Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study.

BACKGROUND: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk. METHODS: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors. RESULTS: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 µmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77). CONCLUSIONS: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.

Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.

Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD. Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10 years of follow-up. Results: We documented 7,031 cases of CKD over a median follow-up of 8.1 years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28-1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10 years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02-1.39). Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.

Body composition and risk of major gynecologic malignancies: Results from the UK Biobank prospective cohort.

OBJECTIVE: To evaluate the association between body composition and subsequent risk of the major gynecologic malignancies. METHODS: This is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. RESULTS: We document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat-free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02-1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49-3.13) times and 1.89 (95% CI 1.31-2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat-free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07-1.31) and postmenopausal women (HR 1.13,95% CI 1.09-1.18). Meanwhile, FM/FFM distributed in the limbs present an U-shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer. CONCLUSION: FM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed.

Body composition and risk of gastric cancer: A population-based prospective cohort study.

The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow-up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat-free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5-unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat-free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer.

Comprehensive analysis of components in Chinese medicines derived from Apocynum venetum and Poacynum pictum in Xinjiang based on HPLC fingerprint and chemometrics / 中国中药杂志

This study established high-performance liquid chromatography(HPLC) fingerprints of Chinese medicines derived from Apocynum venetum and Poacynum pictum in Xinjiang and explored their composition differences with the combination of content determination, similarity analysis, cluster analysis and principal component analysis. The HPLC conditions included Phenomenex Kinetex C_(18) column(4.6 mm ×100 mm, 2.6 μm), acetonitrile-0.01% trifluoroacetic acid aqueous solution as mobile phase, gradient elution, flow rate of 0.6 mL·min~(-1), detection wavelength of 281 nm and column temperature of 25 ℃. The content of chlorogenic acid, quercetin-3-O-sophoroside, rutin, hyperin, isoquercitrin, trifolin and astragalin was determined in 31 batches of medicinal materials, and fingerprint research and chemometric analysis were performed with Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(Version 2004 A) and SPSS 21.0. In the Chinese Pharmacopoeia 2020, the quality of Apocyni Veneti Folium is controlled by character identification, microscopic identification, thin layer chromatography identification and quantitative determination of hyperin. There were 21 common peaks of A. venetum and P. pictum in the HPLC fingerprints, 5 of which were identified as chlorogenic acid, hyperin, isoquercitrin, trifolin and astragalin, with their content also determined. Except for 3 batches of medicinal materials, the similarity of other 28 batches was higher than 0.83, indicating good similarity. Two categories were formed in the cluster analysis based on content determination, which showed that some differences existed in similarities between different regions of Xinjiang. The medicinal materials were ranked by quality with principal component analysis, and the results indicated that the top 15 all came from northern Xinjiang. The quality difference of A. venetum and P. pictum had a correlation with the place of origin. This study provides a reference for the analysis and evaluation of A. venetum and P. pictum from different habitats and the selection of introduction and cultivation areas.

Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study.

BACKGROUND: Uric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear. AIM: To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer. METHODS: In this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders. RESULTS: In total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03). CONCLUSION: SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.

Serum uric acid levels and risk of kidney cancer incidence and mortality: A prospective cohort study.

OBJECTIVE: Epidemiological evidence investigating serum uric acid and kidney cancer risk remains unclear. We conducted this study to examine the relationship between serum uric acid and the incidence and mortality of kidney cancer. METHODS: This is a prospective analysis of 444 462 participants without any cancer from the UK Biobank. Serum uric acid was measured at baseline and the incidence and mortality of kidney cancer was determined through contact with the cancer and death registry. Cox regression models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (95%CI), adjusting for demography, lifestyle style, comorbidities, and medication use. RESULTS: We documented 638 incidence cases and 188 mortality cases of kidney cancer over a median of 6.5 years follow-up. People with the highest quartile had a 45% increased risk of kidney cancer compared to those with the lowest uric acid quartile (HR 1.45, 95%CI 1.08 to 1.93). Subgroup analyses showed that serum uric acid was associated with cancer risk among females but not among males (Q1 vs Q4: females HR1.47, 95%CI 1.01 to 2.16; males HR 1.19, 95%CI 0.91 to 1.56). Although we found serum uric acid was associated with an increased risk of kidney cancer mortality in age-stratified model (HR 2.49, 95% CI 1.61 to 3.84), this association disappeared after further adjustment for other confounders. CONCLUSIONS: High uric acid is associated with a high incidence of kidney cancer, especially in women. More research is needed to confirm our findings.

