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SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR

OBJECTIVE To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or RESULTS There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. Results In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004–0.008) and 0.016 (0.010–0.023), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.024 (0.014–0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062–0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. Conclusion Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

To investigate the association between the amount and intensity of leisure-time physical activity (LTPA) and the risk of end-stage renal disease (ESRD).The study examined a cohort of 543,667 participants aged 20 years and older who participated in a health screening program from January 1, 1996, through December 31, 2017. We identified 2520 individuals undergoing dialysis or who had a kidney transplant by linking participants' encrypted personal identification with the registry for ESRD with a median follow-up of 13 years. We classified participants into 5 categories measured by metabolic equivalent of tasks. Within each category, we analyzed the effect of moderate- and vigorous-intensity LTPA in reducing risk of ESRD. We used a Cox proportional hazards model to calculate hazard ratios (HRs).We observed a dose-response relationship between LTPA and the risk of ESRD. The fully active group had a 12% lower hazard of ESRD compared with the no reported LTPA group (HR, 0.88; 95% CI, 0.80 to 0.98) adjusting for covariates including baseline estimated glomerular filtration rate and proteinuria. Within the same category of LTPA, vigorous-intensity exercise carried a 35% lower HR for ESRD compared with moderate-intensity exercise (HR, 0.65; 95% CI, 0.52 to 0.81). The effect was observed stronger among men, younger participants, and participants with diabetes or hyperlipidemia.Sustained LTPA (≥ 150 minutes per week), particularly with vigorous intensity, significantly lowered the ESRD risk, even among individuals with comorbidities such as diabetes or hyperlipidemia. This finding suggested that patients with no reported LTPA with cardiovascular risks should engage in more LTPA to lower their risk of ESRD.

Supplementary Table S6. Relationship among smoking, bilirubin levels and risk for lung cancer incidence/mortality in female participants of the prospective cohort study

Supplementary Figure S5. Levels of the two individual metabolites of interest measured with LC/MS-MS in a case-control study in three phases

Supplementary Methods. Serum total bilirubin levels and lung cancer incidence and mortality rates in overall males and male smokers

Purpose: We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers.Experimental Design: We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case–control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort composed of 425,660 participants.Results: Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (Pinteraction = 0.001).Conclusion: Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer. Clin Cancer Res; 21(1); 193–200. ©2014 AACR.

Supplemental Table 1. Hazard ratios for cancer incidence for different serum iron levels by smoking status. Supplemental Table 2. Cancer mortality risk for different serum iron levels Supplemental Table 3. Comparison of results of first and second test of serum iron. Supplemental Figure 1. J-shaped relationship between serum iron and cancer risk.

Background There are limited renal replacement therapy (RRT) prediction models with good performance in the general population. We developed a model that includes lifestyle factors to improve predictive ability for RRT in the population at large. Methods We used data collected between 1996 and 2017 from a medical screening in a cohort comprising 442 714 participants aged 20 years or over. After a median follow-up of 13 years, we identified 2212 individuals with end-stage renal disease (RRT, n: 2091; kidney transplantation, n: 121). We built three models for comparison: model 1: basic model, Kidney Failure Risk Equation with four variables (age, sex, estimated glomerular filtration rate and proteinuria); model 2: basic model + medical history + lifestyle risk factors; and model 3: model 2 + all significant clinical variables. We used the Cox proportional hazards model to construct a points-based model and applied the C statistic. Results Adding lifestyle factors to the basic model, the C statistic improved in model 2 from 0.91 to 0.94 (95% confidence interval: 0.94, 0.95). Model 3 showed even better C statistic value i.e., 0.95 (0.95, 0.96). With a cut-off score of 33, model 3 identified 3% of individuals with RRT risk in 10 years. This model detected over half of individuals progressing to RRT, which was higher than the sensitivity of cohort participants with stage 3 or higher chronic kidney disease (0.53 versus 0.48). Conclusions Our prediction model including medical history and lifestyle factors improved the predictive ability for end-stage renal disease in the general population in addition to chronic kidney disease population.

