Interactions among neighborhood conditions, sleep quality, and episodic memory across the adult lifespan.

OBJECTIVES: On average, adults racialized as non-Hispanic Black and Hispanic sleep more poorly than adults racialized as non-Hispanic White (hereafter, Black, Hispanic, White), but associations between factors that may moderate sleep-memory associations in these groups, such as neighborhood conditions, are unclear. Poorer neighborhood conditions (e.g. lower neighborhood cohesion) may be negatively associated with sleep quality and multiplicatively influence sleep-memory associations. We hypothesized lower ratings of neighborhood conditions would be associated with poorer sleep quality and moderate the association between sleep quality and episodic memory, especially in Black and Hispanic adults, who are disproportionately situated in poor neighborhood conditions. DESIGN: Seven-hundred-thirty-six adults across the adult lifespan (27-89 years) were recruited from the northern Manhattan community as a part of the Offspring Study of Racial and Ethnic Disparities in Alzheimer's disease. Sleep quality was assessed using a modified version of the Pittsburgh Sleep Quality Index, and episodic memory was evaluated with the Buschke Selective Reminding Test. With multiple regression models, we measured associations between perceived neighborhood conditions and sleep quality and the interaction between sleep quality and neighborhood conditions on episodic memory stratified by racial/ethnic and gender identity groups. RESULTS: Overall, poorer neighborhood conditions were associated with poorer sleep quality. In Black and Hispanic women, the sleep-memory association was moderated by neighborhood conditions. With more favorable neighborhood conditions, Black women showed an association between higher sleep quality and higher memory performance, and Hispanic women showed a protective effect of neighborhood (higher memory even when sleep quality was poor). CONCLUSION: Poorer neighborhood experiences may contribute to poorer sleep quality across groups. In Black and Hispanic women, the association between sleep quality and episodic memory performance was dependent upon neighborhood conditions. These findings may inform tailored, structural level sleep interventions, aimed to improve neighborhood experiences and thereby sleep quality and episodic memory.

Lifetime trauma exposure and arthritis in older adults.

OBJECTIVE: Experiencing potentially traumatic events across one's lifecourse increases risk for poor physical health outcomes. Existing models emphasize the effects of any lifetime trauma exposure, risk accumulation (multiple traumas over time), and sensitive periods of exposure (specific exposure timepoints leading to lasting consequences). We examined how different indices of trauma exposure across the lifecourse were associated with later life arthritis, a common and debilitating health condition. METHODS: Data include 5,717 Health and Retirement Study participants (age mean = 65.3, SD = 12.9) who reported on lifetime adversity and trauma in 2006-2008. Lifetime trauma exposure was modeled as any trauma, accumulation of traumas, and lifecourse profiles (no exposure, childhood only, adulthood only, childhood and adulthood exposure). Outcomes included prevalent arthritis at baseline and incident arthritis across 12 years of follow-up. Covariate-adjusted generalized linear models for prevalence ratios (PR) and Cox proportional hazards models for hazard ratios (HR) were conducted. RESULTS: Any lifetime trauma was associated with both prevalent arthritis at baseline (PR = 1.13, 95%CI 1.05-1.22) and incident arthritis over 12 years (HR = 1.25, 95%CI 1.17-1.47). Greater trauma accumulation was significantly associated with both prevalent and incident arthritis. Childhood exposure was particularly strongly associated with prevalent and incident cases, with adulthood exposure being unassociated with incident arthritis. Across models, trauma exposure was associated with prevalent cases of both immune-related and osteoarthritis types. CONCLUSIONS: Higher lifetime trauma burden, especially during childhood, may predispose individuals to arthritis later in life. Early intervention or prevention efforts should identify trauma as an important risk factor for musculoskeletal health across the lifecourse.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Evaluation of racial and ethnic heterogeneity in the associations of sleep quality and sleep apnea risk with cognitive function and cognitive decline.

INTRODUCTION: The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity. METHODS: Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity. RESULTS: Higher sleep apnea risk was associated with faster declines in verbal episodic memory (ß^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (ß^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (ß^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory ß^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants. DISCUSSION: Observational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults. Highlights: Sleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

Syntheses of Cannabinoid Metabolites: Ajulemic Acid and HU-210.

