Lifetime Health Research Articles

Populationwide Screening for Chronic Kidney Disease

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated. To compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies. This cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare & Medicaid Services data. Analyses were performed from June 2023 through September 2024. One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually. For those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case. This study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

Tobacco Cessation: Screening and Interventions.

Tobacco use has been the leading cause of disease and death in South Korea. Early detection of tobacco use and evidence-based interventions play pivotal roles in facilitating tobacco cessation. In accordance with the earlier iterations of the Lifetime Health Maintenance Program (2009) and recent recommendations from the United States Preventive Services Task Force (USPSTF; 2021), two themes were chosen for investigation: the identification of and intervention for tobacco use. The USPSTF recommendations were formulated by conducting an overview of reviews. In this study, literature searches and quality assessments of reviews were conducted. The findings highlighted the efficacy of physician-led identification and advising in promoting tobacco cessation, with robust evidence supporting the implementation of behavioral and pharmacological interventions. These interventions significantly increased the likelihood of successful cessation compared with usual care. Digital interventions, such as internet- or mobile-based interventions, showed additive effects for quitting. Identification and targeted interventions are essential for tobacco cessation. By leveraging evidencebased strategies and enhancing access to resources, healthcare providers can empower individuals to achieve successful tobacco cessation and improve overall health outcomes.

Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada

Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice. To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada. For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024. Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty. In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population. In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.

Assessing the Radon Exposure Variability and Lifetime Health Effects across Indoor Microenvironments and Sub-Populations

To assess the health impacts of radon exposure over a lifetime, in the present study, the annual effective dose (AED) and cumulative excess lifetime cancer risk (ELCR-C) were evaluated by considering various indoor microenvironmental exposures based on age-specific time–activity patterns using Monte Carlo simulations. Significant regional variations in indoor radon concentrations across the Republic of Korea were observed, with the highest levels found in schools and single detached houses. Based on the standard annual total of 8760 h spent indoors and outdoors, the AED varied by age group and dwelling type, with the ELCR-C for single detached houses being approximately 1.36 times higher than that for apartments on average. The present study highlights the importance of comprehensive health risk assessments that consider differences across indoor environments and age groups, indicating that limited evaluations of specific sites or areas may distort actual exposure levels.

Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain. We aimed to determine whether gynaecological surveillance was effective and cost-effective in Lynch syndrome. We conducted systematic reviews of the effectiveness and cost-effectiveness of gynaecological cancer surveillance in Lynch syndrome, as well as a systematic review of health utility values relating to cancer and gynaecological risk reduction. Study identification included bibliographic database searching and citation chasing (searches updated 3 August 2021). Screening and assessment of eligibility for inclusion were conducted by independent researchers. Outcomes were prespecified and were informed by clinical experts and patient involvement. Data extraction and quality appraisal were conducted and results were synthesised narratively. We also developed a whole-disease economic model for Lynch syndrome using discrete event simulation methodology, including natural history components for colorectal, endometrial and ovarian cancer, and we used this model to conduct a cost-utility analysis of gynaecological risk management strategies, including surveillance, risk-reducing surgery and doing nothing. We found 30 studies in the review of clinical effectiveness, of which 20 were non-comparative (single-arm) studies. There were no high-quality studies providing precise outcome estimates at low risk of bias. There is some evidence that mortality rate is higher for surveillance than for risk-reducing surgery but mortality is also higher for no surveillance than for surveillance. Some asymptomatic cancers were detected through surveillance but some cancers were also missed. There was a wide range of pain experiences, including some individuals feeling no pain and some feeling severe pain. The use of pain relief (e.g. ibuprofen) was common, and some women underwent general anaesthetic for surveillance. Existing economic evaluations clearly found that risk-reducing surgery leads to the best lifetime health (measured using quality-adjusted life-years) and is cost-effective, while surveillance is not cost-effective in comparison. Our economic evaluation found that a strategy of surveillance alone or offering surveillance and risk-reducing surgery was cost-effective, except for path_PMS2 Lynch syndrome. Offering only risk-reducing surgery was less effective than offering surveillance with or without surgery. Firm conclusions about clinical effectiveness could not be reached because of the lack of high-quality research. We did not assume that women would immediately take up risk-reducing surgery if offered, and it is possible that risk-reducing surgery would be more effective and cost-effective if it was taken up when offered. There is insufficient evidence to recommend for or against gynaecological cancer surveillance in Lynch syndrome on clinical grounds, but modelling suggests that surveillance could be cost-effective. Further research is needed but it must be rigorously designed and well reported to be of benefit. This study is registered as PROSPERO CRD42020171098. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129713) and is published in full in Health Technology Assessment; Vol. 28, No. 41. See the NIHR Funding and Awards website for further award information.

Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Phase-Based and Lifetime Health System Costs of Care for Patients Diagnosed with Leukemia and Lymphoma: A Population-Based Descriptive Study.

Hematologic cancers, notably leukemias and lymphomas, pose significant challenges to healthcare systems globally, due to rising incidence rates and increasing costs. This study aimed to estimate the phase and lifetime health system total costs (not net costs) of care for patients diagnosed with leukemia and lymphoma in Ontario, Canada. We conducted a population-based study of patients diagnosed between 2005 and 2019, using data from the Ontario Cancer Registry linked with health administrative databases. Costs were estimated using a phase-based approach and stratified by care phase and cancer subtype. Acute lymphocytic leukemia (ALL) patients had the highest mean monthly initial (CAD 19,519) and terminal (CAD 41,901) costs among all cancer subtypes, while acute myeloid leukemia (AML) patients had the highest mean monthly cost (CAD 7185) during the continuing phase. Overall lifetime costs were highest for ALL patients (CAD 778,795), followed by AML patients (CAD 478,516). Comparatively, patients diagnosed with Hodgkin lymphoma (CAD 268,184) and non-Hodgkin lymphoma (CAD 321,834) had lower lifetime costs. Major cost drivers included inpatient care, emergency department visits, same-day surgeries, ambulatory services, and specialized cancer drugs. Since 2005, the cost structure has evolved with rising proportions of interventional drug costs. Additionally, costs were higher among males and younger age groups. Understanding these costs can help guide initiatives to control healthcare spending and improve cancer care quality.

Cost-effectiveness of Pembrolizumab in Combination with Chemotherapy as Neoadjuvant Treatment and Continued as a Single Agent Adjuvant Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer in Hong Kong.

The phaseIII randomized KEYNOTE-522 trial demonstrated that pembrolizumab in combination with chemotherapy as neoadjuvant treatment followed by adjuvant pembrolizumab (pembrolizumab + chemotherapy) provided significant improvements in event-free survival (EFS) and overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The objective was to assess the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk eTNBC from a Hong Kong third-party payer perspective. A multistate transition model with four health states (event-free), locoregional recurrence, distant metastases, and death) was developed to assess the lifetime medical costs and health outcomes (3% annual discount), along with incremental cost-effectiveness ratios (ICERs) using efficacy and safety data from the KEYNOTE-522 trial. The health state utilities were derived from KEYNOTE-522 Euro-QoL-five-dimension five-level questionnaire (EQ-5D-5L) data. Costs were expressed in 2022 Hong Kong dollars (HKD).Scenario and sensitivity analyses were performed to assess the robustness of results. Over a 32-year time horizon, base case results showed that pembrolizumab + chemotherapy was associated with a 3.42year longer EFS and expected gains of 3.05 lifeyears (LYs) and 2.45 quality-adjusted lifeyears (QALYs) compared to chemotherapy. The resultant ICERs were HKD135,200 per QALY gained and HKD108,463 per LY gained, which were lower than the World Health Organization (WHO) cost-effectiveness threshold of three times gross domestic product (GDP) per capita for Hong Kong of HKD1,171,308 per QALY. The one-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) showed the results were robust across various inputs and alternative scenarios. On the basis of the analysis conducted for a 56-year-old cohort with high-risk eTNBC and assumptions in the model, pembrolizumab + chemotherapy represents a cost-effective proposition (as the ICER is approximately 35% of the GDP per capita in Hong Kong) for patients with high-risk eTNBC in Hong Kong.

