Understanding older people's voice interactions with smart voice assistants: a new modified rule-based natural language processing model with human input.

The COVID-19 pandemic has expedited the integration of Smart Voice Assistants (SVA) among older people. The qualitative data derived from user commands on SVA is pivotal for elucidating the engagement patterns of older individuals with such systems. However, the sheer volume of user-generated voice interaction data presents a formidable challenge for manual coding. Compounding this issue, age-related cognitive decline and alterations in speech patterns further complicate the interpretation of older users' SVA voice interactions. Conventional dictionary-based textual analysis tools, which count word frequencies, are inadequate in capturing the evolving and communicative essence of these interactions that unfold over a series of dialogues and modify with time. To address these challenges, our study introduces a novel, modified rule-based Natural Language Processing (MR-NLP) model augmented with human input. This reproducible approach capitalizes on human-derived insights to establish a lexicon of critical keywords and to formulate rules for the iterative refinement of the NLP model. English speakers, aged 50 or older and residing alone, were enlisted to engage with Amazon Alexa™ via predefined daily routines for a minimum of 30 min daily spanning three months (N = 35, mean age = 77). We amassed time-stamped, textual data comprising participants' user commands and responses from Alexa™. Initially, a subset constituting 20% of the data (1,020 instances) underwent manual coding by human coder, predicated on keywords and commands. Separately, a rule-based Natural Language Processing (NLP) methodology was employed to code the identical subset. Discrepancies arising between human coder and the NLP model programmer were deliberated upon and reconciled to refine the rule-based NLP coding framework for the entire dataset. The modified rule-based NLP approach demonstrated notable enhancements in efficiency and scalability and reduced susceptibility to inadvertent errors in comparison to manual coding. Furthermore, human input was instrumental in augmenting the NLP model, yielding insights germane to the aging adult demographic, such as recurring speech patterns or ambiguities. By disseminating this innovative software solution to the scientific community, we endeavor to advance research and innovation in NLP model formulation, subsequently contributing to the understanding of older people's interactions with SVA and other AI-powered systems.

Benefit-Harm Analysis of Earlier Initiation of Triple Therapy for Prevention of Acute Exacerbation in Patients with COPD.

Rationale: Reducing the risk of exacerbation is a fundamental goal in managing stable COPD. Guidelines recommend triple therapy (inhaled corticosteroids, long-acting muscarinic antagonists, and long-acting beta-agonists [ICS/LAMA/LABA]) only as a step-up from dual therapy (LAMA/LABA) for patients at continued high risk of exacerbation, due to the trade-off of an increased risk of pneumonia associated with ICS-containing therapies. However, there is little evidence on the optimum timing of initiating triple therapy. Objectives: To perform a benefit-harm analysis to evaluate the net benefit of earlier initiation of triple therapy for the prevention of acute exacerbations in patients with COPD, compared to standard timing recommended in current guidelines. Methods: We used a validated whole disease microsimulation model of COPD in the Canadian general population aged ≥40 years to determine the benefit-harm of earlier initiation of triple therapy over a 20-year time horizon, compared to standard care. We assessed net change in quality-adjusted life-years (QALYs) from the reduction in risk of acute exacerbations and the increased risk of treatment-related pneumonia in subgroups of patients with COPD defined by exacerbation history, symptoms, and disease severity. Model parameters were determined from clinical trials and other published literature. Key parameters were varied in one-way sensitivity analysis. Results: In patients at high risk of acute exacerbation (54.7% female, mean age 74.0, 68% GOLD grade I-II), earlier initiation of triple therapy was associated with a net QALY gain of 4.8 per 100 COPD patients over 20 years, compared to standard care. The net QALY gain increased to 5.9 per 100 patients in the subgroup of patients with a high symptom burden (mMRC>1). Earlier initiation remained net beneficial in all subgroup and sensitivity analysis scenarios. Conclusions: Modeling suggests that earlier initiation of triple therapy is likely to be net beneficial for patients at high risk of acute exacerbation, with an even greater benefit to patients with a high symptom burden. Further clinical research is needed to verify these findings in empirical studies.

