Five-year survival prognosis of young, middle-aged, and elderly adult female invasive breast cancer patients by clinical and lifestyle characteristics.

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.

Skin cancer survivorship and sun protection behaviors in the United States.

BACKGROUND: Skin cancer survivors are more vulnerable to subsequent skin cancers and other malignancies, but previous studies have not examined in detail their sun protection behavior prevalence by sociodemographic factors. We aimed to understand the sociodemographic disparities in the prevalence of three important types of sun protection behaviors: using sunscreen, seeking shade, and wearing protective clothing, among skin cancer survivors and those without skin cancer history. METHODS: We used the 2015 U.S. National Health Interview Survey to analyze 29,523 participants, of which 772 were skin cancer survivors and 28,751 were those without skin cancer history. We assessed overall and specific sun protection behavior prevalence based on using sunscreen, seeking shade, and wearing protective clothing. Weighted Poisson regression was used to estimate prevalence ratios. RESULTS: Melanoma and nonmelanoma skin cancer survivors had similar overall sun protection behavior (p > .05). Among all skin cancer survivors, 36.0% infrequently used sunscreen, 50.2% infrequently wore protective clothing, 47.8% infrequently sought shade, and 30.0% lacked frequent overall sun protection, which significantly differed from those without skin cancer history (p < .0001). The prevalence of frequent overall sun protection behavior was lower for those who were younger at survey, males, less educated, single or never married, or lived in poverty, regardless of their skin cancer history (p < .01). CONCLUSIONS: By identifying subpopulations with higher prevalence of infrequent sun protection among those with or without skin cancer history, our findings may encourage efforts to reduce sociodemographic disparities in sun protection behaviors and promote primary and tertiary skin cancer prevention.

Prevalence of Current Cigarette Smoking by Sociodemographic Characteristics in U.S. Cancer Survivors.

BACKGROUND: Cancer survivors are especially vulnerable to the carcinogenic effects of tobacco smoking, but there lacks a study comprehensively examining the sociodemographic disparities in current smoking prevalence in this population. In this study, we quantified the current cigarette smoking prevalence in cancer survivors and those without cancer history by sociodemographic factors, to identify subpopulations with high current smoking burden. METHODS: We conducted a cross-sectional study of 3,679 cancer survivors and 27,350 participants without cancer history who were 18 years of age or above in the 2019 National Health Interview Survey. Data for the study variables were obtained from computer-assisted personal or telephone interviews. Weighted Poisson regression was used to estimate prevalence ratios and 95% confidence intervals. RESULTS: Although the current smoking prevalence for cancer survivors was slightly lower than for those without cancer history, the prevalence exceeded 30% in cancer survivors in poverty or without health insurance. Individuals with significantly higher current smoking prevalence had lower education levels, were unmarried, did not have health insurance, or lived in poverty. The associations of age, sex, race, health insurance status, and poverty status with current smoking significantly differed between cancer survivors and those without cancer history. Sociodemographic disparities in current smoking prevalence were found in survivors of either smoking-related or nonsmoking-related cancers. CONCLUSION: High current smoking prevalence still exists in subpopulations of cancer survivors and those without cancer history. Our findings may strengthen efforts to reduce sociodemographic disparities in current smoking prevalence and to lower the overall smoking prevalence.

Associations between sociodemographic factors and breast, cervical, and colorectal cancer screening in the United States.

PURPOSE: Cancer is the second leading cause of death globally and in the U.S., but screening can reduce cancer-related deaths. We analyzed data from a nationwide survey to compare how sociodemographic factors were associated with never or not timely screening for multiple types of cancer, and the use of different colorectal cancer screening procedures. METHODS: We analyzed data from the 2019 U.S. National Health Interview Survey. To understand breast, cervical, and colorectal cancer screening participation among those recommended to screen, we respectively analyzed 8,110 women 45 to 74 years of age, 9,583 women 21 to 65 years of age, and 13,497 individuals 50 to 75 years of age at survey. Weighted Poisson regression was used to estimate the unadjusted and confounding-adjusted prevalence ratio and 95% confidence intervals. RESULTS: In our analysis populations, 6.9% never had a mammogram, 14.6% never screened for cervical cancer, and 26.8% never screened for colorectal cancer; the prevalence respectively increased to 24.7%, 23.8%, and 32.3% for not timely screening according to national guidelines. The prevalence of never screening was 81.9% for non-invasive colorectal cancer tests, compared with 32.5% for colonoscopy or sigmoidoscopy. Individuals with lower education level, with no health insurance, or in poverty had higher prevalence of never screening for all three cancers. There was low sociodemographic disparity for the use of non-invasive colorectal cancer screening tests. CONCLUSION: Socioeconomically disadvantaged individuals have higher prevalence of never or not timely screening. The utilization of non-invasive colorectal cancer screening procedures remains low across sociodemographic groups.

Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework.

BACKGROUND: Use of combinations of long-acting ß2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. AIM: The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. METHODS: We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017-2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). RESULTS: Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78-1.01) for the composite events, 0.80 (95% CI, 0.61-1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68-3.25) for unstable angina, 1.00 (95% CI, 0.80-1.24) for congestive heart failure, 0.62 (95% CI, 0.37-1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66-1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. CONCLUSION: Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Interrelationships Between Pregnancy Intention, Antenatal Care, and Sociodemographic Factors: Analysis of a Nationwide Population-Based Cross-Sectional Study in Vietnam.

OBJECTIVES: This study aimed to improve the understanding of the interrelationships between sociodemographic factors, pregnancy intention, and antenatal care by: (1) identifying sociodemographic predictors of unintended pregnancy; (2) examining associations between unintended pregnancy types and antenatal care (ANC) inadequacy; (3) examining how the association between unintended pregnancy and ANC inadequacy is modified by maternal characteristics; and (4) identifying sociodemographic predictors of ANC inadequacy by pregnancy intention status. METHODS: We analyzed women 15-49 years of age who participated in the nationwide cross-sectional Vietnam Multiple Indicator Cluster Survey. Pregnancy intention and ANC adequacy were assessed for the most recent live birth within two years preceding survey completion. Weighted Poisson regression was used to estimate risk ratios. RESULTS: Of the 1,474 study participants, 17.8% had unintended pregnancy and 29.0% had inadequate ANC. There was no significant confounding-adjusted association between unintended pregnancy and ANC inadequacy, except in those currently not working. Women with intended pregnancy or unintended pregnancy had significantly higher ANC inadequacy risk if they lived in rural areas, were less educated, and had no media exposure, lower wealth status, or more than two children. Younger age, ever given birth, having child loss, and positive attitude towards partner violence were significant predictors of ANC inadequacy only in women with intended pregnancy. CONCLUSIONS FOR PRACTICE: ANC inadequacy was more strongly predicted by sociodemographic characteristics rather than pregnancy intention, and the sociodemographic variables' prediction of ANC inadequacy was stronger in women with intended pregnancy than unintended pregnancy.

Subsequent Primary Cancers of the Digestive System Among Childhood and Adolescent Cancer Survivors From 1975 to 2015 in the United States.

INTRODUCTION: Among survivors from first primary cancers that occurred during childhood and adolescence, their risks of developing subsequent primary digestive system cancers are not well understood. Therefore, we conducted the largest and most comprehensive analysis examining risks for diverse types of digestive system cancers after survival from a wide variety of first primary childhood and adolescent cancers. METHODS: We identified 41,249 patients diagnosed with first primary cancer from 1975 to 2015 before 20 years of age from 9 Surveillance, Epidemiology and End Results Program registries. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for digestive system cancers were calculated controlling for age, sex, race, and calendar year. RESULTS: Among 41,249 cancer survivors, 133 developed subsequent primary digestive system cancer, with a median digestive system cancer diagnosis age of 37 years. The SIR and AER for any digestive system cancer were highest among survivors of bone cancer, lymphoma, and neuroblastoma. Among survivors from any first primary cancer, the SIR was significantly elevated for cancer of the esophagus, stomach, small intestine, large intestine, liver, and pancreas, whereas the AER was highest for large intestine cancer. DISCUSSION: Childhood and adolescent cancer survivors diagnosed from 1975 to 2015 have significantly elevated risks of digestive system cancers compared with the US general population. Our detailed findings may contribute to surveillance recommendations of childhood and adolescent cancer survivors and promote future studies to further understand mechanisms by which having various first primary cancers lead to subsequent primary digestive system cancers.

Associations between pediatric asthma and adult non-communicable diseases.

BACKGROUND: To date, there is no comprehensive study examining how asthma diagnosed in childhood or adolescence is associated with diagnoses of subsequent non-communicable diseases (NCDs) during adulthood. Our study aimed to examine the associations between pediatric asthma and several adult NCDs, with temporality and long interval times between asthma and NCD diagnoses. METHODS: We used RAND Indonesian Family Life Survey Fifth Wave (IFLS5) fielded in 2014-2015, to study whether being diagnosed with pediatric asthma at 0-19 years of age was associated with increased risks of hypertension, diabetes, rheumatoid arthritis, stomach diseases, kidney diseases, and heart diseases or stroke diagnosed in adulthood. We used the weighted Poisson regression adjusting for age, sex, urbanicity, and insurance status to estimate risk ratios. Subgroup analyses were performed by sex and age of asthma and other NCD diagnoses. RESULTS: Pediatric asthma significantly increased risks of hypertension, diabetes, and stomach diseases diagnosed at 20 years of age or above. Males with pediatric asthma diagnosed at 0-10 years of age had significantly higher risk of hypertension, while females with pediatric asthma diagnosed at 0-10 years of age had significantly higher risks of diabetes and stomach diseases. Females with pediatric asthma diagnosed at 11-19 years of age had significantly higher risks of diabetes, arthritis, stomach diseases, and kidney diseases. We also found varying associations by age of NCD diagnosis. CONCLUSION: Our results suggest pediatric asthma is associated with increased risks of several adult NCDs, and these associations may vary by sex and age of asthma and other NCD diagnoses.

Associations between high-sensitivity C-reactive protein and non-communicable diseases in an Asian population: findings from the IFLS study.

Background: There has been no comprehensive study on how high-sensitivity C-reactive protein (hs-CRP) levels, a biomarker of inflammation, are associated with subsequent diagnoses of various non-communicable diseases (NCDs) in Asians. Our study is the first to do so to better compare these associations in an Asian population.Methods: This is a nationwide longitudinal study of 3,410 male and 4,004 female participants of the RAND Indonesian Family Life Survey with a mean age of 42.4 years, to examine associations between increasing hs-CRP levels and risks of heart diseases, stroke, hypertension, diabetes, arthritis, non-cancerous stomach or other digestive diseases, and non-cancerous kidney diseases. We used unadjusted and confounding-adjusted weighted Poisson regression models to respectively examine associations involving hs-CRP as a risk predictor or indicator of chronic inflammation. Several stratified subpopulation analyses were also performed.Results: Increasing hs-CRP levels predicted significantly higher risks of being diagnosed with all of the studied NCDs except stomach or other digestive diseases. After adjusting for confounding, increasing hs-CRP levels were significantly associated with higher risks of diabetes, heart diseases, hypertension, and kidney diseases.Conclusions: Our comprehensive findings on the associations between hs-CRP levels and risks of several NCDs in Asians may have clinical implications and promote additional studies on this topic.

Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.

BACKGROUND: Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress. OBJECTIVE: We performed a large comprehensive study on how coffee consumption is associated with telomere length. METHODS: We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables. RESULTS: Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non-coffee drinkers, multivariable ORs for those drinking 2 to <3 and ≥3 cups of coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37). CONCLUSIONS: We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and longevity.

Relationship between plasma 25-hydroxyvitamin D and leucocyte telomere length by sex and race in a US study.

A few studies have examined the association between vitamin D and telomere length, and fewer still have examined the relationship in black or male populations. We investigated the cross-sectional association between the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) concentration in plasma and relative leucocyte telomere length (LTL) in 1154 US radiologic technologists who were 48-93 years old (373 white females, 278 white males, 338 black females, 165 black males). Plasma 25(OH)D concentration was measured by the chemiluminescence immunoassay, and relative LTL was measured by quantitative PCR. Logistic regression was used to obtain OR and 95 % CI for long v. short (based on median) LTL in relation to continuous 25(OH)D, quartiles of 25(OH)D and 25(OH)D deficiency. We found no significant association between continuous 25(OH)D and long LTL in all participants (P trend=0·440), nor in white females (P trend=0·845), white males (P trend=0·636), black females (P trend=0·967) or black males (P trend=0·484). Vitamin D deficiency (defined as 25(OH)D<30 nmol/l), however, was significantly associated with short LTL in whites (P=0·024), but not in other groups. In this population, we found little evidence to support associations between 25(OH)D and long LTL over the entire range of 25(OH)D in the overall study population or by sex and race.

Occupational ionising radiation and risk of basal cell carcinoma in US radiologic technologists (1983-2005).

