The Kidney Failure Risk Equation: Evaluation of Novel Input Variables including eGFR Estimated Using the CKD-EPI 2021 Equation in 59 Cohorts.

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 <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.

Association between plant-based dietary pattern and biological aging trajectory in a large prospective cohort.

BACKGROUND: Aging is a dynamic and heterogeneous process that may better be captured by trajectories of aging biomarkers. Biological age has been advocated as a better biomarker of aging than chronological age, and plant-based dietary patterns have been found to be linked to aging. However, the associations of biological age trajectories with mortality and plant-based dietary patterns remained unclear. METHODS: Using group-based trajectory modeling approach, we identified distinctive aging trajectory groups among 12,784 participants based on a recently developed biological aging measure acquired at four-time points within an 8-year period. We then examined associations between aging trajectories and quintiles of plant-based dietary patterns assessed by overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) among 10,191 participants who had complete data on dietary intake, using multivariable multinomial logistics regression adjusting for sociodemographic and lifestyles factors. Cox proportional hazards regression models were applied to investigate the association between aging trajectories and all-cause mortality. RESULTS: We identified three latent classes of accelerated aging trajectories: slow aging, medium-degree, and high-degree accelerated aging trajectories. Participants who had higher PDI or hPDI had lower odds of being in medium-degree (OR = 0.75, 95% CI: 0.65, 0.86 for PDI; OR = 0.73, 95% CI: 0.62, 0.85 for hPDI) or high-degree (OR = 0.63, 95% CI: 0.46, 0.86 for PDI; OR = 0.62, 95% CI: 0.44, 0.88 for hPDI) accelerated aging trajectories. Participants in the highest quintile of uPDI were more likely to be in medium-degree (OR = 1.72, 95% CI: 1.48, 1.99) or high-degree (OR = 1.70, 95% CI: 1.21, 2.38) accelerated aging trajectories. With a mean follow-up time of 8.40 years and 803 (6.28%) participants died by the end of follow-up, we found that participants in medium-degree (HR = 1.56, 95% CI: 1.29, 1.89) or high-degree (HR = 3.72, 95% CI: 2.73, 5.08) accelerated aging trajectory groups had higher risks of death than those in the slow aging trajectory. CONCLUSIONS: We identified three distinctive aging trajectories in a large Asian cohort and found that adopting a plant-based dietary pattern, especially when rich in healthful plant foods, was associated with substantially lowered pace of aging.

Are e-cigarettes reviving the popularity of conventional smoking among Taiwanese male adolescents? A time-trend population-based analysis for 2004-2017.

INTRODUCTION: In 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. METHODS: We 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). RESULTS: E-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). CONCLUSIONS: The 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.

Smoking Paradox in Stroke Survivors?: Uncovering the Truth by Interpreting 2 Sets of Data.

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.

Air pollution is not 'the new smoking': comparing the disease burden of air pollution and smoking across the globe, 1990-2017.

Air pollution has been labelled the 'new smoking', with news articles bearing titles such as 'If You Live in a Big City You Already Smoke Every Day' and 'The Air Is So Bad in These Cities, You May As Well Be Smoking'. Dr Tedros Adhanom Ghebreyesus, WHO Director-General, highlighted this attention-catching comparison, saying, 'The world has turned the corner on tobacco. Now it must do the same for the 'new tobacco' - the toxic air that billions breathe every day' and 'Globally, with smoking on the decline, air pollution now causes more deaths annually than tobacco' at the First Global Conference on Air Pollution and Health in 2018. The suggestion that the world has turned the corner on tobacco control and the reference to air pollution as the 'new smoking' raise a number of concerns. We generate outputs from GBD Compare (the online data visualisation tool of the Global Burden of Diseases and Injuries (GBD) Study) to demonstrate historical disease burden trends in terms of disability-adjusted life years and age-standardised mortality attributable to air pollution and tobacco use from 1990 to 2017 across the globe. We find that the disease burden caused by ambient air pollution declined significantly faster than the burden caused by tobacco use. We conclude that the world is still far from turning the corner on the tobacco endemic. Further, the suggestion that air pollution is as bad as actual smoking is not only inaccurate but also potentially dangerous to public health.

Tobacco control within and beyond WHO MPOWER: outcomes from Taiwan SimSmoke.

INTRODUCTION: Adult 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Tobacco 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.

Loss of Life Expectancy by 10 Years or More From Elevated Aspartate Aminotransferase: Finding Aspartate Aminotransferase a Better Mortality Predictor for All-Cause and Liver-Related than Alanine Aminotransferase.

OBJECTIVES: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled. METHODS: The cohort, 416,122 adults, came from a self-paying comprehensive health surveillance program during 1994-2008 and was followed up till 2008. Mortality came from National Death Index, with 10,412 deaths identified. Hazard ratios (HRs), computed by Cox model, and life expectancy, by life table method, were presented for 5 levels of AST and ALT with elevated AST or ALT defined as ≥40 IU/L. Liver disease included liver cancer and other liver conditions. RESULTS: There were 3 times more elevated ALT (15.4%) than AST (5.7%). However, those with elevated AST had higher mortality for all-cause (HR = 2.44), for liver disease (HR = 27.2), and for liver cancer (HR = 47.6) than its ALT counterparts (HR = 1.69, 10.8, and 20.2, respectively). Elevated AST also lost more years of life expectancy (10.2) than those lost by ALT (5.2) and larger than most common risks. Elevated AST had increased mortality from all cancers (HR = 3.57), stroke (HR = 1.36), respiratory diseases (HR = 1.34), and injuries (HR = 1.82), other than just liver disease. All-cause mortality remained significantly increased, when high risk groups were excluded, such as frequent drinkers, hepatitis carriers, those died from nonmedical conditions, those died in the first 3 years, or advanced fibrosis index based on 4 factors or aspartate transaminase-to-platelet ratio index. Results were consistent between those returned for second visits and those analyzed in initial visits. DISCUSSION: Those with elevated AST (≥40 IU/L) had life expectancy cut short by 10.2 years, doubled the number of years lost with elevated ALT. For all-cause and for liver-related mortality, AST was an important predictor, better than ALT.

Exploiting a low tax system: non-tax-induced cigarette price increases in Taiwan 2011-2016.

INTRODUCTION: This study aims to analyse the non-tax-induced price increasing strategies adopted by tobacco industry in Taiwan, a high-income country with comprehensive tobacco control policies but low tobacco taxes and a declining cigarette market. METHODS: Using governmental tax, price and inflation data, we analysed cigarette sales volume, affordability, affordability elasticity of demand, market share, pricing and net revenue of the top five tobacco companies in Taiwan from 2011 to 2016 when no tax increases occurred. RESULTS: Total revenue after tax grew significantly for all the major transnational tobacco companies between 2011 and 2016 at the expense of the state-owned Taiwan Tobacco and Liquor Corporation. In terms of market share, Japan Tobacco (JT) was the leading company, despite experiencing a small decline, while British American Tobacco and Imperial Brands remained stable, and Philip Morris International increased from 4.7% to 7.0%. JT adopted the most effective pricing strategy by increasing the real price of its two most popular brands (Mevius and Mi-Ne) and, at the same time, doubling the sales of its cheaper and less popular brand Winston by leaving its nominal retail price unaltered. CONCLUSIONS: Low and unchanged tobacco taxes enable tobacco companies to use aggressive pricing and segmentation strategies to increase the real price of cigarettes without making them less affordable while simultaneously maintaining customers' loyalty. It is crucial to continue monitoring the industry's pricing strategies and to regularly increase taxes to promote public health and to prevent tobacco industry from profiting at the expense of government revenues.

Defining a global research and policy agenda for betel quid and areca nut.

Betel quid and areca nut are known risk factors for many oral and oesophageal cancers, and their use is highly prevalent in the Asia-Pacific region. Additionally, betel quid and areca nut are associated with health effects on the cardiovascular, nervous, gastrointestinal, metabolic, respiratory, and reproductive systems. Unlike tobacco, for which the WHO Framework Convention on Tobacco Control provides evidence-based policies for reducing tobacco use, no global policy exists for the control of betel quid and areca nut use. Multidisciplinary research is needed to address this neglected global public health emergency and to mobilise efforts to control betel quid and areca nut use. In addition, future research is needed to advance our understanding of the basic biology, mechanisms, and epidemiology of betel quid and areca nut use, to advance possible prevention and cessation programmes for betel quid and areca nut users, and to design evidence-based screening and early diagnosis programmes to address the growing burden of cancers that are associated with use.

Diabetes with early kidney involvement may shorten life expectancy by 16 years.

This study aimed to identify the excess risks associated with diabetic patients with early kidney involvement (early diabetic kidney disease). The mortality risks of early diabetic kidney disease, defined as diabetes in early stages 1-3 chronic kidney disease (CKD), were assessed from a cohort of 512,700 adults in Taiwan participating in a health surveillance program from 1994-2008. Three related groups were identified and compared: diabetes without CKD, early diabetic kidney disease, and early CKD without diabetes. Deaths were ascertained through the National Death Registry. One-third of diabetics had early kidney disease, and approximately two-thirds of patients were classified with early CKD due to proteinuria. Patients with early diabetic kidney disease had more lifestyle risks such as inactivity or obesity, which characteristically amplified excess mortality by up to five times. The three-fold increase in all-cause mortality (hazard ratio 3.16) and a 16-year loss in life expectancy made early diabetic kidney disease a serious and yet often overlooked disease, with most patients unaware of their kidney involvement. Mortality for early diabetic kidney disease was nearly twice as high as that for early CKD (hazard ratio 2.01) or diabetes without CKD (hazard ratio 1.79). The 16-year life span loss is much worse than individually from early CKD (six years) or diabetes (ten years). Thus, identifying early proteinuria among diabetic patients and realizing the importance of reducing lifestyle risks like inactivity is a clinical challenge, but can save lives.

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

BACKGROUND: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. METHODS: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. RESULTS: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. CONCLUSIONS: Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Extending Colorectal Cancer Screening to Persons Aged 40 to 49 Years With Immunochemical Fecal Occult Blood Test: A Prospective Cohort Study of 513,283 Individuals.

GOALS: To assess the association between the initial immunochemical fecal occult blood tests (FIT) and subsequent colorectal cancer, and to explore the ability of FIT to identify individuals age 40 to 49 years with a higher cancer risk. BACKGROUND: The number of cancer cases in this age group is increasing globally and the cancers found in younger age tend to be more advanced than in older age. METHODS: A total of 513,283 individuals had FIT as part of their self-paying medical screening program between 1994 and 2008. The initial FIT test was used. When matched with the Taiwan cancer registry, the cohort identified 2138 colorectal cancer cases. The number needed to screen (NNS) to identify 1 cancer was calculated from the reciprocal of cancer incidence cases during the study period. RESULTS: One in 7 colorectal cancers above age 40 years occurred in the age group of 40 to 49 years. Individuals 40 to 49 years old with positive FIT (≥100 ng/mL) had a 3 times larger cancer risk than those 50 to 59 years old and without FIT, or double the cancer risk as those 50 to 69 years old and without FIT, with NNS at 42, 135, and 95, respectively. A similar relationship existed for the cancer incidence rate. The HR for ages 40 to 44 years or 45 to 49 years with a positive FIT was 2.3 or 5.7 times larger than the HR for ages 50 to 54 years. There was a dose-response relationship between increasing FIT values and the cancer risk for each age group, including ages 40 to 49 years. CONCLUSIONS: Offering FIT to individuals 40 to 49 years of age could identify higher-risk individuals earlier for follow-up colonoscopy, and could, in turn, reduce cancer mortality.

Attenuating the mortality risk of high serum uric acid: the role of physical activity underused.

BACKGROUND: High serum uric acid (sUA) has been associated with increased mortality risks, but its clinical treatment varied with potential side effects. The role of physical activity has received limited attention. METHODS: A cohort, consisting of 467 976 adults, who went through a standard health screening programme, with questionnaire and fasting blood samples, was successively recruited between 1996 and 2008. High sUA is defined as uric acid above 7.0 mg/dL. Leisure time physical activity level was self-reported, with fully active defined as those with 30 min per day for at least 5 days a week. National death file identified 12 228 deaths with a median follow-up of 8.5 years. Cox proportional model was used to analyse HRs, and 12 variables were controlled, including medical history, life style and risk factors. FINDINGS: High sUA constituted one quarter of the cohort (25.6%). Their all-cause mortality was significantly increased [HR: 1.22 (1.15-1.29)], with much of the increase contributed to by the inactive (HR: 1.27 (1.17-1.37)), relative to the reference group with sUA level of 5-6 mg/dL. When they were fully active, mortality risks did not increase, but decreased by 11% (HR: 0.89 (0.82-0.97)), reflecting the benefits of being active was able to overcome the adverse effects of high sUA. Given the same high sUA, a 4-6 years difference in life expectancy was found between the active and the inactive. CONCLUSIONS: Physical activity is a valuable alternative to pharmacotherapy in its ability to reduce the increases in mortality risks from high sUA. By being fully active, exercise can extend life span by 4-6 years, a level greater than the 1-4 years of life-shortening effect from high sUA.

Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.

Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.

Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.

Since the first description of the association between chronic kidney disease and heart disease, many epidemiological studies have confirmed and extended this finding. As chronic kidney disease progresses, kidney-specific risk factors for cardiovascular events and disease come into play. As a result, the risk for cardiovascular disease is notably increased in individuals with chronic kidney disease. When adjusted for traditional cardiovascular risk factors, impaired kidney function and raised concentrations of albumin in urine increase the risk of cardiovascular disease by two to four times. Yet, cardiovascular disease is frequently underdiagnosed and undertreated in patients with chronic kidney disease. This group of patients should, therefore, be acknowledged as having high cardiovascular risk that needs particular medical attention at an individual level. This view should be incorporated in the development of guidelines and when defining research priorities. Here, we discuss the epidemiology and pathophysiological mechanisms of cardiovascular risk in patients with chronic kidney disease, and discuss methods of prevention.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Occupational Sitting Time, Leisure Physical Activity, and All-Cause and Cardiovascular Disease Mortality.

Importance: For the first time, the 2020 World Health Organization guidelines on physical activity recommended reducing sedentary behaviors owing to their health consequences. Less is known on the specific association of prolonged occupational sitting with health, especially in the context of low physical activity engagement. Objective: To quantify health risks associated with prolonged occupational sitting and to determine whether there is a certain threshold of physical activity that may attenuate it. Design, Setting, and Participants: This prospective cohort study included participants in a health surveillance program in Taiwan who were followed-up between 1996 and 2017. Data on occupational sitting, leisure-time physical activity (LTPA) habits, lifestyle, and metabolic parameters were collected. Data analysis was performed in December 2020. Main Outcomes and Measures: The all-cause and cardiovascular disease (CVD) mortality associated with 3 occupational sitting volumes (mostly sitting, alternating sitting and nonsitting, and mostly nonsitting) were analyzed applying multivariable Cox regression models to calculate the hazard ratios (HRs) for all participants and by subgroups, including 5 LTPA levels and a personal activity intelligence (PAI)-oriented metric. Deaths occurring within the initial 2 years of follow-up were excluded to prevent reverse causality. Results: The total cohort included 481 688 participants (mean [SD] age, 39.3 [12.8] years; 256 077 women [53.2%]). The study recorded 26 257 deaths during a mean (SD) follow-up period of 12.85 (5.67) years. After adjusting for sex, age, education, smoking, drinking, and body mass index, individuals who mostly sat at work had a 16% higher all-cause mortality risk (HR, 1.16; 95% CI, 1.11-1.20) and a 34% increased mortality risk from CVD (HR, 1.34; 95% CI, 1.22-1.46) compared with those who were mostly nonsitting at work. Individuals alternating sitting and nonsitting at work did not experience increased risk of all-cause mortality compared with individuals mostly nonsitting at work (HR, 1.01; 95% CI, 0.97-1.05). For individuals mostly sitting at work and engaging in low (15-29 minutes per day) or no (<15 minutes per day) LTPA, an increase in LTPA by 15 and 30 minutes per day, respectively, was associated with a reduction in mortality to a level similar to that of inactive individuals who mostly do not sit at work. In addition, individuals with a PAI score exceeding 100 experienced a notable reduction in the elevated mortality risk associated with prolonged occupational sitting. Conclusions and Relevance: As part of modern lifestyles, prolonged occupational sitting is considered normal and has not received due attention, even though its deleterious effect on health outcomes has been demonstrated. In this study, alternating between sitting and nonsitting at work, as well as an extra 15 to 30 minutes per day of LTPA or achieving a PAI score greater than 100, attenuated the harms of prolonged occupational sitting. Emphasizing the associated harms and suggesting workplace system changes may help society to denormalize this common behavior, similar to the process of denormalizing smoking.

Uncovering a dose-response relationship between positive fecal immunochemical test (FIT) and all-cause, cardiovascular and cancer-related mortality.

BACKGROUND: Fecal immunochemical test (FIT) is for colorectal cancer (CRC) screening. Its association with non-CRC mortality has been overlooked. Given the quantitative FIT values, its dose-response relationships with different causes of deaths and years of life shortened were assessed. METHODS: This retrospective study included 546,214 adults aged ≥ 20 who attended a health surveillance program from 1994 to 2017 and were followed up until the end of 2020. FIT ≥ 20 µg Hb/g was defined as positive. The Cox model was used to assess adjusted hazard ratios (aHR). RESULTS: Positive FIT was associated with increased all-cause mortality (aHR: 1.34, 95 % CI: 1.25-1.44) and all-cancer mortality (aHR: 1.71, 95 % CI: 1.55-1.89), with a reduction of life expectancy by 4 years. The association remained even with CRC excluded. With each 10 µg Hb/g increase in FIT above 20 µg Hb/g, life expectancy was reduced by one year, and mortality increased by 4 %. About 18.6 % of deaths with positive FIT were attributed to cardiovascular disease (CVD), followed by CRC (13.5 %) and upper gastrointestinal (GI) cancers (4.5 %). The all-cause mortality rate after excluding CRC for positive FIT was 3.56/1,000 person-year, comparable to the all-cause mortality rate of 3.69/1,000 person-year for hypertension. CONCLUSION: Positive FIT was associated with increased mortality in a dose-response manner and shortened life expectancy by 4 years, an overlooked risk comparable to hypertension, even with CRC excluded. After a negative colonoscopy, subjects with positive FIT should undergo a workup on CVD risk factors and look for other upper GI cancers.