Reducing Loneliness and Improving Social Support among Older Adults through Different Modalities of Personal Voice Assistants.

This study examines the potential of AI-powered personal voice assistants (PVAs) in reducing loneliness and increasing social support among older adults. With the aging population rapidly expanding, innovative solutions are essential. Prior research has indicated the effectiveness of various interactive communication technologies (ICTs) in mitigating loneliness, but studies focusing on PVAs, particularly considering their modality (audio vs. video), are limited. This research aims to fill this gap by evaluating how voice assistants, in both audio and video formats, influence perceived loneliness and social support. This study examined the impact of voice assistant technology (VAT) interventions, both audio-based (A-VAT) and video-based (V-VAT), on perceived loneliness and social support among 34 older adults living alone. Over three months, participants engaged with Amazon Alexa™ PVA through daily routines for at least 30 min. Using a hybrid natural language processing framework, interactions were analyzed. The results showed reductions in loneliness (Z = -2.99, p < 0.01; pre-study loneliness mean = 1.85, SD = 0.61; post-study loneliness mean = 1.65, SD = 0.57), increases in social support post intervention (Z = -2.23, p < 0.05; pre-study social support mean = 5.44, SD = 1.05; post-study loneliness mean = 5.65, SD = 1.20), and a correlation between increased social support and loneliness reduction when the two conditions are combined (ρ = -0.39, p < 0.05). In addition, V-VAT was more effective than A-VAT in reducing loneliness (U = 85.50, p < 0.05) and increasing social support (U = 95, p < 0.05). However, no significant correlation between changes in perceived social support and changes in perceived loneliness was observed in either intervention condition (V-VAT condition: ρ = -0.24, p = 0.37; A-VAT condition: ρ = -0.46, p = 0.06). This study's findings could significantly contribute to developing targeted interventions for improving the well-being of aging adults, addressing a critical global issue.

The Impact of Interaction Time and Verbal Engagement with Personal Voice Assistants on Alleviating Loneliness among Older Adults: An Exploratory Study.

BACKGROUND: Loneliness in older adults is a critical issue that negatively affects their well-being. The potential of personal voice assistant (PVA) devices like Amazon's Alexa Echo in reducing loneliness is an emerging area of interest, but it remains under-researched. OBJECTIVE: this study aims to investigate the effect of interaction time and verbal engagement with PVA devices on reducing loneliness among older adults living alone. METHOD: In this experiment, individuals aged 75 and older (n = 15), living alone, were provided with Amazon Alexa Echo devices. They were instructed to interact with the device at least five times a day for a duration of four weeks. The study measured participants' loneliness levels using the UCLA loneliness scale both before and after the study. Additionally, the interaction time and verbal engagement with the device were measured by the total time of use and the total number of intentional commands spoken to Alexa during the four-week period. RESULTS: The findings revealed that the total time spent interacting with Alexa was a significant predictor of loneliness reduction. A mediation analysis indicated an indirect effect, showing that the number of intentional commands spoken to Alexa contributed to loneliness reduction indirectly by increasing the total time spent with the device (verbal engagement → interaction time → loneliness reduction). CONCLUSIONS: This study suggests that the key to reducing loneliness among older adults through PVA devices is not just initiating verbal interaction, but the overall time devoted to these interactions. While speaking to Alexa is a starting point, it is the duration of engagement that primarily drives loneliness alleviation.

Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. OBJECTIVE: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). DESIGN: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. DATA SOURCES: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. TARGET POPULATION: Persons eligible for gene therapy. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care sector and societal. INTERVENTION: Gene therapy versus common care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. RESULTS OF BASE-CASE ANALYSIS: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. LIMITATION: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. CONCLUSION: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Cost-effectiveness of budesonide-formoterol vs inhaled epinephrine in US adults with mild asthma.

BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.

High-Efficiency Particulate Air Filters for Preventing Wildfire-related Asthma Complications: A Cost-Effectiveness Study.

