Changes in physical activity and all-cause mortality in the oldest old population: Findings from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

BACKGROUND: Insufficient or decreasing physical activity is common in older adults. Most studies on physical activity changes and mortality were conducted in adults younger than 80 years old in developed countries. We aimed to investigate the relationship between changes in physical activity and longevity in the oldest old (80 years or older) population using the Chinese Longitudinal Healthy Longevity Survey. METHODS: Participants aged 80 or older at baseline were categorized into four groups: 1) remaining physically inactive (n = 14,287), 2) remaining physically active (n = 5411), 3) shifting from being inactive to active (n = 1364), and 4) shifting from being active to inactive (n = 1401). We fitted accelerated failure time Weibull survival regression models, adjusting for baseline sociodemographics, lifestyle factors and disease status. We further examined whether the associations differed by subgroups. RESULTS: A total of 15,707 participants died during follow-up (median duration of follow-up = 3.0 years). Compared with participants who remained physically inactive, those who remained active (fully adjusted event time ratio (ETR): 1.14, 95%CI: 1.11-1.17) or shifted from being inactive to active (fully adjusted ETR: 1.14, 95%CI: 1.08-1.20) had statistically significant longer survival time. No significant association was observed between remaining physically inactive and shifting from being active to inactive. Subgroup analyses showed consistent associations in nearly all strata. CONCLUSION: Maintaining frequent physical activity or shifting from being physically inactive to active was consistently associated with longer survival time in the oldest old population. Our findings provide evidence for encouraging older adults to regularly engage in physical activity to gain longevity benefits.

Sex and Age Differences in Association between Physical Activity and Metabolic Syndrome: Results from NHANES 2003-2006.

OBJECTIVE: To examine whether and how sex and age modify the association between accelerometer-based physical activity (PA) and metabolic syndrome (MetS) among American (US) adults. METHOD: Adults aged ≥20 years old who participated in the mobile center examination during 2003-2006 in the National Health and Nutrition Examination Survey were included for analysis. The total minutes per day of moderate-to-vigorous PA (MVPA) was estimated using ActiGraph. Multivariable logistic regression was used to estimate the odds ratio (OR) of having MetS at an increasing MVPA time. The modification effects of gender and age on the association between MetS and MVPA time were examined by testing for two-way and three-way interaction terms of MVPA time, sex, and age in the model after adjusting for relevant covariates. RESULTS: The prevalence of MetS generally decreased with the MVPA time and was lower in females than in males, although the sex difference varied across age groups. After adjusting for demographic and lifestyle covariates, there was a significant sex difference in how an increased MVPA time lowered the odds of MetS. This interactive effect also varied with age. MVPA benefitted young and middle-age populations up until about 65 years old for both sexes, and the protective effect weakened with age. Although the effect of MVPA was stronger for males than females at young ages, the rate at which it attenuated was quicker in males. The OR of MetS between males and females per unit change of MVPA time was 0.73 (95% CI: [0.57, 0.93]) at age = 25 years, compared to OR = 1.00 (95% CI: [0.88, 1.16]) at age = 60 years. Before the age of 50, the gender difference in the protective effect on MetS was larger at low MVPA levels and became smaller at higher MVPA levels. The male advantage was quite stable with an increasing MVPA time for ages 50-60, and no longer significant at older ages. CONCLUSIONS: Young and middle-age populations benefitted from MVPA, lowering the risk of MetS for both sexes. A longer MVPA time was associated with a greater decrease in the risk of MetS in young men than in women, but the sex difference reduced with age and was no longer apparent in older populations.

Serum Nutritional Biomarkers and All-Cause and Cause-Specific Mortality in U.S. Adults with Metabolic Syndrome: The Results from National Health and Nutrition Examination Survey 2001-2006.