Number of natural teeth, denture use and mortality in Chinese elderly: a population-based prospective cohort study.

BACKGROUND: The associations between the number of natural teeth/denture use and all-cause mortality remain unclear due to lake of investigation for the potential interaction between tooth loss and denture use and for the potential changes in these exposures over time in older adults. We undertake this study to evaluate the associations of the number of natural teeth and/or denture use with mortality in Chinese elderly. METHODS: This is a prospective cohort study of 36,283 older adults (median age: 90). The number of natural teeth and denture use were collected with structured questionnaire. We evaluated hazard ratios (HRs) and confidence intervals (CIs) using a Cox proportional hazards model adjusting for demographic factors, education, income, lifestyle factors, and comorbidities. RESULTS: We documented 25,857 deaths during 145,947 person-years of observation. Compared to those with 20+ teeth, tooth loss was associated with a gradual increase in mortality, with an adjusted HR of 1.14 (95% CI, 1.06 to 1.23) for those with 10-19 teeth, 1.23 (95% CI, 1.15 to 1.31) for those with 1-9 teeth, and 1.35 (95% CI, 1.26 to 1.44) for those without natural teeth. Denture use was associated with lower risk of mortality (adjusted HR 0.81; 95% CI, 0.77 to 0.84). Subgroup analyses indicated that the benefit of denture use was greater in men than in women (P = 0.02) and tended to decrease with age (P < 0.001). The effects of denture use did not differ among various degrees of tooth loss (P = 0.17). CONCLUSIONS: Tooth loss was associated with an increased risk of mortality in older adults. Denture use provided a protective effect against death for all degrees of tooth loss however, this effect appeared to be modified by sex and age.

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study.

BACKGROUND: Oxidative stress is an important theory of aging but population-based evidence has been lacking. This study aimed to evaluate the associations between biomarkers of oxidative stress, including plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA), with all-cause mortality in older adults. METHODS: This is a community-based cohort study of 2224 participants (women:1227, median age: 86 years). We included individuals aged 65 or above and with plasma SOD activity and/or MDA tests at baseline. We evaluated the hazard ratios (HRs) and 95% confidence intervals (CIs) by multivariable Cox models. RESULTS: We documented 858 deaths during six years of follow-up. There was a significant interaction effect of sex with the association between SOD activity and mortality (P < 0.001). Compared with the lowest quintile, the risk of all-cause mortality was inversely associated with increasing quintiles of plasma SOD activity in women(P-trend< 0.001), with adjusted HRs for the second through fifth quintiles of 0.73 (95% CI 0.53-1.02), 0.52(95% CI 0.38-0.72), 0.53(95% CI 0.39-0.73), and 0.48(95% CI 0.35-0.66). There were no significant associations between SOD activity and mortality in men (P-trend = 0.64), and between MDA and mortality in all participants (P-trend = 0.79). CONCLUSIONS: Increased activity of SOD was independently associated with lower all-cause mortality in older women but not in men. This epidemiological study lent support for the free radical/oxidative stress theory of aging.

High-Density Lipoprotein Cholesterol and All-Cause and Cause-Specific Mortality Among the Elderly.