Rationale: Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma. Objectives: To evaluate whether government rebates for high-efficiency particulate air (HEPA) filters, which reduce concentrations of smoke particles indoors, are cost effective in managing asthma and preventing exacerbations in British Columbia (BC), Canada. Methods: We used a Markov model to analyze health states for asthma control, exacerbation severity, and death over a retrospective time horizon of 5 years (2018-2022). Concentrations of wildfire smoke-derived particulate matter with an aerodynamic diameter ⩽2.5 µm (PM2.5) from the Canadian Optimized Statistical Smoke Exposure Model and relevant literature informed the model. The base-case analysis assumed continuous use of a HEPA filter. Costs and quality-adjusted life-years (QALYs) resulting from varying rebates were computed for each Health Service Delivery Area (HSDA). Measurements and Main Results: In the base-case analysis, HEPA filter use resulted in increased costs of $83.34 (SE, $1.03) and increased QALYs of 0.0011 (SE, 0.0001) per person. The average incremental cost-effectiveness ratio among BC HSDAs was $74,652/QALY (SE, $3,517), with incremental cost-effectiveness ratios ranging from $40,509 to $89,206 per QALY in HSDAs. Across the province, the intervention was projected to prevent 4,418 exacerbations requiring systemic corticosteroids, 643 emergency department visits, and 425 hospitalizations during the 5-year time horizon. A full rebate was cost effective in 1 of the 16 HSDAs across BC. The probability of cost-effectiveness ranged from 0.1% to 74.8% across HSDAs. A $100 rebate was cost effective in most HSDAs. Conclusions: The cost-effectiveness of HEPA filters in managing wildfire smoke-related asthma issues in BC varies by region. Government rebates up to two-thirds of the filter cost are generally cost effective, with a full rebate being cost effective only in Kootenay Boundary.

Impact of income-based public drug coverage deductibles on adherence to asthma medications.

BACKGROUND: Cost-related nonadherence to medications can be a barrier to asthma management. OBJECTIVE: To quantify the impact of public drug plan deductibles on adherence to asthma medications. METHODS: We used a quasi-experimental regression discontinuity analysis to determine whether thresholds in deductibles for public drug coverage, determined on the basis of annual household income, decreased medication use among lower-income children and adults with asthma in British Columbia from 2013 to 2018. Using dispensed medication records, we evaluated deductible thresholds at annual household incomes of $15,000 (a deductible increase from 0% to 2% of annual household income), and $30,000 (a deductible increase from 2% to 3% annual household income). We evaluated medication costs, use, the ratio of inhaled corticosteroids-containing controller medications to total medications, excessive use of short-acting ß-agonists, and the proportion of days covered by controller therapies. All costs are reported in 2020 Canadian dollars. RESULTS: Overall, 88,935 individuals contributed 443,847 person-years of follow-up (57% of female sex, mean age 31 years). Public drug subsidy decreased by -$41.74 (95% CI, -$28.34 to -$55.13) at the $15,000-deductible threshold, a 28% reduction, and patient costs increased by $48.45 (95% CI, $35.37-$61.53). The $30,000 deductible threshold did not affect public drug costs (P = .31), but patient costs increased by $27.65 (95% CI, $15.22-$40.09), which is an 11% increase. Asthma-related medication use, inhaled corticosteroids-to-total medication ratio, excessive use of short-acting ß-agonists, and proportion of days covered by controller therapies were not impacted by deductible thresholds. CONCLUSION: Income-based deductibles reduced public drug costs with no effect on asthma-related medication use, adherence to controller therapies, or excessive reliever therapy use in lower-income individuals with asthma.

Budget impact analysis of adopting primary care-based case detection of chronic obstructive pulmonary disease in the Canadian general population.