BACKGROUND: There is limited research on the associations between serum nutritional biomarkers and mortality risk in patients with metabolic syndrome (MetS). Existing studies merely investigated the single-biomarker effect. Thus, this study aimed to investigate the combined effect of nutritional biomarker mixtures and mortality risk using the Bayesian kernel machine regression (BKMR) model in patients with MetS. METHODS: We included the MetS patients, defined according to the 2018 Guideline on the Management of Blood Cholesterol from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. A total of 20 serum nutritional biomarkers were measured and evaluated in this study. The Cox proportional hazard model and restricted cubic spline models were used to evaluate the individual linear and non-linear association of 20 nutritional biomarkers with mortality risk. Bayesian kernel machine regression (BKMR) was used to assess the associations between mixture of nutritional biomarkers and mortality risk. RESULTS: A total of 1455 MetS patients had a median age of 50 years (range: 20-85). During a median of 17.1-year follow-up, 453 (24.72%) died: 146 (7.20%) caused by CVD and 87 (5.26%) by cancer. Non-linear and linear analyses indicated that, in total, eight individual biomarkers (α-carotene, ß-carotene, bicarbonate, lutein/zeaxanthin, lycopene, potassium, protein, and vitamin A) were significantly associated with all-cause mortality (all p-values < 0.05). Results from BKMR showed an association between the low levels of the mixture of nutritional biomarkers and high risk of all-cause mortality with the estimated effects ranging from 0.04 to 0.14 (referent: medians). α-Carotene (PIP = 0.971) and potassium (PIP = 0.796) were the primary contributors to the combined effect of the biomarker mixture. The nutritional mixture levels were found to be negatively associated with the risk of cardiovascular disease (CVD) mortality and positively associated with the risk of cancer mortality. After it was stratified by nutrients, the mixture of vitamins showed a negative association with all-cause and CVD mortality, whereas the mixture of mineral-related biomarkers was positively associated with all-cause and cancer mortality. CONCLUSION: Our findings support the evidence that nutritional status was associated with long-term health outcomes in MetS patients. It is necessary for MetS patients to be concerned with certain nutritional status (i.e., vitamins and mineral elements).

Association of Clinical Factors and Degree of Early Background Parenchymal Enhancement on Contrast-Enhanced Mammography.

BACKGROUND. Background parenchymal enhancement (BPE) may impact contrast-enhanced mammography (CEM) interpretation, although factors influencing the degree of BPE on CEM are poorly understood. OBJECTIVE. The purpose of our study was to evaluate relationships between clinical factors and the degree of early BPE on CEM. METHODS. This retrospective study included 207 patients (median age, 46 years) who underwent CEM between April 2020 and September 2021. Two radiologists independently assessed the degree of BPE on CEM as minimal, mild, moderate, or marked on the basis of two criteria (criterion 1, using the first of four obtained views; criterion 2, using the first two of four obtained views). The radiologists reached consensus for breast density on CEM. The EMR was reviewed for clinical factors. Radiologists' agreement for degree of BPE was assessed using weighted kappa coefficients. Univariable and multivariable analyses were performed to assess relationships between clinical factors and degree of BPE, treating readers' independent assessments as repeated measurements. RESULTS. Interreader agreement for degree of BPE, expressed as kappa, was 0.80 for both criteria. For both criteria, univariable analyses found degree of BPE to be negatively associated with age (both OR = 0.94), personal history of breast cancer (OR = 0.22-0.30), history of chemotherapy (OR = 0.18-0.21), history of radiation therapy (OR = 0.20-0.21), perimenopausal status (OR = 0.22-0.34), and postmenopausal status (OR = 0.10-0.11) and to be positively associated with dense breasts (OR = 4.13-4.26) and premenopausal status with irregular menstrual cycles (OR = 7.94-14.02). Among premenopausal patients with regular menstrual cycles, degree of BPE was lowest (using postmenopausal patients as reference) for patients in menstrual cycle days 8-14 (OR = 2.56-3.30). In multivariable analysis for both criteria, the only independent predictors of degree of BPE related to menstrual status and time of menstrual cycle (e.g., using premenopausal patients in days 1-7 as reference: OR = 0.21 for both criteria for premenopausal patients in days 8-14 and OR = 0.03-0.04 for postmenopausal patients). CONCLUSION. Clinical factors, including history of breast cancer or breast cancer treatment, breast density, menstrual status, and time of menstrual cycle, are associated with degree of early BPE on CEM. In premenopausal patients, the degree of BPE is lowest on days 8-14 of the menstrual cycle. CLINICAL IMPACT. Given the potential impact of BPE on diagnostic performance, the findings have implications for CEM scheduling and interpretation.

Interplay between oral health and lifestyle factors for cancer risk in rural and urban China: a population-based cohort study.

