Excess Risk Research Articles

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study

BackgroundThe Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce.MethodsWe compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison.ResultsA total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference.ConclusionsIncreased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Developing and validating intracity spatiotemporal air quality health index in eastern China

BackgroundRecently pilot published city-level air quality health index (AQHI) provides a useful tool for communicating short-term health risks of ambient air pollution, but fails to account for intracity spatial heterogeneity in exposure and associated population health impacts. This study aims to develop the intracity spatiotemporal AQHI (ST-AQHI) via refined air pollution-related health risk assessments. MethodsA three-stage analysis was conducted through integrating province-wide death surveillance data and high-resolution gridded estimates of air pollution and climate factors spanning 2016–2019 in Jiangsu Province, eastern China. First, an individual-level case-crossover design was employed to quantify the short-term risk of nonaccidental mortality associated with residential exposure to individual pollutant (i.e., PM2.5, NO2, O3, and SO2). Second, we accumulated and scaled the excess risks arising from multiple pollutants to formulate daily gridded ST-AQHI estimates at 0.1° × 0.1°, dividing exposure-related risks into low (0–3), moderate (4–6), high (7–9), and extreme high (10+) levels. Finally, the effectiveness of ST-AQHI as composite risk communication was validated through checking the dose-response associations of individual ST-AQHI exposure with deaths from nonaccidental and major cardiopulmonary causes via repeating case-crossover analyses. ResultsWe analyzed a total of 1,905,209 nonaccidental death cases, comprising 785,567 from circulatory diseases and 247,336 from respiratory diseases. In the first-stage analysis, for each 10-μg/m3 rise in PM2.5, NO2, O3, and SO2 exposure at lag-01 day, population risk of nonaccidental death was increased by 0.8% (95% confidence interval: 0.7%, 0.9%), 1.9% (1.7%, 2.0%), 0.4% (0.3%, 0.5%), and 4.1% (3.7%, 4.5%), respectively. Spatiotemporal distribution of ST-AQHI exhibited a consistent declining trend throughout the study period (2016–2019), with annual average ST-AQHI decreasing from 5.2 ± 1.3 to 4.0 ± 1.0 and high-risk days dropping from 15.8% (58 days) to 1.6% (6 days). Exposure associated health risks showed great intracity- and between-city heterogeneities. In the validation analysis, ST-AQHI demonstrated approximately linear, threshold-free associations with multiple death events from nonaccidental and major cardiopulmonary causes, suggesting excellent performance in predicting exposure-related health risks. Specifically, each 1-unit rise in ST-AQHI was significantly associated with an excess risk of 2.0% (1.8%, 2.1%) for nonaccidental mortality, 2.3% (2.1%, 2.6%) for overall circulatory mortality, and 2.7% (2.3%, 3.1%) for overall respiratory mortality, as well as 1.7%–3.0% for major cardiopulmonary sub-causes. ConclusionsST-AQHI developed in this study performed well in predicting intracity spatiotemporal heterogeneity of death risks related to multiple air pollutants, and may hold significant practical importance in communicating air pollution-related health risks to the public at the community scales.

Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79years in 2004-08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12years of follow-up. Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41-1.58), 1.49 (1.38-1.61), 1.42 (1.31-1.54) and 1.64 (1.58-1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20-1.23), 1.28 (1.26-1.29), 1.31 (1.29-1.33) and 1.14 (1.10-1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.

Overall survival and cause-specific mortality in a hospital-based cohort of retinoblastoma patients in São Paulo, Brazil.

Studies are lacking on long-term effects among retinoblastoma patients in low- and middle-income countries. Therefore, we examined cause-specific mortality in a retrospective cohort of retinoblastoma patients treated at Antonio Candido de Camargo Cancer Center (ACCCC), São Paulo, Brazil from 1986 to 2003 and followed up through December 31, 2018. Vital status and cause of death were ascertained from medical records and multiple national databases. We estimated overall and cause-specific survival using the Kaplan-Meier survival method, and estimated standardized mortality ratios (SMRs) and absolute excess risk (AER) of death. This cohort study included 465 retinoblastoma patients (42% hereditary, 58% nonhereditary), with most (77%) patients diagnosed at advanced stages (IV or V). Over an 11-year average follow-up, 80 deaths occurred: 70% due to retinoblastoma, 22% due to subsequent malignant neoplasms (SMNs) and 5% to non-cancer causes. The overall 5-year survival rate was 88% consistent across hereditary and nonhereditary patients (p = .67). Hereditary retinoblastoma patients faced an 86-fold higher risk of SMN-related death compared to the general population (N = 16, SMR = 86.1, 95% CI 52.7-140.5), corresponding to 42.4 excess deaths per 10,000 person-years. This risk remained consistent for those treated with radiotherapy and chemotherapy (N = 10, SMR = 90.3, 95% CI 48.6-167.8) and chemotherapy alone (N = 6, SMR = 80.0, 95% CI 35.9-177.9). Nonhereditary patients had only two SMN-related deaths (SMR = 7.2, 95% CI 1.8-28.7). There was no excess risk of non-cancer-related deaths in either retinoblastoma form. Findings from this cohort with a high proportion of advanced-stage patients and extensive chemotherapy use may help guide policy and healthcare planning, emphasizing the need to enhance early diagnosis and treatment access in less developed countries.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Association of healthy lifestyle factors and genetic liability with bipolar disorder: Findings from the UK Biobank