BACKGROUND: An estimated 70% of Canadians with chronic obstructive pulmonary disease (COPD) have not received a diagnosis, creating a barrier to early intervention, and there is growing interest in the value of primary care-based opportunistic case detection for COPD. We sought to build on a previous cost-effectiveness analysis by evaluating the budget impact of adopting COPD case detection in the Canadian general population. METHODS: We used a validated discrete-event microsimulation model of COPD in the Canadian general population aged 40 years and older to assess the costs of implementing 8 primary care-based case detection strategies over 5 years (2022-2026) from the health care payer perspective. Strategies varied in eligibility criteria (based on age, symptoms or smoking history) and testing technology (COPD Diagnostic Questionnaire [CDQ] or screening spirometry). Costs were determined from Canadian studies and converted to 2021 Canadian dollars. Key parameters were varied in one-way sensitivity analysis. RESULTS: All strategies resulted in higher total costs compared with routine diagnosis. The most cost-effective scenario (the CDQ for all patients) had an associated total budget expansion of $423 million, with administering case detection and subsequent diagnostic spirometry accounting for 86% of costs. This strategy increased the proportion of individuals diagnosed with COPD from 30.4% to 37.8%, and resulted in 4.6 million referrals to diagnostic spirometry. Results were most sensitive to uptake in primary care. INTERPRETATION: Adopting a national COPD case detection program would be an effective method for increasing diagnosis of COPD, dependent on successful uptake. However, it will require prioritisation by budget holders and substantial additional investment to improve access to diagnostic spirometry.

Trends in hospital admissions for chronic obstructive pulmonary disease over 16 years in Canada.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition, and the rate of hospital admissions for COPD is an indicator of the quality of outpatient care. We sought to determine long-term trends in hospital admissions for COPD in Canada. METHODS: Using a comprehensive national database of hospital admissions in Canada, we identified those with a main discharge diagnosis of COPD for patients aged 40 years and older between 2002 and 2017. We calculated sex-specific, age-standardized trends in annual rates of hospital admissions for COPD separately for younger (40-64 yr) and older adults (≥ 65 yr). We used spline regression to examine changes in the admissions trends for each sex and age group. RESULTS: Over 16 years, 1 134 359 hospital admissions were for COPD. Between 2002 and 2017, the total number of admissions increased by 68.8%, from 52 937 to 89 384. The overall crude admission rate increased by 30.0%, from 368 to 479 per 100 000 population, and the sex-and age-standardized admission rate increased by 9.6%, from 437 to 479 per 100 000 population. Age-standardized rates increased by 12.2% among younger females, by 24.4% among younger males and by 29.8% among older females, but decreased by 9.0% among older males. Over the same period, the all-cause sex-and age-standardized admission rate declined by 23.0%. INTERPRETATION: Hospital admissions for COPD have increased since 2010, even after adjusting for population growth and aging, and despite declining rates of all-cause hospital admissions. The secular increase in COPD admissions indicates that the burden of COPD on Canadian health care systems is increasing.

A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.

The root of the problem: diverse vulnerability to xylem cavitation found within the root system of wheat plants.

The propagation of xylem embolism throughout the root systems of drought-affected plants remains largely unknown, despite this process being comparatively well characterized in aboveground tissues. We used optical and X-ray imaging to capture xylem embolism propagation across the intact root systems of bread wheat (Triticum aestivum L. 'Krichauff') plants subjected to drying. Patterns in vulnerability to xylem cavitation were examined to investigate whether vulnerability may vary based on root size and placement across the entire root system. Individual plants exhibited similar mean whole root system vulnerabilities to xylem cavitation but showed enormous 6 MPa variation within their component roots (c. 50 roots per plant). Xylem cavitation typically initiated in the smallest, peripheral parts of the root system and moved inwards and upwards towards the root collar last, although this trend was highly variable. This pattern of xylem embolism spread likely results in the sacrifice of replaceable small roots while preserving function in larger, more costly central roots. A distinct pattern of embolism-spread belowground has implications for how we understand the impact of drought in the root system as a critical interface between plant and soil.

Addressing Health-Related Social Needs Via Community Resources: Lessons From Accountable Health Communities.

The Center for Medicare and Medicaid Innovation launched the Accountable Health Communities (AHC) Model in 2017 to assess whether identifying and addressing Medicare and Medicaid beneficiaries' health-related social needs reduced health care use and spending. We surveyed a subset of AHC Model beneficiaries with one or more health-related social needs and two or more emergency department visits in the prior twelve months to assess their use of community services and whether their needs were resolved. Survey findings indicated that navigation-connecting eligible patients with community services-did not significantly increase the rate of community service provider connections or the rate of needs resolution, relative to a randomized control group. Findings from interviews with AHC Model staff, community service providers, and beneficiaries identified challenges connecting beneficiaries to community services. When connections were made, resources often were insufficient to resolve beneficiaries' needs. For navigation to be successful, investments in additional resources to assist beneficiaries in their communities may be required.