Background Kidney diseases are viewed as continuously progressing diseases from microalbuminuria and chronic kidney disease (CKD), to end-stage renal disease (ESRD) and its mortality including deaths. The report on the association between prolonged sitting and kidney diseases is limited. Methods We examined a cohort of 455,506 participants in a screening program in Taiwan conducted between 1996 and 2017. Data on occupational sedentary behavior and physical activity were collected with a standardized questionnaire. The outcomes of ESRD and death were identified by linking with the Catastrophic Illness Dataset and Cause of Death Data. The association between prolonged sitting and CKD, the incidence of ESRD, and death were assessed using logistic regression models to compute odds ratios (ORs) and Cox proportional hazards models for hazard ratios (HRs). Results More than half of the participants, i.e., 265,948 (58.4%), were categorized as “prolonged sitting” during their work. During a median of 13 years of follow-up, we identified 2227 individuals undergoing dialysis and 25,671 deaths. Prolonged occupational sitting was significantly associated with a higher risk of CKD (OR: 1.26, 95% confidence interval: 1.21, 1.31), ESRD (HR: 1.19, 95% CI 1.03, 1.38), and kidney-specific mortality (HR: 1.43, 95% CI 1.07, 1.91) compared to mostly standing participants after controlling for physical activity and other risk factors. Inactive prolonged sitting carries a significantly higher risk of ESRD than physically active mostly standing participants (HR: 1.34, 95% CI 1.04, 1.73). However, active prolonged sitting decreased the risk of ESRD (HR: 1.03, 95% CI 0.79, 1.34) compared to inactive prolonged sitting. Conclusion The results suggest that prolonged occupational sitting is associated with a greater risk of the spectrum of kidney disease, proteinuria, CKD, dialysis (ESRD), and mortality for all causes and kidney diseases. Physical activity, even at a minimal level of 15 min/day (90 min/week) of moderate-intensity exercise, was associated with a reduction in these risks.

Background: Personal Activity Intelligence (PAI) is a physical activity metric that translates heart rate during physical activity into a simple score, where a weekly score of 100 or greater is associated with a lower risk of cardiovascular disease and mortality. Here, we prospectively investigated the association between PAI and ischemic heart disease (IHD) mortality in a large healthy population from China. Methods: Using data from the China Kadoorie Biobank, we studied 443,792 healthy adults (60% women). The weekly PAI score of each participant was estimated based on the questionnaire data and divided into four groups (PAI scores of 0, ≤50, 51–99, or ≥100). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for fatal IHD and nonfatal myocardial infraction (MI) related to PAI were estimated using Cox proportional hazard regression analyses. Results: There were 3050 IHD deaths and 1808 MI events during a median follow-up of 8.2 years (interquartile range, 7.3–9.1; 3.6 million person-years). After adjustments for multiple confounders, a weekly PAI score ≥ 100 was associated with a lower risk of IHD (aHR: 0.91 (95% CI: 0.83–1.00)), compared with the inactive group (0 PAI). The corresponding aHR for MI was 0.94 (95% CI: 0.83–1.05). In participants aged 60 years or older at baseline, the aHR associated with a weekly PAI score ≥ 100 was 0.84 (95% CI, 0.75–0.93) for IHD and 0.84 (95% CI, 0.73–0.98) for MI. Conclusion: Among healthy Chinese adults, a weekly PAI score of 100 or greater was associated with a lower risk of IHD mortality across all age groups; moreover, a high PAI score significantly lowered the risk of MI but only in those 60 years and older at baseline. The present findings extend the scientific evidence that PAI may have prognostic significance in diverse settings for IHD outcomes and suggest that the PAI metric may be useful in delineating the magnitude of weekly physical activity needed to reduce the risk of IHD mortality.

Objective: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. Research Design and Methods: In this individual participant data meta-analysis, 43 cohorts (N=1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and eGFR (≥60 or Results: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, anti-hypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and body-mass index (and hemoglobin A1c, insulin use, and oral diabetes medication use in those with diabetes). The median C-statistic was 0.774 (interquartile range [IQR]: 0.753, 0.782) in the diabetes/higher eGFR validation cohorts, 0.769 (IQR: 0.758, 0.808) in the diabetes/lower eGFR validation cohorts, 0.740 (interquartile range [IQR]: 0.717, 0.763) in the no diabetes/higher eGFR validation cohorts, and 0.750 (IQR: 0.731, 0.785) in the no diabetes/lower eGFR validation cohorts. Incorporating previous 2-year eGFR slope minimally improved model performance, and only in the higher eGFR cohorts. Conclusions: Novel prediction equations for an eGFR decline of ≥40% eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Background The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. Methods We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. Results During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). Conclusions This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