Impact of Healthy Lifestyle Factors on Life Expectancy and Lifetime Health Care Expenditure: Nationwide Cohort Study.

The association between lifestyle risk factors and the risk of mortality and chronic diseases has been established, while limited research has explored the impact of healthy lifestyle factors on lifetime health care expenditure using longitudinal individual data. We aimed to determine the individual and combined effects of 5 healthy lifestyle factors on life expectancy and lifetime health care expenditure in Taiwan. Using data from the National Health Interview Survey cohort, 5 healthy lifestyle behaviors were defined and analyzed: nonsmoking, avoiding excessive alcohol consumption, engaging in sufficient physical activity, ensuring sufficient fruit and vegetable intake, and maintaining a normal weight. We used a rolling extrapolation algorithm that incorporated inverse probability of treatment weighting to estimate the life expectancy and lifetime health care expenditure of the study populations with and without healthy lifestyle factors. A total of 19,893 participants aged ≥30 (mean age 48.8, SD 13.4) years were included, with 3815 deaths recorded during a median follow-up period of 15.6 years. The life expectancy and per capita estimated lifetime health care expenditures for the overall study population were 35.32 years and US $58,560, respectively. Multivariable-adjusted hazard ratios for all-cause mortality in participants adhering to all 5 healthy lifestyle factors, compared with those adhering to none, were 0.37 (95% CI 0.27-0.49). We found significant increases in life expectancy for nonsmokers (2.31 years; 95% CI 0.04-5.13; P=.03), those with sufficient physical activity (1.85 years; 95% CI 0.25-4.34; P=.02), and those with adequate fruit and vegetable intake (3.25 years; 95% CI 1.29-6.81; P=.01). In addition, nonsmokers experienced a significant reduction in annual health care expenditure (-9.78%; 95% CI -46.53% to -1.45%; P=.03), as did individuals maintaining optimal body weight (-18.36%; 95% CI -29.66% to -8.57%; P=.01). Overall, participants adhering to all 5 healthy lifestyle behaviors exhibited a life gain of 7.13 years (95% CI 1.33-11.11; P=.02) compared with those adhering to one or none, with a life expectancy of 29.19 years (95% CI 25.45-33.62). Furthermore, individuals adopting all 5 healthy lifestyle factors experienced an average annual health care expenditure reduction of 28.12% (95% CI 4.43%-57.61%; P=.02) compared with those adopting one or none. Adopting a healthy lifestyle is associated with a longer life expectancy and a reduction of health care expenditure in Taiwanese adults. This contributes to a more comprehensive understanding of the impact of healthy lifestyle factors on the overall health and economic burden.

Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis

Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Low-dose aspirin, maternal cardiometabolic health, and offspring respiratory health 9 to 14 years after delivery: Findings from the EAGeR Follow-up Study.

Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

SA24 CHIME2 (Chinese Hong Kong Integrated Modeling and Evaluation): An Updated Model to Simulate Lifetime Health Outcomes of Patients with Type 2 Diabetes

SA24 CHIME2 (Chinese Hong Kong Integrated Modeling and Evaluation): An Updated Model to Simulate Lifetime Health Outcomes of Patients with Type 2 Diabetes

Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. Decision analysis using a microsimulation model. Surveillance, Epidemiology, and End Results database; randomized trials. U.S. men aged 55 years with no prior screening or PCa diagnosis. Lifetime. U.S. health care system. Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. Performance of first-line bpMRI was based on second-line mpMRI data. Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. National Cancer Institute.

Mental Health Care Use among Adolescent Sexual Minority Males Before and During COVID-19.