CONTEXT: The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear. OBJECTIVE: To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly. DESIGN: This was a nationwide, community-based, prospective cohort study. PARTICIPANTS: This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P < 0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration >87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P < 0.001 for nonlinearity). CONCLUSIONS: Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

Associations of anxiety with discomfort and tolerance in Chinese patients undergoing esophagogastroduodenoscopy.

OBJECTIVES: To evaluate the associations of pre-endoscopy anxiety with discomfort and tolerance in patients undergoing unsedated esophagogastroduodenoscopy (EGD). METHODS: This is a hospital-based cohort study of 348 patients undergoing routine, non-advanced EGD without sedation. The primary outcomes were discomfort and tolerance. The anxiety before endoscopy was evaluated with a 10-point visual analogue scale (VAS). The associations of pre-endoscopy anxiety with the outcomes were evaluated with logistic regression adjusting for potential confounders like age, sex, and body mass index. RESULTS: Seventy patients reported severe discomfort and 56 patients reported poor tolerance after endoscopy. The risk of severe discomfort increased with pre-endoscopy anxiety and reached a platform around 7-10 points. Compared with the participants with low pre-endoscopy anxiety, those with moderate (adjusted odds ratio [OR] 2.70, 95% confidence interval [CI] 1.17 to 6.22) and high level of anxiety (adjusted OR 6.87, 95% CI 2.16 to 21.79) were associated with a gradual increase in the risk of severe discomfort (P-trend < 0.001). The association between pre-endoscopy anxiety and tolerance was linear, with an adjusted OR of 1.67(95% CI 1.33 to 2.08) for a 1-score increase in pre-endoscopy anxiety VAS. The associations were not modified by age, sex, pharyngitis, duration of endoscopy, and diameter of the endoscope. CONCLUSIONS: Pre-endoscopy anxiety was an independent predictor of severe discomfort and poor tolerance in Chinese patients undergoing unsedated EGD. Our findings suggested the importance of the management of anxiety to reduce adverse endoscopic experience and taking high level of anxiety as an indication for sedation.

Triglycerides Paradox Among the Oldest Old: "The Lower the Better?"

OBJECTIVES: Currently, most treatment guidelines suggest lowering hypertriglyceridemia of any severity, even in elderly individuals. However associations of serum triglycerides (TGs) with adverse health and mortality risk decrease with age, it remains unclear among the oldest old (aged 80 years and older). The study was to investigate the relationship of serum TG concentrations with cognitive function, activities of daily living (ADLs), frailty, and mortality among the oldest old in a prospective cohort study. DESIGN: Longitudinal prospective cohort study. SETTING: Community-based setting in longevity areas in China. PARTICIPANTS: A total of 930 (mean age = 94.0 years) Chinese oldest old. MEASUREMENTS: The TG concentrations were measured at baseline survey in 2009. Cognitive function, ADLs, frailty, and mortality were determined over 5 years of follow-up. Cox proportional hazards models and competing risk models were performed to explore the association, adjusting for potential confounders. RESULTS: Each 1-mmol/L increase in TGs was associated with a nearly 20% lower risk of cognitive decline, ADL decline, and frailty aggravation during the 5 years of follow-up. Consistently, higher TGs (each 1 mmol/L) was associated with lower 5-year all-cause mortality after fully adjustment (hazard ratio [HR] = 0.79; 95% confidence interval [CI] = 0.69-0.89). Nonelevated TG concentrations (less than 2.26 mmol/L) were associated with higher mortality risk (HR = 1.72; 95% CI = 1.22-2.44), relative to TGs of 2.26 mmol/L or more. We observed similar results regarding TG concentrations and mortality in 1-year lag analysis and when excluding participants with identified chronic disease. CONCLUSION: In the oldest old, a higher concentration of TGs was associated with a lower risk of cognitive decline, ADL decline, frailty aggravation, and mortality. This paradox suggests the clinical importance of revisiting the concept of "the lower the better" for the oldest old. J Am Geriatr Soc 67:741-748, 2019.

