United States Life Research Articles

Housing and Inequalities in US Life Expectancy, Child and Youth Mortality, and All-Cause and Cause-Specific Mortality, 1979-2020: Results from the National Longitudinal Mortality Study and the National Vital Statistics System.

Limited research exists on the association between housing, life expectancy, and mortality disparities in the United States (US). Using longitudinal individual-level and pooled county-level mortality data from 1979 to 2020, we examine disparities in life expectancy, child and youth mortality, and all-cause and cause-specific mortality in the US by several housing variables. Using the 1979-2011 National Longitudinal Mortality Study (N=1,313,627) and the 2011-2020 linked county-level National Mortality Database and American Community Survey, we analyzed disparities in life expectancy and all-cause and cause-specific disparities by housing tenure, household crowding, and housing stability. Multivariate Cox proportional hazards regression was used to analyze individual-level mortality differentials by housing tenure. Age-adjusted mortality rates and rate ratios were used to analyze area-level disparities in mortality by housing variables. US homeowners had, on average, a 3.5-year longer life expectancy at birth than renters (74.22 vs. 70.76 years), with advantages in longevity associated with homeownership being greater for males than for females; for American Indians/Alaska Natives, non-Hispanic Whites, and non-Hispanic Blacks than for Asian/Pacific islanders and Hispanics; and for the US-born than for immigrants. Compared with renters, homeowners had 22% lower risks of all-cause mortality, 15% lower child mortality, 17% lower youth mortality, and significantly lower mortality from cardiovascular diseases, all cancers combined, stomach, liver, esophageal and cervical cancer, diabetes, influenza and pneumonia, COPD, cirrhosis, kidney disease, HIV/AIDS, infectious diseases, unintentional injuries, suicide, and homicide. Several aspects of housing are strongly associated with life expectancy, child and youth mortality, and all-cause and cause-specific mortality in the US. Policies that aim to provide well-designed, accessible, and affordable housing to residents of both developed and developing countries are important policy options for addressing one of the most fundamental determinants of health for disadvantaged individuals and communities and for reducing health inequities globally.

The Total Lifetime Cost of Treating Patients (Pts) with CLL in the United States (US)