Adolescent (cisgender) sexual minority males (ASMM) face multiple mental health disparities. Yet surprisingly little is known about use of mental health care among ASMM. The current study examined mental health care use among ASMM, both lifetime use and during the COVID-19 pandemic. ASMM (N=154, ages 14-17 years) enrolled in Spring 2020 for a pilot randomized controlled trial of an online sexual health intervention. Participants were assessed at baseline and 3-month follow-up. Participants reported lifetime (at baseline) and recent (at follow-up) mental health care use. Anxiety and depressive symptoms were assessed at both timepoints. Differences in care use by sociodemographics, healthcare access, and mental health symptoms were established. More than half of participants reported clinically significant anxiety and depressive symptoms at baseline and at follow-up. Of those youth, fifty-three percent reported lifetime mental health care use, while only 28% reported recent care at follow-up. Being out to an accepting guardian (aOR=4.0, 95% CI: 1.9-8.4), having a primary care physician (aOR=2.6, 95% CI: 1.0-6.7), and having clinically significant symptoms (aOR=3.1, 95% CI: 1.5-6.5) were each independently associated with a greater odds of having received lifetime mental health care. Findings indicate that many ASMM in the sample received mental health care in their lifetimes. However, more participants endorsed clinically significant anxiety/depressive symptoms than received care at both timepoints. This disparity was even more pronounced approximately five months into the COVID-19 pandemic. Research and practice efforts must reduce care barriers and augment facilitators for all ASMM, with particular urgency during COVID-19 and its aftermath.

Lifetime Health and Economic Burden of Invasive Pneumococcal Diseases Attributable to V116 Serotypes Among Adults in the United States.

This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18years and above in the USA. A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. For the total population of US adults aged 18years and above in 2021 (approx. 258million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower-934,000, 11,500, and 120,000, respectively-with a total discounted direct lifetime cost of $21.9billion. These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults.

Economic evaluation of trastuzumab in HER2-positive early breast cancer in Indonesia: A cost-effectiveness analysis.

Trastuzumab has significantly enhanced the survival and prognosis of individuals diagnosed with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Considering its relatively high costs, we aimed to examine the cost-effectiveness of trastuzumab plus chemotherapy compared with chemotherapy alone in HER2-positive early breast cancer from an Indonesian healthcare payer's perspective. A Markov model was developed to project the lifetime health benefits and costs associated with trastuzumab treatment for a cohort of women with HER2-positive early breast cancer. Efficacy data and baseline characteristics in the base-case analysis were primarily derived from the 11-year results of the HERA trial. Costs were based on verified reimbursement data from Indonesia's Health and Social Security Agency (BPJS Kesehatan) of the year 2020. A scenario analysis was conducted with efficacy data based on the joint analysis from the NSABP B-31 and NCCTG N9831 trials, allowing for subgroup analysis by age at diagnosis. Univariate and probabilistic sensitivity analyses were conducted to assess the influence of parameter uncertainty. In the base-case analysis, the results indicated that the lifetime costs for trastuzumab plus chemotherapy and chemotherapy alone were US$33,744 and US$22,720, respectively, resulting in substantial incremental savings of US$11,024 per patient for the former. Trastuzumab plus chemotherapy also led to higher total quality-adjusted life years (QALYs) and life years gained (LYG), resulting in incremental cost-effectiveness ratios (ICERs) of US$6,842 per QALY and US$5,510 per LYG. In scenario analysis, the subgroup with an age at diagnosis <40 years old reflected the most cost-effective subgroup. Both the base-case and scenario analyses demonstrated cost-effectiveness with a willingness-to-pay threshold of three-times Gross Domestic Product (GDP). Sensitivity analyses confirmed the robustness of the findings and conclusions. In Indonesia, trastuzumab plus chemotherapy can be considered cost-effective compared to chemotherapy alone at a willingness-to-pay threshold of three times GDP, and it is likely most cost-effective in women <40 years of age.

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program.

Despite remarkable clinical advances in highly effective anti-obesity medications, their high price and potential budget impact pose a major challenge in balancing equitable access and affordability. While most attention has been focused on the amount of weight loss achieved, less consideration has been paid to interventions to sustain weight loss after an individual stops losing weight. Using a policy simulation model, we quantified the impact of a weight-maintenance program following the weight-loss plateau from the initial full-dose glucagon-like peptide 1 (GLP-1) receptor agonists or incretin mimetic use. We measured long-term health care savings and the loss of some health benefits (eg, maintenance of weight loss, improvements in cardiometabolic risk factors, and reductions in diabetes and cardiovascular events). Our model suggested that, compared with continuous long-term full-dose GLP-1 receptor agonists or incretin mimetic drugs, the alternative weight-maintenance program would generate slightly fewer clinical benefits while generating substantial savings in lifetime health care spending. Using less expensive and potentially less effective alternative weight-maintenance programs may provide additional headroom to expand access to anti-obesity medications during the active weight-loss phase without increasing total health care spending.