Cannabinoid metabolites have been reported to be more potent than their parent compounds. Among them, ajulemic acid (AJA) is a side-chain analog of Δ9-THC-11-oic acid, which would be a good template structure for the discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield. A series of compounds was prepared with this condition applied including HU-210, 11-nor-Δ8-tetrahydrocannabinol (THC)-carboxylic acid and Δ9-THC-carboxylic acid.

Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors.

INTRODUCTION: The results of the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials have rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how rational observers would have updated their prior beliefs based on new trial results. METHODS: We used publicly available data from the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials to estimate the effect of reducing amyloid on the clinical dementia rating scale, sum of boxes (CDR-SB) score. A range of prior positions were then updated according to Bayes' theorem using these estimates. RESULTS: After updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR-SB score. DISCUSSION: For a range of starting beliefs and assuming the veracity of the underlying data, rational observers would conclude there is a small benefit of amyloid reductions on cognition. This benefit must be weighed against opportunity cost and side-effect risk. HIGHLIGHTS: The results of recent trials of amyloid-targeting drugs have rekindled discussion on the impact of amyloid reductions achieved with amyloid-targeting drugs on cognition. Prior to the announcement of trial results, beliefs about the effects of altering amyloid levels varied. For a range of starting beliefs, one would conclude there is a small benefit of amyloid reductions due to amyloid-targeting drugs on cognition. The perceived value of individual drugs must balance the magnitude of this benefit against opportunity cost and risk of side effects.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. HIGHLIGHTS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

Spouses of individuals living with mild cognitive impairment or dementia in the United States: A descriptive, population-based study.

BACKGROUND: Little is known about the population of individuals who live with a spouse with cognitive impairment (CI) or dementia. METHODS: Using the US Health and Retirement Study, 2000 to 2018, we estimated the population of adults ≥ 50 years old co-residing with a spouse with probable CI/dementia. We described their socio-demographic and health characteristics and quantified socio-demographic inequities. RESULTS: Among community-dwelling adults ≥ 50 years old, 6% of women and 4% of men co-resided with a spouse with probable CI/dementia. Among those who were married/partnered, the prevalence of spousal dementia was greater for Black and Hispanic adults compared to their White counterparts, and for those with lower versus higher educational attainment. Among spouses, activities of daily living disability, depression, and past 2-year hospitalization was common. DISCUSSION: Millions of older adults, disproportionately Black and Hispanic people and people with lower levels of educational attainment, live with a spouse with CI while also facing their own major health challenges.

State home and community-based services expenditures and unmet care needs in the United States: Has everyone benefitted equally?

OBJECTIVE: To test whether the impacts of Medicaid's Home and Community-Based Services (HCBS) expenditures have been equitable. DATA SOURCES AND STUDY SETTING: This is a secondary data analysis. We linked annual data on state-level Medicaid HCBS expenditures with individual data from U.S. Health and Retirement Study (HRS; 2006-2016). STUDY DESIGN: We evaluated the association between state-level HCBS expenditure quartiles and the risk of experiencing challenges in basic or instrumental activities of daily living (I/ADLs) without assistance (unmet needs for care). We fitted generalized estimating equations (GEE) with a Poisson distribution, log link function, and an unstructured covariance matrix. We controlled demographics, time, and place-based fixed effects and estimated models stratified by race and ethnicity, gender, and urbanicity. We tested the robustness of results with negative controls. DATA COLLECTION/EXTRACTION METHODS: Our analytic sample included HRS Medicaid beneficiaries, aged 55+, who had difficulty with ≥1 I/ADL (n = 2607 unique respondents contributing 4719 person-wave observations). PRINCIPAL FINDINGS: Among adults with IADL difficulty, higher quartiles of HCBS expenditure (vs. the lowest quartile) were associated with a lower overall prevalence of unmet needs for care (e.g., Prevalence Ratio [PR], Q4 vs. Q1: 0.91, 95% CI: 0.84-0.98). This protective association was concentrated among non-Hispanic white respondents (Q4 vs. Q1: 0.82, 95% CI: 0.73-0.93); estimates were imprecise for Hispanic individuals and largely null for non-Hispanic Black participants. We found no evidence of heterogeneity by gender or urbanicity. Negative control robustness checks indicated that higher quartiles of HCBS expenditure were not associated with (1) the risk of reporting I/ADL difficulty among 55+ Medicaid beneficiaries, and (2) the risk of unmet care needs among non-Medicaid beneficiaries. CONCLUSION: The returns to higher state-level HCBS expenditures under Medicaid for older adults with I/ADL disability do not appear to have been equitable by race and ethnicity.