Background:CLL is the most common form of leukemia in pts aged ≥ 19 y and accounts for 38% of all new leukemia cases. The CLL treatment (tx) paradigm changed after the introduction of oral targeted therapies (Bruton tyrosine kinase inhibitors [BTKi] and B-cell lymphoma 2 inhibitors). However, relapses after tx are common, and these txs come with a high cost. Limited data exist evaluating the lifetime cost of treating pts with CLL with current therapies. The objective of this study was to estimate the total lifetime cost of treating pts with CLL in the US from the health system perspective. Methods: A semi-Markov model with a lifetime horizon was developed to estimate the per-pt cost of treating CLL. The model consisted of 6 distinct health states, including tx by line of therapy (LOT; first line [1L] through fifth line and later [5L+]) and death. Pts entered the model in the 1L. CLL txs selected for inclusion were those most commonly used according to market share data and recommended by National Comprehensive Cancer Network guidelines. Tx categories included ibrutinib ± anti-CD20 monoclonal antibody (mAb), acalabrutinib ± anti-CD20 mAb, venetoclax-based regimens, chemoimmunotherapy, and phosphatidylinositol 3-kinase inhibitor-based regimens. Transition probabilities and time spent on each LOT were calculated based on data abstracted from digitized time to next tx (TTNT) and OS Kaplan-Meier curves from real-world studies. Tx-specific data were applied for 1L and second-line (2L) txs, and data pooled across txs for each LOT were applied for third line (3L) through 5L+. TTNT and OS data from the literature were extracted for the duration of available follow-up. Best-fitting parametric survival models were used for reasonable extrapolation of TTNT data beyond the limited follow-up. OS beyond the available follow-up was estimated based on survival data from US life tables adjusted for each tx via a calculated tx-specific HR. Costs associated with drug acquisition and administration of CLL txs, inpatient stays, outpatient visits, emergency department (ED) visits, Richter's transformation (RT), end-of-life care, and other health care resource utilization (HCRU) were included in the model. AE management costs were assumed to be captured within inpatient costs and therefore not included separately in the model. Inputs were derived from published literature and publicly available sources. At the point of entry into the model, the study cohort was assumed to be 70 y old and included 64% males, based on median age and sex distribution reported in the literature (Mato et al. Clin Lymphoma Myeloma Leuk 2023). All costs were converted to a health system perspective, discounted 3% per year, and adjusted to 2023 US dollars (USD). Model outcomes included per-pt total expected lifetime cost and total expected lifespan. A scenario analysis was conducted to calculate per-pt-per-year (PPPY) cost of each LOT. A 1-way sensitivity analysis was conducted to identify key drivers of the total lifetime cost. Results: The total expected lifetime cost of treating a pt with CLL in the US was estimated to be $1,142,357. The estimated total time spent in the model was 8.03 y. Drug costs were the largest driver of the total lifetime cost (77%), followed by inpatient and ED costs (20%; Table). The majority of time was spent in 1L and 2L (6 and 1.68 y, respectively). The probability of receiving 2L, 3L, fourth-line (4L), and 5L+ therapy was estimated to be 44%, 16%, 6%, and 4%, respectively. In the scenario analysis, the annual cost in each LOT ranged from $140,867 to $234,807 PPPY, with costs increasing with each subsequent LOT (Figure). The 1-way sensitivity analysis showed that lifetime costs were mainly driven by drug acquisition costs, especially BTKi such as ibrutinib and acalabrutinib, as well as the cost of venetoclax. Other key drivers of the total expected lifetime cost included hospitalization costs and pt starting age. Conclusions:Study results showed that the expected lifetime cost of treating a pt with CLL in the US is high. Drugs (especially oral targeted txs) were the top drivers of lifetime total cost. As expected, scenario analysis showed that the economic burden increased with each LOT. Given the high lifetime economic burden of this disease, there is a need for potentially more effective 1-time-only tx options.

Economic evaluation of margetuximab vs. trastuzumab for pretreated ERBB2-positive advanced breast cancer in the US and China.

ObjectiveTo assess the economic evaluation of margetuximab plus chemotherapy over trastuzumab plus chemotherapy for women with pretreated ERBB2-positive advanced breast cancer in the United States (US) and China.MethodsBased on the SOPHIA trial, a three-state Markov model was developed to compare the cost and efficacy of margetuximab to trastuzumab for previously treated women with ERBB2-positive advanced breast cancer. The model inputs were derived from existing literature and the US life table. Primary outcomes included lifetime costs in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty.ResultsThe base case analyses demonstrated that margetuximab plus chemotherapy had an increasing cost of $68,132 and $20,540 over trastuzumab plus chemotherapy in the US and China, respectively, with a gain of 0.11 and 0.09 QALYs both favored margetuximab. The ICERs for two treatment strategies were $260,176 in the US and $630,777 in China, resulting in a poor cost-effectiveness at their respective threshold of willingness to play. One-way sensitivity analyses showed that the results to be most sensitive to the price of margetuximab and that of trastuzumab. And an 11 and 82% price reduction of margetuximab would make this regimen cost-effective in the US and China, respectively.ConclusionIn the US and China, margetuximab plus chemotherapy is not likely to be cost-effective for women with pretreated ERBB2-positive advanced breast cancer, whereas price reduction effectively improves insufficient cost-effectiveness.

Economic Value of Lost Productivity Attributable to Human Papillomavirus Cancer Mortality in the United States.

