Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

[Epidemiological consideration for death causes among Japanese: focused on age, time, and birth cohort effects].

This study aimed to clarify the death causes among Japanese. National vital statistics data from 1995 to 2020 were analyzed using the mean polish process. The results showed that deaths from cancer increased after middle age, and deaths from heart disease, pneumonia, and cerebrovascular disease increased after later life (age effect). Recently, mortality from cerebrovascular disease, heart disease, and pneumonia is decreasing (time effect). More individuals in the birth cohort born after 1906 died from cancer compared to that of earlier generations who mainly died from heart disease, pneumonia, and cerebrovascular disease (birth cohort effect). The time effect is more modifiable and/or depending on social conditions and interventions compared to that of the age effect. In Japan, if lifestyle-related diseases that are risk factors for cerebrovascular and heart diseases, such as hypertension, are further prevented or treated, mortality from such diseases will decrease consequently.

Birth Cohort Effects in Breast Cancer Incidence: Global Patterns and Trends.

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect.

Age of eradication and failure rates of clarithromycin-containing triple therapy for Helicobacter pylori: A 15-year population-based study.

BACKGROUND: Failure rates of clarithromycin-containing triple therapy for H. pylori are rising. To determine the trend of failure rates of clarithromycin-containing triple therapy in different age groups in Hong Kong over the past 15 years. MATERIALS AND METHODS: This is a population-based retrospective age-period-cohort study involving all adult H. pylori-infected patients who had received the first course of clarithromycin-containing triple therapy in 2003-2017. Failed eradication was identified by the need of retreatment within 2 years of eradication. Logistic regression model was used to characterize the risk of retreatment. RESULTS: 113,526 H. pylori-infected patients were included. The overall failure rate increased from 4.83% in 2003 to 10.2% in 2016 (p for linear trend <0.001). When stratified by age of eradication, patients 75 years or above had the lowest retreatment rate of 5.11%, which progressively increased in younger patients (60-74 years: OR 1.26, 95% CI 1.15-1.38; 45-59 years: OR 1.36, 95% CI 1.24-1.48; 18-44 years: OR 1.55, 95% CI 1.41-1.69). The results remained consistent when stratified by year of birth, and period of eradication. Other risk factors for retreatment included female (OR 1.24, 95% CI 1.18-1.30), triple therapy containing metronidazole (OR 2.30, 95% CI 2.12-2.50), and shorter duration of therapy (10 days: OR 0.88, 95% CI 0.79-0.97; 14 days: OR 0.67, 95% CI 0.58-0.77 vs 7 days). CONCLUSIONS: While failure rates of clarithromycin-containing triple therapy progressively increased over the past 15 years, the failure rate was particularly high among younger patients, which could undermine the potential benefits of early H. pylori eradication.

Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study.

BACKGROUND: Helicobacter pylori is an important etiologic factor for peptic ulcers and gastric cancer, one of the top ten leading causes of cancer death in Puerto Rico. However, the prevalence of H. pylori infections in this population was previously unknown. The aim of this study was to examine the seroprevalence of H. pylori and its associated risk factors in Puerto Rico. MATERIALS AND METHODS: A cross-sectional study was designed using an existing population-based biorepository. Seropositivity was determined using the Premier™ H. pylori immunoassay. Helicobacter pylori seroprevalence was estimated with 95% confidence using marginal standardization following logistic regression. To assess the risk factors associated with H. pylori seropositivity, a multivariable log-binomial model was fitted to estimate the prevalence ratio (PR) and its 95% confidence interval (95% CI). RESULTS: A total of 528 population-based serum samples were analyzed. The mean age of the study population was 41 ± 12 years, of whom 55.3% were females. The overall seroprevalence of H. pylori was 33.0% (95% CI = 28.3%-38.1%). Increasing age and having <12 years of education were significantly (P < .05) associated with H. pylori seropositivity in the multivariable model; however, residing in counties with low population density reached marginal significance (P = .085). CONCLUSIONS: We report that H. pylori infection is common among Hispanics living in Puerto Rico. The H. pylori seroprevalence observed in Puerto Rico is similar to the seroprevalence reported in the overall population of the United States. The association between H. pylori seroprevalence and the risk factors analyzed offers insight into the epidemiology of gastric cancer in Puerto Rico and warrants further investigation.

Epidemiology and Relative Severity of Influenza Subtypes in Singapore in the Post-Pandemic Period from 2009 to 2010.