Outcomes of Rural Men with Breast Cancer: A Multicenter Population Based Retrospective Cohort Study.

BACKGROUND: Breast cancer is rare in men. This population-based study aimed to determine outcomes of male breast cancer in relation to residence and other variables. METHODS: In this retrospective cohort study, men diagnosed with breast cancer in Saskatchewan during 2000-2019 were evaluated. Cox proportional multivariable regression analyses were performed to determine the correlation between survival and clinicopathological and contextual factors. RESULTS: One hundred-eight eligible patients with a median age of 69 years were identified. Of them, 16% had WHO performance status ≥ 2 and 61% were rural residents. The stage at diagnosis was as follows: stage 0, 7%; I, 31%; II, 42%; III, 11%; IV, 8%. Ninety-eight percent had hormone receptor-positive breast cancer. The median disease-free survival of urban patients was 97 (95% CI: 50-143) vs. 64 (46-82) months of rural patients (p = 0.29). The median OS of urban patients was 127 (94-159) vs. 93 (32-153) months for rural patients (p = 0.27). On multivariable analysis, performance status ≥ 2, hazard ratio (HR) 2.82 (1.14-6.94), lack of adjuvant systemic therapy, HR 2.47 (1.03-5.92), and node-positive disease, HR 2.32 (1.22-4.40) were significantly correlated with inferior disease-free survival in early-stage invasive breast cancer. Whereas stage IV disease, HR 7.8 (3.1-19.5), performance status ≥ 2, HR 3.25 (1.57-6.71), and age ≥ 65 years, HR 2.37 (1.13-5.0) were correlated with inferior overall survival in all stages. CONCLUSIONS: Although residence was not significantly correlated with outcomes, rural men had numerically inferior survival. Poor performance status, node-positive disease, and lack of adjuvant systemic therapy were correlated with inferior disease-free survival.

Long-term survival with sickle cell disease: a nationwide cohort study of Medicare and Medicaid beneficiaries.

To our knowledge, we report the first population-based period life table, the expected lifetime survival for Medicare and Medicaid beneficiaries with sickle cell disease (SCD), and the disparities in survival by insurance types in the United States. We constructed a retrospective cohort of individuals with diagnosed SCD receiving common care (any real-world patterns of care except transplant) based on nationwide Medicare and Medicaid claim data (2008-2016), covering beneficiaries in all 50 states. We analyzed lifetime survival probabilities using Kaplan-Meier curves and projected life expectancies at various ages for all, stratified by sex and insurance types. Our analysis included 94 616 individuals with SCD that have not undergone any transplant. Life expectancy at birth was 52.6 years (95% confidence interval: 51.9-53.4). Compared with the adults covered by Medicaid only, those covered by Medicare for disabilities or end-stage renal disease and those dually insured by Medicare and Medicaid had significantly worse life expectancy. Similarly, for beneficiaries aged ≥65 years, these 2 insurance types were associated with significantly shorter life expectancy than those enrolled in Medicare old age and survivor's insurance. Our study underscores the persistent life expectancy shortfall for patients with SCD, the burden of premature mortality during adulthood, and survival disparities by insurance status.

Evidence for a trade-off between growth rate and xylem cavitation resistance in Callitris rhomboidea.

The ideal plant water transport system is one that features high efficiency and resistance to drought-induced damage (xylem cavitation), however, species rarely possess both. This may be explained by trade-offs between traits, yet thus far, no proposed trade-off has offered a universal explanation for the lack of water transport systems that are both highly drought-resistant and highly efficient. Here, we find evidence for a new trade-off, between growth rate and resistance to xylem cavitation, in the canopies of a drought-resistant tree species (Callitris rhomboidea). Wide variation in cavitation resistance (P50) was found in distal branch tips (<2 mm in diameter), converging to low variation in P50 in larger diameter stems (>2 mm). We found a significant correlation between cavitation resistance and distal branchlet internode length across branch tips in C. rhomboidea canopies. Branchlets with long internodes (8 mm or longer) were significantly more vulnerable to drought-induced xylem cavitation than shorter internodes (4 mm or shorter). This suggests that varying growth rates, leading to differences in internode length, drive differences in cavitation resistance in C. rhomboidea trees. The only distinct anatomical difference found between internodes was the pith size, with the average pith to xylem area in long internodes being five times greater than in short internodes. Understanding whether this trade-off exists within and between species will help us to uncover what drives and limits drought resistance across the world's flora.

