A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Adult Children's Education and Older Parents' Chronic Illnesses in Aging China.

Although intergenerational transmission from parents to children has been widely studied, less is known about human capital spillover from children to parents. Utilizing nationally representative data on both doctor diagnosis and biomarkers, as well as exploiting variations in the implementation of China's Compulsory Education Law, we examine the effects of adult children's education on the prevalence of chronic cardiovascular illnesses among older parents in China and explore potential mechanisms. Instrumental variable estimates indicate that additional years of schooling among adult children decrease the prevalence of hypertension among older parents, whereas no evidence indicates a significant impact on the prevalence of diabetes among the same group. Sons and daughters differentially impact their mothers and fathers. Compared with fathers, mothers benefit more from adult children's education. Although no significant differences are observed in the effects of sons' and daughters' education in urban China, sons' education is more beneficial for parents' health in rural China. Further analyses show that financial support and health support (e.g., diagnosis and management of chronic illnesses and maintenance of health behaviors) are critical pathways for older parents to benefit from their adult children's education.

International differences in interspousal health correlations.

Using objective measures of lung function, we document strong positive associations in health within couples in all European countries but large and significant differences in this correlation within broad European regions, with Southern Europe having by far stronger correlations than elsewhere. We analyze potential explanations for such differences, investigating the role of measures capturing current and past health behaviors, early life circumstances of each spouse, and measures capturing assortative mating in multiple dimensions. We show that marital sorting patterns by dimensions of early life health and socioeconomic position, as well as by geographical subregion within countries, are key to understanding the empirical patterns observed.

The Citizenship Advantage in Psychological Well-being: An Examination of the Hukou System in China.

Given that Chinese migrants with rural hukou status are not considered full citizens in their urban destinations, rural-urban hukou conversion signifies full citizenship attainment in urban China. We assess causal effects of three major types of urban hukou attainment-merit-, policy-, and family-based hukou conversion-on migrants' psychological well-being in middle- and later-life. We further examine how hukou matters-how periods and hukou destinations alter the values of specific urban hukou and their psychological health implications for individuals. We use the China Health and Retirement Longitudinal Study (2015 data) and life history data (for 2014) for analysis. To assess the extent to which the salmon effect contributes to estimation bias for migrants, we compare results from a sample with current migrants and one with current and returned migrants. To address for selection into hukou conversion, we adopt inverse probability-weighted regression adjustment methods. We show that the salmon bias significantly dampened causal estimates. Merit- and policy-based hukou conversion has protective effects on psychological well-being. Policy-based converters have better psychological health than other types of converters. Hukou conversion in the pre-1978 period conveys greater psychological benefits than that in the post-1998 period, when economic and social values of urban hukou have decreased. Hukou converters in the cities with the most resources enjoy better psychological well-being than their counterparts in other cities. Our study joins the emerging literature in investigating how citizenship conveys advantage in health and well-being. We discuss these results in the global context as well as the context of China's decades of evolution of hukou policy and the urbanization process.

Retirement Effect on Health Status and Health Behaviors in Urban China.

This paper analyzes the causal impact of retirement in China on Body Mass Index (BMI) and weight, which are a good gauge of the risk for some diseases. Many middle income developing countries are aging very rapidly and may have to adjust the retirement age to have financially feasible government budgets. It is important to know and understand any plausible health consequences of raising the retirement age in developing countries, and which sub-populations within these countries may be most affected. By using 2011, 2013 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS), our identification strategy uses variation in China's mandatory retirement age with a fuzzy discontinuity design to examine an exogenous shock to retirement behavior. Our study finds that retirement will increase weight and BMI among men. This effect is much larger for men with low education. The channel may be that men with low education drink more and take less vigorous exercises after they get retired. Retirement does not affect weight and BMI for women. These effects are robust with different definitions of retirement, narrow retirement bandwidth for samples as well as dropping samples with rural Hukou.

Early-life Deprivation and Health Outcomes in Adulthood: Evidence from Childhood Hunger Episodes of Middle-aged and Elderly Chinese.

This paper examines long-term health consequences of early-life food deprivation across late-life health indicators. Our analysis relies on retrospective data of hunger drawn from CHARLS - a nationally representative survey of residents ages 45 and over in Continental China. The survey accurately measured hunger episodes in childhood. Exposure to hunger early in life is found to increase the probability of being overweight, having difficulty with ADLs/IADLs and depression in old age. The adverse cognitive impacts of hunger are confined to women due to gender disparity in nutrition and educational opportunities. We find gender-specific interaction effect between hunger episodes and sibling sex composition.

Unbalanced sex ratios in Germany caused by World War II and their effect on fertility: A life cycle perspective.

This paper analyzes the effects of permanently unbalanced sex ratios in Germany caused by World War II on fertility outcomes over the life cycle. Using Census records linked with individual biography data, our analysis confirms the commonly found short-term pattern of decreased fertility rates due to a stark imbalance of the sex ratio. Yet, the long-term effects of such an imbalance crucially depend on when in the life cycle fertility is evaluated. We find that female cohorts with low sex ratios have fewer children at younger ages and a larger fraction remains childless. While childlessness remains higher throughout their life cycle, mothers from affected cohorts catch up and even overcompensate at later ages with respect to the number of children. Our preferred reading of this result is that with low sex ratios women select themselves into late motherhood according to their fertility preferences. This interpretation is consistent with the finding that women from affected cohorts expand their childbearing period and accept lower quality matches in the marriage market. Our findings have important implications for understanding the long-term consequences of large population shocks.

The Long-Term Economic Impact of Criminalization in American Childhoods.

This article documents arrest and conviction histories before age 26 years of Panel Study of Income Dynamics (PSID) respondents using a retrospective module that I designed. I find strong positive cohort effects in rising probabilities of arrest for all demographic subgroups. This increased contact with the criminal justice system across birth cohorts was at a more rapid rate over time among Whites and women. These rising rates of arrests and convictions are associated with lower probabilities of being married, lower weeks worked, lower hourly wages, and lower family incomes during the adult years. The size of the estimated associations is quite large.

Effects of income supplementation on health of the poor elderly: the case of Mexico.

We use an income supplementation experiment we designed in the state of Yucatan in Mexico for residents 70 y and older to evaluate health impacts of additional income. Two cities in the State of Yucatan, Valladolid (treatment) and Motul (control), were selected for the income supplementation experiment. Elderly residents of Valladolid were provided the equivalent of an additional $67 per month, a 44% increase in average household income. We designed a survey given to residents of both cities before and 6 mo after the income supplement about their health and other aspects of overall well-being. Both baseline and follow-up surveys collect self-reported data on health, physical functioning, and biomarkers. Anthropometric measurements for every age-eligible respondent, including height, weight, and waist circumference, were collected. We also collected lung capacity, grip strength, a series of balance tests, and a timed walk. Our results show significant health benefits associated with the additional income. Relative to the control site, there was a statistically significant improvement in lung function and an improvement in memory. These improvements are equivalent to a reduction in age of 5-10 y. Residents used their extra income to go to the doctor, buy their medications, and alleviate their hunger. The fear that this extra income could be undone by reduced transfers from other family members or unwise expenditures by the poor elderly appears to be unfounded.

Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules.

OBJECTIVE: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014. BACKGROUND: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules. METHODS: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates. RESULTS: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8), centrally located tumor (HR 2.5, 95% CI 1.2-5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2-6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4-6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24). CONCLUSIONS: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.

Macroeconomic implications of population ageing and selected policy responses.