A long and resilient life: the role of coping strategies and variability in their use in lifespan among women.

OBJECTIVES: Associations of stress-related coping strategies with lifespan among the general population are understudied. Coping strategies are characterized as being either adaptive or maladaptive, but it is unknown the degree to which variability in tailoring their implementation to different contexts may influence lifespan. METHOD: Women (N = 54,353; Mage = 47) completed a validated coping inventory and reported covariate information in 2001. Eight individual coping strategies (e.g., Acceptance, Denial) were considered separately. Using a standard deviation-based algorithm, participants were also classified as having lower, moderate, or greater variability in their use of these strategies. Deaths were ascertained until 2019. Accelerated failure time models estimated percent changes and 95% confidence intervals (CI) in predicted lifespan associated with coping predictors. RESULTS: In multivariable models, most adaptive and maladaptive strategies were associated with longer and shorter lifespans, respectively (e.g., per 1-SD increase: Active Coping = 4.09%, 95%CI = 1.83%, 6.41%; Behavioral Disengagement = -6.56%, 95%CI = -8.37%, -4.72%). Moderate and greater (versus lower) variability levels were similarly and significantly related to 8-10% longer lifespans. Associations were similar across age, racial/ethnic, residential income, and marital status subgroups. CONCLUSIONS: Findings confirm the adaptive and maladaptive nature of specific coping strategies, and further suggest benefits from both moderate and greater variability in their use for lifespan among women.

The Synthesis of Biphasic Metabolites of Carfentanil.

Carfentanil is an ultra-potent synthetic opioid. The Russian police force used both carfentanil and remifentanil to resolve a hostage incident in Moscow. This reported use sparked an interest in the pharmacology and toxicology of carfentanil in the human body, and data on its metabolites were later published. However, there have been few studies on the synthesis of carfentanil metabolites, and biological extraction has also put forward large uncertainty in subsequent studies. The aim of the present study is to investigate the synthesis of biphasic metabolites that are unique to carfentanil. The purpose was to produce corresponding metabolites conveniently, quickly, and at low cost that can be used for comparison with published structures and to confirm the administration of carfentanil.

Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or Gastroesophageal Adenocarcinoma.

Background: The SPOTLIGHT trial demonstrated that zolbetuximab plus mFOLFOX6 (ZOL-FO) as a first-line regimen compared with placebo plus mFOLFOX6 (PLB-FO) conferred clinical benefits to patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, due to the high cost of zolbetuximab, whether ZOL-FO is cost-effective compared with PLB-FO is unclear. This study aimed to evaluate the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma from the perspective of the Chinese healthcare system. Methods: Markov models with three different health states were developed to assess the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma. Clinical efficacy data were obtained from the SPOTLIGHT trial; the drug's cost was calculated at national bid prices, and other costs and utility values were obtained from the published literature. Outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model's robustness was verified using one-way sensitivity and probabilistic sensitivity analyses. Results: The ZOL-FO group gained 1.64 QALYs at $87,746.35, while the PLB-FO group gained 1.23 QALYs at $11,947.81. The ICER for ZOL-FO versus PLB-FO was $185,353.28 per QALY gained. The parameters exerting an important impact on the model results were the price of zolbetuximab, body surface area, and progression-free survival utility. At a willingness-to-pay threshold of $38,201/QALY, ZOL-FO had a 0% probability of cost-effectiveness compared with PLB-FO. Conclusion: From the perspective of the Chinese healthcare system, ZOL-FO is unlikely to be cost-effective as the first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma.

The Mediating Roles of Neurobiomarkers in the Relationship Between Education and Late-Life Cognition.

