Search

ObjectivesTo compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI.Materials and methodsThis study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann-Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values.ResultsAge, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PEFGT (11.5 vs. 8.0%, adjusted p = 0.018) and SERFGT (7.2 vs. 9.3%, adjusted p = 0.066).ConclusionQuantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE.Clinical relevance statementBRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models.Key pointsExpanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols. Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers. This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations.

The average number of times a person will have surgery in their lifetime, and the amount of surgical healthcare resources they use, is unknown. Lifetime risk is a measure of the risk of an average person having a specific event within their lifetime. We report the lifetime risk of surgery and the change observed during the first year of the COVID-19 pandemic. We conducted a population cohort study using hospital episode statistics to identify all patients undergoing surgery between January 1, 2016, and December 31, 2020, in England. We calculated age- and sex-specific incidence rates of surgery and combined these with routinely available population and mortality data from the Office for National Statistics. We computed the probability of requiring surgery stratified by 5-yr epochs (age 0–4 to ≥90 yr). Our primary analysis calculated lifetime risk for all surgery using the life table method. We assessed the impact of the COVID-19 pandemic, comparing a pre-pandemic and a pandemic period. Between 2016 and 2020, 23 427 531 patients underwent surgery, of which 11 937 062 were first surgeries. The average denominator population for England was 55.9 million. The lifetime risk of first surgery was 60.2% (95% confidence interval 55.1–65.4%) for women and 59.1% (95% confidence interval 54.2–64.1%) for men. The COVID-19 pandemic decreased the lifetime risk of first surgery by 32.3% for women and by 31.7% for men. This estimated lifetime risk should only be applied to the English population. This population epidemiological analysis suggests that approximately 60% of people in England will undergo surgery in their lifetime. [ABSTRACT FROM AUTHOR]

The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004–2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem.

Abstract Background Rates of keratinocyte carcinoma (KC) across Europe are impacted by population demographics and geography. Regional differences in KC occurrence exist, but few European studies investigate incidences of specific subtypes in the secondary healthcare sector on a national level. Objectives To determine geographical differences in incidence rate and lifetime risk of KC subtypes across Denmark, including nodular and superficial basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen's disease (BD), identified in office‐based dermatological practice. Methods Based on a nationwide registry (The Danish Skin Cancer Registry), all patients in Denmark's five regions with a histologically‐ or clinically verified KC or BD registered in a state‐funded office‐based dermatology practice between 2013 and 2022 were included. Trends in national‐ and region‐specific age and sex standardised tumour incidence rates (STIR) were calculated. Further, national lifetime risk of each tumour subtype was estimated. Results Between 2013 and 2022, the combined STIR for KC/BD rose 172% nationally from 180 to 489 per 100,000 person‐years (PY). This increase reflected rising rates of nodular BCC, SCC, and BD, while superficial BCC incidence was relatively stable. Regional differences in STIR for combined KC/BD were observed, with the Capital Region and North Jutland generally demonstrating higher rates than Zealand, Southern‐ and Central Denmark (e.g., North Jutland vs. Southern Denmark: 714 vs. 405/100,000PY). While the estimated lifetime risk of developing at least one KC or BD tumour was 21.8%, risk varied with tumour subtype, resulting in subtype‐specific risks of 16.4%, 5.1%, 1.9% and 1.3% for nodular BCC, superficial BCC, SCC, and BD, respectively. Conclusions In Denmark's secondary dermatological care sector, incidence of nodular BCC, SCC and BD continues to rise with an overall lifetime risk nearing 22%. While KC incidence is increasing in Denmark, the study detected differences in geographical trends and rate increases of specific tumour subtypes.

The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004–2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem. [ABSTRACT FROM AUTHOR]

BackgroundBackground parenchymal enhancement (BPE) is an established breast cancer risk factor. However, the relationship between BPE levels and breast cancer risk stratification remains unclear.PurposeTo evaluate the clinical relationship between BPE levels and breast cancer risk with covariate adjustments for age, ethnicity, and hormonal status.Study typeRetrospective.Population954 screening breast MRI datasets representing 721 women divided into four cohorts: women with pathogenic germline breast cancer (BRCA) mutations (Group 1, N = 211), women with non-BRCA germline mutations (Group 2, N = 60), women without high-risk germline mutations but with a lifetime breast cancer risk of ≥20% using the Tyrer-Cuzick model (Group 3, N = 362), and women with