Between now and 2030, every country will experience population ageing-a trend that is both pronounced and historically unprecedented. Over the past six decades, countries of the world had experienced only a slight increase in the share of people aged 60 years and older, from 8% to 10%. But in the next four decades, this group is expected to rise to 22% of the total population-a jump from 800 million to 2 billion people. Evidence suggests that cohorts entering older age now are healthier than previous ones. However, progress has been very uneven, as indicated by the wide gaps in population health (measured by life expectancy) between the worst (Sierra Leone) and best (Japan) performing countries, now standing at a difference of 36 years for life expectancy at birth and 15 years for life expectancy at age 60 years. Population ageing poses challenges for countries' economies, and the health of older populations is of concern. Older people have greater health and long-term care needs than younger people, leading to increased expenditure. They are also less likely to work if they are unhealthy, and could impose an economic burden on families and society. Like everyone else, older people need both physical and economic security, but the burden of providing these securities will be falling on a smaller portion of the population. Pension systems will be stressed and will need reassessment along with retirement policies. Health systems, which have not in the past been oriented toward the myriad health problems and long-term care needs of older people and have not sufficiently emphasised disease prevention, can respond in different ways to the new demographic reality and the associated changes in population health. Along with behavioural adaptations by individuals and businesses, the nature of such policy responses will establish whether population ageing will lead to major macroeconomic difficulties.

CT Screening for Lung Cancer: Part-Solid Nodules in Baseline and Annual Repeat Rounds.

OBJECTIVE: The purpose of this study was to assess the frequencies of identifying participants with part-solid nodules, of diagnostic pursuit, of diagnoses of lung cancer, and long-term lung cancer survival in baseline and annual repeat rounds of CT screening in the International Early Lung Cancer Action Project. MATERIALS AND METHODS: Screenings were performed under a common protocol. Participants with solid, nonsolid, and part-solid nodules and the diagnoses of lung cancer were documented. RESULTS: Part-solid nodules were identified in 2892 of 57,496 (5.0%) baseline screening studies; 567 (19.6%) of these nodules resolved or decreased in size. Diagnostic pursuit led to the diagnosis of adenocarcinoma in 79 cases, all clinical stage I. At resection, one nodule (12-mm solid component) had a single N2 metastasis. A new part-solid nodule was identified in 541 of 64,677 (0.8%) annual repeat screenings; 377 (69.7%) of these nodules resolved or decreased in size. In eight cases among the 541, the diagnosis of adenocarcinoma manifesting as a part solid nodule was made; on retrospective review the nodule originally had been a nonsolid nodule. In another 20 cases, the cancer originally had manifested as a nonsolid nodule but had progressed to become part-solid at annual repeat screening before any diagnosis was pursued. These 28 annual repeat cases of lung cancer were all pathologic stage IA. Of the 107 cases of lung cancer (79 baseline cases and 28 annual repeat cases), 106 were surgically resected, and one baseline case was followed up with imaging for 4 years. The lung cancer survival rate was 100% with a median follow-up period from diagnosis of 89 months (interquartile range, 52-134 months). CONCLUSION: Lung cancers manifesting as part-solid nodules at repeat screening studies all started as nonsolid nodules. Among 107 cases of adenocarcinoma manifesting as a part-solid nodule, a single lymph node metastasis was found in a single case (solid component, 12 mm).

Financial Education Interventions Targeting Immigrants and Children of Immigrants: Results from a Randomized Control Trial.

We document that immigrants in the United States differ from natives in several aspects relevant for their financial decision making. Based on these differences, we designed novel financial education materials targeted at US immigrants and their children and evaluated their effectiveness using a randomized control trial. To the best of our knowledge, this is the first rigorous evaluation of financial education programs targeted at this population. Compared to a control group, the groups that received the one-time educational intervention were more likely to correctly answer financial knowledge questions immediately after the intervention. The estimated effects of this one-time intervention on knowledge were large, but most of them faded away after six months. Moreover, we find little effect of the treatments on intended financial behavior measures, both immediately and six months later. Our results point to the efficacy of this type of educational material in informing immigrants and their children about important financial information that they are unfamiliar with, including information related to their immigrant status. However, they also suggest that a priority for future research should be to test whether repeated opportunities for learning can increase financial knowledge retention and lead to behavior change.