BACKGROUND: The mediating roles of neuropathologies and neurovascular damage in the relationship between early-life education and later-life cognitive function are unknown. OBJECTIVE: To examine whether Alzheimer's and neurovascular biomarkers mediate the relationships between education and cognitive functions. METHODS: Data were from 537 adults aged 55-94 in the Alzheimer's Disease Neuroimaging Initiative 3. We tested whether the relationships between education (continuous, years) and cognitive function (memory, executive functioning, and language composites) were mediated by neuroimaging biomarkers (hippocampal volumes, cortical gray matter volumes, meta-temporal tau PET standard uptake value ratio, and white matter hyperintensity volumes). Models were adjusted for age, race, sex/gender, cardiovascular history, body mass index, depression, and Apolipoprotein E-ɛ4 status. RESULTS: Hippocampal volumes and white matter hyperintensities partially mediated the relationships between education and cognitive function across all domains (6.43% to 15.72% mediated). The direct effects of education on each cognitive domain were strong and statistically significant. CONCLUSIONS: Commonly measured neurobiomarkers only partially mediate the relationships between education and multi-domain cognitive function.

Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.

Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system. Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted. Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of $30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below $30,300/QALY, TACE-LEN is no longer cost-effective. Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.

The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer.

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.

Excess Mortality With Alzheimer Disease and Related Dementias as an Underlying or Contributing Cause During the COVID-19 Pandemic in the US.

Importance: Adults with Alzheimer disease and related dementias (ADRD) are particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic. Deaths associated with ADRD increased substantially in pandemic year 1. It is unclear whether mortality associated with ADRD declined when better prevention strategies, testing, and vaccines became widely available in year 2. Objective: To compare pandemic-era excess deaths associated with ADRD between year 1 and year 2 overall and by age, sex, race and ethnicity, and place of death. Design, Setting, and Participants: This time series analysis used all death certificates of US decedents 65 years and older with ADRD as an underlying or contributing cause of death from January 2014 through February 2022. Exposure: COVID-19 pandemic era. Main Outcomes and Measures: Pandemic-era excess deaths associated with ADRD were defined as the difference between deaths with ADRD as an underlying or contributing cause observed from March 2020 to February 2021 (year 1) and March 2021 to February 2022 (year 2) compared with expected deaths during this period. Expected deaths were estimated using data from January 2014 to February 2020 fitted with autoregressive integrated moving average models. Results: Overall, 2 334 101 death certificates were analyzed. A total of 94 688 (95% prediction interval [PI], 84 192-104 890) pandemic-era excess deaths with ADRD were estimated in year 1 and 21 586 (95% PI, 10 631-32 450) in year 2. Declines in ADRD-related deaths in year 2 were substantial for every age, sex, and racial and ethnic group evaluated. Pandemic-era ADRD-related excess deaths declined among nursing home/long-term care residents (from 34 259 [95% PI, 25 819-42 677] in year 1 to -22 050 [95% PI, -30 765 to -13 273] in year 2), but excess deaths at home remained high (from 34 487 [95% PI, 32 815-36 142] in year 1 to 28 804 [95% PI, 27 067-30 571] in year 2). Conclusions and Relevance: This study found that large increases in mortality with ADRD as an underlying or contributing cause of death occurred in COVID-19 pandemic year 1 but were largely mitigated in pandemic year 2. The most pronounced declines were observed for deaths in nursing home/long-term care settings. Conversely, excess deaths at home and in medical facilities remained high in year 2.

Effects of Induced Optimism on Subjective States, Physical Activity, and Stress Reactivity.

This study examined effects of experimentally-induced optimism on physical activity and stress reactivity with community volunteers. Using an intervention to induce short-term optimism, we conducted two harmonized randomized experiments, performed simultaneously at separate academic institutions. All participants were randomized to either the induced optimism intervention or to a neutral control activity using essay-writing tasks. Physical activity tasks (Study 1) and stress-related physiologic responses (Study 2) were assessed during lab visits. Essays were coded for intensity of optimism. A total of 324 participants (207 women, 117 men) completed Study 1, and 118 participants (67 women, 47 men, 4 other) completed Study 2. In both studies, the optimism intervention led to greater increases in short-term optimism and positive affect relative to the control group. Although the intervention had limited effects on physical activity and stress reactivity, more optimistic language in the essays predicted increased physical activity and decreased stress reactivity.