Association Between Late-Life Blood Pressure and the Incidence of Cognitive Impairment: A Community-Based Prospective Cohort Study.

OBJECTIVES: To investigate the association between late-life blood pressure and the incidence of cognitive impairment in older adults. DESIGN: Prospective cohort study. SETTING: Community-living older adults from 22 provinces in China. PARTICIPANTS: We included 12,281 cognitively normal [Mini-Mental State Examination (MMSE) ≥ 24] older adults (median age: 81 years) from the Chinese Longitudinal Healthy Longevity Survey. Eligible participants must have baseline blood pressure data and have 1 or more follow-up cognitive assessments. MEASUREMENTS: Baseline systolic (SBP) and diastolic blood pressure (DBP) were measured by trained internists. Cognitive function was evaluated by MMSE. We considered mild/moderate/severe cognitive impairment (MMSE <24, and MMSE decline ≥3) as the primary outcome. RESULTS: The participants with hypertension had a significantly higher risk of mild/moderate/severe cognitive impairment (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.10-1.24). Overall, the associations with cognitive impairment seem to be hockey stick-shaped for SBP and linear for DBP, though the estimated effects for low SBP/DBP were less precise. High SBP was associated with a gradual increase in the risk of mild/moderate/severe cognitive impairment (P trend < .001). Compared with SBP 120 to 129 mmHg, the adjusted HR was 1.17 (95% CI 1.07-1.29) for SBP 130 to 139 mmHg, increased to 1.54 (95% CI 1.35-1.75) for SBP ≥180 mmHg. Analyses for high DBP showed the same increasing pattern, with an adjusted HR of 1.09 (95% CI 1.01-1.18) for DBP 90 to 99 mmHg and 1.19 (95% CI 1.02-1.38) for DBP ≥110 mmHg, as compared with DBP 70 to 79 mmHg. CONCLUSION: Late-life high blood pressure was independently associated with cognitive impairment in cognitively normal Chinese older adults. Prevention and management of high blood pressure may have substantial benefits for cognition among older adults in view of the high prevalence of hypertension in this rapidly growing population.

Associations of Body Mass Index and Waist Circumference with 3-Year All-Cause Mortality Among the Oldest Old: Evidence from a Chinese Community-Based Prospective Cohort Study.

OBJECTIVE: Current international and national guidelines for body mass index (BMI) and waist circumference (WC) have been recommended to all adults. However, whether recommendations applied to the oldest old (aged 80+) is poorly known. The study objective was to investigate the relation of BMI and WC with 3-year all-cause mortality among the oldest old. DESIGN, SETTING, AND PARTICIPANTS: A total of 4361 Chinese oldest old (mean age 91.8) participated in this community-based prospective cohort study. MEASUREMENTS: BMI and WC were measured at baseline in 2011 and were used as continuous variables and as categorized variables by recommendations or by tertiles. Adjusted, sex-stratified Cox models with penalized splines and Cox models were constructed to explore the association. RESULTS: Greater BMI and WC were linearly associated with lower mortality risk in both genders. The mortality risk was the lowest in overweight or obese participants (BMI ≥ 24.0) and was lower in participants with abdominal obesity. Compared to the upper tertile, those in the middle and lower tertile of BMI had a higher risk of mortality for men [hazard ratio (HR): 1.23 (1.02-1.48) and 1.53 (1.28-1.82)] and for women [HR: 1.21 (1.03-1.41) and 1.35 (1.15-1.58)]; it was also found in participants in the middle and lower tertile of WC for men [HR: 1.21 (1.01-1.46) and 1.41 (1.18-1.69)] and for women [HR: 1.35 (1.15-1.58) and 1.55 (1.32-1.81)] (all the P values for trend <.001). These findings were robust in further sensitivity analyses or when using propensity score matching, in subgroup analyses, or in octogenarians, nonagenarians, and centenarians. CONCLUSIONS: In Chinese oldest old, both higher BMI and higher WC predict better survival in both genders. The finding suggests optimal BMI and WC may be sensitive to age, thus, the current recommendations for the oldest old may need to be revisited.

Association of Body Mass Index With Disability in Activities of Daily Living Among Chinese Adults 80 Years of Age or Older.

Importance: Body mass index (BMI) shows a U-shaped association with impaired physical functioning among adults; the association is reduced or eliminated with aging. Objective: To examine whether BMI is associated with subsequent disability in activities of daily living (ADL) in Chinese adults age 80 years or older. Design, Setting, and Participants: Data were obtained on 16 022 adults age 80 years or older who were able to perform ADL independently at baseline from the Chinese Longitudinal Healthy Longevity Study, a community-based prospective cohort study conducted in 23 provinces of China. The study was initiated in 1998, with follow-up and recruitment of new participants in 2000, 2002, 2005, 2008, 2011, and 2014. Main Outcomes and Measures: Disability in ADL was defined as dependence in eating, toileting, bathing, dressing, indoor activities, and/or continence. Results: Among the 16 022 participants, 45.2% were men and 54.8% were women, with a mean (SD) age of 92.2 (7.2) years and a mean (SD) BMI (calculated as weight in kilograms divided by height in meters squared) of 19.3 (3.8). During 70 606 person-years of follow-up, 8113 participants with disability in ADL were identified. Cox proportional hazards regression models with penalized splines showed that BMI was linearly associated with disability in ADL: each 1-kg/m2 increase in BMI corresponded to a 4.5% decrease in the risk of disability in ADL. In comparison with individuals in the fourth quintile for BMI, the adjusted hazard ratio for disability in ADL was 1.38 (95% CI, 1.29-1.48) in the first quintile, 1.37 (95% CI, 1.28-1.47) in the second quintile, 1.11 (95% CI, 1.04-1.19) in the third quintile, and 0.85 (95% CI, 0.79-0.91) in the fifth quintile (P < .001 for trend). When BMI was categorized by Chinese guidelines, the underweight group (BMI <18.5) showed significantly increased risk of disability in ADL (hazard ratio, 1.34; 95% CI, 1.28-1.41) and the overweight or obese group (BMI ≥24.0) showed significantly decreased risk of disability in ADL (hazard ratio, 0.84; 95% CI, 0.78-0.91) compared with the normal weight group (BMI 18.5 to <24.0) (P < .001 for trend). Conclusions and Relevance: Higher BMI was associated with a lower risk of disability in ADL among Chinese adults age 80 years or older, which suggests that current recommendations for BMI may need to be revisited. More attention should be paid on underweight, rather than overweight or obesity, for the prevention of disability in ADL after age 80 years.

Phototherapy for treating foot ulcers in people with diabetes.