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds.

PURPOSE: To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. MATERIALS AND METHODS: A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. RESULTS: A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). CONCLUSION: Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.

A transfer function approach for predicting rare cell capture microdevice performance.

Rare cells have the potential to improve our understanding of biological systems and the treatment of a variety of diseases; each of those applications requires a different balance of throughput, capture efficiency, and sample purity. Those challenges, coupled with the limited availability of patient samples and the costs of repeated design iterations, motivate the need for a robust set of engineering tools to optimize application-specific geometries. Here, we present a transfer function approach for predicting rare cell capture in microfluidic obstacle arrays. Existing computational fluid dynamics (CFD) tools are limited to simulating a subset of these arrays, owing to computational costs; a transfer function leverages the deterministic nature of cell transport in these arrays, extending limited CFD simulations into larger, more complicated geometries. We show that the transfer function approximation matches a full CFD simulation within 1.34 %, at a 74-fold reduction in computational cost. Taking advantage of these computational savings, we apply the transfer function simulations to simulate reversing array geometries that generate a "notch filter" effect, reducing the collision frequency of cells outside of a specified diameter range. We adapt the transfer function to study the effect of off-design boundary conditions (such as a clogged inlet in a microdevice) on overall performance. Finally, we have validated the transfer function's predictions for lateral displacement within the array using particle tracking and polystyrene beads in a microdevice.

CT screening for lung cancer: alternative definitions of positive test result based on the national lung screening trial and international early lung cancer action program databases.

PURPOSE: To determine the usefulness of alternative nodule size thresholds in a population undergoing computed tomographic (CT) screening for lung cancer and to compare the reported International Early Lung Cancer Action Program ( I-ELCAP International Early Lung Cancer Action Program ) results with the National Lung Screening Trial ( NLST National Lung Screening Trial ) results. MATERIALS AND METHODS: The institutional review board approved this retrospective analysis. Informed consent was obtained according to HIPAA compliance. Findings in the CT cohort in the NLST National Lung Screening Trial of 25 813 participants who underwent baseline CT in 2002-2004 were reviewed. The frequency of solid and part-solid pulmonary nodules and the lung cancer diagnoses using an alternative nodule threshold of 5.0, 6.0, 7.0, 8.0, and 9.0 mm were determined. Proportional reduction in the frequency of positive results and their 95% confidence intervals using each of the alternative thresholds were calculated. RESULTS: The frequency of positive results in the baseline round in the CT arm of the NLST National Lung Screening Trial using the definition of a positive result of any parenchymal, solid or part-solid, noncalcified nodule of 5.0 mm or larger was 15.8% (4080 of 25 813). Using alternative thresholds of 6.0, 7.0, 8.0, and 9.0 mm, the frequencies of positive results were 10.5% (2700 of 25 813, 7.2% (1847 of 25 813), 5.3% (1362 of 25 813), and 4.1% (1007 of 25 813), respectively, and the corresponding proportional reduction in additional CT scans would have been 33.8% (1380 of 1480), 54.7% (2233 of 4080), 66.6% (2718 of 4080), and 73.8% (3013 of 4080), respectively. Concomitantly, the proportion of lung cancer diagnoses determined within the first 12 months would be delayed up to 9 months for 0.9% (two of 232), 2.6% (six of 232), 6.0% (14 of 232), and 9.9% (23 of 232) of the patients, respectively. CONCLUSION: The NLST National Lung Screening Trial results are similar to those previously reported for the I-ELCAP International Early Lung Cancer Action Program and suggest that, even for high-risk participants in the NLST National Lung Screening Trial , higher thresholds of nodule size should be considered and prospectively evaluated.