ImportanceIndividuals with prediabetes have a higher risk of death than healthy individuals. However, previous findings have suggested that individuals with reversion from prediabetes to normoglycemia may not have a lower risk of death compared with individuals with persistent prediabetes.ObjectivesTo investigate the associations between changes in prediabetes status and risk of death and to elucidate the roles of modifiable risk factors in these associations.Design, Setting, and ParticipantsThis population-based prospective cohort study used data from 45 782 participants with prediabetes from the Taiwan MJ Cohort Study who were recruited between January 1, 1996, and December 31, 2007. Participants were followed up from the second clinical visit to December 31, 2011, with a median (IQR) follow-up of 8 (5-12) years. Participants were categorized into 3 groups according to changes in their prediabetes status within a 3-year period after initial enrollment: reversion to normoglycemia, persistent prediabetes, and progression to diabetes. Cox proportional hazards regression models were used to examine the associations between changes in prediabetes status at baseline (ie, the second clinical visit) and risk of death. Data analysis was performed between September 18, 2021, and October 24, 2022.Main Outcomes and MeasuresAll-cause mortality, cardiovascular disease (CVD)–related mortality, and cancer-related mortality.ResultsOf 45 782 participants with prediabetes (62.9% male; 100% Asian; mean [SD] age, 44.6 [12.8] years), 1786 (3.9%) developed diabetes and 17 021 (37.2%) reverted to normoglycemia. Progression from prediabetes to diabetes within a 3-year period was associated with higher risks of all-cause death (hazard ratio [HR], 1.50; 95% CI, 1.25-1.79) and CVD-related death (HR, 1.61; 95% CI, 1.12-2.33) compared with persistent prediabetes, while reversion to normoglycemia was not associated with a lower risk of all-cause death (HR, 0.99; 95% CI, 0.88-1.10), cancer-related death (HR, 0.91; 95% CI, 0.77-1.08), or CVD-related death (HR, 0.97; 95% CI, 0.75-1.25). Among individuals who were physically active, reversion to normoglycemia was associated with a lower risk of all-cause death (HR, 0.72; 95% CI, 0.59-0.87) compared with those with persistent prediabetes who were physically inactive. Among individuals with obesity, risk of death varied between those who experienced reversion to normoglycemia (HR, 1.10; 95% CI, 0.82-1.49) and those who had persistent prediabetes (HR, 1.33; 95% CI, 1.10-1.62).Conclusions and RelevanceIn this cohort study, although reversion from prediabetes to normoglycemia within a 3-year period did not mitigate the overall risk of death compared with persistent prediabetes, risk of death associated with reversion to normoglycemia varied based on whether individuals were physically active or had obesity. These findings highlight the importance of lifestyle modification among those with prediabetes status.

Although the link between sugar-sweetened beverages (SSB) and pancreatic cancer has been suggested for its insulin-stimulating connection, most epidemiological studies showed inconclusive relationship. Whether the result was limited by sample size is explored. This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with the National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. We classified the amount of SSB intake into 4 categories: 0–

Background Although biological aging has been proposed as a more accurate measure of aging, few biological aging measures have been developed for Asians, especially for young adults. Methods A total of 521 656 participants were enrolled in the MJ cohort (1996–2011) and were followed until death, loss-to-follow-up, or December 31, 2011, whichever came first. We selected 14 clinical biomarkers, including chronological age, using a random forest algorithm, and developed a multidimensional aging measure (MDAge). Model performance was assessed by area under the curve (AUC) and internal calibration. We evaluated the associations of MDAge and residuals from regressing MDAge on chronological age (MDAgeAccel) with mortality and morbidity, and assessed the robustness of our findings. Results MDAge achieved an excellent AUC of 0.892 in predicting all-cause mortality (95% confidence interval [CI]: 0.889–0.894). Participants with higher MDAge at baseline were at a higher risk of death (per 5 years, hazard ration [HR] = 1.671, 95% CI: 1.662–1.680), and the association remained after controlling for other variables and in different subgroups. Furthermore, participants with higher MDAgeAccel were associated with shortened life expectancy. For instance, compared to men who were biologically younger (MDAgeAccel ≤ 0) at baseline, men in the highest tertiles of MDAgeAccel had shortened life expectancy by 17.23 years. In addition, higher MDAgeAccel was associated with having chronic disease either cross-sectionally (per 1-standard deviation [SD], odds ratio [OR] = 1.564, 95% CI: 1.552–1.575) or longitudinally (per 1-SD, OR = 1.218, 95% CI: 1.199–1.238). Conclusion MDAge accurately predicted mortality and morbidity, which has great potential in the early identification of individuals at higher risk and therefore promoting early intervention.