BACKGROUND: After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated with A(H3N2) and B in Singapore. METHODS: A cohort of 760 participants contributed demographic data and up to 4 blood samples each from October 2009 to September 2010. We compared epidemiology of the 3 subtypes and investigated evidence for heterotypic immunity through multivariable logistic regression using a generalized estimating equation. To examine age-related differences in severity between subtypes, we used LOESS (locally weighted smoothing) plots of hospitalization to infection ratios and explored birth cohort effects referencing the pandemic years (1957; 1968). RESULTS: Having more household members aged 5-19 years and frequent public transport use increased risk of infection, while preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002) and previous influenza infection against heterotypic infections (OR, 0.32; P = .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957, while A(H3N2) severity was least in the youngest individuals and increased until it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P < .001), with no difference in those born between 1957 and 1967 (P = .632). CONCLUSIONS: Our findings suggest that childhood exposures had long-term impact on immune responses consistent with the theory of antigenic sin. This, plus observations on short-term cross-protection, have implications for vaccination and influenza epidemic and pandemic mitigation strategies.

The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations.

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913-1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations.

Using admixture analysis to examine birth-cohort effects on age at onset of bipolar disorder.

OBJECTIVE: It is suggested that age at onset (AAO) of bipolar I disorder (BP-I) is decreasing. We tested for a birth-cohort effect on AAO using admixture analysis. METHOD: A clinical sample of 3896 BP-I cases was analysed using two approaches: (i) in a subsample with untruncated AAO × birth year distribution (n = 1865), we compared the best-fitting model for the observed AAO in patients born ≤1960 and >1960, (ii) to control for potential confounders, two separate subsamples born ≤1960 and >1960 were matched for age at interview (n = 250), and a further admixture analysis was undertaken. RESULTS: The two approaches indicated that the proportion of cases in the early AAO category was significantly greater in cases born >1960; manic onsets were also more frequent in the early onset BP-I cases born >1960. CONCLUSION: The decrease in AAO of BP-I in recent birth-cohorts appears to be associated with an increase in the proportion of cases in the early onset subgroup; not with a decrease in the mean AAO in each putative subgroup. This could indicate temporal changes in exposure to risk factors for mania.

Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer?

The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.

The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development.

Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.

Early-onset colorectal cancer: A review of current knowledge.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC's increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

Generational Differences in the 10-year Incidence of Impaired Contrast Sensitivity.

PURPOSE: To determine if incidence of contrast sensitivity (CS) impairment differs by generation and identify factors to explain these differences. METHODS: The Beaver Dam Eye Study (BDES) and Beaver Dam Offspring Study (BOSS) are cohort studies of aging adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 (BDES) and 2005-2008 (BOSS). Follow-up examinations occurred in five-year intervals. CS testing was conducted with Pelli-Robson letter sensitivity charts; Incident impairment was a log CS score <1.55 in either eye at follow-up. Associations of incidence with generation were investigated using estimated hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Participants (N = 3185) had a mean age of 51.9 years at baseline (standard deviation = 9.9) and 51.9% were female. Ten-year cumulative incidence of CS impairment was 40.1%, was higher among women (41.7%) than men (38.8%), and increased by age group. The risk of incident CS impairment decreased by 39% per generation. In multivariable models, the Baby Boom Generation (HR = 0.42, 95%CI = 0.31, 0.58) and Generation X (HR = 0.56, 95%CI = 0.34, 0.91) had a significantly decreased risk of CS impairment compared to the Greatest Generation. Results were similar in sensitivity analyses excluding those with cataract, age-related macular degeneration, or visual acuity impairment. CONCLUSION: The risk of incident CS impairment decreased by birth cohort, with the greatest reduction in the Baby Boom Generation. The difference in risk suggests that there are unknown modifiable risk factors that may help to further explain the etiology of CS impairment and provide potential pathways for prevention in the future.

MRSA strains with distinct accessory genes predominate at different ages in cystic fibrosis.

RATIONALE: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. OBJECTIVES: To identify MRSA genes associated with low lung function and potential MRSA transmission in CF. METHODS: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies, classified isolates by accessory gene content, and correlated the accessory genome to clinical outcomes. RESULTS: The most prevalent ST were ST5 (N = 55), ST8 (N = 15), and ST105 (N = 14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three clusters of MRSA were identified by accessory genome content. Cluster A, including ST5 and ST105, was highly prevalent at all ages. Cluster B, including ST8, was more limited to younger patients. Cluster C included 6 distantly related strains. Patients 20 years old and younger infected with Cluster A had lower forced expiratory volume in the first second (FEV1 ) and higher sputum biomass compared to similar-aged patients with Cluster B. CONCLUSIONS: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. The most prevalent cluster of MRSA, including ST5 and ST105, was associated with lower FEV1 . ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.

Global Patterns and Trends in Lung Cancer Incidence: A Population-Based Study.

INTRODUCTION: Lung cancer (LC) has been the most common cancer worldwide for several decades. This study comprehensively examines recent geographic patterns and temporal trends in LC incidence from 1978 to 2012 in 43 countries and evaluates the effects of birth cohort and period on temporal trends. METHODS: Data were retrieved from the Cancer Incidence in Five Continents database. Joinpoint regression and age-period-cohort models were applied. RESULTS: The age-standardized rate was highest in Turkey (69.3 per 100,000 person-years) for men and in Denmark (36.7) for women in the period 2008 to 2012. Sex disparities were noted in most countries. From 1978 to 2012, a total of 19 countries had significantly declining trends among men, whereas 26 countries had significantly increasing trends among women (all p < 0.05). Quasi-reversed V-shaped and U-shaped incidence rate ratio trends indicating birth cohort effects were detected in 26 countries for men, with the highest risks mainly occurring in the 1930 to 1950 birth cohorts. However, the risks among recent generations have moderately increased in the People's Republic of China and Japan for men and sharply increased in Lithuania, Belarus, and Republic of Korea for women. Incidence rate ratio increases were steep among earlier birth cohorts and gradual among the post-1930s cohorts in 15 countries for women. Period effects were more evident than birth cohort effects in five countries for both sexes. CONCLUSIONS: Disparities in LC incidence and carcinogenic risk persist worldwide. Our findings identified high-risk target populations for primary prevention to reduce the LC incidence and highlighted the urgent need for etiologic studies to identify the reasons for pronounced cohort-specific risk increases in certain countries.

Trends in aeroallergen sensitization in Germany - An analysis of 2919 serological data sets of a university ENT department.

Background: Recently, population-based birth-cohort studies provided an insight into the allergic march during childhood.Aims: Our study aimed to investigate sensitization pattern until advanced age.Patients and methods: Demographic, clinical and serological characteristics of 2919 patients with positive allergen-specific IgE between 1999 and 2019 were analyzed. We performed subgroup analysis of various age-groups and different years of birth to distinguish between age-dependent changes and birth-cohort-effects.Results: Since 1999, the proportion of sensitized children has significantly increased. The prevalence of sIgE towards most allergens reached its peak in adolescence or young adulthood. Only to mites, the highest rate of sensitization was found in childhood. With further aging, the prevalence of sIgE significantly decreased in most sensitizations. Only to Fagales, the highest rate of sensitization was observed among patients >65 years. The year-of-birth analysis proved the above-mentioned changes to be age-dependent. Further, it revealed various sensitization trends from older to younger generations.Conclusions and significance: The increased proportion of children with sensitization during the last 20 years outlines the allergy epidemic. Probably due to immunosenescence, the aeroallergen sensitization rates decreased with aging, except for Fagales. Over time, different aeroallergens gained or lost relevance, potentially due to environmental and life-style changes.

Sex-specific intergenerational trends in morbidity burden and multimorbidity status in Hong Kong community: an age-period-cohort analysis of repeated population surveys.

OBJECTIVES: Prevalence of multimorbidity has been increasing worldwide. While population ageing undoubtedly contributes, secular trends have seldom been decomposed into age, period and cohort effects to investigate intergenerational differences. This study examines the birth cohort effect on morbidity burden and multimorbidity in Hong Kong community. DESIGN: Sex-specific age-period-cohort analysis with repeated cross-sectional surveys. SETTING: A territory-wide population survey database. PARTICIPANTS: 69 636 adults aged 35 or above who participated in the surveys in 1999, 2001, 2005 or 2008. MAIN OUTCOME MEASURES: Morbidity burden was operationalised as number of chronic conditions from a list of 14, while multimorbidity was defined as a dichotomous status of whether participants had two or more conditions. RESULTS: For both sexes, there was an upward inflection (positive change) of risk of increased morbidity burden starting from cohort 1955-1959. For men born after 1945-1954, there was a trend of lower risk (relative risk=0.63, 95% CI 0.50 to 0.80 for 1950-1954 vs 1935-1939) which continued through subsequent cohorts but with no further declines. In women, there had been a gradual increase of risk, although only significant for cohort 1970-1974 (relative risk=1.90, 95% CI 1.08 to 1.34 vs 1935-1939). Similar results were found for dichotomous multimorbidity status. CONCLUSIONS: The trend of lower risk starting from men born in 1945-1954 may be due to a persistent decline in smoking rates since the 1980s. On the other hand, the childhood obesity epidemic starting from the late 1950s coincided with the observed upward inflection of risk for both sexes, that is, notably more drastic increase of risk in women and the levelling-off of the decline of risk in men. These findings highlight that the cohort effects on morbidity burden and multimorbidity may be sex-specific and contextual. By examining such effects in different world populations, localised sex-specific and generation-specific risk factors can be identified to inform policy-making.

Transgenerational telomere erosion in the monogametic sex: human telomeres progressively erode in the female germline and do not lengthen in aged testes.

Long telomeres, the protective caps of eukaryotic chromosomes, which erode during aging, have been the symbol of youth and regenerative potential. It therefore came as a surprise, when several cross-sectional studies reported that telomeres in sperm cells of old men are longer than in young men and that paternal age is positively linked to telomere length of children. To explain the puzzling data, several theories have been put forward, from Darwinian selection to high telomerase activity or alternative telomere lengthening in sperms of geriatrics. Unfortunately, the idea of a birth-cohort effect has been ignored, despite existing theoretical models and despite findings of progressive telomere erosion between human generations. The old theoretical model of progressive telomere erosion in the female germline is discussed here and updated with the hypothesis that progressive telomere erosion is tied to the monogametic sex in all higher animals. Longitudinal studies of germline telomere length in humans are much needed, since a limited regenerative capacity of somatic tissues will most likely result in an increase in and earlier onset of the so-called age-associated diseases.

The age-related blood pressure trajectories from young-old adults to centenarians: A cohort study.

BACKGROUND: Blood pressure (BP) trajectories among older adults, especially among the oldest-old, are still poorly characterized. OBJECTIVE: To investigate the longitudinal trajectories of four BP components with age and their potential influential factors. METHODS: This population-based prospective cohort study included 3315 participants (age 60-105 years, 64.6% women) who were regularly examined from 2001 to 2004 through 2013-2016. The longitudinal trajectories of systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) with age were estimated using linear mixed-effects models. RESULTS: Overall, SBP and PP increased with age until ∼80 years and then declined, whereas DBP and MAP decreased constantly after 60 years of age. The age-related BP trajectories varied by survival time, birth cohort, use of antihypertensive drugs, and heart disease. Specifically, people who survived <2 years after the last visit showed higher levels of BP components before ∼80 years, followed by steeper declines in SBP and PP. At the same age, people who were born earlier showed higher BP than those who were born later. People who used antihypertensive drugs had higher BP than those who did not until ∼80-90 years old, thereafter BP showed no significant difference. After ∼80 years old, people with heart disease showed steeper declines in SBP and PP than those without. CONCLUSIONS: The late-life longitudinal BP trajectories with age vary with demographics, clinical conditions, and contextual factors. These findings may help better understand the age-dependent relationship of BP with health outcomes as well as help achieve optimal BP control in older people. PERSPECTIVES: Competency in medical knowledge: Understanding the age-related blood pressure trajectories and potential influential factors may help improve blood pressure management in older people. Translational outlook 1: Blood pressure trajectories with age in older adults vary by birth cohort, survival time, antihypertensive therapy, and heart disease. The age-related blood pressure trajectories by birth cohorts are featured with lower blood pressure levels at the same age in more recent birth cohorts, which may partially reflect the improvement of blood pressure control over time. Translational outlook 2: The age-related blood pressure trajectories in the oldest old (e.g., age ≥ 85 years) are characterized by steeper and faster blood pressure declines associated with heart disease and short survival (e.g., <2 years). This may have implications for the optimal management of blood pressure as well as for the interpretation of the relationships between blood pressure and health outcomes (e.g., death) among the oldest old.

Effect of age, period and birth-cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD-deficiency across age groups and birth cohorts was investigated using Age-Period-Cohort analysis. METHODS: Data were collected from the clinical records of 11,252 patients (6975 women, age range 17-94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency. RESULTS: Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age-Period-Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively). CONCLUSIONS: These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues. Key message The frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication.

The Risk of Breast Cancer in Women Using Menopausal Hormone Replacement Therapy in Taiwan.

Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health Insurance claim data of a 200,000-person national representative cohort. A total of 22,929 women aged ≥45 years in 1997 without previous diagnosis of breast cancer were enrolled and stratified into two birth cohorts born before or after 1933. HRT prescriptions were traced in outpatient data files and incident breast cancer cases were identified from 1997 to 2004. The Cox proportional hazards model was used to analyze breast cancer hazard ratio (HR). HRT users were censored after they discontinued HRT. The results showed that women born during 1933-1952 had a twofold increased risk of breast cancer (HR = 2.10, 95% CI = 1.47-3.00) compared with women born before 1933, when adjusted for HRT use. When adjusted for the birth-cohort difference, HRT users had significantly increased breast cancer HR versus non-users after four years of use (adjusted HR = 1.48, 95% CI = 1.03-2.13); the HR further increased to 1.95 (95% CI = 1.34-2.84) after eight years of use. In conclusion, a longer duration of current HRT use was associated with a higher risk of breast cancer independent of the birth-cohort difference.