Lifetime medical costs attributable to sickle cell disease among nonelderly individuals with commercial insurance.

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity, mortality, and a disproportionate burden on Black and Hispanic communities. Our objective was to estimate the total healthcare costs and out-of-pocket (OOP) costs attributable to SCD among commercially insured individuals over their nonelderly lifetimes (0 to 64 years of age). We constructed a retrospective cohort of individuals with diagnosed SCD using Truven Health Marketscan commercial claims data from 2007 through 2018, compared with matched control subjects from the Medical Expenditure Panel Survey. We estimated Kaplan-Meier sample average costs using previously reported survival curves for SCD and control subjects. Individuals with SCD (20 891) and control subjects (33 588) were included in our analysis. The SCD sample had a mean age of 25.7 (standard deviation, 17.4) years; 58.0% were female. Survival-adjusted costs of SCD peaked at age 13 to 24 years and declined at older ages. There was no significant difference in total medical costs or OOP costs between the sexes. SCD-attributable costs over 0 to 64 years of age were estimated to be $1.6 million (95% confidence interval [CI], $1.3M-$1.9M) and $1.7 million (95% CI, $1.4M-$2.1M) for females and males with SCD, respectively. The corresponding OOP estimates were $42 395 (95% CI, $34 756-$50 033) for females and $45 091 (95% CI, $36 491-$53 691) for males. These represent a 907% and 285% increase in total medical and OOP costs over control subjects, respectively. Although limited to the commercially insured population, these results indicate that the direct economic burden of SCD is substantial and peaks at younger ages, suggesting the need for curative and new medical therapies.

Generalizability of Risk Stratification Algorithms for Exacerbations in COPD.

BACKGROUND: Contemporary management of COPD relies on exacerbation history to risk-stratify patients for future exacerbations. Multivariable prediction models can improve the performance of risk stratification. However, the clinical utility of risk stratification can vary from one population to another. RESEARCH QUESTION: How do two validated exacerbation risk prediction models (Acute COPD Exacerbation Prediction Tool [ACCEPT] and the Bertens model) compared with exacerbation history alone perform in different patient populations? STUDY DESIGN AND METHODS: We used data from three clinical studies representing populations at different levels of moderate to severe exacerbation risk: the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421; annual risk, 0.22), the Long-term Oxygen Treatment Trial (LOTT; N = 595; annual risk, 0.38), and Towards a Revolution in COPD Health (TORCH; N = 1,091; annual risk, 0.52). We compared the area under the receiver operating characteristic curve (AUC) and net benefit (measure of clinical utility) among three risk stratification algorithms for predicting exacerbations in the next 12 months. We also evaluated the effect of model recalibration on clinical utility. RESULTS: Compared with exacerbation history, ACCEPT showed better performance in all three samples (change in AUC, 0.08, 0.07, and 0.10, in SUMMIT, LOTT, and TORCH, respectively; P ≤ .001 for all). The Bertens model showed better performance compared with exacerbation history in SUMMIT and TORCH (change in AUC, 0.10 and 0.05, respectively; P < .001 for both), but not in LOTT. No algorithm was superior in clinical utility across all samples. Before recalibration, the Bertens model generally outperformed the other algorithms in low-risk settings, whereas ACCEPT outperformed others in high-risk settings. All three algorithms showed the risk of harm (providing lower net benefit than not using any risk stratification). After recalibration, risk of harm was mitigated substantially for both prediction models. INTERPRETATION: Exacerbation history alone is unlikely to provide clinical utility for predicting COPD exacerbations in all settings and could be associated with a risk of harm. Prediction models have superior predictive performance, but require setting-specific recalibration to confer higher clinical utility.