BackgroundThe interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. MethodsA cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6–7), intermediate (scores 4–5), or unfavorable (scores 0–3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. ResultsDuring the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76–3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83–3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14–9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40–3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16–0.58). ConclusionsOur findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.

Diet modifies the association between alcohol consumption and severe alcohol-related liver disease incidence

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption.

Exploring the characteristics and source-attributed health risks associated with polycyclic aromatic hydrocarbons and metal elements in atmospheric PM2.5 during warm and cold periods in the northern metropolitan area of Taiwan

Polycyclic aromatic hydrocarbons (PAHs) and metal elements are commonly considered hazardous air pollutants due to their toxic, mutagenic, and carcinogenic properties. However, few studies have simultaneously examined their potential sources and health effects. This study aimed to quantify the PAHs and metal elements in atmospheric PM2.5, investigating their characteristics and potential sources to assess associated health risks in the northern metropolitan area of Taiwan. The measurements indicated that the mean concentrations of total PAHs and metal elements in PM2.5 were 0.97 ± 0.52 ng m−3 and 590 ± 200 ng m−3, respectively. Utilizing the positive matrix factorization profiles, the PAH pollution was classified into two sources: industrial emissions, traffic emissions, and coal combustion (69%) were the predominant sources of PAHs, with petroleum volatilization and biomass burning (31%) making a lesser contribution. Similarly, we traced metal elements to three potential sources: natural sources (48%), a combined source of industrial emissions, coal combustion, and traffic exhaust (32%), and a blend of non-exhaust emissions from traffic and waste incineration sources (20%). Results from the potential source contribution function model suggested that the emissions of PAHs and metals could be influenced by the eastern regions of China, although local sources, including waste incinerators, traffic, shipping, and harbor activities, were identified as the primary contributors. Source-attributed excess cancer risk revealed that industry, traffic, and coal combustion had the highest cancer risk posed by PAHs in the cold period (1.0 × 10−5), while the greatest cancer risk among metal elements was linked to non-exhaust emissions from traffic and waste incineration emissions (2.0 × 10−5). This research underscores the importance of considering source contributions to health risk and emission reduction when addressing PM2.5 pollution. These findings have direct implications for policymakers, providing them with valuable insights to develop strategies that protect public health from the detrimental effects of PAH and metal element exposure.

Improving life’s essential 8 mitigates myocardial infarction risk attributed to abnormal birth weight in later life

BackgroundTo prospectively assess the individual and joint effects of birth weight and the life’s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. MethodsIn 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. ResultsLow birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02–1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71–11.15), P < 0.001). Participants with low birth weight and low CVH (vs. participants with normal birth weight and high CVH) had HR of 5.97 (2.94–12.14) for MI incidence. The relative excess risk due to interaction of low birth weight and low CVH on MI was −4.11 (−8.12, −0.11), indicating a negative interaction on an additive scale. A consistent decreasing trend of MI risk along with increased LE8 score was observed across all three birth weight groups. ConclusionLow birth weight was associated with increased MI risk, emphasizing the importance of the prenatal factor in risk prediction and prevention of MI. Improving LE8 can mitigate MI risk attributed to low birth weight.

