use potentially misused and/or abused gabapentin in a large commercial claims database. Multiple comorbidities and drug use were associated with gabapentin misuse and/or abuse. Monitoring requirements and individualized safety measures should be put in place for patients at elevated risks of gabapentin misuse and/or abuse.

Prevalence and outcomes of hypertension in pregnancy in non-metropolitan and metropolitan communities.

OBJECTIVES: Hypertension during pregnancy is a leading cause of birthing parent mortality and adverse pregnancy outcomes. Since non-metropolitan communities face higher rates of several risk factors for hypertension in pregnancy and shortages in obstetrical services, persons residing in non-metropolitan areas may be at increased risk for adverse events compared to those living in metropolitan areas. Our study objectives were to examine by non-metropolitan vs. metropolitan birthing parent residence (1) the prevalence of chronic hypertension (cHTN) and hypertensive disorders of pregnancy (HDP), and (2) the prevalence of cesarean delivery, preterm birth, low birth weight, APGAR <7 at 5 min, NICU admission, and stillbirth/neonatal death among the group of birthing parents with cHTN and among the group of birthing parents with HDP. METHODS: Using U.S. Natality data from 2016 to 2018, we described the prevalence of cHTN and HDP and the association of each with several birthing parent and neonatal outcomes, stratified by non-metropolitan versus metropolitan county of birthing parent residence. Multivariable Poisson regression models were used to calculate adjusted prevalence ratios for these adverse outcomes. RESULTS: The prevalence of cHTN among pregnant individuals was 2.2% in non-metropolitan areas and 1.8% in metropolitan areas. For HDP, the prevalence was 7.4% in non-metropolitan areas and 6.6% in metropolitan areas. After adjusting for several sociodemographic characteristics among those with HDP, the prevalence ratio for an APGAR score < 7 at 5 min (aPR 1.34, 95% CI 1.29-1.38) and stillbirth/neonatal death (aPR 1.36, 95% CI 1.15-1.62) was increased among offspring born to birthing parents who resided in non-metropolitan counties. Similar results were seen among those with cHTN. CONCLUSIONS: The prevalence of cHTN and HDP is elevated among birthing parents residing in non-metropolitan areas. Also, the prevalence of APGAR <7 and stillbirth//neonatal death following pregnancies complicated by hypertension were higher among neonates born to birthing parents residing in non-metropolitan areas. Further research should investigate the robustness of these findings using alternate definitions of rural and urban areas and the possible link between low APGAR score, low NICU admission, and stillbirth/neonatal death among birthing parents residing in non-metropolitan counties.

Retrospective Observational Real-World Outcome Study to Evaluate Safety Among Patients With Erectile Dysfunction (ED) With Co-Possession of Tadalafil and Anti-Hypertensive Medications (anti-HTN).

BACKGROUND: Erectile dysfunction (ED) is a common condition affecting male adults and may be associated with hypertension, diabetes, hyperlipidemia, and obesity. Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are the first-line drug therapy for ED. Studies and the current prescribing information of these PDE5 inhibitors indicate they are mechanistic mild vasodilators and, as such, concomitant use of a PDE5 inhibitor with anti-hypertensive medication may lead to drops in blood pressure due to possible drug-drug interaction. AIM: Evaluate risks of hypotensive/cardiovascular outcomes in a large cohort of patients with ED that have co-possession of prescriptions for tadalafil and hypertensive medications versus either medication/s alone. METHODS: A cohort study conducted within an electronic health record database (Optum) representing hospitals across the US. Adult male patients prescribed tadalafil and/or anti-hypertensive medications from January 2012 to December 2017 were eligible. Possession periods were defined by the time patients likely had possession of medication, with propensity score-matched groups used for comparison. OUTCOMES: Risk of hypotensive/cardiovascular outcomes were measured using diagnostic codes and NLP algorithms during possession periods of tadalafil + anti-hypertensive versus either medication/s alone. RESULTS: In total there were 127,849 tadalafil + anti-hypertensive medication possession periods, 821,359 anti-hypertensive only medication possession periods, and 98,638 tadalafil only medication possession periods during the study; 126,120 were successfully matched. Adjusted-matched incidence rate ratios (IRRs) for the anti-hypertensive only possession periods compared with tadalafil + anti-hypertensive periods of diagnosed outcomes were all below 1. Two outcomes had a 95% confidence interval (CI) that did not include 1.0: ventricular arrhythmia (IRR 0.79; 95% CI 0.66, 0.94) and diagnosis of hypotension (IRR 0.79; 95% CI 0.71, 0.89). CLINICAL IMPLICATIONS: Provides real world evidence that co-possession of tadalafil and anti-hypertensive medications does not increase risk of hypotensive/cardiovascular outcomes beyond that observed for patients in possession of anti-hypertensive medications only. STRENGTHS AND LIMITATIONS: EHR data are valuable for the evaluation of real world outcomes, however, the data are retrospective and collected for clinical patient management rather than research. Prescription data represent the intent of the prescriber and not use by the patient. Residual bias cannot be ruled out, despite propensity score matching, due to unobserved patient characteristics and severity that are not fully reflected in the EHR database. CONCLUSION: In the studied real world patients, this study did not demonstrate an increased risk of hypotensive or cardiovascular outcomes associated with co-possession of tadalafil and anti-hypertensive medications beyond that observed for patients in possession of anti-hypertensive medications only. Nunes AP, Seeger JD, Stewart A, et al., Retrospective Observational Real-World Outcome Study to Evaluate Safety Among Patients With Erectile Dysfunction (ED) With Co-Possession of Tadalafil and Anti-Hypertensive Medications (anti-HTN). J Sex Med 2022;19:74-82.

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.

Heart failure among US nursing home residents with diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of developing heart failure. However, few recent studies have examined the characteristics of older adults living in US nursing homes with heart failure and diabetes mellitus. This study is important for clinical practice and public health action plans for heart failure. OBJECTIVE: To estimate the prevalence of, and factors associated with, heart failure in long-stay nursing home residents with diabetes mellitus. METHODS: We conducted a cross-sectional study using the US 2016 Minimum Data Set data consisting of all residents with diabetes aged ≥65 years in Medicare/Medicaid certified nursing homes (n = 297,570). Diabetes mellitus and heart failure were operationalized using the resident's transfer notes at admission and the progress notes during admission through physical examination findings and current treatment orders. RESULTS: Among all residents with diabetes, 26.4% had heart failure. Increasing age of residents, and comorbidities including coronary artery disease (aOR: 1.34; 95% CI: 1.31-1.37), end stage renal disease (aOR: 1.30; 95% CI: 1.26-1.35), and chronic obstructive pulmonary disease (aOR: 1.60; 95% CI: 1.57-1.63) were associated with a higher odds of heart failure. CONCLUSIONS: This is one of the first U.S studies to examine the prevalence and factors associated with heart failure in nursing home residents with diabetes mellitus. It highlights a clinically complex population with multiple comorbid conditions. Future research is needed to understand the pharmacological management of these residents and the extent to which appropriate management can improve quality of life for a medically vulnerable population.

Cardiovascular Outcome Risks in Patients With Erectile Dysfunction Co-Prescribed a Phosphodiesterase Type 5 Inhibitor (PDE5i) and a Nitrate: A Retrospective Observational Study Using Electronic Health Record Data in the United States.

BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for erectile dysfunction (ED). Approximately 1-4% of PDE5i recipients co-possess nitrates, despite this combination potentially producing clinically significant hypotension. Real-world data in these patients and insights into prescriber rationales for co-prescription are limited. AIM: This study investigated whether PDE5i and nitrate co-possession is associated with increased rates of cardiovascular (CV) outcomes. METHODS: Adult males with ED and PDE5i prescription and males with nitrate prescription were identified from a U.S. electronic health record database (2012-2016). Quantitative comparisons were made between patients with ED and co-possession (ED + PDE5i + nitrate), only nitrate possession (ED + nitrate and nitrate only [without ED]), and only PDE5i possession (ED + PDE5i). OUTCOMES: We quantified incidence of CV outcomes in co-possession and comparator periods, calculating incidence rate ratios after propensity score matching. Prescriber rationales were derived by reviewing virtual patient records. RESULTS: Over 168,000 patients had ≥1 PDE5i prescription (∼241,000 possession periods); >480,000 patients had ≥1 nitrate prescription (∼486,000 possession periods); and 3,167 patients had 3,668 co-possession periods. Non-significantly different or lower rates of CV outcomes were observed for co-possession periods vs ED + nitrate and nitrate only periods. Most CV outcome rates were non-significantly different between co-possession and ED + PDE5i periods (myocardial infarction, hospitalized unstable angina and fainting were higher with co-possession). From qualitative assessment of patient records with co-possession, 131 of 252 (52%) documented discussion with a physician regarding co-possession; 69 of 131 (53%) warned or instructed on safely managing these contraindicated medications. CLINICAL IMPLICATIONS: Findings from this real-world study indicate that co-possession of nitrate and PDE5i prescriptions is not associated with increased rates of CV outcomes, relative to possession of nitrates alone. Physicians should and often do discuss the risks of using both medications together with their patients. STRENGTHS & LIMITATIONS: Strengths of this study are the large size of the U.S. real-world patient cohort with data available for analysis, and our ability to utilize natural language processing to explore co-prescription rationales and patient-physician interactions. Limitations are the retrospective nature of the analysis and inability to establish whether recorded prescriptions were filled or the medication was consumed. CONCLUSION: Co-exposure of PDE5i and nitrates should continue to be avoided; however, co-possession of PDE5i and nitrate prescriptions is not necessarily associated with increased CV risk. Co-possession can be successfully managed in suitable circumstances. Nunes AP, Seeger JD, Stewart A, et al. Cardiovascular Outcome Risks in Patients With Erectile Dysfunction Co-Prescribed a Phosphodiesterase Type 5 Inhibitor (PDE5i) and a Nitrate: A Retrospective Observational Study Using Electronic Health Record Data in the United States. J Sex Med 2021;18:1511-1523.

Prevalence and the factors associated with oral anticoagulant use among nursing home residents.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulants are indicated for treatment and prevention of several clinical conditions. Prior studies have examined anticoagulant utilization for specific indications and in community-dwelling populations. Decision-making regarding anticoagulant prescribing in the nursing home setting is particularly challenging because advanced age and clinical complexity places most residents at increased risk for adverse drug events. To estimate the prevalence of oral anticoagulant (OAC) use (overall, warfarin, direct oral anticoagulants (DOACs)) and identify factors associated with oral anticoagulant use among the general population of residents living in nursing homes. METHODS: This point prevalence study was conducted among 506,482 residents in US nursing homes on 31 October 2016 who were enrolled in Medicare fee-for-service. Covariates including demographics, clinical conditions, medications, cognitive impairment and functional status were obtained from Minimum Data Set 3.0 assessments and Medicare Part A and D claims. Oral anticoagulant use was identified using dispensing dates and days supply information from Medicare Part D claims. Robust Poisson models estimated adjusted prevalence ratios (aPR) for associations between covariates and 1) any anticoagulant use, and 2) DOAC versus warfarin use. RESULTS AND DISCUSSION: Overall, 11.8% of residents used oral anticoagulants. Among users, 44.3% used DOACs. Residents with body mass index (BMI) ≥40 kg/m2 (aPR: 1.66; 95% CI: 1.61 -1.71), with functional dependency in activities of daily living, polypharmacy and higher CHA2 DS2 -VASc risk ischaemic stroke scores, had a higher prevalence of oral anticoagulant use. Women (aPR: 0.78; 95% CI: 0.76-0.79), residents with limited life expectancy (aPR 0.80; 95% CI: 0.76-0.83), those with moderate-to-severe cognitive impairment (aPR: 0.67; 95% CI: 0.65-0.68), those using NSAIDs or antiplatelets, and non-white racial/ethnic groups had a lower prevalence of anticoagulant use. Residents with higher levels of polypharmacy, BMI and age had a lower prevalence of DOAC use (versus warfarin). WHAT IS NEW AND CONCLUSION: Approximately one in eight general nursing home residents use oral anticoagulants and among oral anticoagulant users, only slightly more residents used warfarin than DOACs. The lower prevalence of anticoagulation among women and non-white racial/ethnic groups raises concerns of potential inequities in quality of care. Lower oral anticoagulant use among residents with limited life expectancy suggests possible deprescribing at the end of life. Further research is needed to inform resident-centred shared decision-making that explicitly considers treatment goals and individual-specific risks and benefits of anticoagulation at all stages of the medication use continuum.

Multiple imputation to quantify misclassification in observational studies of the cognitively impaired: an application for pain assessment in nursing home residents.

BACKGROUND: Despite experimental evidence suggesting that pain sensitivity is not impaired by cognitive impairment, observational studies in nursing home residents have observed an inverse association between cognitive impairment and resident-reported or staff-assessed pain. Under the hypothesis that the inverse association may be partially attributable to differential misclassification due to recall and communication limitations, this study implemented a missing data approach to quantify the absolute magnitude of misclassification of pain, pain frequency, and pain intensity by level of cognitive impairment. METHODS: Using the 2016 Minimum Data Set 3.0, we conducted a cross-sectional study among newly admitted US nursing home residents. Pain presence, severity, and frequency is assessed via resident-reported measures. For residents unable to communicate their pain, nursing home staff document pain based on direct resident observation and record review. We estimate a counterfactual expected level of pain in the absence of cognitive impairment by multiply imputing modified pain indicators for which the values were retained for residents with no/mild cognitive impairment and set to missing for residents with moderate/severe cognitive impairment. Absolute differences (∆) in the presence and magnitude of pain were calculated as the difference between documented pain and the expected level of pain. RESULTS: The difference between observed and expected resident reported pain was greater in residents with severe cognitive impairment (∆ = -10.2%, 95% Confidence Interval (CI): -10.9% to -9.4%) than those with moderate cognitive impairment (∆ = -4.5%, 95% CI: -5.4% to -3.6%). For staff-assessed pain, the magnitude of apparent underreporting was similar between residents with moderate impairment (∆ = -7.2%, 95% CI: -8.3% to -6.0%) and residents with severe impairment (∆ = -7.2%, 95% CI: -8.0% to -6.3%). Pain characterized as "mild" had the highest magnitude of apparent underreporting. CONCLUSIONS: In residents with moderate to severe cognitive impairment, documentation of any pain was lower than expected in the absence of cognitive impairment. This finding supports the hypothesis that an inverse association between pain and cognitive impairment may be explained by differential misclassification. This study highlights the need to develop analytic and/or procedural solutions to correct for recall/reporter bias resulting from cognitive impairment.

Pain Behaviors and Pharmacological Pain Management Among Newly Admitted Nursing Home Residents.

BACKGROUND: Clinicians may place more weight on vocal complaints of pain than the other pain behaviors when making decisions about pain management. OBJECTIVES: We examined the association between documented pain behaviors and pharmacological pain management among nursing home residents. METHODS: We included 447,684 residents unable to self-report pain, with staff-documented pain behaviors (vocal, nonverbal, facial expressions, protective behaviors) and pharmacological pain management documented on the 2010-2016 Minimum Data Set 3.0. The outcome was no pharmacological pain medications, as needed only (pro re nata [PRN]), as scheduled only, or as scheduled with PRN medications. We estimated adjusted odds ratios and 95% confidence intervals from multinomial logistic models. RESULTS: Relative to residents with vocal complaints only, those with one pain behavior documented (i.e., nonverbal, facial, or protective behavior) were more likely to lack pain medication versus scheduled and PRN medications. Residents with multiple pain behaviors documented were least likely to have no treatment relative to scheduled with PRN medications, PRN only, or scheduled only pain medication regimens. DISCUSSION: The type and number of pain behaviors observed are associated with pharmacological pain management regimen. Improving staff recognition of pain among residents unable to self-report is warranted in nursing homes.

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

PURPOSE: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. METHODS: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI - hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. RESULTS: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. CONCLUSIONS: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Prevalence of Pain on Admission by Level of Cognitive Impairment in Nursing Homes.

PURPOSE: To provide contemporary estimates of pain by level of cognitive impairment among US nursing home residents without cancer. METHODS: Newly admitted US nursing home residents without cancer assessed with the Minimum Data Set 3.0 at admission (2010-2016) were eligible (n=8,613,080). The Cognitive Function Scale was used to categorize level of cognitive impairment. Self-report or staff-assessed pain was used based on a 5-day look-back period. Estimates of adjusted prevalence ratios (aPR) were derived from modified Poisson models. RESULTS: Documented prevalence of pain decreased with increased levels of cognitive impairment in those who self-reported pain (68.9% no/mild, 32.9% severe) and those with staff-assessed pain (50.6% no/mild, 37.2% severe staff-assessed pain). Relative to residents with no/mild cognitive impairment, pharmacologic pain management was less prevalent in those with severe cognitive impairment (self-reported: 51.3% severe vs 76.9% in those with no/mild; staff assessed: 52.0% severe vs 67.7% no/mild). CONCLUSION: Pain was less frequently documented in those with severe cognitive impairment relative to those with no/mild impairments. Failure to identify pain may result in untreated or undertreated pain. Interventions to improve evaluation of pain in nursing home residents with cognitive impairment are needed.