OBJECTIVE: To determine risk for incident basal cell carcinoma from cumulative low-dose ionising radiation in the US radiologic technologist cohort. METHODS: We analysed 65,719 Caucasian technologists who were cancer-free at baseline (1983-1989 or 1994-1998) and answered a follow-up questionnaire (2003-2005). Absorbed radiation dose to the skin in mGy for estimated cumulative occupational radiation exposure was reconstructed for each technologist based on badge dose measurements, questionnaire-derived work history and protection practices, and literature information. Radiation-associated risk was assessed using Poisson regression and included adjustment for several demographic, lifestyle, host and sun exposure factors. RESULTS: Cumulative mean absorbed skin dose (to head/neck/arms) was 55.8 mGy (range 0-1735 mGy). For lifetime cumulative dose, we did not observe an excess radiation-related risk (excess relative risk/Gy=-0.01 (95% CI -0.43 to 0.52). However, we observed that basal cell carcinoma risk was increased for radiation dose received before age 30 (excess relative risk/Gy=0.59, 95% CI -0.11 to 1.42) and before 1960 (excess relative risk/Gy=2.92, 95% CI 1.39 to 4.45). CONCLUSIONS: Basal cell carcinoma risk was unrelated to low-dose radiation exposure among radiologic technologists. Because of uncertainties in dosimetry and sensitivity to model specifications, both our null results and our findings of excess risk for dose received before age 30 and exposure before 1960 should be interpreted with caution.

Work history and mortality risks in 90,268 US radiological technologists.

OBJECTIVES: There have been few studies of work history and mortality risks in medical radiation workers. We expanded by 11 years and more outcomes our previous study of mortality risks and work history, a proxy for radiation exposure. METHODS: Using Cox proportional hazards models, we estimated mortality risks according to questionnaire work history responses from 1983 to 1989 through 2008 by 90,268 US radiological technologists. We controlled for potential confounding by age, birth year, smoking history, body mass index, race and gender. RESULTS: There were 9566 deaths (3329 cancer and 3020 circulatory system diseases). Mortality risks increased significantly with earlier year began working for female breast (p trend=0.01) and stomach cancers (p trend=0.01), ischaemic heart (p trend=0.03) and cerebrovascular diseases (p trend=0.02). The significant trend with earlier year first worked was strongly apparent for breast cancer during baseline through 1997, but not 1998-2008. Risks were similar in the two periods for circulatory diseases. Radiological technologists working ≥5 years before 1950 had elevated mortality from breast cancer (HR=2.05, 95% CI 1.27 to 3.32), leukaemia (HR=2.57, 95% CI 0.96 to 6.68), ischaemic heart disease (HR=1.13, 95% CI 0.96 to 1.33) and cerebrovascular disease (HR=1.28, 95% CI 0.97 to 1.69). No other work history factors were consistently associated with mortality risks from specific cancers or circulatory diseases, or other conditions. CONCLUSIONS: Radiological technologists who began working in early periods and for more years before 1950 had increased mortality from a few cancers and some circulatory system diseases, likely reflecting higher occupational radiation exposures in the earlier years.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Plasma vitamin D biomarkers and leukocyte telomere length.

Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In the present study, we examined the association between vitamin D and relative leukocyte telomere length by using both plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) biomarkers. Vitamin D biomarker levels and leukocyte telomere length were measured using plasma samples collected in 1989-1990 from participants of the Nurses' Health Study, a study of nurses from 11 US states. In total, 1,424 participants had their 25(OH)D levels assessed and 837 had their 1,25(OH)2D levels assessed. Genotyping was performed on 480 participants on 12 single nucleotide polymorphisms in vitamin D-related genes. Linear and logistic regression models were used. Higher 25(OH)D levels were significantly associated with longer telomere length (P for trend = 0.05), and the odds ratio increased from 1.07 (P = 0.65) when comparing the second lowest quartile of 25(OH)D with the lowest to 1.59 (P = 0.01) when comparing the highest quartile with the lowest. Vitamin D-related single nucleotide polymorphisms and 1,25(OH)2D levels were not significantly associated with telomere length. Total calcium intake significantly modified the association between 25(OH)D and telomere length (P for interaction = 0.05). Higher plasma 25(OH)D levels may be associated with longer telomeres, and this association may be modified by calcium intake.

Positive Consensus of Fractional-Order Multiagent Systems Over Directed Graphs.

This article investigates the positive consensus problem of a special kind of interconnected positive systems over directed graphs. They are composed of multiple fractional-order continuous-time positive linear systems. Unlike most existing works in the literature, we study this problem for the first time, in which the communication topology of agents is described by a directed graph containing a spanning tree. This is a more general and new scenario due to the interplay between the eigenvalues of the Laplacian matrix and the controller gains, which renders the positivity analysis fairly challenging. Based on the existing results in spectral graph theory, fractional-order systems (FOSs) theory, and positive systems theory, we derive several necessary and/or sufficient conditions on the positive consensus of fractional-order multiagent systems (PCFMAS). It is shown that the protocol, which is designed for a specific graph, can solve the positive consensus problem of agents over an additional set of directed graphs. Finally, a comprehensive comparison study of different approaches is carried out, which shows that the proposed approaches have advantages over the existing ones.