Risk Assessment and Prevention of Falls in Older Community-Dwelling Adults: A Review.

Importance: Falls are reported by more than 14 million US adults aged 65 years or older annually and can result in substantial morbidity, mortality, and health care expenditures. Observations: Falls result from age-related physiologic changes compounded by multiple intrinsic and extrinsic risk factors. Major modifiable risk factors among community-dwelling older adults include gait and balance disorders, orthostatic hypotension, sensory impairment, medications, and environmental hazards. Guidelines recommend that individuals who report a fall in the prior year, have concerns about falling, or have gait speed less than 0.8 to 1 m/s should receive fall prevention interventions. In a meta-analysis of 59 randomized clinical trials (RCTs) in average-risk to high-risk populations, exercise interventions to reduce falls were associated with 655 falls per 1000 patient-years in intervention groups vs 850 falls per 1000 patient-years in nonexercise control groups (rate ratio [RR] for falls, 0.77; 95% CI, 0.71-0.83; risk ratio for number of people who fall, 0.85; 95% CI, 0.81-0.89; risk difference, 7.2%; 95% CI, 5.2%-9.1%), with most trials assessing balance and functional exercises. In a meta-analysis of 43 RCTs of interventions that systematically assessed and addressed multiple risk factors among individuals at high risk, multifactorial interventions were associated with 1784 falls per 1000 patient-years in intervention groups vs 2317 falls per 1000 patient-years in control groups (RR, 0.77; 95% CI, 0.67-0.87) without a significant difference in the number of individuals who fell. Other interventions associated with decreased falls in meta-analysis of RCTs and quasi-randomized trials include surgery to remove cataracts (8 studies with 1834 patients; risk ratio [RR], 0.68; 95% CI, 0.48-0.96), multicomponent podiatry interventions (3 studies with 1358 patients; RR, 0.77; 95% CI, 0.61-0.99), and environmental modifications for individuals at high risk (12 studies with 5293 patients; RR, 0.74; 95% CI, 0.61-0.91). Meta-analysis of RCTs of programs to stop medications associated with falls have not found a significant reduction, although deprescribing is a component of many successful multifactorial interventions. Conclusions and Relevance: More than 25% of older adults fall each year, and falls are the leading cause of injury-related death in persons aged 65 years or older. Functional exercises to improve leg strength and balance are recommended for fall prevention in average-risk to high-risk populations. Multifactorial risk reduction based on a systematic clinical assessment for modifiable risk factors may reduce fall rates among those at high risk.

Polypharmacy, chemotherapy receipt, and medication-related out-of-pocket costs at end of life among commercially insured adults with advanced cancer.

BACKGROUND: Polypharmacy raises the risk of drug-drug interactions and adverse events among patients with cancer. Most polypharmacy research has focused on adults age 65 or older enrolled in Medicare insurance. To better inform pharmacy practice and cancer care delivery, data are needed on polypharmacy among commercially insured patients with cancer and those younger than 65. METHODS: We performed a retrospective analysis of insurance enrollment and claims files linked to the Puget Sound Cancer Surveillance System for adults age 18 and older who were commercially insured, diagnosed with stage IV cancer, survived 30+ days after diagnosis, and did not enroll in hospice. We describe the prevalence of polypharmacy, chemotherapy use, and medication-related out-of-pocket (OOP) costs in the last month of life. RESULTS: Of 606 patients, 390 (64%) experienced polypharmacy (i.e. 5+ medications) in the last 30 days of life. Almost half (n = 297, 49%) received chemotherapy or targeted agents; chemotherapy was associated with significantly higher odds of polypharmacy (odds ratio (OR) 2.93, 95% confidence interval (CI) 2.04-4.20). The most commonly prescribed medications at end of life were opioids, benzodiazepines and anti-emetics. Among 484 patients (80%) incurring medication-related costs in the last month of life, median total OOP cost was $82 (interquartile range $30-$200). Seven patients (1%) had total costs above $5,000. The median chemotherapy-related OOP cost was $446 (IQR $150-$1896); 32 patients (7%) had chemotherapy-related OOP costs between $1,000 and $5,000. CONCLUSION: Most patients with advanced cancer experienced polypharmacy at end of life, although most medications observed herein are commonly used for supportive care. Patients receiving chemotherapy had higher medication-related OOP costs, and chemotherapy was significantly associated with polypharmacy at end of life. Evaluation of polypharmacy at end of life may represent an important opportunity to improve quality of life and reduce costs for patients and families.

BBCIC Research Network Analysis of First-Cycle Prophylactic G-CSF Use in Patients Treated With High-Neutropenia Risk Chemotherapy.

BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is prevented or minimized with granulocyte colony-stimulating factors (G-CSFs). Several G-CSF biosimilars are approved in the United States. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a nonprofit initiative whose objective is to provide scientific evidence on real-world use and comparative safety and effectiveness of biologics and biosimilars using the BBCIC distributed research network (DRN). PATIENTS AND METHODS: We describe real-world G-CSF use in patients with breast or lung cancer receiving first-cycle chemotherapy associated with high FN risk. We assessed hospitalizations for FN, availability of absolute neutrophil counts, and G-CSF-induced adverse events to inform future observational comparative effectiveness studies of G-CSF reference products and their biosimilars. A descriptive analysis of 5 participating national health insurance plans was conducted within the BBCIC DRN. RESULTS: A total of 57,725 patients who received at least one G-CSF dose were included. Most (92.5%) patients received pegfilgrastim. FN hospitalization rates were evaluated by narrow (<0.5%), intermediate (1.91%), and broad (2.99%) definitions. Anaphylaxis and hyperleukocytosis were identified in 1.15% and 2.28% of patients, respectively. This analysis provides real-world evidence extracted from a large, readily available database of diverse patients, characterizing G-CSF reference product use to inform the feasibility of future observational comparative safety and effectiveness analyses of G-CSF biosimilars. We showed that the rates of FN and adverse events in our research network are consistent with those reported by previous small studies. CONCLUSIONS: Readily available BBCIC DRN data can be used to assess G-CSF use with the incidence of FN hospitalizations. Insufficient laboratory result data were available to report absolute neutrophil counts; however, other safety data are available for assessment that provide valuable baseline data regarding the effectiveness and safety of G-CSFs in preparation for comparative effectiveness studies of reference G-CSFs and their biosimilars.

The landscape of real-world evidence of rituximab utilization and clinical outcomes in patients with cancer, rheumatoid arthritis, and multiple sclerosis: A scoping review.

BACKGROUND: Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used to treat various conditions in cancer, rheumatoid arthritis (RA), and multiple sclerosis (MS). Although RTX has been used in the United States for almost 3 decades, questions remain regarding its real-world utilization and effectiveness. OBJECTIVE: To describe the state of observational research and real-world evidence evaluating RTX in oncology, RA, and off-label use in MS. METHODS: A broad search was conducted in MEDLINE, Embase, and CINAHL covering the period of January 2010 to June 2022. Two reviewers independently screened all identified records for each disease category (cancer, RA, MS) beginning with title review, followed by abstract, and full-text review to identify relevant publications to include in the final analysis. Data were extracted and summarized for each disease based on overall trends, similarities, and differences across included studies and stratified by disease state. RESULTS: A total of 260 studies met eligibility criteria, with 79 studies for the RA cohort, 144 for cancer, and 37 for MS. Across all disease cohorts, most studies (n = 189; 72.7%) were retrospective. 171 (65.8%) studies used hospital or electronic health record data as their data source and 65 (23.2%) used registry databases. Most studies (n = 153; 58.8%) assessed the effectiveness of RTX measured by disease-specific endpoints, followed by safety (n = 60; 23.1%), treatment patterns (n = 32; 12.3%), and descriptive analyses assessing treatment adherence and economic burden of disease (n = 16; 6.2%). Although safety was not the primary outcome for most studies, the majority of studies across all disease states still reported some form of safety measure. Conclusive statements on RTX's benefit varied across disease states, with MS having the most (n = 30; 81.1%) studies suggesting the drug's positive benefit. There were limited studies assessing RTX use, associated economic burden, and biosimilar switching. CONCLUSIONS: The findings underscore the need for health care providers to better understand the treatment landscape and utilization of RTX, particularly in terms of patient selection, timing of initiation, and long-term outcomes. Real-world evidence can help support health care decisions and treatment using rituximab.