Background: Although poor oral health and several lifestyle factors have been found to be associated with cancer risk, their joint relationship has rarely been studied. Methods: We prospectively examined the associations of oral health and healthy lifestyle factors with cancer risk among 0.5 million rural and urban residents from the China Kadoorie Biobank (2004-2015). Oral health status was assessed from self-reported baseline questionnaires. A healthy lifestyle index comprising non-smoking, non-drinking, ideal body shape, physical activity and healthy diet was calculated for each participant, and categorized into favorable, intermediate and unfavorable lifestyle behavior. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) relating oral health and healthy lifestyle index to cancer risk using Cox proportional hazards models. We estimated the population attributable risk percent (PAR%) and 95% CIs using multivariate models. Results: During a median follow-up of 9 years, 23,805 new cancer cases were documented, with 52% from rural areas and 48% from urban areas. Compared with those with good oral health and favorable lifestyle, participants with poor oral health and unfavorable lifestyle had a higher risk of developing cancer in both rural (adjusted HR, 1.55 [95% CI, 1.39-1.74]; P for trend < 0.001) and urban areas (adjusted HR, 1.44 [95% CI, 1.24-1.67]; P for trend < 0.001). A significant multiplicative interaction between oral health and healthy lifestyle index on cancer risk was found in rural residents (P for interaction = 0.004) rather than in urban residents (P for interaction = 0.973). Assuming poor oral health as an additional risk factor, the PAR% of total cancer increased by 3.0% and 1.1% for participants with intermediate lifestyle and unfavorable lifestyle, respectively. Conclusions: These findings suggest a joint effect of oral health and common lifestyle factors on cancer risk. Promotion of healthy lifestyle by integration of good oral health would be beneficial to consider in cancer prevention strategies.

Gamma-glutamyl transpeptidase has different efficacy on biliary atresia diagnosis in different hospital patient groups: an application of machine learning approach.

OBJECTIVES: Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. METHODS: Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children's Hospital of Fudan University were enrolled, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups. RESULTS: Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC = 0.855) for patients with hemoglobin (HGB) ≤ 105 g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB > 105 g/L (AUC = 0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p = 0.002) prediction performance. CONCLUSIONS: This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT.

Identifying factors that may influence the classification performance of radiomics models using contrast-enhanced mammography (CEM) images.

BACKGROUND: Radiomics plays an important role in the field of oncology. Few studies have focused on the identification of factors that may influence the classification performance of radiomics models. The goal of this study was to use contrast-enhanced mammography (CEM) images to identify factors that may potentially influence the performance of radiomics models in diagnosing breast lesions. METHODS: A total of 157 women with 161 breast lesions were included. Least absolute shrinkage and selection operator (LASSO) regression and the random forest (RF) algorithm were employed to construct radiomics models. The classification result for each lesion was obtained by using 100 rounds of five-fold cross-validation. The image features interpreted by the radiologists were used in the exploratory factor analyses. Univariate and multivariate analyses were performed to determine the association between the image features and misclassification. Additional exploratory analyses were performed to examine the findings. RESULTS: Among the lesions misclassified by both LASSO and RF ≥ 20% of the iterations in the cross-validation and those misclassified by both algorithms ≤5% of the iterations, univariate analysis showed that larger lesion size and the presence of rim artifacts and/or ripple artifacts were associated with more misclassifications among benign lesions, and smaller lesion size was associated with more misclassifications among malignant lesions (all p <  0.050). Multivariate analysis showed that smaller lesion size (odds ratio [OR] = 0.699, p = 0.002) and the presence of air trapping artifacts (OR = 35.568, p = 0.025) were factors that may lead to misclassification among malignant lesions. Additional exploratory analyses showed that benign lesions with rim artifacts and small malignant lesions (< 20 mm) with air trapping artifacts were misclassified by approximately 50% more in rate compared with benign and malignant lesions without these factors. CONCLUSIONS: Lesion size and artifacts in CEM images may affect the diagnostic performance of radiomics models. The classification results for lesions presenting with certain factors may be less reliable.

Poor oral health and risks of total and site-specific cancers in China: A prospective cohort study of 0.5 million adults.