The association between long-term exposure to ambient formaldehyde and respiratory mortality risk: A national study in China

IntroductionWhile ambient formaldehyde (HCHO) concentrations are increasing worldwide, there was limited research on its health effects. ObjectivesTo assess the association of long-term exposure to ambient HCHO with the risk of respiratory (RESP) mortality and the associated mortality burden in China. MethodsAnnual and seasonal RESP death and tropospheric HCHO vertical columns data were collected in 466 counties/districts across China during 2013–2016. A difference-in-differences approach combined with a generalized linear mixed-effects regression model was employed to assess the exposure-response association between long-term ambient HCHO exposure and RESP mortality risk. Additionally, we computed the attributable fraction (AF) to gauge the proportion of RESP mortality attributable to HCHO exposure. ResultsThis analysis encompassed 560,929 RESP deaths. The annual mean ambient HCHO concentration across selected counties/districts was 8.02×1015 ± 2.22×1015 molec.cm−2 during 2013–2016. Each 1.00×1015 molec.cm−2 increase in ambient HCHO was associated with a 1.61 % increase [excess risk (ER), 95 % confidence interval (CI): 1.20 %, 2.03 %] in the RESP mortality risk. The AF of RESP mortality attributable to HCHO was 12.16 % (95 %CI:9.33 %, 14.88 %), resulting in an annual average of 125,422 (95 %CI:96,404, 153,410) attributable deaths in China. Stratified analyses suggested stronger associations in individuals aged ≥65 years old (ER=1.87 %, 95 %CI:1.43 %, 2.32 %), in cold seasons (ER=1.00 %, 95 %CI:0.56 %, 1.44 %), in urban areas (ER=1.65 %, 95 %CI:1.15 %, 2.16 %), and in chronic obstructive pulmonary disease patients (ER=1.95 %, 95 %CI:1.42 %, 2.48 %). ConclusionsThis study suggested that long-term HCHO exposure may significantly increase the risk of RESP mortality, leading to a substantial mortality burden. Targeted measures should be implemented to control ambient HCHO pollution promptly.

Impact of Intraoperative Femoral Fractures During Cemented Hemiarthroplasty for Femoral Neck Fractures

BackgroundThere have been several studies on intraoperative femoral fractures (IFFs) during primary total hip arthroplasty, but it is not well understood how this complication affects the patient population undergoing cemented hemiarthroplasty. This study aimed to analyze the impact of IFFs sustained during cemented hemiarthroplasty for the treatment of femoral neck fractures. MethodsA retrospective review was conducted of all patients who were treated for Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association 31B fractures with cemented hemiarthroplasty between January 1, 2000 and December 31, 2021, at a single academic level 1 trauma center. An initial cohort was constructed of all patients who sustained an IFF during their surgery, yielding 31 patients after excluding those who sustained a pathologic fracture or had incomplete data. These patients were matched 1:2 on age, sex, and body mass index to patients in a control cohort. The primary outcome measure was implant failure. Secondary outcome measures included complications, all-cause mortality, and radiographic outcomes (subsidence, femoral component loosening, acetabular wear, and heterotopic ossification) postoperatively. ResultsSubsequent implant revision was required in 3.2% (n = 1) of patients who sustained an IFF and 1.6% (n = 1) of patients who did not. After adjusting for comorbidities, there was no observed excess risk of implant failure in the fracture cohort when compared to the control cohort (hazard ratio [HR] = 0.30, P = 0.740). There was no observed excess risk of morbidity (HR = 0.69, P = 0.621) or all-cause mortality (HR = 0.23, P = 0.330). Radiographic outcomes also did not significantly differ between the 2 cohorts (P > 0.05). ConclusionsIntraoperative fractures during cemented hemiarthroplasty do not contribute to an increased risk of secondary surgery, morbidity, or mortality after surgery. They also do not adversely affect radiographic outcomes postoperatively. Level of EvidenceLevel III, Retrospective Comparative Study.

Genomic ascertainment of CHEK2-related cancer predisposition.

There is clear evidence that deleterious germline variants in CHEK2 increases risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Genomic ascertainment was used to quantify cancer risk in CHEK2 germline pathogenic variant heterozygotes. Germline CHEK2 variants were extracted from two exome-sequenced biobanks linked to the electronic health record: UK Biobank (n= 469,765) and Geisinger MyCode (n=170,503). Variants were classified as per American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) criteria. Heterozygotes harbored a CHEK2 pathogenic/likely pathogenic (P/LP) variant; controls harbored benign/likely benign CHEK2 variation or wildtype CHEK2. Tumor phenotype and demographic data were retrieved; to adjust for relatedness, association analysis was performed with SAIGE-GENE+ with Bonferroni correction. In CHEK2 heterozygotes in both MyCode and UK Biobank, there was a significant excess risk of all cancers tested, including breast cancer (C50; OR=1.54 and 1.84, respectively), male genital organ cancer (C60-C63; OR=1.61 and 1.77 respectively), urinary tract cancer (C64-C68; OR=1.56 and 1.75, respectively) and lymphoid, hematopoietic, and related tissue cancer (C81-C96; OR=1.42 and 2.11, respectively). Compared to controls, age-dependent cancer penetrance in CHEK2 heterozygotes was significantly younger in both cohorts; no significant difference was observed between the penetrance of truncating and missense variants for cancer in either cohort. Overall survival was significantly decreased in CHEK2 heterozygotes in UK Biobank but there was no statistical difference in MyCode. Using genomic ascertainment in two population-scale cohorts, this investigation quantified the prevalence, penetrance, cancer phenotype and survival in CHEK2 heterozygotes. Tailored treatment options and surveillance strategies to manage those risks are warranted.