BACKGROUND: Foot ulcers are a disabling complication of diabetes that affect 15% to 25% of people with diabetes at some time in their lives. Phototherapy is a relatively new, non-invasive, and pain-free treatment method, which promotes the ulcer repair process through multiple mechanisms such as increased cell growth and vascular activity. Phototherapy may be used as an alternative approach for the treatment of foot ulcers in people with diabetes, but the evidence for its effect compared with placebo or other treatments has not yet been established. OBJECTIVES: To assess the effects of phototherapy for the treatment of foot ulcers in people with diabetes. SEARCH METHODS: We searched the Cochrane Wounds Specialised Register (11 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 10), Ovid MEDLINE (11 October 2016), Ovid MEDLINE (In-Process & Other Non-Indexed Citations) (11 October 2016), Ovid Embase (11 October 2016), EBSCO CINAHL Plus (11 October 2016), and China National Knowledge Infrastructure (24 June 2017). We also searched clinical trials registries for ongoing and unpublished studies on 24 June 2017, and screened reference lists to identify additional studies. We used no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: Randomised controlled trials or cluster randomised controlled trials that 1) compared phototherapy with sham phototherapy, no phototherapy, or other physical therapy modalities, 2) compared different forms of phototherapy, or 3) compared phototherapy of different output power, wavelength, power density, or dose range, in adults with diabetes and an open foot ulcer of any severity, in any setting. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and 'Risk of bias' assessment. We combined the study outcomes when appropriate. MAIN RESULTS: Eight trials with 316 participants met the inclusion criteria. Most of the included studies were single-centre studies that were carried out in clinics or hospitals with a sample size ranging from 14 to 84. We generally considered the included studies to be at unclear or high risk of bias, as they had one domain at high risk of bias, or three or more domains at unclear risk of bias.We did not identify any studies that reported valid data for time to complete wound healing. Meta-analysis of four studies including 116 participants indicated that participants receiving phototherapy may experience a greater proportion of wounds completely healed during follow-up compared with those receiving no phototherapy/placebo (64.5% for the phototherapy group versus 37.0% for the no phototherapy/placebo group; risk ratio 1.57, 95% confidence interval 1.08 to 2.28; low-quality evidence, downgraded for study limitations and imprecision). Two studies mentioned adverse events in the results; one study with 16 participants suggested that there were no device-related adverse events, and the other study with 14 participants suggested that there was no clear difference between phototherapy and placebo group.Four studies reported change in ulcer size, but primarily due to high heterogeneity, they were not combined. Results from individual trials (including 16 participants to 84 participants) generally suggested that after two to four weeks of treatment phototherapy may result in a greater reduction in ulcer size but the quality of the evidence was low due to unclear risk of bias in the original trial and small sample size. We based the analyses for quality of life and amputations on only one study each (28 participants and 23 participants respectively); both outcomes showed no clear difference between the phototherapy group and the no phototherapy/placebo group. AUTHORS' CONCLUSIONS: This systematic review of randomised trials suggested that phototherapy, when compared to no phototherapy/placebo, may increase the proportion of wounds completely healed during follow-up and may reduce wound size in people with diabetes, but there was no evidence that phototherapy improves quality of life. Due to the small sample size and methodological flaws in the original trials, the quality of the evidence was low, which reduces our confidence in these results. Large, well-designed randomised controlled trials are needed to confirm whether phototherapy could be an effective option for the treatment of foot ulcers in people with diabetes.

EGFR mutation testing in blood for guiding EGFR tyrosine kinase inhibitor treatment in patients with nonsmall cell lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation testing in tumor tissue is now a common practice in selecting non-small cell lung cancer (NSCLC) patients for EGFR tyrosine kinase inhibitor (TKI) treatment. However, tumor tissues are often absent or insufficient for the testing. Blood is a potential substitute providing a noninvasive, easily accessible and repeatedly measureable source of genotypic information. However which is the best blood EGFR mutation testing method remains unclear. We undertake this study to investigate the best blood EGFR mutation testing method for selecting EGFR TKI treatment in patients with NSCLC. METHODS: This study was registered in PROSPERO (CRD42017055263). PubMed, EMBASE, Cochrane library, and NIHR Health Technology Assessment program will be searched. Studies fulfill the following criteria will be eligible: (1) randomized controlled trials or cohort studies; (2) included patients with NSCLC; (3) reported response, progression-free survival, or overall survival for EGFR TKI by the EGFR mutation status in blood sample. Diagnostic accuracy of blood EGFR mutation tests for predicting response to TKI will be pooled. Tumor response, progression-free survival, and overall survival according to different blood EGFR mutation testing methods will be evaluated and compared. RESULTS: Based published data and combined analysis, this study will quantitatively compare the blood EGFR mutation testing methods according to their accuracy for predicting treatment response and relationship with clinical outcome in NSCLC patients treated with EGFR TKIs. CONCLUSION: This protocol will determine the best blood EGFR mutation testing method.

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. RESULTS: A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). MATERIALS AND METHODS: PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. CONCLUSION: This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardized mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 liters, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I2 = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.