IntroductionIn Taiwan, national tobacco use surveys show that e-cigarette use has increased since 2014 among youth, while, at the same time, conventional cigarette smoking has continuously decreased. The purpose of this study is to examine whether the increased popularity of e-cigarettes has undermined this favourable declining trend for cigarette smoking.MethodsWe examined conventional cigarette and e-cigarette prevalence among male high school students (aged 16–18 years) and adults from 2004 to 2017, using data from cross-sectional nationally representative surveys. Applying interrupted time series analysis, we assessed whether there was a change in trend in 2014, when e-cigarette use started to gain popularity from long-term trends in prior years (2004–2013).ResultsE-cigarette use prevalence increased from 2.5% in 2014 to 6.4% in 2017 among male high school students but was negligible among male adults, declining from 1.4% in 2015 to 0.8% in 2017. The annual relative decline in the cigarette smoking rate after e-cigarettes started to gain popularity was greater (−10%) than the long-term trend (−2%) among high school students. Among adults, the change in trend over time after e-cigarettes started to gain popularity was not significant (ie, not significantly different from 0).ConclusionsThe increased popularity of e-cigarettes since 2014 is associated with a greater decline in youth smoking, compared with previous years. On the contrary, e-cigarette use has remained very low among Taiwanese male adults and no additional impact on the conventional smoking trend is found.

BackgroundFor the first time, the 2020 WHO guidelines on physical activity recommend reducing sedentary behaviors due to their health consequences. Less is known on the effect of prolonged occupational sitting, especially in the context of low physical activity engagement.This study aims at quantifying cardiovascular risk associated with prolonged occupational sitting and determining the additional amount of physical activity that may be needed to attenuate it.MethodsA cohort comprising 481,688 participants in a health surveillance program in Taiwan was followed between 1996 and 2017, collecting data on occupational sitting time, leisure-time physical activity (LTPA) habits, lifestyle, and metabolic parameters. The all-cause and expanded cardiovascular disease (CVD + diabetes mellitus + kidney disease) mortality associated with three occupational sitting volumes (mostly sitting, alternating sitting and non-sitting, mostly non-sitting) was analyzed applying multivariate Cox regression models to calculate the hazard ratios (HRs) for all participants and by subgroups, including five levels of LTPA. Deaths in the first two years of follow-up were excluded to avoid reverse causality.ResultsThe study recorded 26,257 deaths during a mean follow-up period of 12.85 years. Individuals mostly sitting at work had a higher mortality risk than those mostly non-sitting, both from all causes (HR: 1.16, 95% CI: 1.11-1.20) and from expanded CVD (HR:1.46, 95% CI:1.35-1.58), after adjusting for gender, age, education, smoking, drinking, and body mass index. Individuals alternating sitting and non-sitting at work did not experience increased risk for all-cause mortality, compared to individuals mostly non-sitting at work (HR: 1.01, 95% CI: 0.97-1.05), but did experience higher risk of deaths due to expanded CVD (HR: 1.13, 95% CI: 1.04-1.23). Individuals engaged in low (15-29 min/day) or no (

Key Points Question What happens to lung cancer incidence when lung cancer screening is promoted to a population with a smoking prevalence of less than 5%? Findings In this population-based ecological cohort study of approximately 12 million Taiwanese women, the promotion of lung cancer screening was associated with a 6-fold increase in the incidence of early-stage (stages 0-I) lung cancer from 2004 to 2018, whereas there was no change in the incidence of late-stage (stages II-IV) lung cancer. Five-year survival rates have more than doubled to 40% despite stable lung cancer mortality. Meaning Lung cancer screening in a largely nonsmoking population was associated with considerable overdiagnosis and spuriously high 5-year survival rates., This cohort study investigates whether opportunistic screening for lung cancer among Taiwanese women who rarely smoke is associated with overdiagnosis of lung cancer., Importance As smoking continues to decline in many developed countries, the proportion of lung cancers in nonsmokers will rise. This shift may create substantial pressure to further expand lung cancer screening to lower-risk groups. Objective To determine the association of lung cancer incidence with the promotion of screening in a largely nonsmoking population. Design, Setting, and Participants This population-based ecological cohort study of stage-specific lung cancer incidence used the Taiwan Cancer Registry to identify women diagnosed with lung cancer from January 1, 2004, to December 31, 2018. Smoking prevalence among Taiwanese women has been less than 5% since 1980. Data were analyzed from February 13, 2020, to November 10, 2021. Exposures Low-dose computed tomography (LDCT) screening for lung cancer, initiated during the early 2000s. Main Outcomes and Measures Change in stage-specific lung cancer incidence. An effective cancer screening program will not only increase the incidence of early-stage cancer but also decrease the incidence of cancer presenting at a late stage. Results A total of 57 898 women were diagnosed with lung cancer in a population of approximately 12 million Taiwanese women. After the introduction of LDCT screening, the incidence of early-stage (stages 0-I) lung cancer in women increased more than 6-fold, from 2.3 to 14.4 per 100 000 population (absolute difference, 12.1 [95% CI, 11.3-12.8]) from 2004 to 2018. There was no change, however, in the incidence of late-stage (stages II-IV) lung cancer, from 18.7 to 19.3 per 100 000 (absolute difference, 0.6 [95% CI, –0.5 to 1.7]). Because the additional 12.1 per 100 000 early-stage cancers were not accompanied by a concomitant decline in late-stage cancers, virtually all the additional cancers detected represent overdiagnosis. Despite stable mortality, 5-year survival more than doubled from 2004 to 2013, from 18% to 40%, which is arguably the highest lung cancer survival rate in the world. Conclusions and Relevance This population-based ecological cohort study found that low-dose computed tomographic screening of mostly nonsmoking Asian women was associated with considerable lung cancer overdiagnosis. Five-year survival is biased by the increased LDCT detection of indolent early-stage lung cancers. Unless randomized trials can demonstrate some value to low-risk groups, LDCT screening should remain targeted only to heavy smokers.

Background Prediction models of colorectal cancer (CRC) had limited application for not being user-friendly. Whether fecal immunochemical tests (FITs) can help predict CRC has been overlooked. Patients and methods With 1972 CRCs identified, 234 044 adults aged ≥40 years were successively enrolled between 1994 and 2008. Prediction models were developed by questionnaire/medical screening and quantitative FIT. NNS (number needed to scope to find one cancer) is time dependent, spanning entire study period. Significant ‘risk factors’ were family history, body mass index, smoking, drinking, inactivity, hypertension, diabetes, carcinoembryonic antigen, and C-reactive protein. Results Positive FIT (≥20 μg/g hemoglobin/feces) had cancer risk 10-fold larger than negative FIT, and within each age group, another 10-fold difference. The C statistic of FIT (0.81) with age and sex alone was superior to the ‘common risk-factors’ model (0.73). NNS, stratified by age and by FIT values, demonstrated a scorecard of cancer risks, like 1/15 or 1/25, in 5 years. When FIT was negative, cancer risk was small (1/750-1/3000 annually). The larger the FIT, the sooner the appearance of CRC. For every 80-μg/g increase of FIT, there were 1.5-year earlier development of CRC incidence and 1-year earlier development of CRC mortality, respectively. Given the same FIT value, CRC events appeared in the proximal colon sooner than the distal colon. Conclusions A simple user-friendly model based on a single FIT value to predict CRC risk was developed. When positive, NNS offered a simple quantitative value, with a better precision than most risk factors, even combined. When FIT is negative, risk is very small, but requiring a repeat every other year to rule out false negative. FIT values correlated well with CRC prognosis, with worst for proximal CRC., Highlights • By incorporating a single FIT test, a user-friendly CRC scorecard showed C statistic at 0.81, implying great accuracy. • A simple score sheet with FIT value stratified by age facilitates the risk prediction for colonoscopy referral. • For each positive FIT value, an NNS can be looked up from the scorecard. • When FIT was negative, risks were very small but required repetition every other year to guard against false negative.

