Association of Pre-Pandemic Telehealth With Emergency Department and Telehealth Usage During the Pandemic.

Objectives Aims were to quantify the association of pre-COVID-19 pandemic telehealth use and separately: 1) likelihood of an emergency department (ED) visit, 2) likelihood of a telehealth visit in older people during the pandemic. Design A retrospective cohort study to measure odds ratios (ORs) of telehealth usage before the pandemic and likelihood of an ED visit and telehealth visit during the study period. Setting and Patients Adults 65 years of age and older (N = 39,214) in the University of California COVID Research Data Set (UC CORDS). Main Outcomes Primary outcome was occurrence of one or more ED visits. Secondary outcome was occurrence of one or more telehealth visits. Results A telehealth visit before the pandemic was associated with reduced likelihood of an ED visit with an OR of 0.33 (95% confidence interval [CI] 0.200.55). Pre-pandemic telehealth was associated with an increased likelihood of telehealth use during the pandemic with an OR of 4.66 (95% CI 3.52-6.18). Conclusion Older people who utilized telehealth before the pandemic were less likely to receive emergency care and were more likely to use telehealth during the pandemic. Approaches to enhance and measure telehealth access for older people are necessary.

Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022.

BACKGROUND: Recent Food and Drug Administration approvals of glucagon-like peptide 1 (GLP-1) receptor agonists linked to substantial weight loss have generated interest in demand projections. However, a longitudinal analysis in a large, diverse, current, real-world database has not been published. OBJECTIVES: The study objective was to determine user frequency of GLP-1 receptor agonist products overall and by type 2 diabetes (T2D), cardiovascular disease (CVD), and overweight or obese status. Secondary objective was monthly growth rate estimation by product since first appearance in University of California Health. METHODS: This retrospective cohort study included patients who were dispensed a GLP-1 receptor agonist from 2014 to 2022 in the University of California Health Data Warehouse. Exponential growth rates were estimated using a log-linear regression model. RESULTS: Between 2014 and 2018, only Trulicity and Victoza exceeded 5000 annual users. Ozempic users increased from 569 in 2019 to 7667 in 2020. Use accelerated with more than 13,310 users in 2021 to surpass Trulicity. Ozempic count was 22,891 in 2022. Wegovy rose from 989 in 2021 to 2992 in 2022. Mounjaro increased to 1508 users in 2022. Although generally similar trends were observed for T2D, CVD, and overweight or obese subgroups, the ascent of Ozempic as most frequently used was more apparent in the overweight or obese group. The monthly growth rates were 83.9% for Ozempic, 119.2% for Wegovy, 84.8% for Rybelsus, 53.3% for Saxenda, 12.9% for Adlyxin, 78.8% for Trulicity, and 254.3% for Mounjaro. CONCLUSION: This first cohort study of weight loss-associated GLP-1 receptor agonists in a large, diverse, state-wide health system demonstrated a rapid increased use that represents a clear and likely durable transition in utilization for this category. Informed decision making and longitudinal studies are needed to ensure evidence-concordant prescribing and supply stability.

Considerations on the Weight Loss-Associated Glucagon-like Peptide-1 Receptor Agonists for Older People.

Obesity rates for older people have increased around the world1 with rates tripling over the past four decades.² While previously considered a phenomenon of developed countries, the increased prevalence of obesity is now established in developing countries as well.³ Factors stimulating this epidemic include modifications in the global food supply chain, rise in consumption and availability of energy-dense, low-nutrient foods, sedentary occupations, expanding urbanization, changes in transportation means, as well as environmental components.³ The increasing prevalence of obesity in older people in the United States over time has been well documented by federal agencies. Over the time periods 1999-2002, 2003-2006, and 2007-2010, a linear increase in the prevalence of obesity among older men in all age groups was observed. The obesity prevalence among men 65 to 74 years of age increased from about 31.6% in 1999-2002 to 41.5% in 2007-2010. In men older than 74 years of age, obesity prevalence increased from 17.7% in 1999-2002 to 26.5% in 2007-2010. Of interest is that, in women, the change over the same time period was not statistically significant for the older age groups (40.3% obesity in 65- to 74-year-old women and 28.7% in women older than 74 years of age in the 2007-2010 analysis period).4.

Exploring Concomitant Acetylcholinesterase Inhibitor and Overactive Bladder Anticholinergic Use and Risk of Hospitalization in Medicare and Dual-Eligible Medicare-Medicaid Populations in a Historic Database.

Overactive bladder prevalence increases in older adults often complicating the management of other comorbidities. The theoretical antagonism between the parasympathetic-blocking anticholinergic agent and the parasympathetic stimulatory agents concomitantly used by patients is only recently being explored. The primary aim was to determine the frequency of the annual use of acetylcholinesterase inhibitors, overactive bladder anticholinergics, and the use of both agents in the same year. The secondary aim was measurement of the association between annual hospitalization and same-year use of both acetylcholinesterase inhibitors and anticholinergics. The US nationally representative MarketScan® Medicare databases were analyzed. In the Medicare enrollees, there were 122 020, 141 920, and 15 639 users of acetylcholinesterase inhibitors, anticholinergics, and both agents, respectively. The percentage of acetylcholinesterase inhibitor users who also used anticholinergics was 12.8%. Comparing users of both acetylcholinesterase inhibitors and anticholinergics to those using AChEI alone, 5 608 of the former experienced a hospitalization (35.9%) compared to 33 182 of the latter (31.2%). There was an increased risk of hospitalization for those using both acetylcholinesterase inhibitors and anticholinergics in the same year, with an odds ratio (OR) of 1.23 (95% CI, 1.19, 1.28). Clinicians should consider improved monitoring of the usage of both medications and clarify alternative regimens that avoid anticholinergics in at-risk older adults.

Effectiveness of letermovir for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplant recipients: A global systematic review.

OBJECTIVE(S): Letermovir (LET), a novel antiviral, has largely supplanted more traditional preemptive therapy (PET) for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplant (allo-HCT) patients. Use of LET demonstrated efficacy against placebo in phase III randomized controlled trials, but is considerably more expensive than PET. This review aimed to evaluate the real-world effectiveness of LET in preventing clinically significant CMV infection (csCMVi) for allo-HCT recipients and related outcomes. DESIGN: A systematic literature review was performed using an a priori protocol using PubMed, Scopus, and ClinicalTrials.gov from January 2010 to October 2021. SETTING AND PARTICIPANTS: Studies were included if they met the following criteria: LET compared with PET, CMV-related outcomes, patients aged 18 years or older, and English language-only articles. Descriptive statistics were used to summarize study characteristics and outcomes. OUTCOME MEASURES: CMV viremia, csCMVi, CMV end-organ disease, graft-versus-host-disease, all-cause mortality. RESULTS: A total of 233 abstracts were screened, with 30 included in this review. Randomized trials demonstrated efficacy of LET prophylaxis in preventing csCMVi. Observational studies demonstrated varying degrees of effectiveness of LET prophylaxis compared with use of PET alone. All studies with a comparator group resulted in lower rates of csCMVi for patients using LET. Included studies varied widely by CMV viral load threshold cutoff and CMV test units, limiting synthesis of results owing to high heterogeneity. CONCLUSION: LET reduces risk of csCMVi, but lack of standardized clinical definitions on how to evaluate csCMVi and related outcomes largely prevent synthesis of results. Clinicians must consider this limitation in the context of evaluating the effectiveness of LET to other antiviral therapies, especially for patients at risk of late-onset CMV. Future studies should focus on prospective data collection through registries and concordance of diagnostic definitions to mitigate study heterogeneity.

The Critical Role of Pharmacists in Treating Older People in the Opioid Crisis.

Pharmacy-based Opioid Use Disorder (OUD) treatment has been identified as a central pillar in curbing the spiraling opioid epidemic that claimed more than 100,000 lives in the United States in a one year period for the first time. This epidemic is also partially responsible for the plummeting US life expectancy that began prior to the COVID-19 pandemic and has now claimed more than 500,000 lives since 1999 with more than 70% of the 70,630 overdose deaths in 2019 involved with an opioid. Older people are at increased risk of both OUD and OUD-related complications. Recent studies have demonstrated that people older than 65 years of age were more likely to die of OUD-related complications, and - because of an increased likelihood of polypharmacy - are more likely to experience a drug interaction that magnifies the risk of an opioid-related misadventure.

Cost Effectiveness of Letermovir for Cytomegalovirus Prophylaxis Compared with Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the United States.

PURPOSE: The aim of this study was to assess the cost effectiveness of letermovir prophylaxis with the option for subsequent pre-emptive therapy (PET) for the prevention of cytomegalovirus (CMV) infection compared with a PET-only scenario in adult allogeneic hematopoietic stem cell transplant (allo-HCT) recipients in the United States over a 10-year time horizon. MATERIALS AND METHODS: A publicly available decision tree model was constructed using a commercial third-party payer perspective to simulate an allo-HCT recipient's clinical trajectory in the first-year post-transplant, followed by entry to a Markov model to simulate years 2 through 10. Clinical inputs and utility estimates were derived from published literature. Costs were derived from published literature and US Department of Veterans Affairs Federal Supply Schedule drug pricing. Outcomes assessed included life expectancy, quality-adjusted life-years (QALYs), direct medical costs, and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the findings. RESULTS: Compared with PET alone, letermovir prophylaxis was projected to increase life-years per person (4.99 vs. 4.70 life-years), and increase QALYs (3.29 vs. 3.08) and costs (US$83.411 vs. US$70,698), yielding an ICER of US$59,356 per QALY gained. One-way sensitivity analyses indicated our model was sensitive to mortality (ICER: $164,771/QALY) and utility (letermovir ICER: $117,447/QALY; PET ICER: $107,290/QALY) in the first-year post-transplant. In 57.1% of the PSA simulations, letermovir was a cost-effective option using a willingness-to-pay threshold of US$100,000 per QALY. CONCLUSIONS: Letermovir prophylaxis is cost effective compared with PET alone with a willingness-to-pay threshold of US$100,000 per QALY gained. Sensitivity analysis results indicate future research is required to understand the impact of mortality and quality of life in the first-year post-transplant to arrive at a conclusive decision on letermovir adoption.

Minding the gap and the value of metrics: Count of working pharmacists in the United States.

BACKGROUND: The Bureau of Labor Statistics (BLS) uses a single Standard Occupational Classification (SOC) code (29-1051) that reflects a traditional definition of pharmacist job functions. Pharmacists working in nontraditional roles would be categorized under other SOC codes and not included in the BLS pharmacist count. Knowing the magnitude of how many working pharmacists may not be included in the BLS pharmacist count would help determine whether the gap is a minor margin of error or a significant problem affecting pharmacist workforce projections. OBJECTIVES: The primary objective of this paper was to estimate the gap between the number of possibly working pharmacists and the BLS pharmacist count in 2019. A secondary objective was to examine BLS pharmacist counts in nontraditional roles and compare with published industry data. METHODS: The annual number of individuals receiving their first professional pharmacy degree from 1965 to 2019 (55 graduation cohorts) was adjusted using the expected survival rate to 2019 by age and gender and workforce participation rate in 2019 for pharmacists for each cohort and then summed across cohorts. Data sources included Accreditation Council for Pharmacy Education, U.S. Vital Statistics reports, and American Consumer Survey. One-way and scenario-based sensitivity analyses were conducted to vary professional occupation mortality advantage and pharmacist workforce participation rate assumptions. RESULTS: Based on the number of individuals receiving their first professional pharmacy degree between 1965 and 2019 (442,409), there were 356,998 possibly working pharmacists in 2019. This value indicates 45,798 more pharmacists (15%) may have been working in 2019 than the 311,200 employee pharmacists reported by BLS for 2019. A gap of 8000 to 46,000 more working pharmacists (3%-15%) versus BLS persisted after sensitivity analyses. CONCLUSION: The magnitude of possibly working pharmacists not included in BLS counts warrants further consideration of current pharmacist job projections, methods, and metrics to improve future projections and monitoring of the pharmacist labor force.

Federal and State Pharmacy Regulations and Dispensing Barriers to Buprenorphine Access at Retail Pharmacies in the US.

This Viewpoint describes federal and state pharmacy regulations that may create barriers to buprenorphine access at pharmacies and suggests policy changes to address those barriers.

Effects of financial toxicity on prescription drug use and mental well-being in cancer patients.

Background: In the US, medical costs for cancer patients have grown from $27 billion in 1990 to $174 billion in 2020. The increased financial strain that cancer patients and survivors endure is referred to as financial toxicity. Objective: To quantify the relationship between indicators of financial toxicity and health utilization and quality of life in patients ever diagnosed with cancer. Methods: Adult cancer patients and survivors in 2017 were identified using the Medical Expenditure Panel Survey. Multiple logistic regression models were used to quantify the relationship between three financial toxicity exposures (concern for keeping an income, paying large medical bills, and going into debt or borrowing money) and two discrete outcomes of being able to purchase prescriptions and often worrying that cancer would worsen or come back. Results: This study assessed 609 respondents. After survey weighting was applied, that represented 16,215,673 individuals. Patients who reported concern for keeping an income were at 2.91 (95% Confidence Interval [CI], 1.16 to 7.31) and 2.97 (95% CI, 2.01 to 2.67) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Patients who reported worry about paying large medical bills were at 4.46 (95% CI, 2.15 to 9.24) and 2.80 (95% CI, 1.98 to 3.96) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Patients who reported borrowing money or going into debt were at 3.04 (95% CI, 1.19 to 7.76) and 2.42 (95% CI, 1.54 to 3.18) times increased odds to report avoiding purchase of prescriptions and worry of cancer status, respectively, versus those who did not. Conclusions: Financial toxicity is associated with decreased prescription utilization and quality of life in the form of excessive worry among cancer patients including cancer survivors.

Risk of Negative Health Outcomes and High Costs for People With Diabetes and Unmet Psychological Needs in the United States.

Measuring the population-level relationship between compromised mental health and diabetes care remains an important goal for clinicians and health care decision-makers. We evaluated the impact of self-reported unmet psychological need on health care resource utilization and total health care expenditure in people with type 2 diabetes. Patients who reported unmet psychological needs were more likely than those who did not to incur a higher annual medical expenditure, have greater resource utilization, and have a higher risk of all-cause mortality.

Examination of Medication Use Patterns by Age Group, Comorbidity, and Month in COVID-19 Positive Patients in a Large Statewide Health System During the Pandemic in 2020.

Background: Understanding medication use patterns for patients with COVID-19 will provide needed insight into the evolution of COVID-19 treatment over the course of the SARS-CoV-2 pandemic and aid clinical management considerations. Objectives: To systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was use measurement of medications considered potential therapeutic options. Methods: Retrospective cohort study was performed using data from the University of California COVID Research Data Set (UC CORDS) patients between March 10, 2020, and December 31, 2020. Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status for COVID-19 patients. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time. Results: Dataset included 22 896 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12 154 [53%] women). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Dexamethasone use increased from fewer than 50 total hospitalized patients through April who had received the medication, to more than 500 patients by mid-August. Cumulative count of enoxaparin users was the largest throughout the study period. Conclusion and Relevance: In this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted toward more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.

When Can Nonrandomized Studies Support Valid Inference Regarding Effectiveness or Safety of New Medical Treatments?

The randomized controlled trial (RCT) is the gold standard for evaluating the causal effects of medications. Limitations of RCTs have led to increasing interest in using real-world evidence (RWE) to augment RCT evidence and inform decision making on medications. Although RWE can be either randomized or nonrandomized, nonrandomized RWE can capitalize on the recent proliferation of large healthcare databases and can often answer questions that cannot be answered in randomized studies due to resource constraints. However, the results of nonrandomized studies are much more likely to be impacted by confounding bias, and the existence of unmeasured confounders can never be completely ruled out. Furthermore, nonrandomized studies require more complex design considerations which can sometimes result in design-related biases. We discuss questions that can help investigators or evidence consumers evaluate the potential impact of confounding or other biases on their findings: Does the design emulate a hypothetical randomized trial design? Is the comparator or control condition appropriate? Does the primary analysis adjust for measured confounders? Do sensitivity analyses quantify the potential impact of residual confounding? Are methods open to inspection and (if possible) replication? Designing a high-quality nonrandomized study of medications remains challenging and requires broad expertise across a range of disciplines, including relevant clinical areas, epidemiology, and biostatistics. The questions posed in this paper provide a guiding framework for assessing the credibility of nonrandomized RWE and could be applied across many clinical questions.

When Are Treatment Blinding and Treatment Standardization Necessary in Real-World Clinical Trials?

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence in the evaluation of new treatments or products. Real-world clinical trials or pragmatic trials often differ from traditional clinical trials in the use of open-label or nonblinded treatments delivered by real-world clinicians in community practice settings. Blinding and standardization of treatment may sometimes be necessary for internal validity, but they may also obscure or distort meaningful differences between treatments. When investigators consider whether blinding of clinicians, patients, or assessors is necessary, we suggest they consider several specific questions: Will clinicians, patients, and assessors have expectations or preferences regarding benefits or adverse effects? How might those expectations affect treatment uptake, treatment adherence, or assessment of outcomes? Will expectations differ in the settings where trial results will be applied? How would blinding of treatment reduce biases? How would blinding obscure true differences between treatments? How would procedures necessary for blinding reduce acceptability or increase risk of trial participation? When investigators consider how strictly treatments should be standardized, we suggest they consider several specific questions: How would treatment effectiveness or safety vary according to clinician experience or expertise? What level of experience or expertise is available in potential trial settings and settings where trial results would be applied? Is some level of standardization necessary for valid inference? Considering any special vulnerabilities of the study population, is some level of standardization necessary to assure participant safety?

When Can We Trust Real-World Data To Evaluate New Medical Treatments?

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products. RWE studies often rely on real-world data (RWD), including data extracted from healthcare records or data captured by mobile phones or other consumer devices. Global assessments of RWD sources are not helpful in assessing whether any specific RWD element is fit for any specific purpose. Instead, evidence generators and evidence consumers should clearly identify the specific health state or clinical phenomenon of interest and then consider each step between that clinical phenomenon and its representation in a research database. We propose specific questions regarding potential error or bias affecting each of those steps: Would a person experiencing this clinical phenomenon present for care in this setting or interact with this recording device? Would this clinical phenomenon be accurately recognized or assessed? How might the recording environment or tools affect accurate and consistent recording of this clinical phenomenon? Can data elements from different sources be harmonized, both technically (same format) and semantically (same meaning)? Can the original data elements be consistently reduced to a useful clinical phenotype? Addressing these questions requires a range of clinical, organizational, and technical expertise. Transparency regarding each step in the creation of RWD is essential if evidence consumers are to rely on RWE studies.

When Can We Rely on Real-World Evidence to Evaluate New Medical Treatments?

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products. The RWE label has been used to refer to a variety of departures from the methods of traditional randomized controlled trials. Recognizing this complexity and potential confusion, the National Academies of Science, Engineering, and Medicine convened a series of workshops to clarify and address questions regarding the use of RWE to evaluate new medical treatments. Those workshops identified three specific dimensions in which RWE studies might differ from traditional clinical trials: use of real-world data (data extracted from health system records or data captured by mobile devices), delivery of real-world treatment (open-label treatments delivered in community settings by community practitioners), and real-world treatment assignment (including nonrandomized comparisons and variations on random assignment such as before-after or stepped-wedge designs). For any RWE study, decisions regarding each of these dimensions depends on the specific research question, characteristics of the potential study settings, and characteristics of the settings where study results would be applied.

Transferring Key Success Factors from Ambulatory Care into the Community Pharmacy in the United States.

In the United States, pharmacists' scope of practice continues to expand, with increasing opportunities for pharmacists in all practice settings to enhance health in society. In ambulatory care, pharmacists remain integral members on the healthcare team and have demonstrated positive impacts on patient care. Sharing similar characteristics as pharmacists in the community setting, a deeper look into common elements of a successful ambulatory care practice that can be applied in the community pharmacy setting is warranted. Key success factors identified from ambulatory care include (1) maximizing a pharmacist's unique knowledge base and skill set, (2) forming collaborations with physicians and other providers, (3) demonstrating outcomes and value, and (4) maintaining sustainability. Opportunities exist for pharmacists in the community setting to utilize these success factors when developing, implementing, and/or expanding direct patient care services that improve accessibility to quality care and population health.