Time trends of 16 modifiable risk factors on the burden of major cancers among the Chinese population.

The cancer burden in China is increasing. We aimed to assess the time trends in the prevalence of 16 modifiable risk factors involved in lifestyle, diet, infection, and air pollution between 1997 and 2025 based on the China Health and Nutrition Survey, the Global Burden of Disease website, and publically available studies. The population attributable fraction (PAF) and its 95% uncertainty interval (UI) from 2007 to 2035 were calculated to quantify the attributable cancer burden in major 12 anatomic sites using the comparative risk assessment method, considering a 10-year lag effect. As a result, 1,559,476 cancer cases (PAF = 54.1%, 95% UI: 36.8%-65.8%) from the 12 anatomic sites were attributable to these modifiable risk factors in 2007, with lung, liver, and gastric cancer raging the top three. It was predicted that by 2035, the attributable cancer cases would reach 1,680,098 (PAF = 44.2%, 95% UI: 29.1%-55.5%), with the top three of lung, liver, and colorectal cancer. Smoking, physical inactivity, insufficient fruit consumption, HBV infection, and Helicobacter pylori infection were the most attributable risk factors in 2007, contributing to 480,352, 233,684, 215,009, 214,455, and 187,305 associated cancer cases, respectively. In 2035, the leading factors for cancer would be smoking, physical inactivity, insufficient fruit intake, HPV infection, and HBV infection, resulting in 427,445, 424,327, 185,144, 156,535, and 154,368 cancer cases, respectively. Intervention strategies should be swiftly established and dynamically altered in response to risk factors like smoking, physical inactivity, poor fruit intake, and infectious factors that may cause a high cancer burden in the Chinese population.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Experimental laboratory models as tools for understanding modifiable dementia risk.

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

Supermarket Proximity and Risk of Hypertension, Diabetes, and CKD: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Living in environments with low access to food may increase the risk of chronic diseases. We investigated the association of household distance to the nearest supermarket (as a measure of food access) with the incidence of hypertension, diabetes, and chronic kidney disease (CKD) in a metropolitan area of the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 777,994 individuals without hypertension, diabetes, or CKD at baseline within the HealthLNK Data Repository, which contains electronic health records from 7 health care institutions in Chicago, Illinois. EXPOSURE: Zip code-level average distance between households and nearest supermarket. OUTCOME: Incidence of hypertension, diabetes, and CKD based on presence of ICD-9 code and/or blood pressure≥140/90mm Hg, hemoglobin A1c≥6.5%, and eGFR<60mL/min/1.73m2, respectively. ANALYTICAL APPROACH: Average distance to nearest supermarket was aggregated from street-level metrics for 56 Chicagoland zip codes. The cumulative incidence of hypertension, diabetes, and CKD from 2007-2012 was calculated for each zip code in patients free of these diseases in 2006. Spatial analysis of food access and disease incidence was performed using bivariate local indicator of spatial association (BiLISA) maps and bivariate local Moran I statistics. The relationship between supermarket access and outcomes was analyzed using logistic regression. RESULTS: Of 777,994 participants, 408,608 developed hypertension, 51,380 developed diabetes, and 56,365 developed CKD. There was significant spatial overlap between average distance to supermarket and incidence of hypertension and diabetes but not CKD. Zip codes with large average supermarket distances and high incidence of hypertension and diabetes were clustered in southern and western neighborhoods. Models adjusted only for neighborhood factors (zip code-level racial composition, access to vehicles, median income) revealed significant associations between zip code-level average distance to supermarket and chronic disease incidence. Relative to tertile 1 (shortest distance), ORs in tertiles 2 and 3, respectively, were 1.27 (95% CI, 1.23-1.30) and 1.38 (95% CI, 1.33-1.43) for diabetes, 1.03 (95% CI, 1.02-1.05) and 1.04 (95% CI, 1.02-1.06) for hypertension, and 1.18 (95% CI, 1.15-1.21) and 1.33 (95% CI, 1.29-1.37) for CKD. Models adjusted for demographic factors and health insurance showed significant and positive association with greater odds of incident diabetes (tertile 2: 1.29 [95% CI, 1.26-1.33]; tertile 3: 1.35 [95% CI, 1.31-1.39]) but lesser odds of hypertension (tertile 2: 0.95 [95% CI, 0.94-0.97]; tertile 3: 0.91 [95% CI, 0.89-0.92]) and CKD (tertile 2: 0.80 [95% CI, 0.78-0.82]; tertile 3: 0.73 [95% CI, 0.72-0.76]). After adjusting for both neighborhood and individual covariates, supermarket distance remained significantly associated with greater odds of diabetes and lesser odds of hypertension, but there was no significant association with CKD. LIMITATIONS: Unmeasured neighborhood and social confounding variables, zip code-level analysis, and limited individual-level information. CONCLUSIONS: There are significant disparities in supermarket proximity and incidence of hypertension, diabetes, and CKD in Chicago, Illinois. The relationship between supermarket access and chronic disease is largely explained by individual- and neighborhood-level factors.

