Widening Gender Gap in Life Expectancy in the US, 2010-2021

Yan, Brandon W.; Arias, Elizabeth; Geller, Alan C.; Miller, Donald R.; Kochanek, Kenneth D.; Koh, Howard K.

doi:10.1001/jamainternmed.2023.6041

Cited by 11 publications

(3 citation statements)

References 6 publications

(19 reference statements)

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“…The importance of answering these questions is underscored by declines in US life expectancy, which has fallen behind other high-income countries due in part to increases in deaths from COVID-19, heart disease, chronic liver disease, and mental health conditions including substance use disorder and suicide . These declines underscore the importance of addressing shortfalls in evidence generation on priorities affecting public health so the health care delivery system can focus on paying for the most effective interventions.…”

Section: Introductionmentioning

confidence: 99%

Why Evidence Generation Should Matter to Payers and How They Can Help

Abbasi,

Curtis,

Fleisher

et al. 2024

JAMA

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ImportanceThe US leads the world in bringing new medical products to market, but the ability to generate evidence to inform clinical practice in postmarket settings needs improvement. Although a diverse group of stakeholders is working to improve postmarket evidence generation, the role of private payers has been underappreciated.ObservationsPayers are crucial allies in improving evidence generation because better data would better inform coverage decisions, their policies and practices influence the conduct of care and research, and their claims data are a source of real-world evidence used in medical product evaluation. In addition, payers have a stake in improving evidence generation because the kinds of evidence needed to inform health care and coverage decisions are often not available when a product enters the market and may not be generated without their involvement. Here, we describe several key steps payers could take to improve evidence generation, including participating in efforts to reduce administrative and financial barriers to the conduct of clinical trials, directly incentivizing evidence generation on high-priority questions by funding potential cost-saving trials, increasing engagement with the medical products industry on evidentiary needs for coverage decisions, and improving usability of claims data by reducing data lags and routinely recording unique device identifiers. Broad payer engagement with US Food and Drug Administration recommendations regarding evidence generation will ensure that the opportunities to participate in clinical research are extended to all communities and that evidence needed to inform care is generated in trials and surveillance systems that reflect the clinical reality across the US.Conclusions and RelevanceIncreasing payer involvement in evidence generation can benefit all participants in the medical innovation ecosystem. The importance of payers in these efforts will continue to grow in response to imperatives to increase integration of care and research, engage a diverse set of communities in clinical research, and move toward alternative payment models.

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Section: Introductionmentioning

confidence: 99%

Why Evidence Generation Should Matter to Payers and How They Can Help

Abbasi,

Curtis,

Fleisher

et al. 2024

JAMA

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“…The most significant risk factor for Alzheimer's disease is age, as the likelihood of developing the disease doubles every 5 years after the age of 65 [5]. Sex differences in life expectancy contribute to a greater lifetime risk of dementia in women, as females outlive males by 4-7 years on average worldwide [6,7]. Women with Alzheimer's also have significantly longer life expectancies than men with the disease [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Age, Sex and Alzheimer’s disease: A longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients

Barber,

del Genio,

Swain

et al. 2023

Preprint

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BackgroundAging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women are not only nearly twice as likely to develop Alzheimer’s, but they also experience worse neuropathological burden and cognitive decline despite living longer with the disease. It remains unclear how and when sex differences in biological aging emerge and contribute to Alzheimer’s disease pathogenesis. We hypothesized that these differences lead to distinct pathological and molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development.MethodsWe aged male and female, 3xTg-AD and B6129 (WT) control mice across their respective lifespans while longitudinally collecting brain, liver, spleen, and plasma samples (n=3-8 mice per sex, strain, and age group). We performed histological analyses on all tissues and assessed neuropathological hallmarks of Alzheimer’s disease, markers of hepatic inflammation, as well as splenic mass and morphology. Additionally, we measured concentrations of cytokines, chemokines, and growth factors in the plasma. We conducted RNA sequencing (RNA-Seq) analysis on bulk brain tissue and examined differentially expressed genes (DEGs) between 3xTg-AD and WT samples and across ages in each sex. We also examined DEGs between clinical Alzheimer’s and control parahippocampal gyrus brain tissue samples from the Mount Sinai Brain Bank (MSBB) study in each sex.Results3xTg-AD females significantly outlived 3xTg-AD males and exhibited progressive Alzheimer’s neuropathology, while 3xTg-AD males demonstrated progressive hepatic inflammation, splenomegaly, circulating inflammatory proteins, and next to no Alzheimer’s neuropathological hallmarks. Instead, 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females, further suggesting distinct inflammatory disease trajectories between the sexes. Clinical investigations revealed that 3xTg-AD brain aging phenotypes are not an artifact of the animal model, and individuals with Alzheimer’s disease develop similar sex-specific alterations in canonical pathways related to neuronal signaling and immune function. Interestingly, we observed greater upregulation of complement-related gene expression, and lipopolysaccharide (LPS) was predicted as the top upstream regulator of DEGs in diseased males of both species.ConclusionsOur data demonstrate that chronic inflammation and complement activation are associated with increased mortality, revealing that age-related changes in immune response act as a primary driver of sex differences in Alzheimer’s disease trajectories. We propose a model of disease pathogenesis in 3xTg-AD males in which aging and transgene-driven disease progression trigger an inflammatory response, mimicking the effects of LPS stimulation despite the absence of infection.

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“…US men live shorter lives than US women as the gap in life expectancy worsens. The gender gap in 2021 was 5.8 years, the largest since 1996, according to a research letter published in JAMA Internal Medicine 1…”

mentioning

confidence: 99%