Objectives: To estimate years of potential life lost (YPLL) and present value of future lost productivity (PVFLP) associated with premature mortality due to HPV-attributable cancers, specifically those targeted by nonavalent HPV (9vHPV) vaccination, in the United States (US) before vaccine use.Methods: YPLL was estimated from the reported number of deaths in 2017 due to HPV-related cancers, the proportion attributable to 9vHPV-targeted types, and age- and sex-specific US life expectancy. PVFLP was estimated as the product of YPLL by age- and sex-specific probability of labor force participation, annual wage, value of non-market labor, and fringe benefits markup factor.Results: An estimated 7,085 HPV-attributable cancer deaths occurred in 2017 accounting for 154,954 YPLL, with 6,482 deaths (91%) and 141,019 YPLL (91%) attributable to 9vHPV-targeted types. The estimated PVFLP was $3.8 billion for cancer deaths attributable to 9vHPV-targeted types (84% from women). The highest productivity burden was associated with cervical cancer in women and anal and oropharyngeal cancers in men.Conclusions: HPV-attributable cancer deaths are associated with a substantial economic burden in the US, much of which could be vaccine preventable.

Abstract PS9-33: Cost-effectiveness of neratinib for the extended adjuvant treatment of adult patients with early-stage, HR+, HER2-overexpressed/amplified breast cancer who initiated neratinib within 1 year of completing trastuzumab in the US

Abstract Background: Neratinib, an oral, irreversible tyrosine kinase inhibitor of multiple human epidermal growth factor receptors (HERs), is indicated for the extended adjuvant treatment of adult patients with, HER2-positive early-stage breast cancer (eBC) to follow adjuvant trastuzumab-based therapy in the United States (US). However, greater efficacy has been seen in patients with hormone receptor-positive (HR+) breast cancer and who initiated neratinib within 1 year of completing trastuzumab. Objective: This study explores the cost-effectiveness of neratinib versus placebo from a US third-party payer perspective in adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Methods: A Markov model was constructed to model costs and health outcomes of neratinib and placebo over a lifetime horizon. The model consisted of five health states representing the primary stages of disease in eBC—disease-free, local recurrence, remission, distant recurrence, and dead—and corresponds to the primary and secondary endpoints in the neratinib ExteNET trial. Overall survival was modeled based on a combination of post-distant recurrence survival and general population mortality, assuming all cancer-related mortality would occur through the distant recurrence health state. Statistical extrapolation of invasive disease-free survival and post-distant recurrence survival were derived from the ExteNET clinical trial data as well as the proportion of local and distant recurrence and number of adverse events. Non-breast cancer-related mortality was derived from US life tables. Costs per treatment arm were calculated based on drug acquisition, administration, and monitoring costs as well as treatment costs for adverse events and health state-related medical resource use. Quality-adjusted life-years (QALYs) were estimated per health state, and disutilities were applied per adverse event independent of treatment. Utility values for the invasive disease-free survival health state and diarrhoea were estimated using the EQ-5D-3L data collected in ExteNET. Additional health state utilities and adverse events disutilities were identified from the literature. Costs were adjusted to 2020 US dollars. One-way (OWSA) and probabilistic sensitivity analyses (PSA) and scenario analyses were performed to investigate the robustness of the results. Further, analyses were performed to investigate the cost-effectiveness for the subgroup of patients who did not achieve a pathologic complete response (pCR) after neoadjuvant therapy. Results: The results of the base case analysis showed that, compared with placebo, neratinib treatment generated an additional 0.88 incremental QALYs, 0.99 incremental life-years, and a resulting cost per QALY gained of $56,367. The results were robust across multiple scenario analyses with incremental cost-effectiveness ratios (ICERs) below $70,000. OWSA showed that the parameters that most influenced the results were variations in treatment-related costs, efficacy, and health state utility values. The PSA indicated that the probability of neratinib being cost-effective at a $100,000 per QALY threshold was above 75%. The analysis for the subgroup of patients who did not achieve a pCR after neoadjuvant therapy resulted in an improved ICER. Conclusions: The current cost-effectiveness analysis shows that neratinib is a cost-effective therapy for treating adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy in the US and in patients who did not achieve a pCR after neoadjuvant treatment. Citation Format: Thor-Henrik Brodtkorb, Cheryl McDade, Deepa Lalla, Frankie Ann Holmes. Cost-effectiveness of neratinib for the extended adjuvant treatment of adult patients with early-stage, HR+, HER2-overexpressed/amplified breast cancer who initiated neratinib within 1 year of completing trastuzumab in the US [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-33.

Marked Disparities in Life Expectancy by Education, Poverty Level, Occupation, and Housing Tenure in the United States, 1997-2014.

Objectives:Socioeconomic disparities in life expectancy in the United States (US) are marked and have widened over time. However, there is limited research using individual-level socioeconomic variables as such information is generally lacking or unreliable in vital records used for life table construction. Using longitudinal cohort data, we computed life expectancy for US adults by social determinants such as education, income/poverty level, occupation, and housing tenure.Methods:We analyzed the 1997-2014 National Health Interview Survey prospectively linked to mortality records in the National Death Index (N=1,146,271). Standard life table methodologies were used to compute life expectancy and other life table functions at various ages according to socioeconomic variables stratified by sex and race/ethnicity.Results:Adults with at least a Master’s degree had 14.7 years higher life expectancy at age 18 than those with less than a high school education and 8.3 years higher life expectancy than those with a high school education. Poverty was inversely related to life expectancy. Individuals living in poverty had 10.5 years lower life expectancy at age 18 than those with incomes ≥400% of the poverty threshold. Laborers and those employed in craft and repair occupations had, respectively, 10.9 years and 8.6 years lower life expectancy at age 18 than those with professional and managerial occupations. Male and female renters had, respectively, 4.0 years and 4.6 years lower life expectancy at age 18 than homeowners. Women in the most advantaged socioeconomic group outlived men in the most disadvantaged group by 23.5 years at age 18.Conclusions and Global Health Implications:Marked socioeconomic gradients in US life expectancy were found across all sex and racial/ethnic groups. Adults with lower education, higher poverty levels, in manual occupations, and with rental housing had substantially lower life expectancy compared to their counterparts with higher socioeconomic position.

Inequalities in Life Expectancy and All-Cause Mortality in the United States by Levels of Happiness and Life Satisfaction: A Longitudinal Study.

Background:Despite having one of the highest Gross Domestic Product (GDP) per capita levels, United States (US) ranks lower in subjective well-being, including happiness and life satisfaction, compared with European countries. Studies of the impact of happiness and life satisfaction on life expectancy and mortality in the US are limited or non-existent. Using a national longitudinal dataset, we examined the association between levels of happiness/life satisfaction and US life expectancy and all-cause mortality.Methods:We analyzed the 2001 National Health Interview Survey (NHIS) prospectively linked to 2001-2014 mortality records in the National Death Index (NDI) (N=30,377). Cox proportional hazards regression was used to model survival time as a function of happiness, life satisfaction, and sociodemographic and behavioral covariates.Results:Life expectancies at age 18 among adults with high levels of happiness and life satisfaction were, respectively, 7.5 and 8.9 years higher compared to those with low levels of happiness and life satisfaction. In Cox models with 14 years of mortality follow-up, all-cause mortality risk was 82% higher (hazard ratio [HR]=1.82; 95% CI=1.59,2.08) in adults with little or no happiness, controlling for age, and 36% higher (HR=1.36; 95% CI=1.17,1.57) in adults with little/no happiness, controlling for sociodemographic, behavioral and health characteristics, when compared with adults reporting happiness all of the time. Mortality risk was 107% higher (HR=2.07; 95% CI=1.80,2.38) in adults who were very dissatisfied with their life, controlling for age, and 39% higher (HR=1.39; 95% CI=1.20,1.60) in adults who were very dissatisfied, controlling for all covariates, when compared with adults who were very satisfied.Conclusions and Global Health Implications:Adults with higher happiness and life satisfaction levels had significantly higher life expectancy and lower all-cause mortality risks than those with lower happiness and satisfaction levels. These findings underscore the significance of addressing subjective well-being in the population as a strategy for reducing all-cause mortality.

Comparing population health in the United States and Canada.