Risks and Benefits of Different Dietary Patterns in CKD.

Food has the potential to cause and exacerbate many lifestyle diseases. Or it can be used to prevent and treat illnesses like primary hypertension, the metabolic syndrome, and insulin resistance. In parallel, there is also a growing body of evidence of the role of diet in the treatment of kidney disease and its ensuing complications. Popular diets for this purpose have included low-carbohydrate diets, including the ketogenic diet, and higher carbohydrate diets like Mediterranean diets and other plant-based dietary patterns. Low-carbohydrate diets have not shown harm in patients with kidney disease and may benefit a select few. Mediterranean diets have an established record of cardioprotective benefits but also may be beneficial for the kidney. Intermittent fasting has benefits for metabolic health, but limited research exists on the risk or benefit for patients with kidney disease. Plant-based diets, especially those that are lower in protein, may slow kidney disease progression, mitigate uremia, and delay dialysis initiation. Although each dietary pattern has its unique pros and cons, most healthful dietary patterns favor the inclusion of whole, unprocessed foods, preferably from plant-based sources. In this perspective, we discuss the risks and benefits of major popular diets to help guide health care professionals in treating patients with kidney disease.

Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and comorbidity is uncertain. STUDY DESIGN: Multicenter, parallel group, randomized controlled trial. SETTINGS & PARTICIPANTS: Adults 55 years and older with estimated glomerular filtration rate (eGFR) of 15 to <45 mL/min/1.73 m2 enrolled from centers in Baltimore and Boston. INTERVENTION: Twelve months of in-center supervised exercise training incorporating majority aerobic but also muscle strengthening activities or a group health education control intervention, randomly assigned in 1:1 ratio. OUTCOME: Primary outcomes were cardiorespiratory fitness and submaximal gait at 6 and 12 months quantified by peak oxygen consumption (Vo2peak) on graded exercise treadmill test and distance walked on the 6-minute walk test, respectively. Secondary outcomes were changes in lower extremity function, eGFR, albuminuria, glycemia, blood pressure, and body mass index. RESULTS: Among 99 participants, the mean age was 68 years, 62% were African American, and the mean eGFR was 33 mL/min/1.73 m2; 59% had diabetes, and 29% had coronary artery disease. Among those randomized to exercise, 59% of exercise sessions were attended in the initial 6 months. Exercise was well tolerated without excess occurrence of adverse events. At 6 months, aerobic capacity was higher among exercise participants (17.9 ± 5.5 vs 15.9 ± 7.0 mL/kg/min, P = 0.03), but the differences were not sustained at 12 months. The 6-minute walk distance improved more in the exercise group (adjusted difference: 98 feet [P = 0.02; P = 0.03 for treatment-by-time interaction]). The exercise group had greater improvements on the Timed Up and Go Test (P = 0.04) but not the Short Physical Performance Battery (P = 0.8). LIMITATIONS: Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated. CONCLUSIONS: Among adults aged ≥55 years with CKD stages 3b-4 and a high level of medical comorbidity, a 12-month program of in-center aerobic and resistance exercise training was safe and associated with improvements in physical functioning. FUNDING: Government grants (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01462097.

