Frailty and uptake of angiotensin receptor neprilysin inhibitor for heart failure with reduced ejection fraction.

BACKGROUND: Frail older adults may be less likely to receive guideline-directed medical therapy (GDMT)-renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists-for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF. METHODS: Using 2015-2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index. Logistic regression was used to identify clinical characteristics associated with ARNI initiation. Cox proportional hazards regression was used to examine the association of GDMT use in 2015 and death or heart failure hospitalization in 2016-2019. RESULTS: Among 147,506-180,386 beneficiaries with HFrEF (mean age: 77 years; 27% women; 42.6-49.1% frail) in 2015-2019, the proportion of patients receiving ARNI increased in both non-frail (0.4%-16.4%) and frail (0.3%-13.7%) patients (p for yearly-trend-by-frailty = 0.970). Among those not receiving a renin-angiotensin system blocker, patients with age ≥ 85 years (odds ratio [95% CI], 0.89 [0.80-0.99]), dementia (0.88 [0.81-0.96]), and frailty (0.87 [0.81-0.94]) were less likely to initiate ARNI. The proportion of patients receiving all 3 GDMT classes increased in non-frail patients (22.0%-27.0%) but changed minimally in frail patients (19.6%-21.8%). Regardless of frailty status, treatment with at least 1 class of GDMT was associated with lower death or heart failure hospitalization than no GDMT medications (hazard ratio [95% CI], 0.94 [0.91-0.97], 0.92 [0.89-0.94], 0.94 [0.91-0.97] for 1, 2, and 3 classes, respectively). CONCLUSIONS: Our results suggest an evidence-practice gap in the use of ARNI and GDMT in Medicare beneficiaries with HFrEF, particularly those with frailty. Efforts to narrow this gap are needed to reduce the burden of HFrEF in older adults.

An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free survival (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up. Fit and <60 y patients were mostly treated with full intensity, whereas frail and ≥70 y patients usually received DR. Hematological and non-hematological SAE were more frequently seen in frail versus ≥70 y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (P=0.0245/P<0.0001), whereas in age-based subgroups, OS and PFS differences did not reach significance (P=0.1362/P=0.0569). Non-hematological SAE were another negative predictor for impaired OS and PFS (P=0.0054/P=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% versus deteriorated in only 10% of patients. In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.

[Assessment and treatment options for transplant-ineligible patients with multiple myeloma].

At diagnosis, approximately 40% of patients with multiple myeloma are older than 75 years. Thus, treatments for multiple myeloma should take into consideration the following factors: 1) disease-related factors, such as chromosomal abnormalities and speed of progression; 2) therapy-related factors, such as drug resistance and toxicity; and 3) patient-specific factors, such as age, organ dysfunction, and availability of family support. Moreover, with the development of novel therapeutic agents, including antibodies, overcoming the high risk of disease-related factors, even in older patients, is becoming possible by attaining favorable responses to treatment. However, the premise is to continue highly effective treatments from an early stage and maximize the performance of the selected treatments. Therefore, treatments must be provided regularly while adjusting its intensity and duration. Furthermore, for older patients with high frailty, improving and maintaining the health-related quality of life may be necessary. Hence, various treatments and frailty assessments here are described here, including therapeutic ingenuity and supportive care strategies for developing individualized treatments for transplant-ineligible patients.

Opioid trends in Finland: a register-based nationwide follow-up study.

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009-2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3-6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain - a type of pain where the risk-benefit ratio of opioids is controversial.

Benefits of medicines optimisation for older people living with frailty.

Medicines optimisation involves ensuring that medicines are administered safely and effectively. In the UK, an ageing population and an increasing prevalence of polypharmacy mean that interprofessional medicines reviews and medicines optimisation are vital. This article uses a case study of an older person living with frailty to provide a critical analysis of the medicines optimisation process in optimising health outcomes. The case study focuses on the medicines prescribed, the issues that can arise such as polypharmacy, and the benefits of a medicines-optimisation approach.

Assessment, prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Medication exposure and frailty in older community-dwelling patients: a cross-sectional study.

Objective To investigate the association between the medication exposure, measured by the polypharmacy/excessive polypharmacy and the anticholinergic and/or sedative drug exposure, on frailty status among French older community-dwelling patients. Setting day-care unit in France (Lyon), with retrospective data from July, 2017 to March, 2018. Method This monocentric cross-sectional study included community-dwelling patients aged 65 years and over and admitted at the day-care unit for a geriatric evaluation. Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and excessive polypharmacy were defined as the concomitant use of 5-9 and 10 or more drugs, respectively. The cumulative anticholinergic and sedative exposure was measured using the drug burden index (DBI). The DBI score was presented in 4 differentiated scores: a null score (DBI = 0), a combined score (anticholinergic and sedative score), an anticholinergic score, and a sedative score. The association between medication and frailty was assessed by logistic regression models controlled for multiple potential confounders. Main outcome measure Association between medication exposure (polypharmacy, anticholinergic and sedative exposure) and frailty. Results In this study, 403 patients were included: 44.7% were frail and 40.7% were pre-frail. Polypharmacy and excessive polypharmacy affected 44.7% and 17.1% of the population respectively. The mean DBI was 0.33 ± 0.43, with 16.4% of patients with only sedative exposure, 9.7% with only anticholinergic exposure and 33.0% with both exposures. After adjustment, polypharmacy and excessive polypharmacy were associated with frailty with adjusted odds ratios (95% confidence interval) of 2.18 (1.03-4.22) and 2.72 (1.01-7.37) respectively. The cumulative exposure to anticholinergic and sedative drugs (combined score) was significantly associated to an increased risk for frailty with adjusted odds ratios (95% confidence interval) of 3.54 (1.47-8.57). Conclusion The study showed that polypharmacy and cumulative anticholinergic and sedative exposure are associated with frailty. Further research should address the potential benefit of collaborative medication review for preventing medication-associated frailty.

Identification and assessment of frailty in older patients with chronic myeloid leukemia and myelofibrosis, and indications for tyrosine kinase inhibitor treatment.

The incidence of cancer, including myeloproliferative neoplasms (MPNs), is projected to increase significantly due to the growing proportion of people aged > 65 years. These older individuals are a heterogeneous population in terms of fitness, comorbidity, and psychological reserve. Therefore, age per se does not always provide an accurate indication of condition in patients with cancer. Frailty has been proposed as an alternative measure of vulnerability that might better indicate which patients can tolerate standard cancer treatment and those who may benefit from treatment adjustment. A number of methods can be used to assess frailty in older patients with hematological malignancies, including the Cardiovascular Health Study Frailty Screening Measure, the FRAIL (Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight) questionnaire, the Clinical Frailty Scale (CFS), and the Gérontopôle Frailty Screening Tool. In addition to physical frailty, comorbidity and quality of life should also be included in the assessment. Prior to the introduction of tyrosine kinase inhibitors (TKIs), age was considered a marker of poor prognosis in patients with MPNs. In contrast, data show that age is not necessarily a contraindication for TKI use. In CML, the efficacy of TKIs has been shown to be independent of age. The JAK1/2 inhibitor ruxolitinib also seems to be effective across a range of patient ages. Available data suggest that chronological age itself should not necessarily be a contraindication for many new therapies in patients with MPNs, and that frailty does provide a better measure of vulnerability. There is a need for specific methods to assess frailty in patients with MPNs, particularly the context of effective new treatment options, such as TKIs and ruxolitinib.

Examining the Effect of Medication Adherence on Risk of Subsequent Fracture Among Women with a Fragility Fracture in the U.S. Medicare Population.

BACKGROUND: In the United States, osteoporosis affects approximately 10 million people, of whom 80% are women, and it contributes a significant clinical burden to the community. Poor adherence to osteoporosis medications adds to the overall burden of illness. OBJECTIVE: To examine the association of osteoporosis medication adherence and the risk of a subsequent fracture among Medicare-enrolled women with a previous fragility fracture. METHODS: This study was a retrospective observational analysis of U.S. administrative claims data among female Medicare beneficiaries who had a nontrauma closed fragility fracture between January 1, 2011, and December 31, 2011. Patients were required to have continuous medical and pharmacy enrollment 12 months pre- and postfracture date. In addition, patients were required to have an osteoporosis medication prescription for a bisphosphonate (alendronate, risedronate, pamidronate, etidronate, zoledronate, and tiludronate), calcitonin, denosumab, raloxifene, or teriparatide during the follow-up period. Adherence was calculated using cumulative medication possession ratio (MPR) from the treatment initiation date in 30-day increments. MPR was stratified into high adherence (MPR ≥ 80%), moderate adherence (50% ≤ MPR > 80%), and low adherence (MPR < 50%). Outcomes included first subsequent fracture after treatment initiation; patients were censored at treatment discontinuation, or end of the 12-month period posttreatment initiation. Covariates included demographics, comorbidities, osteoporosis medications, medications associated with falls, and health care utilization. Cox regression was used to model subsequent fractures with time-dependent cumulative MPR. RESULTS: Of the 1,292,248 Medicare enrollees who had a fracture in 2011, a total of 103,852 (8.0%) women aged ≥ 65 years with a fragility fracture were identified. Overall, 27,736 (26.7%) patients were treated with osteoporosis medication within 12 months of the fragility fracture (mean time to treatment initiation was 85.0 ± 84.6 days). Over half of the patients were highly adherent (MPR ≥ 80%) to osteoporosis medications during the follow-up (n = 14,112; 50.9%). Almost a third of the patients had low adherence (MPR < 50%; n = 9,022, 32.5%), followed by patients with moderate adherence (50% ≤ MPR > 80%; n = 4,602, 16.6%). After adjusting for demographics and clinical characteristics, patients with low and moderate adherence to osteoporosis medications were 33% (hazard ratio [HR] = 1.33; 95% CI = 1.17-1.50, P < 0.001) and 19% (HR = 1.19; 95% CI = 1.02-1.38, P = 0.026) more likely to have a subsequent fracture, respectively, compared with patients with high adherence. Low adherence patients had a 32% and 34% increased risk for a hip/pelvis/femur fracture (HR = 1.32; 95% CI = 1.09-1.59, P = 0.005) and a clinical vertebral fracture (HR = 1.34; 95% CI = 1.09-1.63, P = 0.005), respectively, compared with high adherence patients. CONCLUSIONS: Medicare-enrolled women with low and moderate adherence to osteoporosis medications had a higher risk of a subsequent fracture compared with high adherence patients. These results highlight the importance of improving osteoporosis medication adherence among women enrolled in Medicare. DISCLOSURES: This study was funded by Eli Lilly. Xie, Keshishian, and Baser are employees of STATinMED Research, a paid consultant to Eli Lilly in connection with the study design, data analysis, and development of the manuscript for this study. Boytsov, Burge, Lombard, and Zhang are employees and stock owners of Eli Lilly. At the time of research, Krohn was an employee of Eli Lilly. Study concept and design were contributed by Burge and Lombard, along with the other authors. Xie, Baser, and Keshishian took the lead in data collection, assisted by the other authors. Data interpretation was performed by Krohn and Zhang, with assistance from the other authors. The manuscript was written by Keshishian and Boytsov, along with the other authors, and revised by Boytsov, Keshishian, and Burge, along with the other authors.