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished “modest drinker” (no more than one drink a day) from “regular drinker”. Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65–1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86–0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35–1.52) and shortened life by 6.9 years (95% CI 6.6–7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6–2.4 years) in modest drinker and 10.3 years (95% CI 9.8–10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38–4.01) and esophageal (HR 3.83, CI 1.90–7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.

IntroductionAdult smoking prevalence in Taiwan rapidly declined from 26.5% in 2005 to 20.0% in 2015. Nevertheless, future projections on smoking-attributable deaths and current per capita consumption do not paint an equally bright picture.MethodsWe used SimSmoke, a tobacco control simulation model to assess the impact of tax increases and other policies by predicting past and projecting over future decades smoking rates and smoking-attributable mortality.ResultsThe model accurately depicts the decline in smoking prevalence observed in Taiwan from 2000 to 2015. Nonetheless, under the ‘status quo’ scenario, smoking-attributable mortality is projected to continue growing, peaking at 26 602 annual deaths in 2039 and cumulative deaths >1 million by 2044. By comparing projections with current policies with a counterfactual scenario based on the 2000 policy levels, SimSmoke estimates that tobacco control in Taiwan has been able to reduce smoking prevalence by 30% in 2015 with 450 000 fewer smoking-attributable deaths by 2060. Modified scenarios show that doubling the retail price of cigarettes and fully implementing the remaining MPOWER measures would avert approximately 45 000 lives by 2040 and 130 000 by 2060.ConclusionsTobacco will be a leading cause of death in Taiwan for the coming decades, showing yet again the long-term consequences of smoking on public health. The MPOWER package, even if adopted at the highest level with a large tax increase, is unlikely to reduce smoking prevalence to the endgame goal of 5% in the next five decades.

Importance Personal activity intelligence (PAI) is a novel activity metric that can be integrated into self-assessment heart rate devices, and translates heart rate variations during exercise into a weekly score. Previous studies relating to PAI have been conducted in the same populations from Norway where the PAI metric has been derived, limiting generalizability of the results. Objective To test whether PAI is associated with total and cause-specific mortality in a large cohort from the United States. Design Aerobics Center Longitudinal Study (ACLS) - a prospective cohort between January 1974 and December 2002 with a mean follow-up of 14.5 years. Setting Population-based. Participants 56,175 relatively healthy participants (26.5% women) who underwent extensive preventive medical examinations at Cooper Clinic (Dallas, TX). Exposure Personal activity intelligence (PAI) score per week was estimated and divided into 4 groups (PAI scores of 0, ≤50, 51-99, and ≥100). Main outcomes and measures Total and cause-specific mortality. Results During a median follow-up time of 14.9 (interquartile range, 6.7-21.4) years, there were 3434 total deaths including 1258 cardiovascular (CVD) deaths. Compared with the inactive (0 PAI) group, participants with a baseline weekly ≥100 PAI had lower risk of mortality: adjusted hazard ratio (AHR), 0.79: 95% CI, 0.71-0.87 for all-cause mortality, and AHR, 0.72: 95% CI, 0.60-0.87 for CVD mortality among men; AHR, 0.85: 95% CI, 0.64-1.12 for all-cause mortality, and AHR, 0.48: 95% CI, 0.26-0.91 for CVD mortality among women. For deaths from ischemic heart disease (IHD), PAI score ≥100 was associated with lower risk in both men and women (AHR, 0.70: 95% CI, 0.55-0.88). Obtaining ≥100 weekly PAI was also associated with significantly lower risk of CVD mortality in pre-specified age groups, and in participants with known CVD risk factors. Participants with ≥100 weekly PAI gained 4.2 (95% CI, 3.5-4.6) years of life when compared with those who were inactive at baseline. Conclusions and relevance PAI is associated with long-term all-cause, CVD, and IHD, mortality. Clinicians and the general population can incorporate PAI recommendations and thresholds in their physical activity prescriptions and weekly physical activity assessments, respectively, to maximize health outcomes. Key points Question: What is the association between personal activity intelligence (PAI), a novel activity metric, and mortality in a large cohort from the United States? Findings In this prospective study of 56,175 healthy participants at baseline, followed-up for a mean of 14.5 years, ≥100 PAI score/week was associated with significant 21% lower risk of all-cause and 30% lower risk of CVD mortality in comparison with inactive people. Participants with ≥100 PAI/week lived on average 4.2 years longer compared with inactive. Meaning: PAI is associated with long-term all-cause and CVD mortality. Clinicians and general population may incorporate PAI recommendations into weekly physical activity assessments to maximize CVD prevention.

Background and objectives: Mortality risk of resting heart rate (RHR) has been shown to be an independent risk factor for mortality but attracted limited attention, particularly compared to hypertension. We focused on high normal RHR (80-99 beats/min), and sought equivalent risks at levels of blood pressure in hypertension. Methods: The cohort, 515,303 subjects free of heart disease, recruited successively from a health surveillance program between 1994 and 2008. Resting HR was determined from ECG. Deaths, 16,849, were identified from national death file as of 2011. A CVD-free sub-cohort was created by excluding those with hypertension, diabetes, smoking or high cholesterol. Life table method for life expectancy and Cox models for Hazard Ratios were calculated using RHR at 60-69/min and BP at ≦120/80 mmHg, as a common reference. Results: One quarter of the cohort had high normal RHR, but only 1/3 of high normal RHR had hypertension, implying a limited contribution of risks from hypertension to RHR. High normal RHR (80-99/min) as a whole had similar all-cause mortality risks (1.73), and similar number of life years shortened (6.7 years) as hypertension (≧140/90 mm Hg), but larger than JACC hypertension (≧130/80). RHR at 90-99/min had similar mortality risks (2.17) and years shortened (9.5 years) as Grade 2 hypertension (≧160/100 mmHg). In these comparisons, HR for CVD mortality, however, were slightly smaller for high normal RHR than hypertension. Other than increased CVD mortality, high normal RHR had more increases in diabetes, cancer, cirrhosis, kidney and COPD, Mortality risk of hypertension amplified by 20% when combined with high normal RHR. Conclusion: High normal RHR had larger risk than hypertension with BP at≧130/80, but similar as BP at ≧140/90 mmHg. RHR is as important as hypertension, in terms of all-cause mortality or in number of life years shortened. The CVD mortality risks of RHR, however, were slightly less, implying a more important role of hypertension in CVD.

Background and Purpose— The observation that smokers with stroke could have better outcome than nonsmokers led to the term “smoking paradox.” The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods— Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994–2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results— A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions— “The more you smoke, the earlier you stroke, and the longer sufferings you have to cope.” Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.

Background Biological markers of suicide risk have the potential to inform prevention and treatment efforts. It has recently been hypothesised that inflammation may influence mood and in turn suicide risk. We investigated the association between indicators of systemic inflammation and suicide in a large cohort of Taiwanese adults.Methods White blood cell (WBC) count and levels of C-reactive protein (CRP) weremeasured in 462,747 and 359,849 adults in the Taiwan MJ cohort, respectively. The associations between WBC, CRP and suicide risk were investigated using Coxproportional hazards models adjusting for a range of potential confounding factors.Results During a mean 15.1 and 15.8 years of follow-up, 687 and 605 suicides were identified in participants who had information on WBC and CRP respectively. There was an association of suicide with WBC count (adjusted hazard ratio [aHR] = 1.13 per 1 standard deviation increase of log-transformed WBC, 95% confidence interval [CI] 1.09, 1.77). The association was driven by the highest quintile of WBC count (aHR = 1.39, 95% CI 1.09, 1.77; reference: the lowest quintile). No association between CRP and suicide was found. Limitations Our cohort was from a privately-run health check-up programme and had a lower suicide rate than that in the general population.Conclusions Individuals with the highest WBC counts may have increased risk ofsuicide. Peripheral markers of inflammation are potential biomarkers of suicide risk; however, this seems to vary by population and the marker investigated and could be influenced by a range of confounding factors.

Introduction: The COVID-19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo-temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID-19. Method: Using the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22-59 years. Results: Among the infected Chinese healthcare workers whose symptoms onset appeared during the same ten-day period, the percentage of those in severe conditions decreased statistical significantly from 19.7% (Jan 11 – 20) to 14.4% (Jan 21 – 31) to 8.7% (Feb 1 – 11). Across the country, there was also a significant difference in the disease severity among patients symptoms onset during the same period, with Wuhan being the most severe (17%), followed by Hubei Province (10.4%), and the rest of China (7.0%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20-59 years -- 0.3% (5/1,688) vs. 0.65% (193/29,798), respectively. Conclusion: The disease severity improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID-19 for those who have access to quality healthcare. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest.