Association of Opioid and Concurrent Benzodiazepine, Skeletal Muscle Relaxant, and Gabapentinoid Usage on Healthcare Expenditure and Resource Utilization: A Serial Cross-Sectional Study, 2009 to 2019.

BACKGROUND: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified. We sought to characterize healthcare costs and expenditures associated with a population reporting concurrent CNS depressants and opioid use compared with nonopioid analgesics in the United States from 2009 to 2019. METHODS: A serial cross-sectional design was used to compare the healthcare expenditures of adult Medical Expenditure Panel Survey respondents who were prescribed nonopioid analgesics, opioids only, opioids/benzodiazepines (BZD), opioids/BZD/skeletal muscle relaxants (SMR), or opioids/gabapentin (gaba) using pooled data from 2009 to 2019. Expenditure (cost and resource utilization) categories included inpatient, outpatient, office-based, and prescription medicine. Average marginal effects were used to compare survey-weighted annual costs and resource utilizations across the groups as compared to nonopioid analgesic respondents, adjusted for covariates. RESULTS: A weighted total of 34 241 838 individuals were identified. Most were opioid-only respondents (46.5%), followed by nonopioid analgesic (43.4%), opioid/BZD (5.3%), opioid-gaba (3.5%), and opioid/BZD/SMR respondents (1.3%). In comparison to the study groups with nonopioid analgesics, opioid-gaba users had the highest significant incremental cost difference among the different pairings (+$11 684, P < .001). Opioid-gaba, opioid/BZD, and opioid/BZD/SMR respondents had significantly higher inpatient, emergency department, and prescription drug costs and use compared to nonopioid analgesic respondents. Opioid-only respondents had higher outpatient and office-based costs and visits compared to nonopioid analgesic respondents. CONCLUSIONS: As healthcare providers seek to utilize fewer opioids for pain management, attention must be paid to ensuring safe and effective use of concurrent CNS depressants to mitigate high healthcare costs and burden.

Rural-Urban Disparities in Colorectal Cancer Screening, Diagnosis, Treatment, and Survivorship Care: A Systematic Review and Meta-Analysis.

BACKGROUND: Rural residents have a higher prevalence of colorectal cancer (CRC) mortality compared to urban individuals. Policies have been aimed at improving access to CRC screening to reduce these outcomes. However, little attention has been paid to other determinants of CRC-related outcomes, such as stage at diagnosis, treatment, or survivorship care. The main objective of this analysis was to evaluate literature describing differences in CRC screening, stage at diagnosis, treatment, and survivorship care between rural and urban individuals. MATERIALS AND METHODS: We conducted a systematic review of electronic databases using a combination of MeSH and free-text search terms related to CRC screening, stage at diagnosis, treatment, survivorship care, and rurality. We identified 921 studies, of which 39 were included. We assessed methodological quality using the ROBINS-E tool and summarized findings descriptively. A meta-analysis was performed of studies evaluating CRC screening using a random-effects model. RESULTS: Seventeen studies reported disparities between urban and rural populations in CRC screening, 12 on treatment disparities, and 8 on staging disparities. We found that rural individuals were significantly less likely to report any type of screening at any time period (pooled odds ratio = 0.81, 95% CI, 0.76-0.86). Results were inconclusive for disparities in staging at diagnosis and treatment. One study reported a lower likelihood of use of CRC survivorship care for rural individuals compared to urban individuals. CONCLUSION: There remains an urgent need to evaluate and address CRC disparities in rural areas. Investigators should focus future work on assessing the quality of staging at diagnosis, treatment, and survivorship care in rural areas.

Effect of Metformin Use on Vitamin B12 Deficiency Over Time (EMBER): A Real-World Evidence Database Study.

OBJECTIVE: To examine the extent to which metformin increases the risk of vitamin B12 deficiency and borderline deficiency over time in participants with type 2 diabetes mellitus (T2DM). METHODS: Using the All of Us database, adults aged ≥18 years with T2DM and a documented history of metformin use were included for the evaluation of B12 deficiency. Those with B12 deficiency before metformin use were excluded. Adjusted logistic regression models were used to evaluate the association between metformin use and long-term metformin use (≥4 years) and the risk of B12 deficiency. We conducted a subgroup analysis comparing differences in borderline B12 deficiency in metformin and non-metformin users. RESULTS: Of 36 740 participants with T2DM, 6221 (16.9%) had documented metformin use. The mean age of metformin users was 65.3 years. B12 deficiency was confirmed in 464 (7.5%) metformin users, and 1919 of 30 519 participants (6.3%) did not use metformin. Metformin users had a 4.7% increased risk of developing B12 deficiency compared with nonmetformin users (P = .44). Each additional year of metformin use was associated with 5% increased likelihood of deficiency (P < .05). Metformin use for ≥4 years resulted in a 41.0% increased odds of B12 deficiency, compared with those who used <4 years of metformin (P < .05). Metformin use increased the odds of borderline B12 deficiency by 27.0% (P < .05). CONCLUSION: Long-term metformin use was associated with an increased risk of B12 deficiency in patients with T2DM, with compounding risk over time.

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.

Predicted Health Literacy Disparities Between Immigrant and US-Born Racial/Ethnic Minorities: a Nationwide Study.

BACKGROUND: Racial/ethnic minorities in the USA exhibit reduced health literacy (HL) proficiency, leading to increased health disparities. It is unclear how the effect of birth status (immigrant/US-born) affects HL proficiency among racial/ethnic minorities. OBJECTIVE: To identify the direct, indirect, and total effects of birth status on HL proficiency among a nationally representative population of racial/ethnic minority adults in the USA. DESIGN: A cross-sectional study of 2019 data from the Medial Expenditure Panel Survey. PARTICIPANTS: Participants aged 18 or older reporting as racial/ethnic minorities (Black, Asian, or Hispanic) with non-missing data. MAIN MEASURES: We predicted HL proficiency for each participant using a previously published model. Path analysis was used to estimate the direct, indirect, and total effects of birth status on HL proficiency, accounting for several other covariates. Prevalence ratios were estimated using adjusted Poisson regression to evaluate differences in the "Below Basic" HL category. KEY RESULTS: An estimated weighted 81,092,505 participants were included (57.5% US-born, 42.5% immigrant). More racial/ethnic minority immigrant participants fell into the lowest category of HL proficiency, "Below Basic" (14.3% vs 5.5%, p < 0.05). Results of the path analysis indicated a significant, negative direct effect of birth status on HL proficiency (standardized coefficient = - 0.24, SE = 0.01, 95%CI: - 0.26, - 0.23) in addition to an indirect effect mediated through insurance status, health-system resource use, and English proficiency. The total effect of birth status on HL proficiency was found to be - 0.29. The immigrant participant group had 81% higher prevalence of falling into the "Below Basic" HL category compared to US-born participants (prevalence ratio = 1.81, 95%CI: 1.52, 2.16). CONCLUSIONS: Immigrant status has a strong, negative, direct effect on HL proficiency among racial/ethnic minorities in the USA. This may be a result of barriers that prevent equitable access to resources that improve proper HL proficiency. US policymakers may consider several methods to reduce this disparity at the health-system-, provider-, and patient-levels.

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.

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.

Trends in healthcare expenditures and resource utilization among a nationally representative population with opioids in the United States: a serial cross-sectional study, 2008 to 2017.

BACKGROUND: Previous reports on healthcare costs and expenditures associated with populations prescribed an opioid primarily focused on populations who chronically use opioids or have opioid use disorder. However, studies that characterize the healthcare and expenditures costs among the wider number of people prescribed opioids in a nationally representative population are unavailable. We sought to characterize the healthcare costs and expenditures associated with a population prescribed an opioid in the U.S. from 2008 to 2017. METHODS: A serial cross-sectional design was used to compare the economic burden of adult household respondents who were prescribed and not prescribed an opioid using pooled data from the Medical Expenditure Panel Survey (MEPS) between 2008 and 2017. Respondents with an opioid prescription were matched to respondents without an opioid prescription using propensity score match methods with survey weights. Two-part generalized linear models were used to estimate the survey-weighted annual healthcare expenditures and resource utilization adjusting for multiple covariates. Additionally, 10-year trend comparisons between the groups were performed. Costs were adjusted to 2019 US dollars. RESULTS: There was a weighted total of 31,696,671 respondents with an opioid and 31,536,639 respondents without an opioid after propensity score matching. The sample had a mean (SD) age of 50.63 years (18.03), 58.9% females, and 81.6% Whites. Total annual economic burden among RPOs was $524 billion. Annual total expenditures per respondent with and without an opioid were $16,542 and $7067, respectively (P < 0.001). Similarly, adjusted prescription, outpatient, emergency department, and inpatient expenditures were significantly higher for respondents with an opioid compared to respondents without an opioid. Average annual increases in expenditures were significantly greater among respondents with an opioid compared to respondents without an opioid for total (+$185; 95% CI: $37-$334) and prescription (+$78; 95% CI: $28-$128) expenditures. There were no differences in the average annual trends for outpatient, emergency department, and inpatient expenditures between respondents with and without an opioid. CONCLUSIONS: Respondents with an opioid prescription had higher healthcare expenditures and resource utilization compared to respondents without an opioid prescription from 2008 to 2017. Specifically, significant annual increases were observed for total and prescription expenditures. Additionally, 10-year trends in total and prescription expenditures were higher among respondents with an opioid than respondents without an opioid.

A multicenter analysis of the clinical microbiology and antimicrobial usage in hospitalized patients in the US with or without COVID-19.

BACKGROUND: Past respiratory viral epidemics suggest that bacterial infections impact clinical outcomes. There is minimal information on potential co-pathogens in patients with coronavirus disease-2019 (COVID-19) in the US. We analyzed pathogens, antimicrobial use, and healthcare utilization in hospitalized US patients with and without severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). METHODS: This multicenter retrospective study included patients with > 1 day of inpatient admission and discharge/death between March 1 and May 31, 2020 at 241 US acute care hospitals in the BD Insights Research Database. We assessed microbiological testing data, antimicrobial utilization in admitted patients with ≥24 h of antimicrobial therapy, and length of stay (LOS). RESULTS: A total of 141,621 patients were tested for SARS-CoV-2 (17,003 [12.0%] positive) and 449,339 patients were not tested. Most (> 90%) patients tested for SARS-CoV-2 had additional microbiologic testing performed compared with 41.9% of SARS-CoV-2-untested patients. Non-SARS-CoV-2 pathogen rates were 20.9% for SARS-CoV-2-positive patients compared with 21.3 and 27.9% for SARS-CoV-2-negative and -untested patients, respectively. Gram-negative bacteria were the most common pathogens (45.5, 44.1, and 43.5% for SARS-CoV-2-positive, -negative, and -untested patients). SARS-CoV-2-positive patients had higher rates of hospital-onset (versus admission-onset) non-SARS-CoV-2 pathogens compared with SARS-CoV-2-negative or -untested patients (42.4, 22.2, and 19.5%, respectively), more antimicrobial usage (68.0, 45.2, and 25.1% of patients), and longer hospital LOS (mean [standard deviation (SD)] of 8.6 [11.4], 5.1 [8.9], and 4.2 [8.0] days) and intensive care unit (ICU) LOS (mean [SD] of 7.8 [8.5], 3.6 [6.2], and 3.6 [5.9] days). For all groups, the presence of a non-SARS-CoV-2 pathogen was associated with increased hospital LOS (mean [SD] days for patients with versus without a non-SARS-CoV-2 pathogen: 13.7 [15.7] vs 7.3 [9.6] days for SARS-CoV-2-positive patients, 8.2 [11.5] vs 4.3 [7.9] days for SARS-CoV-2-negative patients, and 7.1 [11.0] vs 3.9 [7.4] days for SARS-CoV-2-untested patients). CONCLUSIONS: Despite similar rates of non-SARS-CoV-2 pathogens in SARS-CoV-2-positive, -negative, and -untested patients, SARS-CoV-2 was associated with higher rates of hospital-onset infections, greater antimicrobial usage, and extended hospital and ICU LOS. This finding highlights the heavy burden of the COVID-19 pandemic on healthcare systems and suggests possible opportunities for diagnostic and antimicrobial stewardship.

Emergency Department Visits for Psychotropic-Related Adverse Drug Events in Older Adults With Alzheimer Disease, 2013-2014.

Background: More than 1.3 million emergency department visits have been associated with adverse drug events (ADEs) in older adults. Increasing Alzheimer's disease (AD) prevalence in the geriatric population poses an additive risk of ADEs because of the array of psychotropic medications prescribed for AD patients. Scant research has been conducted at a nationwide level on psychotropic-related ADEs in this population. Objective: This study aimed to determine the incidence and economic burden of psychotropic ADEs in the geriatric AD population compared with the non-AD geriatric population. Methods: A retrospective analysis was conducted of geriatric AD patients who visited the ED in 2013 with a psychotropic-related ADE to determine the incidence and resource utilization of these events. The relationship between presence of AD and an ADE was analyzed using multiple logistic regression. Results: There were 427 969 Alzheimer's ED visits compared with 20 492 554 ED visits without. Of the AD cases, 1.04% were associated with at least 1 adverse event. AD cases more frequently were admitted as inpatients (64.90% vs 34.92%, P < 0.01). Common drug classes associated with AD-related ADEs were benzodiazepines, antipsychotics, and autonomic nervous system-affecting agents (adrenergic agonists, antimuscarinic agents, anticholinergic agents). There was a significantly higher likelihood for Alzheimer's cases to experience any psychotropic-related adverse event (OR = 1.66; 95% CI = 1.20, 1.82). Conclusion and Relevance: Alzheimer's patients more frequently experienced psychotropic-related adverse events and related adverse outcomes than older adults without Alzheimer's. Application of these findings should be implemented in protocol development to reduce future psychotropic-related adverse outcomes for this population.

Resource utilization and charges of patients with and without diagnosed venous thromboembolism during primary hospitalization and after elective inpatient surgery: a retrospective study.

AIMS: To assess incremental charges of patients experiencing venous thromboembolisms (VTE) across various types of elective inpatient surgical procedures with administration of general anesthesia in the US. METHODS: The authors performed a retrospective study utilizing data from a nationwide hospital operational records database from July 2014 through June 2015 to compare a group of inpatients experiencing a VTE event post-operatively to a propensity score matched group of inpatients who did not experience a VTE. Patients included in the analysis had a hospital admission for an elective inpatient surgical procedure with the use of general anesthesia. Procedures of the heart, brain, lungs, and obstetrical procedures were excluded, as these procedures often require a scheduled ICU stay post-operatively. Outcomes examined included VTE events during hospitalization, length of stay, unscheduled ICU transfers, number of days spent in the ICU if transferred, 3- and 30-day re-admissions, and total hospital charges incurred. RESULTS: The study included 17,727 patients undergoing elective inpatient surgical procedures. Of these, 36 patients who experienced a VTE event were matched to 108 patients who did not. VTE events occurred in 0.2% of the study population, with most events occurring for patients undergoing total knee replacement. VTE patients had a mean total hospital charge of $60,814 vs $48,325 for non-VTE patients, resulting in a mean incremental charge of $11,979 (p < .05). Compared to non-VTE patients, VTE patients had longer length of stay (5.9 days vs 3.7 days, p < .001), experienced a higher rate of 3-day re-admissions (3 vs 0 patients) and 30-day re-admissions (7 vs 2 patients). CONCLUSIONS: Patients undergoing elective inpatient surgical procedures with general anesthesia who had a VTE event during their primary hospitalization had a significantly longer length of stay and significantly higher total hospital charges than comparable patients without a VTE event.