Selective breeding for high levels of voluntary exercise in mice does not reduce lifetime reproductive success or lifespan

The ways locomotor abilities may interact with life history traits are complicated and may involve shifts in resource allocation. For example, individuals that have large litters may have reduced energy available to support the organ systems required for high locomotor performance abilities. Alternatively, energy spent on excess physical activity might subtract from that available for somatic maintenance, and thus be negatively related to lifespan or to other fitness components that contribute to lifetime reproductive success (LRS). We studied lifetime reproductive successes, life span, and health span in mice from a long-term (&gt;100 generations) artificial selection experiment that includes 4 replicate High Runner (HR) lines bred for voluntary locomotor activity on wheels and 4 lines that serve as non-selected Controls (C). Since reaching selection limits at around generation 17-27 (depending on line and sex), the HR mice have been running ~3-fold farther on a daily basis as compared with C mice, for both sexes, which leads to substantially increased energy expenditure and food consumption. Importantly, when housed without wheels, HR mice are not only more active, but also consume more food than C mice. In the present study, we tested for differences in LRS between the HR and C lines. We are also comparing lifespan (median, maximum) and healthspan (e.g., by measurement of maximal oxygen consumption [VO2max] during forced exercise and maximal sprint speed. Twelve male-female pairs per line from generation 97 (born Oct. 2021) are being maintained until their end of life. In addition to total number of pups weaned per pair, we record components of LRS, such as age at first and last litter for the pairs, number of litters, and inter-birth intervals. Here, we present a subset of results through the first 2+ years of the experiment. Only two of 100 pairs never gave birth to any litters, and 89 of 100 pairs weaned at least one litter. The total number of litters born to pairs ranged from 0 to 12, and the number of litters from which at least one pup was weaned ranged from 0 to 11, with a mean of 3.96+0.73 (SE) for C lines and 3.43+0.65 for HR lines (P=0.61). The total number of pups weaned (our measure of LRS) ranged from 0 to 80, with a mean of 29.1+8.1 (SE) for C lines and 25.8+4.4 for HR lines (P=0.73). Thus, we found no evidence that Darwinian fitness has been reduced by artificial selection for high voluntary exercise. As of 1 Nov. 2023, approximately 17% of the breeders are still alive, and preliminary analyses do not indicate significant differences between the C and HR lines in median or maximum lifespan. Supported by U.S. National Science Foundation grant IOS-2038528. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rapid Simulation of Electro-Chemo-Mechanical Deformation of Li-ion Batteries Based On Porous Electrode Theory

Lithium-ion batteries change their geometric dimensions during cycling as a macroscopic result of a series of microscale mechanisms, including but not limited to diffusion-induced expansion/shrinkage, gas evolution, growth of solid-electrolyte interphase, and particle cracking. Predicting the nonlinear dimensional changes with mathematical models is critical to the lifetime prediction, health management, and non-destructive assessment of batteries. In this study, we present an approach to implement an elastoplasticity model for powder materials into the porous electrode theory (PET). By decomposing the overall deformation into elastic, plastic, and diffusion-induced portions and using the powder plasticity model to describe the plastic portion, the model can capture the reversible thickness change caused by Li-ion (de-)intercalation as well as the irreversible thickness change due to the rearrangement and consolidation of particles. For real-world applications of the model to predict battery health and safety, the key lies in solving the mathematical equations rapidly. Here, we implemented the coupled model into the open-source software PETLION for millisecond-scale simulation. The computational model is parameterized using values gathered from literature, tested under varying conditions, briefly compared to real-world observations, and qualitatively analyzed to find parameter-output relations.