Factors Associated With Hospital Admission in the Last Month: A Retrospective Single Center Analysis.

CONTEXT: Driven by concerns about care quality, patient experience, and national metrics, health systems are increasingly focusing on identifying risk factors for patients who are hospitalized in the last month of life. OBJECTIVE: To evaluate patient factors associated with hospital admission in the last month (30 days). METHODS: We analyzed a retrospective cohort of 8488 patients with a primary care visit in a tertiary health system in the last year of life using a linked electronic health record and decedent dataset. We examined healthcare utilization (primary care, emergency, hospital, intensive care unit encounters) and end-of-life related outcomes (palliative care consultation, do-not-resuscitate orders, advance care planning documentation, hospice at hospital discharge, death in health system). Multivariable logistic regressions identified patient factors associated with admission in the last month. RESULTS: About 2202 (25.9%) patients had a hospital admission in the last month. Among the 1282 (15.1%) who died in a health system facility, most (1103/1282, 86.0%) were admitted to the hospital in the last month. Among patients with a hospital admission and discharged in the last month, 60.9% (686/1126) were discharged on hospice. Compared to those without these diseases, metastatic cancer, liver disease, or heart failure had the highest odds of admission in the last month (adjusted OR 2.36 95%CI 2.05-2.72; 2.28, 95%CI 1.98-2.62; and 2.17 95%CI 1.93-2.45 respectively). CONCLUSIONS: As patients with heart or liver disease or metastatic cancer had the highest odds of admission in the last month, collaborative interventions between primary, palliative, and specialty care may improve quality of care at the end of life.

Criteria for Enrollment of Patients With COPD in Palliative Care Trials: A Systematic Review.

CONTEXT: Use of palliative care interventions in chronic obstructive pulmonary disease (COPD) has increased in recent years and inclusion criteria used to identify patients with COPD appropriate for palliative care vary widely. We evaluated the inclusion criteria to identify ways to improve enrollment opportunities for patients with COPD. OBJECTIVES: To determine inclusion criteria used to select patients with COPD for palliative care trials. METHODS: A systematic review was conducted to determine criteria used to select patients with COPD for palliative care randomized controlled trials. A narrative synthesis was conducted for all trials. RESULTS: Inclusion criteria were highly heterogeneous. Most studies (n = 11, 79%) used a combination of criteria to identify patients with COPD. Commonly used criteria included hospitalization for an acute exacerbation of COPD (n = 8, 57%), home supplemental oxygen use (n = 8, 57%), and spirometry values confirming COPD (n = 6, 43%). Three studies (21.4%) used Modified Medical Research Council score and two studies (21%) used physician prognosis or a performance scale. CONCLUSION: The most common criteria, a hospitalization for acute exacerbation of COPD or supplemental oxygen use at home, both have the benefit of selecting patients who have a higher symptom burden or higher healthcare utilization who might therefore benefit more from palliative care. By describing the landscape and variability of previously used inclusion criteria, this article serves as a resource for clinicians and researchers. Developing a consistent set of inclusion criteria in the future would help generate generalizable results that can be translated into clinical practice to improve the lives of patients with COPD. PROSPERO REGISTRATION NUMBER: CRD42022306752.

Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation.

We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplantation. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (n = 132) or unrelated (n = 176) donors, and received postgrafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in 9 patients, 8 of whom had a total MPA Css less than 3 µg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades III to IV acute graft-versus-host disease and increased nonrelapse mortality but not with day 28 T cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 µg/mL could lower grades III to IV acute graft-versus-host disease and nonrelapse mortality in patients receiving an unrelated donor graft.

Effect of the COVID-19 Pandemic on Place of Death Among Medicaid and Commercially Insured Patients With Cancer in Washington State.

PURPOSE: The COVID-19 pandemic-related disruptions in health care delivery might have affected end-of-life care in patients with cancer. We examined changes in place of death and hospice support for Medicaid and commercially insured patients during the pandemic. PATIENTS AND METHODS: We linked Washington State cancer registry records with claims from Medicaid and two commercial insurers for patients with solid tumor age 18-64 years. The study included 322 Medicaid and 162 commercial patients who died between March 2017 and June 2019 (pre-COVID-19), along with 90 Medicaid and 47 commercial patients who died between March and June 2020 (COVID-19). Place of death was categorized as hospital, hospice (home or nonhospital facility), and home without hospice. Place of death was compared using adjusted multinomial logistic regressions stratified by payer and time period (pre-COVID-19 v COVID-19). The clinical and sociodemographic factors associated with dying at home without hospice were examined, and adjusted marginal effects (ME) are reported. RESULTS: In the adjusted pre-COVID-19 analysis, Medicaid patients were more likely than commercially insured patients to die in hospital (48% v 36%; adjusted ME, 11%; P = .02). In the pre-COVID-19/COVID-19 analysis, Medicaid patients' place of death shifted from hospital (48% v 32%; ME, -16%; P < .01) to home without hospice (19.9% v 38.0%; ME, 16.5%; P < .01). However, there were no statistically significant changes pre-COVID-19/COVID-19 for commercial patients. As a result, during COVID-19, Medicaid patients were more likely than commercial patients to die at home without hospice (38% v 22%; ME, 16%; P = .04) as were male versus female patients (ME, 16%; P < .01). CONCLUSION: The pandemic might have disproportionately worsened the end-of-life experience for Medicaid enrollees with cancer. Attention should be paid to societal and health system factors that decrease access to care for Medicaid patients.

Utilization, user characteristics, and adverse outcomes of insulin glargine originators and follow-on drug in patients with diabetes in the United States.

BACKGROUND: The first follow-on drug (Basaglar) of the originator insulin glargine (Lantus), a long-acting insulin for treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM), was approved in 2015 in the United States. Information on the uptake, user characteristics, and outcomes of follow-on insulin remains sparse. OBJECTIVE: To describe the utilization, user characteristics, and health outcomes of the follow-on insulin glargine and insulin glargine originators in a large, distributed network of primarily commercially insured patients in the United States. METHODS: We used health care claims data in the US Food and Drug Administration's Sentinel common data model format across 5 research partners in the Biologics & Biosimilars Collective Intelligence Consortium distributed research network. Sentinel analytic tools were used to identify adult users of insulin glargine between January 1, 2011, and February 28, 2021, and describe patient demographics, baseline clinical characteristics, and adverse health events among users of the originators and the follow-on drug, stratified by diabetes type. RESULTS: We identified 508,438 users of originator drugs and 63,199 users of the follow-on drug. The proportions of the follow-on drug users among total insulin glargine users were 9.1% (n = 7,070) for T1DM and 11.4% (n=56,129) for T2DM. Follow-on use rose from 8.2% in 2017 to 24.8% in 2020, accompanied by a steady decrease in the use of originator drugs. Demographics of the users of the originators and follow-on drug were similar among the T1DM and T2DM groups. Overall, follow-on users had poorer baseline health profile and higher proportions of episodes with adverse events in the follow-up. CONCLUSIONS: We found evidence of increased uptake of the follow-on drug relative to the originator products in the post-2016 period. The differences in the base-line clinical characteristics between users of the originator products and the follow-on drug and their relationship with health outcomes merit further research. DISCLOSURES: Sengwee Toh consults for Pfizer, Inc., and TriNetX, LLC. This study was funded by the BBCIC.