Abstract Background The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. Methods 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. Results The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16–1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51–1.75), respectively. Conclusions The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Background: Background parenchymal enhancement (BPE) is an established breast cancer risk factor. However, the relationship between BPE levels and breast cancer risk stratification remains unclear. Purpose: To evaluate the clinical relationship between BPE levels and breast cancer risk with covariate adjustments for age, ethnicity, and hormonal status. Study Type: Retrospective. Population: 954 screening breast MRI datasets representing 721 women divided into four cohorts: women with pathogenic germline breast cancer (BRCA) mutations (Group 1, N = 211), women with non‐BRCA germline mutations (Group 2, N = 60), women without high‐risk germline mutations but with a lifetime breast cancer risk of ≥20% using the Tyrer‐Cuzick model (Group 3, N = 362), and women with <20% lifetime risk (Group 4, N = 88). Field Strength/Sequence: 3 T/axial non‐fat‐saturated T1, short tau inversion recovery, fat‐saturated pre‐contrast, and post‐contrast T1‐weighted images. Assessment: Data on age, body mass index, ethnicity, menopausal status, genetic predisposition, and hormonal therapy use were collected. BPE levels were evaluated by two breast fellowship‐trained radiologists independently in accordance with BI‐RADS, with a third breast fellowship‐trained radiologist resolving any discordance. Statistical Tests: Propensity score matching (PSM) was utilized to adjust covariates, including age, ethnicity, menopausal status, hormonal treatments, and prior bilateral oophorectomy. The Mann–Whitney U test, chi‐squared test, and univariate and multiple logistic regression analysis were performed, with an odds ratio (OR) and corresponding 95% confidence interval. Weighted Kappa statistic was used to assess inter‐reader variation. A P value <0.05 indicated a significant result. Results: In the assessment of BPE, there was substantial agreement between the two interpreting radiologists (κ = 0.74). Patient demographics were not significantly different between patient groups after PSM. The BPE of Group 1 was significantly lower than that of Group 4 and Group 3 among premenopausal women. In estimating the BPE level, the OR of gene mutations was 0.35. Data Conclusion: Adjusting for potential confounders, the BPE level of premenopausal women with BRCA mutations was significantly lower than that of non‐high‐risk women. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: The literature presents conflicting results regarding the potential protective effect of prevalent cancer on the development of dementia and Alzheimer's disease (AD). Objective: Association between cancer and subsequent risk of dementia and/or AD was reported previously, but survival bias has been of concern. Here, we aimed to calculate the lifetime risk of dementia and AD and evaluate the association of cancer history with these two conditions. Methods: In this retrospective analysis, we included 292,654 participants aged 60+ y during the follow-up and free of dementia at baseline, within the UK Biobank cohort. Lifetime risks of dementia and AD were estimated in individuals with and without cancer history, and different durations of cancer exposure and cancer types. Results: During a median of 12.5 follow-up years, 5,044 new dementia and 2,141 AD cases were reported. Lifetime risks of dementia and AD were lower in cancer survivors compared to those without cancer, and this effect was more pronounced in participants with cancer history exposure≥5 years. Similar relationship was observed in individual cancer types, except for breast cancer. Conclusions: Results suggested an inverse association between cancer history and lifetime risk of dementia and AD, which may be modified by different cancer types and cancer exposure time. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the radiation dose effect of a lowdose chest computed tomography (CT) protocol implemented in our hospital during the outbreak of Coronavirus disease 2019 (COVID-19) by estimating lifetime attributable risk (LAR). Materials and Methods: A total of 583 patients were randomly included in this study. The values of volumetric CT dose index (CTDIvol, mGy) and dose length product (DLP, mGy.cm) were extracted from CT console. CT-Expo is a CT dose software that was used to estimate effective dose (E) and organ doses. Lifetime attributed risk (LAR) of cancer incidence were calculated according to the Biological Effects of Ionizing Radiation (BEIR) VII report. Results: Of the 583 patients included in this study, 262 (44.9%) were men and 321 (55.1%) were women. The third quartile of CTDIvol and DLP were 2.5 mGy and 79.4 mGy.cm, respectively. The mean value of E was 1.1 ± 0.3 mSv, and it was statistically higher in females. Esophagus, lung and thymus received highest doses, and also in females breast received highest dose. The mean LAR of lung cancer was 5.3 per 100,000 patients, while the mean LAR of liver cancer was 0.1 per 100,000 patients. Conclusions: Despite the large number of chest CT scans during the Covid-19 era, the low-dose chest CT protocol implemented in our hospital caused low doses to organs and very low cancer risks. [ABSTRACT FROM AUTHOR]

Abstract Introduction Herpes zoster (HZ) is a painful disease that mainly affects individuals whose immune system has been weakened because of increasing age (> 50 years) or certain diseases or treatments. We estimated the complete burden of HZ. Methods This population-based register study analysed healthcare data from the VEGA and Digitalis databases of Västra Götaland Region (VGR), Sweden. The VEGA database includes all patients in VGR, covering both hospital and primary care. The Digitalis records prescribed medications. The study population included patients aged ≥ 18 years with at least one registered primary or secondary HZ diagnosis (based on International Classification of Diseases [ICD] codes) between 2005 and 2021. Incidence rates (95% confidence intervals [CI]) were stratified by age, sex and diagnosis/analgesic prescription. Results Overall HZ incidence increased from 2.5 (95% CI 2.4–2.6) in 2005 to 4.2 (95% CI 4.1–4.3) in 2021. The increase in incidence was rapid from 2005 to 2013, followed by a plateauing trend. From 2014–2019, the lifetime risk of HZ, excluding recurrent cases, was 36.5% (95% CI 35.5–37.4%). Municipal differences ranged from 34.4% (95% CI 32.5–36.4%) to 43.6% (95% CI 39.9–47.4%). Recurrence rates of HZ were 8.7% and 9.1% with follow-up periods of 5.5 and 10.5 years, respectively. Reported postherpetic neuralgia (PHN) cases increased five-fold over the study period. In 2019, 19% of all HZ patients developed HZ-related neuropathic pain; 13.6% had signs of persistent pain (> 90 days; i.e. PHN). An increased occurrence of cerebral and cardiovascular disease was observed in HZ patients. Among high-risk groups the occurrence of HZ peaked among those with inflammatory and autoimmune diseases. Conclusion HZ and PHN risk in Sweden is comparable to that in other European countries prior to implementing HZ national vaccination programs. Municipal differences suggest that the lifetime risk of HZ in Sweden is at least 36.5%. Clinical Trial Registration NCT Number ( www.clinicaltrials.gov ). Graphical Abstract

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18–64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10−4 or 5.57 × 10−4 in the full PUMA cohort and 7.50 × 10−4 or 7.66 × 10−4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10−4 to 9.2 × 10−4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes. [ABSTRACT FROM AUTHOR]

Background The lifetime risk of maternal death quantifies the probability that a 15-year-old girl will die of a maternal cause in her reproductive lifetime. Its intuitive appeal means it is a widely used summary measure for advocacy and international comparisons of maternal health. However, relative to mortality, women are at an even higher risk of experiencing life-threatening maternal morbidity called 'maternal near miss' (MNM) events—complications so severe that women almost die. As maternal mortality continues to decline, health indicators that include information on both fatal and non-fatal maternal outcomes are required. Methods We propose a novel measure—the lifetime risk of MNM—to estimate the cumulative risk that a 15-year-old girl will experience a MNM in her reproductive lifetime, accounting for mortality between the ages 15 and 49 years. We apply the method to the case of Namibia (2019) using estimates of fertility and survival from the United Nations World Population Prospects along with nationally representative data on the MNM ratio. Results We estimate a lifetime risk of MNM in Namibia in 2019 of between 1 in 40 and 1 in 35 when age-disaggregated MNM data are used, and 1 in 38 when a summary estimate for ages 15–49 years is used. This compares to a lifetime risk of maternal death of 1 in 142 and yields a lifetime risk of severe maternal outcome (MNM or death) of 1 in 30. Conclusions The lifetime risk of MNM is an urgently needed indicator of maternal morbidity because existing measures (the MNM ratio or rate) do not capture the cumulative risk over the reproductive life course, accounting for fertility and mortality levels. [ABSTRACT FROM AUTHOR]

We compare different models on estimating the probability of default over a time horizon, considering censored data. Models were fitted from a survival analysis perspective, considering both classic models (Cox Proportional Hazard) with penalized variations and ensemble machine learning methods (boosting and bagging). Using a dataset of credit card refinancing operations, we assess accuracy performance in both out-of-sample and out-of-time observations. We assess well-established metrics, such as the concordance index, and measures that indicate calibration power (integrated Brier score and time-dependent dynamic AUC). Results show that a boosting approach with component-wise regression as base learner outperform other models for short term operations (36 months), in contrast to longer term transactions (60 months), where Cox Proportional Hazard (with and without penalization) depicted better results. [ABSTRACT FROM AUTHOR]

Introduction: Herpes zoster (HZ) is a painful disease that mainly affects individuals whose immune system has been weakened because of increasing age (> 50 years) or certain diseases or treatments. We estimated the complete burden of HZ. Methods: This population-based register study analysed healthcare data from the VEGA and Digitalis databases of Västra Götaland Region (VGR), Sweden. The VEGA database includes all patients in VGR, covering both hospital and primary care. The Digitalis records prescribed medications. The study population included patients aged ≥ 18 years with at least one registered primary or secondary HZ diagnosis (based on International Classification of Diseases [ICD] codes) between 2005 and 2021. Incidence rates (95% confidence intervals [CI]) were stratified by age, sex and diagnosis/analgesic prescription. Results: Overall HZ incidence increased from 2.5 (95% CI 2.4–2.6) in 2005 to 4.2 (95% CI 4.1–4.3) in 2021. The increase in incidence was rapid from 2005 to 2013, followed by a plateauing trend. From 2014–2019, the lifetime risk of HZ, excluding recurrent cases, was 36.5% (95% CI 35.5–37.4%). Municipal differences ranged from 34.4% (95% CI 32.5–36.4%) to 43.6% (95% CI 39.9–47.4%). Recurrence rates of HZ were 8.7% and 9.1% with follow-up periods of 5.5 and 10.5 years, respectively. Reported postherpetic neuralgia (PHN) cases increased five-fold over the study period. In 2019, 19% of all HZ patients developed HZ-related neuropathic pain; 13.6% had signs of persistent pain (> 90 days; i.e. PHN). An increased occurrence of cerebral and cardiovascular disease was observed in HZ patients. Among high-risk groups the occurrence of HZ peaked among those with inflammatory and autoimmune diseases. Conclusion: HZ and PHN risk in Sweden is comparable to that in other European countries prior to implementing HZ national vaccination programs. Municipal differences suggest that the lifetime risk of HZ in Sweden is at least 36.5%. Clinical Trial Registration: NCT Number (www.clinicaltrials.gov). Plain Language Summary: What is the context? The varicella-zoster virus (VZV) can reactivate after primary infection and cause herpes zoster or shingles. Shingles is painful and mostly affects people aged > 50 years or those who have weakened immunity due to age, illness or medical treatments. The National Immunization Program (NIP) in Sweden does not currently include vaccination against shingles. We evaluated how often individuals from Västra Götaland Region, Sweden, experienced shingles and its complications. What is new? Overall, the number of shingles and PHN cases increased significantly from 2005 to 2021. We found that 14% of patients with shingles had pain persisting for > 3 months after a shingles episode. Most people developing shingles (about 70%) are healthy individuals without comorbidities, although those with underlying health issues have more risk of getting shingles. Over a follow-up period of 5.5 years, 8.7% of patients with shingles had more than one shingles episode. What is the impact? The occurrence of shingles and postherpetic neuralgia in Sweden is higher than what was reported previously and is comparable to other European countries before the implementation of shingles vaccination programmes. [ABSTRACT FROM AUTHOR]

Abstract Background Incidence and prevalence do not capture the risk of developing diabetes during a defined period and only limited evidence exists on the lifetime risk of diabetes based on longer and continuous follow-up studies in India. Lacunae in evidence on lifetime risk can be attributed primarily to the absence of comprehensive and reliable information on diabetes incidence, mortality rates and lack of longitudinal studies in India. In light of the scarcity of evidence in India, the objective of this study was to estimate the incidence of diabetes and its lifetime risk in an urban community of Mumbai. Methods The research study utilized data which is extracted from the electronic medical records of beneficiaries covered under the Contributory Health Service Scheme in Mumbai. The dataset included information on 1652 beneficiaries aged 40 years and above who were non-diabetic in 2011–2012, capturing their visit dates to medical center and corresponding laboratory test results over a span ten years from January, 2012- December, 2021. Survival analysis techniques are applied to estimate the incidence of diabetes. Subsequently, the remaining life years from the life table were utilized to estimate the lifetime risk of diabetes for each gender, stratified by age group. Results A total of 546 beneficiaries developed diabetes in ten years, yielding an unadjusted incidence rate of 5.3 cases per 1000 person-years (95% CI: 4.9- 5.8 cases/ 1000 person years). The age-adjusted lifetime risk of developing type II diabetes in this urban community is estimated to be 40.3%. Notably, males aged 40 years and above had 41.5% chances of developing diabetes in their lifetime as compared to females with a risk of 39.4%. Moreover, the remaining lifetime risk of diabetes decreased with advancing age, ranging from 26.4% among 40–44 years old to 4.2% among those age 70 years and above. Conclusion The findings stress the significance of recognizing age specific lifetime risk and implementing early interventions to prevent or delay diabetes onset and to focus on diabetes management programs in India.

Colorectal cancer and breast cancer are among the most common types of cancer in the United States, and cancer screening is an effective way to detect and treat these cancers early. Health news stories, medical websites, and media campaigns regularly highlight the national lifetime risks of specific cancers and their screening rates, but recent research suggests that people tend to overestimate the prevalence of health problems but underestimate the prevalence of disease prevention behaviors in the absence of numerical information. This study featured two online experiments, one focused on breast cancer (N = 632) and one focused on colorectal cancer (N = 671), to examine the effects of communicating national cancer lifetime risks and screening rates among samples of screening‐eligible adults in the United States. Findings confirmed prior work in showing that people overestimated colorectal/breast cancer lifetime risks but underestimated colorectal/breast cancer screening rates. Communicating the national lifetime risk of dying from colorectal/breast cancer lowered people's national risk estimates, which in turn was associated with lower perceived cancer risks for themselves. In contrast, communicating the national colorectal/breast cancer screening rate increased people's estimates of the prevalence of cancer screening, which in turn was associated with higher perceived self‐efficacy to engage in cancer screening and greater screening intentions. We conclude that efforts to promote cancer screening may benefit from messages that include data on national cancer screening rates but may not benefit from including national rates of lifetime cancer risks. [ABSTRACT FROM AUTHOR]

[Display omitted] The lifetime risk of cancer is a measure of the cumulative risk of cancer over a specific age range and has a clear, intuitive appeal. However, comparative assessments of cancer-specific risk across populations are limited. We used the adjusted for multiple primaries method to estimate the lifetime risk of cancer from the obtained data from GLOBOCAN for 185 countries/regions for the year 2020, alongside all-cause mortality and population data from the United Nations. The estimated global lifetime risk of cancer from birth to death was 25.10% (95% confidence interval (CI): 25.08%–25.11%) in 2020; the risk was 26.27% (95% CI: 26.24%–26.30%) in men and 23.96% (95% CI: 23.93%–23.98%) in women. Significant differences were observed in the risks between countries/regions within world areas and by the human development level. The lifetime risk of cancer was 38.48%, 25.38%, 11.36%, and 10.34% in countries/regions with very high, high, medium, and low Human Development Index, respectively. Globally, prostate and breast cancers were associated with the greatest lifetime risks among men and women (4.65% and 5.90%, respectively). The lifetime risk of cancer decreased with age, with a remaining risk of 12.61% (95% CI: 12.60%–12.63%) from the age of 70 years. The lifetime risk from birth to death translates to approximately one in four persons developing cancer, with men and women having similar risk levels. The identified age-specific variations in cancer risk at the population level can provide crucial information to support targeted cancer prevention and health system planning. [ABSTRACT FROM AUTHOR]

Aims: Although trials have proven the group‐level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime‐perspective for Heart Failure (LIFE‐HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. Methods and results: Cox proportional hazards functions with age as the time scale were developed in the PARADIGM‐HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non‐cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N‐terminal pro‐B‐type natriuretic peptide, and glomerular filtration rate. The functions were combined in life‐tables to predict individual overall and HF hospitalization‐free survival. External validation was performed in the SwedeHF registry, ASIAN‐HF registry, and DAPA‐HF trial (n = 51 286). Calibration of 2‐ to 10‐year risk was adequate, and c‐statistics were 0.65–0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium–glucose cotransporter 2 inhibitor, and angiotensin receptor–neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7–3.7) and 3.7 (IQR 2.4–5.5) additional years of overall and HF hospitalization‐free survival, respectively. Conclusion: The LIFE‐HF model enables estimation of lifelong overall and HF hospitalization‐free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision‐making. [ABSTRACT FROM AUTHOR]

We aimed to predict lifetime risk for cardiovascular disease (CVD). The sample consisted of 1988 participants with complete CVD data during the 20-year follow-up (50% men, 45 ± 14 years) of the ATTICA study. Lifetime risk for CVD was predicted at specific index ages (40, 50, and 60 years), based on the life-table method, with death free-of-CVD treated as a competing event. 718 participants experienced a fatal or nonfatal CVD event, corresponding to a crude CVD incidence of 36.1% (men: 40.2%, women: 32.1%, P -value <.001). Overall, women and men had similar lifetime CVD risk (P -value =.245); at index age of 40, the lifetime risk for CVD was 68% for men and 63% for women, with a progressive decline to 56% and 50% at the index age of 50, and to 55% for both men and women, at the index age of 60 years, respectively. These results on lifetime risk for CVD can guide the allocation of resources to improve public health and preventive services, especially in ages below 50 years, in both men and women. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary artery calcium scanning is a routine test for assessing the severity of atherosclerosis in asymptomatic individuals. This inexpensive, noninvasive test quantifies the calcium deposition in the 4 principal coronary arteries. Correct interpretation is important to the physician (for recommending therapy) and to the patient (for determining his or her lifetime risk of a cardiovascular event). A score of 0 indicates that a cardiovascular event is extremely unlikely in the next 5 years. In contrast, a score greater than 0 portends a coronary event. The higher the score, the greater the risk. Both the arterial location of the calcium and the number of coronary arteries involved alter the interpretation of the calcium score. At any given age, females have significantly lower scores than males. One-third of individuals with scores greater than 1000 will have a cardiovascular event within 3 years. For all elevated calcium scores, aggressive treatment is warranted, including significant lifestyle changes and medications to reduce low-density lipoprotein cholesterol. Understanding the importance of the coronary artery calcium score will result in improved therapy and patient compliance. [ABSTRACT FROM AUTHOR]

Background: Incidence and prevalence do not capture the risk of developing diabetes during a defined period and only limited evidence exists on the lifetime risk of diabetes based on longer and continuous follow-up studies in India. Lacunae in evidence on lifetime risk can be attributed primarily to the absence of comprehensive and reliable information on diabetes incidence, mortality rates and lack of longitudinal studies in India. In light of the scarcity of evidence in India, the objective of this study was to estimate the incidence of diabetes and its lifetime risk in an urban community of Mumbai. Methods: The research study utilized data which is extracted from the electronic medical records of beneficiaries covered under the Contributory Health Service Scheme in Mumbai. The dataset included information on 1652 beneficiaries aged 40 years and above who were non-diabetic in 2011–2012, capturing their visit dates to medical center and corresponding laboratory test results over a span ten years from January, 2012- December, 2021. Survival analysis techniques are applied to estimate the incidence of diabetes. Subsequently, the remaining life years from the life table were utilized to estimate the lifetime risk of diabetes for each gender, stratified by age group. Results: A total of 546 beneficiaries developed diabetes in ten years, yielding an unadjusted incidence rate of 5.3 cases per 1000 person-years (95% CI: 4.9- 5.8 cases/ 1000 person years). The age-adjusted lifetime risk of developing type II diabetes in this urban community is estimated to be 40.3%. Notably, males aged 40 years and above had 41.5% chances of developing diabetes in their lifetime as compared to females with a risk of 39.4%. Moreover, the remaining lifetime risk of diabetes decreased with advancing age, ranging from 26.4% among 40–44 years old to 4.2% among those age 70 years and above. Conclusion: The findings stress the significance of recognizing age specific lifetime risk and implementing early interventions to prevent or delay diabetes onset and to focus on diabetes management programs in India. [ABSTRACT FROM AUTHOR]

We introduce a methodology for estimating the risk posed to the space environment by a spacecraft over an arbitrary period of time following a risk mitigation strategy, in terms of aggregate collision probability. Our methodology enables estimation of residual risk and maneuver frequency, where residual risk is defined conceptually as the risk to a spacecraft which remains even after adherence to a risk mitigation strategy. The key parameters considered which affect residual risk for a general risk mitigation strategy are the risk mitigation maneuver (RMM) threshold, the risk reduction factor, and the maneuver execution time. We present an analytic result regarding the necessary residual risk (per-satellite) to ensure the total aggregate collision probability of a satellite constellation of arbitrary size be below a target value. This approach offers a more complete model of spacecraft safety and potential risk to the space environment by studying more than just the RMM threshold, which has historically been used as a common benchmark in space situational awareness and regulatory compliance literature. Our analysis shows that the RMM threshold is but one of a few factors which have significant effects on residual risk. We provide evidence that the RMM threshold alone is an incomplete indicator of the actual risk posed to the space environment by an operational spacecraft. We demonstrate the effectiveness of this methodology by presenting numerical results which model realistic satellites and satellite constellations and draw key insights from this analysis which will aid in managing the safety and sustainability of the space environment and inform risk mitigation strategies for large satellite constellations. [ABSTRACT FROM AUTHOR]

In the last few years, the tendency to utilization of bottled water has significantly expanded. Therefore, its radioactivity level must be strictly evaluated. This work aims to measure the activity concentrations of gross beta and alpha in bottled drinking water to evaluate its quality and annual effective dose as well as the lifetime risk. The radioactivity of 30 bottled mineral water samples from several brands was analyzed with Wallac Quantulus 1220 LSC. The measurement results showed that the gross beta and alpha activity concentrations in bottled mineral water samples ranged from 29 to 49 mBqL-1 with an average of 38.7 mBqL-1 and 48 to 76 mBqL-1 with an average of 60.8 mBqL-1 respectively. Furthermore, Annual effective doses ranged from 30.11 to 48.3 µSv y-1 with an average value of 38.54 µSv y-1, which is below the 0.1 mSv y−1 as reference dose limit. The variation of lifetime risk is from 1.70 × 10-4 to 2.60 × 10-4 with an average of 2.14 × 10-4. According to this study’s results, radiologically, these bottled mineral waters can be considered safe drinking water in Iran.

The purpose of this study was to investigate the radiological quality of drinking water in Ma'an governorate, which includes the archeological city of Petra and is one of Jordan's most important tourist destinations. To the best of the authors' knowledge, this is the first study in southern Jordan that investigates radioactivity in drinking water and its potential to cause cancer. A liquid scintillation detector was used to measure gross alpha and gross beta activities in tap water samples from Ma'an governorate. A high-purity Germanium detector was used to measure the activity concentrations of 226Ra and 228Ra. Gross alpha, gross beta, 226Ra, and 228Ra activities were < 110–724 mBq/l, < 220–362 mBq/l, < 11–241 mBq/l, and < 32–49 mBq/l, respectively. The results were compared to internationally recommended levels and literature values. Annual effective doses ( D eff ) from 226 and 228Ra intake were calculated for infants, children, and adults. The highest doses were found for children while the lowest were found for infants. For each water sample, the lifetime risk of radiation-induced cancer (LTR) was calculated for the whole population. All of the LTR values were lower than the value recommended by the World Heath Organisation. It is concluded that there are no significant radiation-related health risks associated with consumption of tap water from the studied region. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to estimate the current and future lifetime risks (LTR) of herpes zoster (HZ) and postherpetic neuralgia (PHN), as well as their respective number of annual incident cases in Beijing, China, if individuals were not vaccinated against HZ. Study design: Mathematical model built in Microsoft Excel, de novo. Methods: A hypothetical cohort of 1,000 people was simulated from age 0–100 or until death to generate LTRs of HZ/PHN in Beijing, China. LTR was defined as the risk of developing HZ/PHN at least once in the person’s lifetime. The current number of annual incident HZ/PHN cases were also calculated by multiplying up-to-date population data and the annual age-specific incidence of HZ/PHN. For both LTR and annual incident cases, current estimates were projected into the year 2035 to investigate the impact of an aging population. Scenario and deterministic sensitivity analyses (DSA) were conducted to validate the model outcomes. Results: In Beijing, the current and future LTRs of HZ (PHN) were 32.4% (2.8%) and 34.8% (3.3%), respectively. The current and future annual incident cases of HZ (PHN) of individuals aged ≥50 years were 68,394 (7,801) cases among 7.04 million individuals and 88,676 (9,649) cases among 9.08 million individuals, respectively. The scenario analyses demonstrated that modelled results were likely to underestimate the LTR of HZ. Results were robust under the DSA. Conclusions: Given an aging population, HZ poses a significant, growing burden on individuals, the society, and healthcare system of China, highlighting the need for preventative measures such as vaccination.

Background The 10‐year and lifetime cardiovascular disease risk in the population with stage 1 hypertension and the effects of recovery from and progression of stage 1 hypertension remain undetermined. Methods and Results This prospective cohort study included 96 268 individuals with blood pressure measurements obtained in 2006 and again in 2010. The 10‐year cardiovascular disease risk was estimated using the multivariable Cox proportional hazards model, and the lifetime risk was calculated using a modified survival analysis that accounted for the competing risk of death. Stage 1 hypertension was detected in 30.83% of the cohort. The 10‐year cardiovascular disease risk was 2.80%, and the lifetime risk was 16.61%. Compared with the normal blood pressure group, the stage 1 hypertension group had a 35% higher 10‐year risk (hazard ratio [HR], 1.35 [95% CI, 1.19–1.52]) and a 36% higher lifetime risk (HR, 1.36 [95% CI, 1.25–1.49]). By 2010, 12.57% of the participants with stage 1 hypertension had progressed to stage 2, with a significant 156% increase in 10‐year risk (HR, 2.56 [95% CI, 2.11–3.11]) and an increased lifetime risk of 129% (HR, 2.29 [95% CI, 1.89–2.77]). There was no appreciable change in risk in those with stage 1 hypertension whose blood pressure returned to the normal‐elevated range. Conclusions Stage 1 hypertension was associated with a significant increase in 10‐year and lifetime cardiovascular disease risk. Progression to stage 2 hypertension was associated with a marked increase in lifetime risk. The current guidelines require revision to promote early detection and appropriate management of blood pressure.

The longitudinal trajectories of body mass index (BMI) can reflect the pattern of BMI changes. Lifetime risk quantifies the cumulative risk of developing a disease over the remaining life of a person. We aimed to identify the trajectory of BMI and explore its association with cardiovascular disease (CVD) in the Chinese population. A total of 68,603 participants with a mean age of 55.46 years were included from the Kailuan cohort in Tangshan, China, who were free of CVD and cancer and with repeated measurements of BMI from 2006 to 2010. A latent mixture model was used to identify BMI trajectories. An improved Kaplan-Meier estimator was used to predict the lifetime risk of CVD according to BMI trajectories. During a median follow-up of 7.0 years, 3325 participants developed CVD. Five BMI trajectories were identified at three index ages (35, 45, and 55) respectively. For index age 35 years, compared with the stable low-normal weight group (22.7% [95% CI, 20.0%–25.4%]), the stable high-normal weight (27.6% [25.6%–29.5%]), stable overweight (29.4% [27.4%–31.4%]), stable-low obesity (32.8% [30.0%–35.5%]), and stable-high obesity (38.9% [33.3%–44.5%]) groups had a higher lifetime risk of CVD (P < 0.05). We observed similar patterns for stroke and myocardial infarction. Similarly, the lifetime risk of CVD was higher in the long-term overweight and obese groups at 45 and 55 index ages. Long-term overweight and obesity were associated with an increased lifetime risk of CVD. Our findings could assist in predicting the population burden of CVD. • This is the first study to report the effect of BMI trajectory on lifetime risk of first CVD in a large population. • We identified 5 distinct trajectory patterns of BMI in current population. • The lifetime risk of CVD increased consistently with the level of BMI trajectory. [ABSTRACT FROM AUTHOR]

Abstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data. Conclusions We conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications.

Objectives: To compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI., Materials and Methods: This study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann-Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values., Results: Age, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PE FGT (11.5 vs. 8.0%, adjusted p = 0.018) and SER FGT (7.2 vs. 9.3%, adjusted p = 0.066)., Conclusion: Quantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE., Clinical Relevance Statement: BRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models., Key Points: Expanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols. Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers. This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations., (© 2024. The Author(s).)

Abstract Background Breast cancer is one of the most common cancers among women worldwide and the leading cause of death among Iraqi women. Breast cancer cases in Iraq were found to have increased from 26.6/100,000 in 2000 to 31.5/100,000 in 2009. The present study aims to assess the established risk factors of breast cancer among Iraqi women and to highlight strategies that can aid in reducing the incidence. Methods 1093 Iraqi females were enrolled in this cross-sectional study by purposive sampling methods. Data collection occurred from July 2019 to September 2019. 1500 women participated in the study, and 407 women were ultimately excluded. The questionnaire was conducted as a self-administrated form in an online survey. Ethical approval was obtained from the College of Medicine in the University of Baghdad. The Gail Model risk was calculated for each woman by the Breast Cancer Risk Assessment Tool (BCRAT), an interactive model developed by Mitchell Gail that was designed to estimate a woman’s absolute risk of developing breast cancer in the upcoming five years of her life and in her lifetime. Results The ages of the participants ranged from 35 to 84 years old. The mean 5–year risk of breast cancer was found to be 1.3, with 75.3% of women at low risk and 24.7% of women at high risk. The mean lifetime risk of breast cancer was found to be 13.4, with 64.7% of women at low risk, 30.3% at moderate risk, and 5.0% at high risk. The results show that geographically Baghdad presented the highest 5-year risk, followed by Dhi Qar, Maysan, and Nineveh. However, the highest lifetime risk was found in Najaf, followed by Dhi Qar, Baghdad, and Nineveh, successively. Conclusion Breast cancer is a wide-spreading problem in the world and particularly in Iraq, with Gail Model estimations of high risk in several governorates. Prevention programs need to be implemented and awareness campaigns organized in order to highlight the importance of early detection and treatment.

Abstract Background The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited. Methods We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing. Results Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS. Conclusions TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

Abstract Aims Previous studies suggested an adverse association between higher fasting blood glucose (FBG) variability and cardiovascular disease (CVD). Lifetime risk provides an absolute risk assessment during the remainder of an individual’s life. However, the association between FBG variability and the lifetime risk of CVD is uncertain. Objective We aimed to investigate the effect of the visit-to-visit FBG variability on the lifetime risk of CVD. Methods This study included participants from the Kailuan Study who did not have CVD at index ages 35, 45, and 55 years. The FBG variability was defined as the coefficient of variation (CV) of three FBG values that were measured during the examination periods of 2006–2007, 2008–2009, and 2010–2011. We used a modified Kaplan-Merrier method to estimate lifetime risk of CVD according to tertiles of FBG variability. Results At index age 35 years, the study sample comprised 46,018 participants. During a median follow-up of 7.0 years, 1889 participants developed CVD events. For index age 35 years, participants with high FBG variability had higher lifetime risk of CVD (32.5%; 95% confidence interval [CI]: 28.9–36.1%), compared with intermediate (28.3%; 95% CI: 25.5 –31.1%) and low (26.3%; 95% CI: 23.0–29.5%) FBG variability. We found that higher FBG variability was associated with increased lifetime risk of CVD in men but not women. Similar patterns were observed at index ages 45 and 55 years. Conclusions Higher FBG variability was associated with increased lifetime risk of CVD at each index age. Focusing on the FBG variability may provide an insight to the clinical utility for reducing the lifetime risk of CVD.

Digestive tract cancers are the common cause of cancer deaths in both China and worldwide. This study aimed to describe the burden, recent trends and lifetime risks in the incidence and mortality of digestive tract cancers in an urban district of Shanghai, China. Our study extracted data on stomach, colon, rectum and liver cancers diagnosed in Changning District between 2010 and 2019 from the Shanghai Cancer Registry. We calculated age-standardized incidence and mortality rates, the risks of developing and dying from cancer, and the estimated annual percent changes. Between 2010 and 2019, 8619 new cases and 5775 deaths were registered with digestive tract cancers in the district. The age-standardized incidence rates (ASIRs) of liver cancer decreased steadily, whereas the ASIRs of stomach, colon and rectum cancers remained stable from 2010 to 2019. The age-standardized mortality rates (ASMRs) of stomach and liver cancers showed significant declining changes from 2010 to 2019 in both sexes, but that of colon and rectum cancers remained stable during the entire period. The risks of developing and dying from digestive tract cancers were substantially higher in men than women. The burden of digestive tract cancer and its disparities between sex and age group remain major public health challenges in urban Shanghai. To reduce the burden of digestive tract cancers, the government and researchers should develop and promote a healthy diet, organize a screening, and reduce the prevalence of smoking, alcohol drinking, and hepatitis B virus and hepatitis C virus infections. [ABSTRACT FROM AUTHOR]

Background: Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult. Methods: We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results: SORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data. Conclusions: We conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications. [ABSTRACT FROM AUTHOR]

Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC).

Abstract Background The accuracy of subjective risk perception is a matter of concern in breast cancer development. The objective of this study was to evaluate the accuracy of self-perceived risk assessment of breast cancer development and compared to actual risk in Iranian women. Methods The demographic, clinical, and reproductive characteristics of 800 women aged 35–85 years were collected with an in-person interview. The self-perceived risk and the actual risk were assessed using the visual analog scale (VAS) and he Gail model respectively. Gail’s cutoff of 1.66% risk was used to categorize the estimated 5-year actual risk as low/average risk ( actual risk, then individuals were considered as overestimating. Similarly, in high-risk women, if the perceived risk

Abstract Background Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG). Methods Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan–Meier analysis, Cox models adjusted for the competing risk of death, and Irwin’s restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40–59 years) and older (60–79 years) adults with FPG

BackgroundCardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia.ObjectivesThe clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study.MethodsOf 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model.ResultsUC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11).ConclusionsLong-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.

AimsPatients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).MethodsMESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol ≤ 200 mg/dL, systolic BP ≤ 139 mmHg, and diastolic BP ≤ 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100.ResultsOver 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively.ConclusionsWhile 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications.

Background and Aims: The relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status.Methods and Results: Dynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan-Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%-41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%-42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%-45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%-30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years).Conclusions: Recovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD. [ABSTRACT FROM AUTHOR]

Lifetime risk measures the cumulative risk for developing a disease over one's lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R. [ABSTRACT FROM AUTHOR]

Background: The residual lifetime risk (RLR) of developing heart failure (HF) may have changed over time because of the increasing population burden of hypertension, obesity, and diabetes; greater survival after myocardial infarction; and a greater lifespan.Objectives: The authors assessed changes in the RLR for HF in two 25-year epochs (1965-1989 and 1990-2014).Methods: We compared the RLR of HF at age 50 years (adjusting for competing risk of death) in the 2 epochs in Framingham Study participants overall and in the following strata: sex, body mass index, blood pressure, and diabetes.Results: Mean life expectancy increased from 75.9 to 82.1 years in women and 72.5 to 78.1 years in men. We observed 624 HF events over 111,351 person-observations in epoch 1, and 875 HF events over 128,903 person-observations in epoch 2. The mean age at onset of HF increased across the epochs by 6.6 years (women) to 7.2 years (men). The RLR of HF at age 50 years increased across epochs from 18.86% to 22.55% (absolute increase 3.69; 95% CI: 0.90-6.49; P = 0.01) in women, and from 19.19% to 25.25% (absolute increase 6.06; 95% CI: 3.08-9.04; P < 0.001) in men. The increase in RLR of HF in the second epoch was consistent across strata with excess body mass index or higher blood pressure (relative increase of 28%-47%) and in participants without prior myocardial infarction (relative increase of 23%).Conclusions: The RLR of HF has increased in our community-based sample of White individuals over the last 5 decades, possibly caused by an increase in life expectancy. [ABSTRACT FROM AUTHOR]

Abstract Background In hypertensive patients, reducing plasma low-density lipoprotein cholesterol level (LDL-C) is one of the main interventions for preventing chronic cardiovascular diseases (CVD). However, LDL-C control remains generally insufficient, also in patients with hypertension. We analyzed Electronic Health Record (EHR) data of 7117 hypertensive patients to find the most potential age and sex subgroups in greatest need for improvement in real life dyslipidemia treatment. Taking into account the current discussion on lifetime CVD risk, we focused on the age dependence in LDL-C control. Methods In this observational cross-sectional study, based on routine electronic health record (EHR) data, we investigated LDL-C control of hypertensive, non-diabetic patients without renal dysfunction or CVD, aged 30 years or more in Finnish primary care setting. Results More than half (54% of women and 53% of men) of untreated patients did not meet the LDL-C target of

Summary: Background: Neurodegeneration with brain iron accumulation (NBIA) are a group of clinically and genetically heterogeneous diseases characterized by iron overload in basal ganglia and progressive neurodegeneration. Little is known about the epidemiology of NBIA disorders. In the absence of large-scale population-based studies, obtaining reliable epidemiological data requires innovative approaches. Methods: All pathogenic variants were collected from the 13 genes associated with autosomal recessive NBIA (PLA2G6, PANK2, COASY, ATP13A2, CP, AP4M1, FA2H, CRAT, SCP2, C19orf12, DCAF17, GTPBP2, REPS1). The allele frequencies of these disease-causing variants were assessed in exome/genome collections: the Genome Aggregation Database (gnomAD) and our in-house database. Lifetime risks were calculated from the sum of allele frequencies in the respective genes under assumption of Hardy-Weinberg equilibrium. Findings: The combined estimated lifetime risk of all 13 investigated NBIA disorders is 0.88 (95% confidence interval 0.70–1.10) per 100,000 based on the global gnomAD dataset (n = 282,912 alleles), 0.92 (0.65–1.29) per 100,000 in the European gnomAD dataset (n = 129,206), and 0.90 (0.48–1.62) per 100,000 in our in-house database (n = 44,324). Individually, the highest lifetime risks (>0.15 per 100,000) are found for disorders caused by variants in PLA2G6, PANK2 and COASY. Interpretation: This population-genetic estimation on lifetime risks of recessive NBIA disorders reveals frequencies far exceeding previous population-based numbers. Importantly, our approach represents lifetime risks from conception, thus including prenatal deaths. Understanding the true lifetime risk of NBIA disorders is important in estimating disease burden, allocating resources and targeting specific interventions.