Parametric control of collision rates and capture rates in geometrically enhanced differential immunocapture (GEDI) microfluidic devices for rare cell capture.

The enrichment and isolation of rare cells from complex samples, such as circulating tumor cells (CTCs) from whole blood, is an important engineering problem with widespread clinical applications. One approach uses a microfluidic obstacle array with an antibody surface functionalization to both guide cells into contact with the capture surface and to facilitate adhesion; geometrically enhanced differential immunocapture is a design strategy in which the array is designed to promote target cell­obstacle contact and minimize other interactions (Gleghorn et al. 2010; Kirby et al. 2012). We present a simulation that uses capture experiments in a simple Hele-Shaw geometry (Santana et al. 2012) to inform a target-cell-specific capture model that can predict capture probability in immunocapture microdevices of any arbitrary complex geometry. We show that capture performance is strongly dependent on the array geometry, and that it is possible to select an obstacle array geometry that maximizes capture efficiency (by creating combinations of frequent target cell­obstacle collisions and shear stress low enough to support capture), while simultaneously enhancing purity by minimizing nonspecific adhesion of both smaller contaminant cells (with infrequent cell­obstacle collisions) and larger contaminant cells (by focusing those collisions into regions of high shear stress).

Retrospective review of lung cancers diagnosed in annual rounds of CT screening.

OBJECTIVE: The purpose of this study was to review the records of patients with diagnoses of lung cancer in annual repeat rounds of CT screening in the International Early Lung Cancer Action Program to determine whether the cancer could have been identified in the previous round of screening. MATERIALS AND METHODS: Three radiologists reviewed the scans of 104 lung cancer patients and assigned the findings to one of three categories: 1, cancer was not visible at previous CT screening; 2, cancer was visible at previous CT screening but not identified; 3, abnormality was identified at previous CT screening but not classified as malignant. Nodule size, nodule consistency, cell type, and stage at the previous screening and when identified for further workup for each of the three categories were tabulated. RESULTS: Twenty-four (23%) patients had category 1 findings; 56 (54%) category 2; and 24 (23%) category 3. When diagnosed, seven (29%) category 1, 10 (18%) category 2, and four (17%) category three cancers had progressed beyond stage I. All cancers seen in retrospect were in clinical stage I at the previous screening. Category 1 cancers, compared with categories 2 and 3, had faster growth rates, were less frequently adenocarcinomas (29% vs 54% and 67%, p = 0.01), and were more often small cell carcinomas (29% vs 14% and 12%, p = 0.12). CONCLUSION: Lung cancers found on annual repeat screenings were frequently identified in the previous round of screening, suggesting that review of the varied appearance and incorporation of advanced image display may be useful for earlier detection.

The long shadow cast by childhood physical and mental problems on adult life.

In this article we assess and compare long-term adult socioeconomic status impacts from having experienced psychological and physical health problems in childhood. To do so, we use unique prospective data from the British National Child Development Study, a continuing panel study of a cohort of 17,634 children born in Great Britain during a single week in March 1958. To date there have been nine waves for this birth cohort to monitor their physical, educational, and social development, during childhood (at birth and 7, 11, and 16 y) and adulthood (age 23, 33, 42, 46, and 50 y). Excellent contemporaneous information exists throughout childhood on physical and psychological health, captured by doctor and nurse-led medical examinations and detailed parental and teacher questionnaires. This information is combined with a wealth of contemporaneous information on adult health and economic experiences collected from cohort members. Information includes their economic circumstances (earnings, labor supply, and other sources of family income), physical and psychological health, and relationship status. Large effects are found due to childhood psychological problems on the ability of affected children to work and earn as adults and on intergenerational and within-generation social mobility. Adult family incomes are reduced by 28% by age 50 y, with sustained impacts on labor supply, marriage stability, and the conscientiousness and agreeableness components of the "Big Five" personality traits. Effects of psychological health disorders during childhood are far more important over a lifetime than physical health problems.