Identification of cancer chemotherapy regimens and patient cohorts in administrative claims: challenges, opportunities, and a proposed algorithm.

BACKGROUND: Real-world evidence is a valuable source of information in healthcare. This study describes the challenges and successes during algorithm development to identify cancer cohorts and multi-agent chemotherapy regimens from claims data to perform a comparative effectiveness analysis of granulocyte colony stimulating factor (G-CSF) use. METHODS: Using the Biologics and Biosimilars Collective Intelligence Consortium's Distributed Research Network, we iteratively developed and tested a de novo algorithm to accurately identify patients by cancer diagnosis, then extract chemotherapy and G-CSF administrations for a retrospective study of prophylactic G-CSF. RESULTS: After identifying patients with cancer and subsequent chemotherapy exposures, we observed only 12% of patients with cancer received chemotherapy, which is fewer than expected based on prior analyses. Therefore, we reversed the initial inclusion criteria to identify chemotherapy receipt, then prior cancer diagnosis, which increased the number of patients from 2,814 to 3,645, or 68% of patients receiving chemotherapy had diagnoses of interest. Additionally, we excluded patients with cancer diagnoses that differed from those of interest in the 183 days before the index date of G-CSF receipt, including early-stage cancers without G-CSF or chemotherapy exposure. By removing this criterion, we retained 77 patients who were previously excluded. Finally, we incorporated a 5-day window to identify all chemotherapy drugs administered (excluding oral prednisone and methotrexate, as these medications may be used for other non-malignant conditions) as patients may fill oral prescriptions days to weeks prior to infusion. This increased the number of patients with chemotherapy exposures of interest to 6,010. The final cohort of included patients, based on G-CSF exposure, increased from 420 from the initial algorithm to 886 using the final algorithm. CONCLUSIONS: Medications used for multiple indications, sensitivity and specificity of administrative codes, and relative timing of medication exposure must all be evaluated to identify patient cohorts receiving chemotherapy from claims data.

Cholinesterase inhibitor adjunctive therapy for cognitive impairment and depressive symptoms in older adults with depression.

OBJECTIVE: To review the primary literature regarding the use of cholinesterase inhibitors (ChEIs) as adjunctive therapy for cognitive enhancement and improvement of depressive symptoms for older adults with depression. DATA SOURCES: A literature search of MEDLINE (1950-September 2011) was conducted, using the search term depression in combination with cholinesterase inhibitor, donepezil, galantamine, or rivastigmine. A search of reference citations was conducted to identify additional references. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials were evaluated. Studies that included subjects with Alzheimer's disease, dementia, Parkinson disease, bipolar disorder, or schizophrenia were excluded. Four clinical studies met our criteria. DATA SYNTHESIS: We identified 4 randomized, double-blind, placebo-controlled trials that ranged in sample size from 20 to 130. Galantamine 16 mg daily was evaluated in 2 trials lasting 8 and 24 weeks. Neither study found a statistically significant difference in measures of cognition or Hamilton Rating Scale for Depression scores. Donepezil augmentation was evaluated in a 1-year and a 2-year trial. Donepezil was found to improve global cognition at 1 year, but the benefit did not persist at year 2. Subjects with mild cognitive impairment at baseline who received donepezil experienced higher depression recurrence than did those who took placebo (p = 0.03); this effect was not observed in cognitively intact subjects (p = 0.39). CONCLUSIONS: There is no clear benefit for ChEI therapy as an adjunct to antidepressant therapy for depressed older adults.

Complementary and alternative medicine use among newly diagnosed prostate cancer patients.

PURPOSE: We surveyed prostate cancer patients about complementary and alternative medicine (CAM) use and evaluated patient factors that correlated with CAM use 6 months following diagnosis. METHODS: The Prostate CAncer Therapy Selection study was a prospective, observational multi-site study of men's treatment decision-making process after a diagnosis of local stage prostate cancer. Recruitment occurred in community urology practices in Washington State, hospital-based urology clinics affiliated with the University of Southern California, and Kaiser Permanente in Northern California. Eligible study participants included men over age 21 diagnosed with local stage prostate cancer between May 1, 2005 and December 31, 2006. RESULTS: Fifty-two percent of survey respondents (379) reported using one or more types of CAM. Of the patients, 51% used one CAM method, 26% used two methods, and 23% used three or more methods. The most commonly reported category was mind-body therapies (65%). Only 43% of patients discussed their CAM use with a health professional; of those, 20% informed their primary care physician and 30% told the doctor managing their prostate cancer care. Less than half thought the CAM they used was "very helpful", but a majority thought it was somewhat helpful for their condition. CONCLUSIONS: Further research is needed to characterize the goals prostate cancer patients have for CAM, whether the treatments met those goals, and how this translates into the perceived helpfulness of these therapies. The implications of patients not discussing CAM use with health professionals at the time of prostate cancer treatment need further studies.

Health insurer policies toward risk-stratified colorectal cancer screening: a survey of health plan medical directors.

OBJECTIVES: We sought to determine whether health insurance coverage of colorectal cancer (CRC) screening varied based on risk. BACKGROUND: Population-wide screening guidelines for cancer often incorporate risk information, with modified screening recommendations for those at higher risk due to family history or other factors. METHODS: In a nationwide Internet- and mail-based survey of health insurance plan medical directors, respondents were asked about their organization's policies towards coverage of CRC screening for persons at average and higher risk of CRC. Additional questions asked about whether the insurer had a definition of increased risk, and coverage of genetic testing for familial CRC syndromes. RESULTS: Survey invitations were sent to 1158 medical directors; 133 (11%) completed the survey. All plans covered screening for average and high-risk persons. The onset of screening was earlier and intervals were more frequent for higher risk compared to average risk persons, with most respondents stating coverage was determined by "physician discretion." While 75% had a definition of high risk, only 55% covered genetic testing. CONCLUSIONS: Most insurers offer enhanced coverage of CRC screening, most commonly following the discretion of the physician. Whether this coverage results in earlier, more frequent, or more complete screening of higher risk persons remains uncertain.

Advance Care Planning Documentation and Intensity of Care at the End of Life for Adults With Congestive Heart Failure, Chronic Kidney Disease, and Both Illnesses.

CONTEXT: Heart failure (HF) and chronic kidney disease (CKD) are associated with high morbidity and mortality, especially in combination, yet little is known about the impact of these conditions together on end-of-life care. OBJECTIVES: Compare end-of-life care and advance care planning (ACP) documentation among patients with both HF and CKD to those with either condition. METHODS: We conducted a retrospective analysis of deceased patients (2010-2017) with HF and CKD (n = 1673), HF without CKD (n = 2671), and CKD without HF (n = 1706), excluding patients with cancer or dementia. We compared hospitalizations and intensive care unit (ICU) admissions in the last 30 days of life, hospital deaths, and ACP documentation >30 days before death. RESULTS: 39% of patients with HF and CKD were hospitalized and 33% were admitted to the ICU in the last 30 days vs. 30% and 28%, respectively, for HF, and 26% and 23% for CKD. Compared to patients with both conditions, those with only 1 were less likely to be admitted to the hospital [HF: adjusted odds ratio (aOR) 0.72, 95%CI 0.63-0.83; CKD: aOR 0.63, 95%CI 0.53-0.75] and ICU (HF: aOR 0.83, 95%CI 0.71-0.94; CKD: aOR 0.68, 95%CI 0.56-0.80) and less likely to have ACP documentation (aOR 0.53, 95%CI 0.47-0.61 and aOR 0.70, 95%CI 0.60-0.81). CONCLUSIONS: Decedents with both HF and CKD had more ACP documentation and received more intensive end-of-life care than those with only 1 condition. These findings suggest that patients with co-existing HF and CKD may benefit from interventions to ensure care received aligns with their goals.

Health care use and primary prophylaxis with colony-stimulating factors.

OBJECTIVES: We examined health care use in conjunction with primary prophylaxis use of colony stimulating factors (CSF) during patients' initial course of chemotherapy. METHODS: This retrospective cohort study identified adults aged 25 years and older with a diagnosis of breast, colorectal, or nonsmall cell lung cancer between 2002 and 2005 from the Western Washington Surveillance Epidemiology and End Results Puget Sound registry. We linked these records to health insurance claims from four payers representing 75% of those insured in the state. Claims records were used to determine chemotherapy regimen type, CSF use, febrile neutropenia occurrences, and supportive care. Chemotherapy regimens were categorized as conferring high, intermediate, or low risk of myelosuppression according to the National Comprehensive Cancer Network guidelines. CSF use was described as primary prophylaxis, other, or none. Antibiotics and antifungal and antiviral agents per National Comprehensive Cancer Network guidelines for supportive care for cancer infection were categorized using Healthcare Common Procedure Coding System and National Drug Code assignments. RESULTS: Use of CSF as primary prophylaxis is not significantly associated with a reduction in antibiotic use or inpatient or outpatient visits. Primary prophylactic CSF use was associated with less use of antiviral drugs. CONCLUSIONS: CSF use is not associated with a reduction in health care use, with the exception of antiviral drug use. Given the expense associated with CSF use, pragmatic trials and additional research are needed to further assess the affects of CSF on health care use.

Utilization patterns and characteristics of users of biologic anti-inflammatory agents in a large, US commercially insured population.

We report utilization patterns and characteristics of patients treated with biologic anti-inflammatory agents in a large commercially insured patient population in the United States. We identified adult (age ≥18 years) patients receiving biologic anti-inflammatory agents between 1 January 2012 and 31 March 2019 across the five Research Partners in the Biologic and Biosimilars Collective Intelligence Consortium's Distributed Research Network. We examined the number of incident use episodes for each biologic, as well as patient demographic and clinical characteristics. Curated data and analytic tools from the Food and Drug Administration's Sentinel System were used to perform the analyses. We identified 90,360 incident episodes of tumor necrosis factor-alpha inhibitors (TNFi) and 70,506 incident episodes of non-TNFi medications. Adalimumab was the most common TNFi drug (47% of all TNFi episodes) and showed a steady increase in utilization during the study period compared to other TNFi agents. Rituximab was the most commonly initiated non-TNFi medication (44% of non-TNFi episodes). Other non-TNFi agents, namely, ustekinumab, vedolizumab, and secukinumab, demonstrated notable increases in utilization over time. Biosimilar use was limited; we observed 653 incident episodes for infliximab-dyyb and 39 incident episodes for infliximab-abda. As more biologics enter the market, greater variation in the use of biologics with similar indications and between biologic originators and biosimilars is anticipated. Because information on efficacy and safety at the time of drug approval is limited, post-marketing surveillance and research is needed to monitor medication safety and evaluate effectiveness between biologic drugs using real-world data.

Methodological Challenges for Epidemiologic Studies of Deprescribing at the End of Life.

PURPOSE OF REVIEW: To describe approaches to measuring deprescribing and associated outcomes in studies of patients approaching end of life (EOL). RECENT FINDINGS: We reviewed studies published through 2020 that evaluated deprescribing in patients with limited life expectancy and approaching EOL. Deprescribing includes reducing the number of medications, decreasing medication dose(s), and eliminating potentially inappropriate medications. Tools such as STOPPFrail, OncPal, and the Unnecessary Drug Use Measure can facilitate deprescribing. Outcome measures vary and selection of measures should align with the operationalized deprescribing definition used by study investigators. SUMMARY: EOL deprescribing considerations include medication appropriateness in the context of patient goals for care, expected benefit from medication given life expectancy, and heightened potential for medication-related harm as death nears. Additional data are needed on how EOL deprescribing impacts patient quality of life, caregiver burden, and out-of-pocket medication-related costs to patients and caregivers. Investigators should design deprescribing studies with this information in mind.

Patient Characteristics and Utilization Patterns of Short-Acting Recombinant Granulocyte Colony-Stimulating Factor (G-CSF) Biosimilars Compared to Their Reference Product.

BACKGROUND: Data on short-acting recombinant granulocyte colony-stimulating factor (G-CSF) biosimilar utilization from claims data in the USA are limited. OBJECTIVE: To evaluate patient baseline characteristics and utilization patterns for short-acting G-CSF products with particular focus on the assessment of filgrastim biosimilar usage relative to the originator product. PATIENTS AND METHODS: We examined filgrastim, filgrastim-sndz, and tbo-filgrastim use among adult patients between January 2012 and March 2019 across the five health-plan research partners in the BBCIC Distributed Research Network. The publicly available Sentinel System analytic toolkit was used to perform the distributed analyses. RESULTS: We evaluated over 38 million eligible health-plan members representing more than 88 million person-years of data. We identified 45,204 incident treatment episodes, including 33,118 episodes with filgrastim, 6525 episodes with filgrastim-sndz, and 5,561 episodes with tbo-filgrastim. We observed that the demographic and clinical characteristics of users were comparable across products. While total use of all filgrastim products remained consistent, the proportion of incident episodes of the originator filgrastim steadily decreased since 2014, with filgrastim-sndz and tbo-filgrastim making up the difference. Utilization for the G-CSF biosimilar, filgrastim-sndz, increased from 40 (1%) of 6823 total filgrastim product episodes in 2015, to 2486 (44%) of a total 5668 episodes of filgrastim products in 2018 (partial data for 2018). CONCLUSION: New episodes of short-acting biosimilar filgrastim products have increased over time while the overall number of new users remained flat. Although barriers to biosimilar use in oncology have been noted, uptake has begun and continues to grow.

The Association of Advance Care Planning Documentation and End-of-Life Healthcare Use Among Patients With Multimorbidity.

PURPOSE: Multimorbidity is associated with increased intensity of end-of-life healthcare. This association has been examined by number but not type of conditions. Our purpose was to understand how intensity of care is influenced by multimorbidity within specific chronic conditions to provide guidance for interventions to improve end-of-life care for these patients. METHODS: We identified adults cared for in a multihospital healthcare system who died between 2010-2017. We categorized patients by 4 primary chronic conditions: heart failure, pulmonary disease, renal disease, or dementia. Within each condition, we examined the effect of multimorbidity (presence of 4 or more chronic conditions) on hospital and ICU admission in the last 30 days of life, in-hospital death, and advance care planning (ACP) documentation >30 days before death. We performed logistic regression to estimate associations between multimorbidity and end-of-life care utilization, stratified by the presence or absence of ACP documentation. RESULTS: ACP documentation >30 days before death was associated with lower odds of in-hospital death for all 4 conditions both in patients with and without multimorbidity. With the exception of patients with renal disease without multimorbidity, we observed lower odds of hospitalization and ICU admission for all patients with ACP >30 days before death. CONCLUSIONS: Patients with dementia and multimorbidity had the highest odds of high-intensity end-of-life care. For patients with dementia, heart failure, or pulmonary disease, ACP documentation >30 days before death was associated with lower likelihood of in-hospital death, hospitalization, and ICU use at end-of-life, regardless of multimorbidity.