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

The effects of hypothetical behavioral interventions on the 13-year incidence of overweight/obesity in children and adolescents.

BACKGROUND: In view of the high burden of childhood overweight/obesity (OW/OB), it is important to identify targets for interventions that may have the greatest effects on preventing OW/OB in early life. Using methods of causal inference, we studied the effects of sustained behavioral interventions on the long-term risk of developing OW/OB based on a large European cohort. METHODS: Our sample comprised 10 877 children aged 2 to < 10 years at baseline who participated in the well-phenotyped IDEFICS/I.Family cohort. Children were followed from 2007/08 to 2020/21. Applying the parametric g-formula, the 13-year risk of developing OW/OB was estimated under various sustained hypothetical interventions on physical activity, screen time, dietary intake and sleep duration. Interventions imposing adherence to recommendations (e.g. maximum 2 h/day screen time) as well as interventions 'shifting' the behavior by a specified amount (e.g. decreasing screen time by 30 min/day) were compared to 'no intervention' (i.e. maintaining the usual or so-called natural behavior). Separately, the effectiveness of these interventions in vulnerable groups was assessed. RESULTS: The 13-year risk of developing OW/OB was 30.7% under no intervention and 25.4% when multiple interventions were imposed jointly. Meeting screen time and moderate-to-vigorous physical activity (MVPA) recommendations were found to be most effective, reducing the incidence of OW/OB by -2.2 [-4.4;-0.7] and -2.1 [-3.7;-0.8] percentage points (risk difference [95% confidence interval]), respectively. Meeting sleep recommendations (-0.6 [-1.1;-0.3]) had a similar effect as increasing sleep duration by 30 min/day (-0.6 [-0.9;-0.3]). The most effective intervention in children of parents with low/medium educational level was being member in a sports club; for children of mothers with OW/OB, meeting screen time recommendations and membership in a sports club had the largest effects. CONCLUSIONS: While the effects of single behavioral interventions sustained over 13 years were rather small, a joint intervention on multiple behaviors resulted in a relative reduction of the 13-year OW/OB risk by between 10 to 26%. Individually, meeting MVPA and screen time recommendations were most effective. Nevertheless, even under the joint intervention the absolute OW/OB risk remained at a high level of 25.4% suggesting that further strategies to better prevent OW/OB are required.

Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study.

BACKGROUND: Association between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations. METHODS: Sixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results. RESULTS: There was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; ORpooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; ORpooled = 1.22, 95%CI 0.95 to 1.50). CONCLUSION: Using a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.

Effect of obstructive sleep apnea on prognosis in patients with acute coronary syndromes with varying numbers of standard modifiable risk factors: insight from the OSA-ACS study.

BACKGROUND: Standard modifiable risk factors (SMuRFs) increase the risk of cardiovascular events in patients with acute coronary syndrome (ACS) and are also strongly associated with obstructive sleep apnea (OSA) in a bidirectional relationship. However, the association of OSA with recurrent cardiovascular events in ACS patients based on the number of SMuRFs remains unclear. Hence, we aimed to elucidate the prognostic implication of OSA in ACS patients stratified by the number of SMuRFs. METHODS: This was a post hoc analysis of the OSA-ACS study (NCT03362385), including 1927 patients admitted for ACS and undergoing portable sleep monitoring. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE) including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or heart failure, and ischemia-driven revascularization. Cox proportional hazards model and Kaplan-Meier analysis were used to investigated the relationship between OSA and subsequent cardiovascular events after patients were stratified by the number of SMuRFs. RESULTS: Among 1927 patients enrolled, 130 (6.7%) had no SMuRF, 1264 (65.6%) exhibited 1-2 SMuRFs and 533 (27.7%) presented 3-4 SMuRFs. With the increase of the number of SMuRFs, the proportion of OSA in ACS patients tended to increase (47.7% vs. 51.5% vs. 56.6%), but there was no significant difference between them (P = 0.08). After the stratification of ACS patients via SMuRF numbers and adjustment for confounding factors, fully adjusted Cox regression indicated that OSA increased the risk of MACCE (adjusted HR, 1.65; 95%CI, 1.06-2.57; P = 0.026) and ischemia-driven revascularization (adjusted HR, 2.18; 95%CI, 1.03-4.65; P = 0.042) in ACS patients with 3-4 SMuRFs. CONCLUSIONS: In hospitalized ACS patients, OSA is associated with an increased risk of MACCE and ischemia-driven revascularization among patients with 3-4 SMuRFs. Therefore, screening for OSA should be emphasized in ACS patients with 3-4 SMuRFs, and intervention trials should be prioritized in these high-risk patients.

Impact of the preoperative nutritional status on postoperative kyphosis in geriatric patients undergoing cervical laminoplasty.

PURPOSE: This study aimed to determine the association of preoperative malnutrition with an increased risk of cervical kyphosis after laminoplasty in geriatric patients with cervical spondylotic myelopathy (CSM). METHODS: Geriatric patients who underwent cervical laminoplasty were included. Malnutrition was defined as a geriatric nutritional risk index < 98 before surgery. The C2-7 angle and the global alignment parameters were analyzed on standing radiographs. The postoperative kyphosis was defined as a C2-7 angle < 0° during a 2-year follow-up. RESULTS: Ninety patients without preoperative kyphotic alignment were enrolled (mean age, 73.5 years old; 41.1% female). Twenty-one patients (23.3%) had malnutrition status (74.2 years old). Preoperatively, the global alignment parameters were comparable between the malnutrition and normal nutrition groups (SVA, 43.3 mm vs. 42.4 mm; T1S, 29.7° vs. 28.4°; TPA, 21.4° vs. 17.8°), with no significant difference in the C2-7 angle (15.1° vs. 15.2°). At 2 years postoperatively, the malnutrition group showed a significantly lower C2-7 angle than the normal nutrition group (9.3° vs. 15.8°, P = 0.03). Postoperative kyphosis was more prevalent in the malnutrition group (33.3% vs. 7.2%, P = 0.005). The preoperative nutritional status and C2-7 angle were independent predictors of postoperative kyphosis. The predictive C2-7 angles differed by preoperative nutritional status (malnutrition group, 11°; normal nutrition group, 7°). CONCLUSION: Among geriatric CSM patients, preoperative malnutrition was closely associated with the increased occurrence of cervical kyphosis after laminoplasty. Our results underscore the importance of preoperative nutritional assessment and management in geriatric populations undergoing cervical spine surgery, as malnutrition is a perioperative modifiable risk factor.

Dietary Patterns as Modifiable Risk Factors for Depression: a Narrative Review.

BACKGROUND: The role of nutrition in treating clinical depression has been widely discussed. Unhealthy lifestyle patterns, like lack of physical activity, junk food consumption, and irregular sleep patterns are common in depressed patients. Considering the mental and physical side-effects, the daily nutrition of these patients seems to be a plausible option for reducing depressive symptoms and enhancing treatment results. METHODS: A PubMed search was done for meta-analyses published from January 2018 to June 2023 with the query: (diet) AND (psychiatric disorder) AND (depression). We selected meta-analyses that met specific criteria like including the entire diet or specific diet patterns and having depression or depressive symptoms as a primary or secondary outcome. RESULTS: Out of 28 papers found, the 9 meta-analyses, selected for review, revealed different types of correlation between dietary patterns and the symptoms of depression and anxiety. Healthy diets were associated with higher intake of fruits, vegetables, nuts, and lower intake of pro-inflammatory food items like processed meats and trans fats. Adherence to such diets showed a negative association with incident depression in cross-sectional and longitudinal studies. A diet mostly including ultra-processed foods was associated with higher odds of depressive and anxiety symptoms. Women were found to be more susceptible than men both in developing the depressive symptoms with unhealthy diet and in reducing the symptoms of depression and anxiety with improvement of diet quality. Statistically significant improvement in symptoms of depression and anxiety in both sexes was observed in study groups assigned for individual consultations of a dietician and a psychotherapist when compared with group sessions or general recommendations. CONCLUSIONS: Research on the correlation of healthy dietary patterns and symptoms of depression and anxiety has mainly focused on non-clinical populations. The evidence supports an inverse association between healthy eating habits and symptoms of depression. Further research should be encouraged on the eating habits of clinically depressed individuals and the underlying physiological mechanisms of uncontrolled food intake.

Plasma Lead Concentration and Risk of Late Kidney Allograft Failure: Findings From the TransplantLines Biobank and Cohort Studies.

RATIONALE & OBJECTIVE: Heavy metals are known to induce kidney damage, and recent studies have linked minor exposures to cadmium and arsenic with increased risk of kidney allograft failure, yet the potential association of lead with late graft failure in kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Prospective cohort study in The Netherlands. SETTING & PARTICIPANTS: We studied outpatient KTRs (n = 670) with a functioning graft for ≥1 year recruited at a university setting (2008-2011) and followed for a median of 4.9 (interquartile range, 3.4-5.5) years. Additionally, patients with chronic kidney disease (n = 46) enrolled in the ongoing TransplantLines Cohort and Biobank Study (2016-2017, ClinicalTrials.gov identifier NCT03272841) were studied at admission for transplant and at 3, 6, 12, and 24 months after transplant. EXPOSURE: Plasma lead concentration was log2-transformed to estimate the association with outcomes per doubling of plasma lead concentration and also considered categorically as tertiles of lead distribution. OUTCOME: Kidney graft failure (restart of dialysis or repeat transplant) with the competing event of death with a functioning graft. ANALYTICAL APPROACH: Multivariable-adjusted cause-specific hazards models in which follow-up of KTRs who died with a functioning graft was censored. RESULTS: Median baseline plasma lead concentration was 0.31 (interquartile range, 0.22-0.45) µg/L among all KTRs. During follow-up, 78 (12%) KTRs experienced graft failure. Higher plasma lead concentration was associated with increased risk of graft failure (hazard ratio, 1.59 [95% CI, 1.14-2.21] per doubling; P = 0.006) independent of age, sex, transplant characteristics, estimated glomerular filtration rate, proteinuria, smoking status, alcohol intake, and plasma concentrations of cadmium and arsenic. These findings remained materially unchanged after additional adjustment for dietary intake and were consistent with those of analyses examining lead categorically. In serial measurements, plasma lead concentration was significantly higher at admission for transplant than at 3 months after transplant (P = 0.001), after which it remained stable over 2 years of follow-up (P = 0.2). LIMITATIONS: Observational study design. CONCLUSIONS: Pretransplant plasma lead concentrations, which decrease after transplant, are associated with increased risk of late kidney allograft failure. These findings warrant further studies to evaluate whether preventive or therapeutic interventions to decrease plasma lead concentration may represent novel risk-management strategies to decrease the rate of kidney allograft failure.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