Impact of sex on outcomes associated with polyvascular disease in patients after PCI

Atherosclerosis in more than one vs. one arterial bed is associated with increased risk for major adverse cardiovascular events (MACE). This study aimed to determine whether the risk of post percutaneous coronary intervention (PCI) MACE associated with polyvascular disease (PVD) differs by sex. We analyzed 18,721 patients undergoing PCI at a tertiary-care center between 2012-2019. Polyvascular disease was defined as history of peripheral artery and/or cerebrovascular disease. The primary endpoint was MACE, a composite of all-cause death, myocardial infarction, or stroke at 1 year. Multivariate Cox regression was used to adjust for differences in baseline risk between patients with PVD vs. coronary artery disease (CAD) alone and interaction testing was used to assess risk modification by sex. Women represented 29.2% (N=5,467) of the cohort and were more likely to have PVD than men (21.7% vs. 16.1%; p<0.001). Among both sexes, patients with PVD were older with higher prevalence of comorbidities and cardiovascular risk factors. Women with PVD had the highest MACE rate (10.0%), followed by men with PVD (7.2%), women with CAD alone (5.0%), and men with CAD alone (3.6%). Adjusted analyses revealed similar relative MACE risk associated with PVD vs. CAD alone in women and men (adjusted hazard ratio [aHR] 1.54, 95% confidence interval [CI] 1.20-1.99; p<0.001 and aHR 1.31, 95% CI 1.06-1.62; p=0.014, respectively; p-interaction=0.460). Women and men derive similar excess risk of MACE from PVD after PCI. The heightened risk associated with PVD needs to be addressed with maximized use of secondary prevention in both sexes.

Integration of Diabetes Mellitus and Hypertension on Major Cardiovascular Events: An Experience From a 15-year Follow-up Cohort Study in EMR.

Patients with hypertension and diabetes are more susceptible to cardiovascular diseases (CVD) and mortality. This study aimed to evaluate the individual and combined effects of hypertension and diabetes on cardiovascular events and mortality in a Middle Eastern population-based cohort. Fifteen-year follow-up data were collected for 6323 adults aged 35 years and older who were free from CVD at baseline. The subjects were categorized into different groups according to hypertension and diabetes at baseline. Cox proportional hazards regression was implemented to estimate hazard ratios (HRs) of hypertension and diabetes for cardiovascular events (CVE), CVD mortality, and all-cause mortality. Population-attributable hazard fraction (PAHF) was used to assess the proportion of hazards of CVE and mortality attributable to hypertension or diabetes. The incidence rates (95% CI) of CVE, CVE mortality, and all-cause mortality in the total population were 13.77(12.84-14.77), 3.01(2.59-3.49), and 9.92(9.15-10.77) per 1000 persons per year respectively. The HR of hypertension for CVE in the diabetic population was 1.98 (1.47-2.66) with a PAHF of 27.65(15.49-39.3). When the HRs and PAHF of diabetes were evaluated in hypertensive patients, they were statistically significant for CVE, CVE mortality, and all-cause mortality. Our study indicated that the joint effect of diabetes and hypertension is the dramatic increased risk of CVE. A considerable fraction of the excess risk of CVE in patients with diabetes was attributable to hypertension, on the other hand, diabetes was associated with a substantial hazard fraction of CVE and mortality in hypertensive patients.

Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort

Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997–2000 with a risk of 5.6% and lowest between 2013–2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.

A mini review of plan quality and secondary cancer risk in CyberKnife M6 radiosurgery for benign intracranial tumors.

With advancements in medical technology, stereotactic radiosurgery (SRS) has become an essential option for treating benign intracranial tumors. Due to its minimal side effects and high local control rate, SRS is widely applied. This paper evaluates the plan quality and secondary cancer risk (SCR) in patients with benign intracranial tumors treated with the CyberKnife M6 system. The CyberKnife M6 robotic radiosurgery system features both multileaf collimator (MLC) and IRIS variable aperture collimator systems, providing different treatment options. The study included 15 patients treated with the CyberKnife M6 system, examining the differences in plan quality and SCR between MLC and IRIS systems. Results showed that MLC and IRIS plans had equal PTV (planning target volume) coverage (98.57% vs. 98.75%). However, MLC plans demonstrated better dose falloff and conformity index (CI: 1.81 ± 0.26 vs. 1.92 ± 0.27, P = 0.025). SCR assessment indicated that MLC plans had lower cancer risk estimates, with IRIS plans having average LAR (lifetime attributable risk) and EAR (excess absolute risk) values approximately 25% higher for cancer induction and 15% higher for sarcoma induction compared to MLC plans. The study showed that increasing tumor volume increases SCR probability, but there was no significant difference between different plans in PTV and brainstem analyses.

Aspirin-Free Strategy for Percutaneous Coronary Intervention in Patients With Oral Anticoagulation: Prespecified Subgroup Analysis From the STOPDAPT-3 Trial.

The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46). The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Long-term spatiotemporal variation of benzo[a]pyrene in Japan: Significant decrease in ambient concentrations, human exposure, and health risk

Although Benzo[a]pyrene (BaP) is considered carcinogenic to humans, the health effects of exposure to ambient levels have not been sufficiently investigated. This study estimated the long-term spatiotemporal variation of BaP in Japan over nearly two decades at a fine spatial resolution of 1 km. This study aimed to obtain an accurate spatiotemporal distribution of BaP that can be used in epidemiological studies on the health effects of ambient BaP exposure. The annual BaP concentrations were estimated using an ensemble machine learning approach using various predictors, including the concentrations and emission intensities of the criteria air pollutants, and meteorological, land use, and traffic-related variables. The model performance, evaluated by location-based cross-validation, exhibited satisfactory accuracy (R2 of 0.693). Densely populated areas showed higher BaP levels and greater temporal reduction, whereas BaP levels remained higher in some industrial areas. The population-weighted BaP in 2018 was 0.12 ng m−3, a decrease of approximately 70% from its 2000 value of 0.44 ng m−3, which was also reflected in the estimated excess number of lung cancer incidences. Accordingly, the proportion of BaP exposure below 0.12 ng m−3, which is the BaP concentration associated with an excess lifetime cancer risk of 10−5, reached 67% in 2018. Our estimates can be used in epidemiological studies to assess the health effects of BaP exposure at ambient concentrations.

Is Declined Cognitive Function Predictive for Fatal Accidents Involving Aging Pilots?

Background. Civil aviation comprises airlines/charters and general aviation (GA). Currently, airlines are experiencing a pilot shortage, partly reflecting scheduled retirements mandatory for airline (but not GA) pilots aged 65 years, fueling a debate as to whether the retirement age should be increased. Herein, using 16–40 years-of-age aviators as a reference, we determined whether GA pilots aged 60+ years (i) incurred an elevated accident rate, employing, for the first time, age-tiered flight time as a measure of risk exposure and (ii) carried an excess risk for cognitive deficiency-related fatal accidents. Methods. Airplane accidents (2002–2016) involving Class 3 medical certificated pilots were per the National Transportation Safety Board (NTSB) databases. Age-tiered pilot risk exposure represented a summation of flight hours per Class 3 medical applications. Cognitive decline measures were per NTSB field codes. Statistical analyses employed Chi-Square, Mann–Whitney, logistic regression, and binomial tests. Results. Using flight hours as the denominator, the fatal accident rate for older pilots (41–80 years) was unchanged compared with aviators aged 16–40 years. In the logistic regression, no cognitive deficiency measure was predictive (p = 0.11, p = 0.15) for pilots aged 61+ years who were involved in fatal accidents. Conclusion. These findings question the necessity of an automatic disqualification of air transport pilots at 65 years of age.

Assessing the Radon Exposure Variability and Lifetime Health Effects across Indoor Microenvironments and Sub-Populations

To assess the health impacts of radon exposure over a lifetime, in the present study, the annual effective dose (AED) and cumulative excess lifetime cancer risk (ELCR-C) were evaluated by considering various indoor microenvironmental exposures based on age-specific time–activity patterns using Monte Carlo simulations. Significant regional variations in indoor radon concentrations across the Republic of Korea were observed, with the highest levels found in schools and single detached houses. Based on the standard annual total of 8760 h spent indoors and outdoors, the AED varied by age group and dwelling type, with the ELCR-C for single detached houses being approximately 1.36 times higher than that for apartments on average. The present study highlights the importance of comprehensive health risk assessments that consider differences across indoor environments and age groups, indicating that limited evaluations of specific sites or areas may distort actual exposure levels.