BackgroundThe objective of the paper is to compare population health in the United States (US) and Canada. Although the two countries are very similar in many ways, there are potentially important differences in the levels of social and economic inequality and the organization and financing of and access to health care in the two countries.MethodsData are from the Joint Canada/United States Survey of Health 2002/03. The Health Utilities Index Mark 3 (HUI3) was used to measure overall health-related quality of life (HRQL). Mean HUI3 scores were compared, adjusting for major determinants of health, including body mass index, smoking, education, gender, race, and income. In addition, estimates of life expectancy were compared. Finally, mean HUI3 scores by age and gender and Canadian and US life tables were used to estimate health-adjusted life expectancy (HALE).ResultsLife expectancy in Canada is higher than in the US. For those < 40 years, there were no differences in HRQL between the US and Canada. For the 40+ group, HRQL appears to be higher in Canada. The results comparing the white-only population in both countries were very similar. For a 19-year-old, HALE was 52.0 years in Canada and 49.3 in the US.ConclusionsThe population of Canada appears to be substantially healthier than the US population with respect to life expectancy, HRQL, and HALE. Factors that account for the difference may include access to health care over the full life span (universal health insurance) and lower levels of social and economic inequality, especially among the elderly.

Pediatric Research and Scholarship: Another Gordian Knot?

Peter J. Davis, MD Appearing in this issue of the journal are four clinical papers on the use of dexmedetomidine in children (1–4). Previous studies of the use of this drug in children have dealt with sedation in the intensive care unit (5), prevention of postoperative agitation associated with sevoflurane anesthesia (6,7), and sedation for noninvasive procedures (8–12). These articles also illustrate a number of subtle concerns that are relevant to drug development in children and the ethical principles that guide research in human subjects as proposed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and summarized in the Belmont Report. In a randomized study of 30 pediatric cardiac surgical patients anesthetized with isoflurane and undergoing cardiopulmonary bypass (CPB), Mukhtar et al. (1) evaluated the effects of a continuous dexmedetomidine infusion on patients’ underlying hemodynamics and neuroendocrine system compared with patients receiving a saline control infusion. The authors infused dexmedetomidine after anesthetic induction until the termination of CPB. Dexmedetomidine attenuated the increase in the neuroendocrine markers of stress caused by sternotomy and CPB. In addition, dexmedetomidine provided better intraoperative hemodynamic stability in children with congenital heart disease. The report focused on hemodynamic outcome and did not address how this drug affected tracheal extubation time, recovery, length of hospital stay, or long-term outcome. Thus, the reader is left to ponder whether the reduction in the cortisol and norepinephrine, markers of neuroendocrine response, affect outcome. Moreover, we do not know how to titrate dexmedetomidine or if the optimum dose was administered. Are there dexmedetomidine doserelated adverse effects in this population? Should the dose be altered at the start of CPB? What is the effect of the fluctuation in the patient’s temperature (37° to 25° and return) on plasma levels achieved using a standard infusion rate? Why was dexmedetomidine not continued until the end of surgery? Why did the dexmedetomidine infusion not allow for less anesthetic administration, as had been shown in an adult study (13)? Did dexmedetomidine improve hemodynamic stability after bypass? Although this study measured biochemical endpoints to assess stress response, can we infer that the effect of this drug will be as salutary as the effect of opioids in the mortality of children having surgery for congenital heart disease? These questions were not answered because the study was not funded, limiting the number of subjects and the resources available to the investigators. Had this study been funded by the pharmaceutical manufacturer, the authors could have enrolled more patients, perhaps included other study centers, assayed blood for dexmedetomidine concentrations, developed pharmacokinetic models of dexmedetomidine in this population, and performed a pharmacodynamic concentration-versus-response analysis. In a study of 60 children undergoing magnetic resonance imaging, From the Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Anesthesia, Stanford University, Stanford, California; Department of Anesthesiology, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania. Accepted for publication March 22, 2006. Address correspondence and reprint requests to Peter J. Davis, MD, Professor of Anesthesia and Pediatrics Anesthesiologistin-Chief, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA 15213. Address e-mail to davispj@anes.upmc.edu. Copyright © 2006 International Anesthesia Research Society DOI: 10.1213/01.ANE.0000220033.34889.CE