Association Between Ultraprocessed Food Consumption and Risk of Incident CKD: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Ultraprocessed foods have become readily available in the global food supply in the past few decades. Several adverse health outcomes have been linked with higher consumption of ultraprocessed foods. However, the impact of ultraprocessed foods on chronic kidney disease (CKD) risk remains unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 14,679 middle-aged adults without CKD at baseline in the Atherosclerosis Risk in Communities (ARIC) study. EXPOSURE: Ultraprocessed foods consumption (servings per day) calculated using dietary data collected via a food frequency questionnaire at visit 1 and visit 3. OUTCOME: Incident CKD defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 accompanied by ≥25% eGFR decline, CKD-related hospitalization or death, or kidney failure with kidney replacement therapy. ANALYTICAL APPROACH: Multivariable-adjusted Cox proportional hazards models were used to assess the association between ultraprocessed foods consumption and CKD. Restricted cubic splines were used to examine the shape of the association. RESULTS: During a median follow-up period of 24 years, there were 4,859 cases of incident CKD. The incidence rate for the highest quartile of ultraprocessed foods consumption was 16.5 (95% CI, 15.6-17.4) per 1,000 person-years and 14.7 (95% CI, 13.9-15.5) per 1,000 person-years for the lowest quartile of consumption. After adjusting for a range of confounders including lifestyle factors, demographic characteristics, and health behaviors, participants in the highest quartile of ultraprocessed foods consumption had a 24% higher risk (HR, 1.24 [95% CI, 1.15-1.35]) of developing CKD compared with those in the lowest quartile. There was an approximately linear relationship observed between ultraprocessed food intake and risk of CKD. By substituting 1 serving of ultraprocessed foods with minimally processed foods, there was a 6% lower risk of CKD observed (HR, 0.94 [95% CI, 0.93-0.96]; P < 0.001). LIMITATIONS: Self-reported data and residual confounding. CONCLUSIONS: Higher ultraprocessed foods consumption was independently associated with a higher risk of incident CKD in a general population.

Coffee and Caffeine Consumption and Risk of Kidney Stones: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Coffee and caffeine consumption have been associated with a lower risk of kidney stones in observational studies. We conducted a Mendelian randomization study to assess the causal nature of these associations. STUDY DESIGN: Mendelian randomization analysis. SETTING & PARTICIPANTS: Independent genetic variants associated with coffee and caffeine consumption at the genome-wide significance level were selected from previously published meta-analyses as instrumental variables. Summary-level data for kidney stones were obtained from the UK Biobank study (6,536 cases and 388,508 noncases) and the FinnGen consortium (3,856 cases and 172,757 noncases). EXPOSURE: Genetically predicted coffee and caffeine consumption. OUTCOME: Clinically diagnosed kidney stones. ANALYTICAL APPROACH: Mendelian randomization methods were used to calculate causal estimates. Estimates from the 2 sources were combined using the fixed-effects meta-analysis methods. RESULTS: Genetically predicted coffee and caffeine consumption was associated with a lower risk of kidney stones in the UK Biobank study, and the associations were directionally similar in the FinnGen consortium. The combined odds ratio of kidney stones was 0.60 (95% CI, 0.46-0.79; P < 0.001) per a genetically predicted 50% increase in coffee consumption and 0.81 (95% CI, 0.69-0.94; P = 0.005) per a genetically predicted 80-mg increase in caffeine consumption. LIMITATIONS: Genetic influence on kidney stone risk via pathways not involving coffee or caffeine. CONCLUSIONS: Using genetic data, this study provides evidence that higher coffee and caffeine consumption may cause a reduction in kidney stones.

Healthy Lifestyle and Mortality Among Adults Receiving Hemodialysis: The DIET-HD Study.

RATIONALE & OBJECTIVE: A healthy lifestyle promotes cardiovascular health and reduces cardiac-related mortality in the general population, but its benefits for people receiving maintenance hemodialysis are uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 5,483 of 9,757 consecutive adults receiving maintenance hemodialysis (January 2014 to June 2017, median dialysis vintage: 3.6 years) in a multinational private dialysis network and with complete lifestyle data. EXPOSURE: Based on the American Heart Association's recommendations for cardiovascular prevention, a modified healthy lifestyle score was the sum of 4 components addressing use of smoking tobacco, physical activity, diet, and control of systolic blood pressure. OUTCOME: Cardiovascular and all-cause mortality. ANALYTICAL APPROACH: Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between lifestyle score (low [0-2 points] as the referent, medium [3-5], and high [6-8]) and mortality. Associations were expressed as adjusted hazard ratio (AHR) with 95% CI. RESULTS: During a median of 3.8 years (17,451 person-years in total), there were 2,163 deaths, of which 826 were related to cardiovascular disease. Compared with patients who had a low lifestyle score, the AHRs for all-cause mortality among those with medium and high lifestyle scores were 0.75 (95% CI, 0.65-0.85) and 0.64 (95% CI, 0.54-0.76), respectively. Compared with patients who had a low lifestyle score, the AHRs for cardiovascular mortality among those with medium and high lifestyle scores were 0.73 (95% CI, 0.59-0.91) and 0.65 (95% CI, 0.49-0.85), respectively. LIMITATIONS: Self-reported lifestyle, data-driven approach. CONCLUSIONS: A healthier lifestyle is associated with lower all-cause and cardiovascular mortality among patients receiving maintenance hemodialysis.

Self-reported Physical Activity and Cardiovascular Events in Adults With CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: In the general population, there is an association between higher levels of physical activity and lower risk for cardiovascular events and mortality, but this relationship has not been well evaluated in chronic kidney disease (CKD). We investigated the association between self-reported physical activity and outcomes in a CKD cohort. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,926 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Time-updated self-reported physical activity assessed by (1) quartile of moderate-to-vigorous physical activity (MVPA) and (2) meeting guideline-recommended level of physical activity (categorized as active, meeting guidelines; active, not meeting guidelines; or inactive). OUTCOME: Atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, and all-cause and cardiovascular death. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: At baseline, compared with the lowest MVPA quartile, those in the highest quartile were more likely to be younger, male, not have prevalent cardiovascular disease, and have higher estimated glomerular filtration rate. Overall, 51% met the physical activity guidelines; of those who did not, 30% were inactive. During the median follow-up period of 13.4 years, there were 772 atherosclerotic events, 848 heart failure events, and 1,553 deaths, and 420 cardiovascular deaths. Compared with the participants in the lowest MVPA quartile, the highest quartile had a lower risk of atherosclerotic events (HR, 0.64 [95% CI, 0.51-0.79]), incident heart failure (HR, 0.71 [95% CI, 0.58-0.87]), and all-cause and cardiovascular death (HRs of 0.54 [95% CI, 0.46-0.63] and 0.47 [95% CI, 0.35-0.64], respectively). The findings were similar for analyses evaluating recommended level of physical activity. LIMITATIONS: Self-reported physical activity may result in some degree of misclassification. CONCLUSIONS: Higher self-reported physical activity was associated with lower risk of cardiovascular events and mortality in CKD patients, which may have important implications for clinical practice and the design of interventional studies. PLAIN-LANGUAGE SUMMARY: In this long-term study of 3,926 adults with chronic kidney disease, we found that individuals with higher levels of physical activity were less likely to experience an atherosclerotic event (for example, a heart attack, stroke, or peripheral arterial disease), new-onset heart failure, and death as compared with those with lower levels of physical activity. The findings were similar for the analyses evaluating adherence to guideline-recommended level of physical activity (that is, for more than 150 minutes per week), and they strengthen the evidence supporting the current guideline recommendations.

Modifiable and non-modifiable risk factors for obstetric anal sphincter injury in a Norwegian Region: a case-control study.

BACKGROUND: Obstetric anal sphincter injury (OASI) is a common and severe complication of vaginal delivery and may have short- and long-term consequences, including anal incontinence, sexual dysfunction and reduced quality of life. The rate of OASI varies substantially between studies and national birth statistics, and a recent meta-analysis concluded that there is a need to identify unrecognized risk factors. Our aim was therefore to explore both potential modifiable and non-modifiable risk factors for OASI. METHODS: We performed a case-control study in a single center maternity clinic in South-Eastern Norway. Data were extracted retrospectively from an institutional birth registry. The main outcome measure was the occurrence of the woman's first-time 3rd or 4th degree perineal lesion (OASI) following singleton vaginal birth after 30 weeks' gestation. For each woman with OASI the first subsequent vaginal singleton delivery matched for parity was elected as control. The study population included 421 women with OASI and 421 matched controls who gave birth during 1990-2002. Potential risk factors for OASI were assessed by conditional logistic regression analyses. RESULTS: The mean incidence of OASI was 3.4% of vaginal deliveries, but it increased from 1.9% to 5.8% during the study period. In the final multivariate regression model, higher maternal age and birthweight for primiparous women, and higher birthweight for the multiparous women, were the only non-modifiable variables associated with OASI. Amniotomy was the strongest modifiable risk factor for OASI in both primi- (odds ratio [OR] 4.84; 95% confidence interval [CI] 2.60-9.02) and multiparous (OR 3.76; 95% CI 1.45-9.76) women, followed by augmentation with oxytocin (primiparous: OR 1.63; 95% CI 1.08-2.46, multiparous: OR 3.70; 95% CI 1.79-7.67). Vacuum extraction and forceps delivery were only significant risk factors in primiparous women (vacuum: OR 1.91; 95% CI 1.03-3.57, forceps: OR 2.37; 95% CI 1.14-4.92), and episiotomy in multiparous women (OR 2.64; 95% CI 1.36-5.14). CONCLUSIONS: Amniotomy may be an unrecognized independent modifiable risk factor for OASI and should be further investigated for its potential role in preventive strategies.

Dietary Plant Protein and Mortality Among Patients Receiving Maintenance Hemodialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Although greater dietary intake of protein has been associated with beneficial health effects among patients receiving maintenance hemodialysis (MHD), the effects of plant protein intake are less certain. We studied the association of the proportion of protein intake derived from plant sources with the risk of mortality among patients receiving MHD and explored factors that may modify these associations. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,119 Chinese hemodialysis patients aged over 18 years receiving MHD in 2014-2015. PREDICTORS: The proportion of plant protein intake to total protein intake. OUTCOMES: All-cause mortality and cardiovascular disease (CVD) mortality. ANALYTICAL APPROACH: Segmented regression models were fit to examine the association of plant protein intake proportion with the risk of all-cause mortality and CVD mortality. Multivariable-adjusted Cox proportional and cause-specific hazards models were used to estimate the hazard ratios (HR) and 95% CI for these outcomes. RESULTS: The means of plant protein intake normalized to ideal body weight and plant protein intake proportion were 0.6±0.2 (SD) g/kg per day and 0.538±0.134, respectively. During a median follow-up period of 28.0 months, 249 deaths occurred, with 146 of these deaths resulting from CVD. Overall, there was a U-shaped association between plant protein intake proportion and the risk of all-cause mortality, with an inflection point at 45%. Among patients with a plant protein intake proportion<45%, there was a 17% lower rate of mortality with each 5% greater plant protein intake proportion (HR, 0.83 [95% CI, 0.73-0.96]). Among patients with plant protein intake proportion≥45%, there was a 9% greater rate of mortality with each 5% greater plant protein intake proportion. A similar U-shaped association was observed for CVD mortality, with an inflection point at 44%. LIMITATIONS: Observational study, potential unmeasured confounding. CONCLUSIONS: There was a U-shaped association between plant protein intake proportion and the risk of all-cause and cardiovascular mortality in MHD patients. If confirmed, these findings suggest a potential avenue to improve outcomes in this patient population.