Background: There is a strong connection between oral health and overall wellness. We aim to examine the association between poor oral health and the risk of developing or dying of cancer, and whether the association differs by residential area. Methods: Between 2004 and 2008, a total of 510,148 adults free of cancer were included from the China Kadoorie Biobank study and thereafter followed up to 2015. Poor oral health was assessed from a self-reported baseline questionnaire and defined as a combination of rarely brushing teeth and always gum bleeding. We used Cox proportional hazards models to estimate the hazard ratio (HR) of cancer risk and its associated 95% confidence interval (CI) according to oral health status. Findings: Overall, 14.9% of participants (19.7% in rural areas and 8.8% in urban areas) reported poor oral health at baseline. After 4,602,743 person-years of follow-up, we identified 23,805 new cancer cases and 11,973 cancer deaths, respectively. Poor oral health was associated with higher risks of total cancer incidence (HR: 1.08, 95% CI: 1.04-1.12) and death (HR: 1.10, 95% CI: 1.05-1.16). For the site-specific cancers, poor oral health was significantly associated with higher risk of stomach cancer incidence (cases: 2964, HR: 1.10, 95% CI: 1.00-1.22), esophageal cancer incidence (cases: 2119, HR: 1.19, 95% CI: 1.07-1.33), esophageal cancer death (cases: 1238, HR: 1.29, 95% CI: 1.12-1.49), liver cancer incidence (cases: 2565, HR: 1.18, 95% CI: 1.06-1.32), and liver cancer death (cases: 1826, HR: 1.20, 95% CI: 1.05-1.36). This positive association was stronger among rural residents compared to urban residents (interaction test P < 0.01). Interpretation: Our findings indicate that poor oral health is associated with higher risk for cancers, especially digestive system cancers. Promotion of oral health in the general population, especially for rural residents, could have valuable public health significance in preventing major systemic diseases. Funding: Supported by grants (2021YFC2500400, 2016YFC0900500, 2016YFC0900501, 2016YFC0900504) from the National Key Research and Development Program of China, grants from the Kadoorie Charitable Foundation in Hong Kong and grants grants (088158/Z/09/Z, 104085/Z/14/Z, 202922/Z/16/Z) from Wellcome Trust in the UK. CKB is supported by the Kadoorie Charitable Foundation (KCF) in Hong Kong.

Association of Stool Frequency and Consistency with the Risk of All-Cause and Cause-Specific Mortality among U.S. Adults: Results from NHANES 2005-2010.

BACKGROUND: Prior studies on the relationship between bowel health and mortality have generally focused on the individual association of stool frequency or consistency with mortality but did not present a joint association. Therefore, we aimed to systematically evaluate the individual and joint associations of stool frequency and consistency with all-cause and cause-specific mortality in this study. METHODS: A total of 14,574 participants from the National Health and Nutrition Examination Survey 2005-2010 were incorporated in this analysis. Survey sample-weighted Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HRs) between bowel health measures and mortality risks. RESULTS: During a median of 7.6 years of follow-up, 1502 deaths occurred, including 357 cancer deaths and 284 cardiovascular disease (CVD) deaths. The bowel habit of the most participants was 7 times/week (50.7%), and the most common type was "Like a sausage or snake, smooth and soft" (51.8%). Stool frequency displayed a parabolic relationship with all-cause mortality, and less than 7 times/week is a significant risk factor for mortality (HR for 1 time/week: 1.43, p-values = 0.04. HR for 6 times/week: 1.05, p-value = 0.03). Analyzing the joint association of stool frequency and consistency on mortality clarified the limitations of only inspecting the effects of either individual factor. Compared with 7 times/week of normal stool, infrequent soft stools at 4 times/week were associated with 1.78-, 2.42-, and 2.27-times higher risks of all-cause, cancer, and CVD mortality, respectively. CONCLUSION: Analyses of bowel health should consider the joint effects of stool frequency and stool consistency. Self-appraisal of stool frequency and consistency may be a simple but useful tool for informing about major chronic illnesses.

Survival analysis of second primary malignancies after cervical cancer using a competing risk model: implications for prevention and surveillance.

BACKGROUND: Previous studies have reported an increased risk for second primary malignancies (SPMs) after cervical cancer (CC). This study aims to quantify and assess the risk of developing SPMs in long-term survivors of CC. METHODS: A population-based cohort of CC patients aged 20-79 years was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk model and corresponding nomogram were constructed to predict the 3-, 5-, and 10-year cumulative risks of SPMs. A Fine-Gray plot was created to validate the model. Finally, we performed decision curve analysis (DCA) to evaluate the clinical usefulness of the model by calculating the net benefit. RESULTS: A total of 34,295 patients were identified, and approximately 6.3% of the study participants developed SPMs. According to the multivariable competing-risk model, older black CC survivors with localized disease who were treated with radiation therapy were more susceptible to SPMs. The 3-, 5-, and 10-year cumulative incidences of SPMs were 2.5%, 3.6%, and 6.2%, respectively. Calibration curves showed good agreement between the predicted and observed models. The DCA yielded a wide range of risk thresholds at which the net benefits could be obtained from our proposed model. CONCLUSIONS: This study provides physicians with a practical, individualized prognostic estimate to assess the risk of SPMs among CC survivors. CC survivors remain at a high risk of developing SPMs, and further surveillance should focus especially on the patients with black race, older age, localized disease, or those having received radiation therapy.

Accuracy of random-forest-based imputation of missing data in the presence of non-normality, non-linearity, and interaction.

BACKGROUND: Missing data are common in statistical analyses, and imputation methods based on random forests (RF) are becoming popular for handling missing data especially in biomedical research. Unlike standard imputation approaches, RF-based imputation methods do not assume normality or require specification of parametric models. However, it is still inconclusive how they perform for non-normally distributed data or when there are non-linear relationships or interactions. METHODS: To examine the effects of these three factors, a variety of datasets were simulated with outcome-dependent missing at random (MAR) covariates, and the performances of the RF-based imputation methods missForest and CALIBERrfimpute were evaluated in comparison with predictive mean matching (PMM). RESULTS: Both missForest and CALIBERrfimpute have high predictive accuracy but missForest can produce severely biased regression coefficient estimates and downward biased confidence interval coverages, especially for highly skewed variables in nonlinear models. CALIBERrfimpute typically outperforms missForest when estimating regression coefficients, although its biases are still substantial and can be worse than PMM for logistic regression relationships with interaction. CONCLUSIONS: RF-based imputation, in particular missForest, should not be indiscriminately recommended as a panacea for imputing missing data, especially when data are highly skewed and/or outcome-dependent MAR. A correct analysis requires a careful critique of the missing data mechanism and the inter-relationships between the variables in the data.

Drug resistance and epidemiology characteristics of multidrug-resistant tuberculosis patients in 17 provinces of China.

As China is one of high MDR-TB burden countries, it is important to determine the drug resistant pattern and clinical characteristics of multidrug resistant tuberculosis (MDR-TB). We conducted a comprehensive and nationwide study on MDR-TB in 17 provinces for the period from June 2009 to June 2015, and a total of 1154 cases of MDR-TB were finally investigated. The study sought to assess the clinical features and contrast drug susceptibility profiles of MDR-TB patients in China. Cavitary disease, young age, and long duration of TB disease among MDR-TB patients were important predictors. A high resistance proportion of first-line drugs was observed in Beijing, Shanghai and Tianjin. Resistant proportions of second-line anti-TB drugs in western region for amikacin, aminosalicylic acid, and levofloxacin were higher than eastern and central regions. High levels of drug resistance were seen in earlier cases (before 2011) and outpatients. We found high levels of resistance to 1st- and 2nd-line drugs in all settings, with considerable variabilities in terms of different Directly Observed Treatment Short Course (DOTS) programme, level of economic development(eastern, central and western regions) and patient source (inpatients and outpatients). Timely drug susceptibility testing (DST) and effective management are necessary to ensure an early detection of MDR-TB and its proper treatment.

Efficacy of Jia Wei Yang He formula as an adjunctive therapy for asthma: study protocol for a randomized, double blinded, controlled trial.

BACKGROUND: Over the past two or three decades, the prevalence of asthma has significantly increased worldwide; therefore, effective treatment without side effects is of utmost importance. Traditional Chinese medicine (TCM) plays a vital role in reducing symptoms and improving the quality of life in persistent-asthma patients. The aim of this study is to evaluate the efficacy of the Jia Wei Yang He (JWYH) formula in the treatment of asthma and to explore the relationship between the airway microbiome and TCM treatment in asthma patients. METHODS/DESIGN: This multicenter, parallel-arm, randomized, double-blinded, placebo-controlled trial will assess the efficacy of JWYH in asthma patients with usual care. Persistent-asthma patients without life-threatening disease will be enrolled on a random basis and are equally assigned to a high- or a low-dose JWYH plus usual care group, or a placebo plus usual care group. Patients are followed up for 4 months. Accordingly, 240 patients will yield sufficient statistical power to determine a difference between groups. Based on modified intent-to-treat (mITT) analyses, the three groups will be compared at 4 weeks after the beginning of treatment. The primary efficacy measurement is the mean change in the Asthma Control Test (ACT) score from baseline to 4 weeks post treatment. Secondary outcomes include forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and asthma exacerbations. This trial also includes analyses of the associations between airway microbiome and asthma treatment. DISCUSSION: In this study, a randomized clinical trial design is described. The results are based on several outcomes that estimate the efficacy of the JWYH formula and prospective links between the airway microbiome and asthma treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03299322 . Registered on 3 October 2017.

A sample size planning approach that considers both statistical significance and clinical significance.

BACKGROUND: The CONSORT statement requires clinical trials to report confidence intervals, which help to assess the precision and clinical importance of the treatment effect. Conventional sample size calculations for clinical trials, however, only consider issues of statistical significance (that is, significance level and power). METHOD: A more consistent approach is proposed whereby sample size planning also incorporates information on clinical significance as indicated by the boundaries of the confidence limits of the treatment effect. RESULTS: The probabilities of declaring a "definitive-positive" or "definitive-negative" result (as defined by Guyatt et al., CMAJ 152(2):169-173, 1995) are controlled by calculating the sample size such that the lower confidence limit under H 1 and the upper confidence limit under H 0 are bounded by relevant cut-offs. Adjustments to the traditional sample size can be directly derived for the comparison of two normally distributed means in a test of nonequality, while simulations are used to estimate the sample size for evaluating the hazards ratio in a proportional-hazards model. CONCLUSIONS: This sample size planning approach allows for an assessment of the potential clinical importance and precision of the treatment effect in a clinical trial in addition to considerations of statistical power and type I error.

Safety of the direct-acting anticoagulants in patients with atrial fibrillation: a meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) is known as one of the independent risk factors for stroke and might significantly increase its risk. Nowadays, direct-acting oral anticoagulants (DOACs) have been developed and demonstrated a more promising option to warfarin, the conclusion for safety is heterogeneous in different studies. It indicates the importance of comprehensive comparison of safety between DOACs and warfarin. MATERIAL AND METHODS: Four studies including ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY and ROCKET-AF were included in the meta-analysis to perform separate meta-analyses for high-dose regimen, low-dose regimen and their combination. The events included major bleeding, intracranial haemorrhage, gastrointestinal bleeding, non-major clinically relevant and minor bleeding. RESULTS: Regardless of high dose or low dose regimen, DOACs were associated with lower risk of intracranial haemorrhage but due to no significant association for gastrointestinal bleeding, the overall effect measured by the major bleeding was also insignificant (High dose: RR=0.86, 95% CI 0.73 to 1.01; Low dose: RR=0.63, 95% CI 0.38 to 1.04). However, the combined result of high-dose and low-dose regimens showed DOACs were associated with lower risk of major bleeding events (RR=0.77, 95% CI 0.63 to 0.95). CONCLUSIONS: Meta-analyses have showed the comparative safety of the direct-acting oral anticoagulants than warfarin in most endpoints and even better in intracranial haemorrhage. Therefore, without the need of INR monitoring, DOACs demonstrated promising alternatives to warfarin in prevention of stroke in patients with AF.

Meta-analysis of efficacy and safety of the new anticoagulants versus warfarin in patients with atrial fibrillation.

OBJECTIVE: To assess the efficacy and safety of the new oral anticoagulants versus warfarin in patients with atrial fibrillation by the meta-analyses performed for 5 studies ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and J-ROCKET. METHODS: The events including primary efficacy endpoint (stroke and systemic embolism), ischemic stroke, hemorrhagic stroke, all-cause mortality, and myocardial infarction were used for efficacy analysis and those including major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were used for safety analysis. Instead of combining both doses to 1 meta-analysis, the high-dose groups of RE-LY (150 mg twice daily) and ENGAGE AF-TIMI 48 (60 mg twice daily) were combined with the single dose studies ARISTOTLE, ROCKET-AF, and J-ROCKET. A separate meta-analysis was done for the low-dose groups of RE-LY (110 mg twice daily) and ENGAGE AF-TIMI 48 (30 mg twice daily). RESULTS: The high-dose regimen had better performance than low dose in efficacy. In addition, low-dose regimen demonstrated to significantly reduce the risk of hemorrhagic stroke, all-cause mortality, and intracranial hemorrhage. CONCLUSIONS: The new oral anticoagulants demonstrated promising alternatives to warfarin in prevention of stroke in patients with atrial fibrillation.

Developing a predictive tool for psychological well-being among Chinese adolescents in the presence of missing data.

BACKGROUND: Multi-dimensional behavioral rating scales like the CBCL and YSR are available for diagnosing psychosocial maladjustment in adolescents, but these are unsuitable for large-scale usage since they are time-consuming and their many sensitive questions often lead to missing data. This research applies multiple imputation to tackle the effects of missing data in order to develop a simple questionnaire-based predictive instrument for psychosocial maladjustment. METHODS: Questionnaires from 2919 Chinese sixth graders in 21 schools were collected, but 86% of the students were missing one or more of the variables for analysis. Fifteen (10 training, 5 validation) samples were imputed using multivariate imputation chain equations. A ten-variable instrument was constructed by applying stepwise variable selection algorithms to the training samples, and its predictive performance was evaluated on the validation samples. RESULTS: The instrument had an AUC of 0.75 (95% CI: 0.73 to 0.78) and a calibration slope of 0.98 (95% CI: 0.86 to 1.09). The prevalence of psychosocial maladjustment was 18%. If a score of > 1 was used to define a negative test, then 80% of the students would be classified as negative. The resulting test had a diagnostic odds ratio of 5.64 (95% CI: 4.39 to 7.24), with negative and positive predictive values of 88% and 43%, and negative and positive likelihood ratios of 0.61 and 3.41, respectively. CONCLUSIONS: Multiple imputation together with internal validation provided a simple method for deriving a predictive instrument in the presence of missing data. The instrument's high negative predictive value implies that in populations with similar prevalences of psychosocial maladjustment test-negative students can be confidently excluded as being normal, thus saving 80% of the resources for confirmatory psychological testing.

A survey of variable selection methods in two Chinese epidemiology journals.

BACKGROUND: Although much has been written on developing better procedures for variable selection, there is little research on how it is practiced in actual studies. This review surveys the variable selection methods reported in two high-ranking Chinese epidemiology journals. METHODS: Articles published in 2004, 2006, and 2008 in the Chinese Journal of Epidemiology and the Chinese Journal of Preventive Medicine were reviewed. Five categories of methods were identified whereby variables were selected using: A--bivariate analyses; B--multivariable analysis; e.g. stepwise or individual significance testing of model coefficients; C--first bivariate analyses, followed by multivariable analysis; D--bivariate analyses or multivariable analysis; and E--other criteria like prior knowledge or personal judgment. RESULTS: Among the 287 articles that reported using variable selection methods, 6%, 26%, 30%, 21%, and 17% were in categories A through E, respectively. One hundred sixty-three studies selected variables using bivariate analyses, 80% (130/163) via multiple significance testing at the 5% alpha-level. Of the 219 multivariable analyses, 97 (44%) used stepwise procedures, 89 (41%) tested individual regression coefficients, but 33 (15%) did not mention how variables were selected. Sixty percent (58/97) of the stepwise routines also did not specify the algorithm and/or significance levels. CONCLUSIONS: The variable selection methods reported in the two journals were limited in variety, and details were often missing. Many studies still relied on problematic techniques like stepwise procedures and/or multiple testing of bivariate associations at the 0.05 alpha-level. These deficiencies should be rectified to safeguard the scientific validity of articles published in Chinese epidemiology journals.

Identifying high-risk regions for schistosomiasis in Guichi, China: a spatial analysis.

Schistosomiasis epidemic is reemerging in some areas of China. The extensive snail habitat is a major challenge for a sustainable schistosomiasis control. Direct surveillance on snails for the disease control is no longer a desirable disease control approach due to current low density of infected snails and reduced funding. In this study the benefit of indirect monitoring of acute schistosomiasis cases, using spatial methods including disease mapping and spatial clustering analysis was explored in Guichi, China. Significant global clustering existed for acute cases and two statistically significant spatial clusters were detected, and subsequently validated by field surveys. Our study indicates that the application of geographic information system (GIS) and spatial methods are useful in the epidemiologic surveillance and risk assessment for acute schistosomiasis, providing an alternative approach with minimal funds required.

Delays in maturation among adolescents with hemophilia and a history of inhibitors.

Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV(-) adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV(+) patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors.