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Rationale Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09–1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18–1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12–1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35–3.04; P

Background Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older. Methods Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012–2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Results Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI. Conclusions Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

As the proportion of the elderly population increases, more and more people suffer from aging-related diseases. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases, and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Current research and exploration in the field of materials related to aging are expanding tremendously. Here, we present a summary of recent research in the field of nanomaterials relevant to aging. Some nanomaterials, such as silica nanomaterials (NMs) and carbon nanotubes, cause damage to the cells similar to aging processes. Other nanomaterials such as fullerenes and metalbased nanomaterials can protect the body from endogenous and exogenous harmful substances such as ROS by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, tetrahedral framework nucleic acids, works effectively against cell damage. This material selectively clears existing senescent cells in the tissue and thus prevents the development of the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that nanomaterials have tremendous potential to advance the understanding and treatment of aging-related disorders, and today's research only represents the beginning stages.

ObjectivesTo evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.MethodsThis population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.ResultsAt baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3–9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).ConclusionsRegular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Background Evidence of the trend of the incidence of activities of daily living (ADL) disability among Chinese older people is limited. We aimed to investigate the time trends and potential risk factors for the incidence of ADL disability among Chinese older people (≥65 years). Methods We established two consecutive and nonoverlapping cohorts (6,857 participants in the 2002 cohort and 5,589 participants in the 2008 cohort) from the Chinese Longitudinal Healthy Longevity Survey. ADL disability was defined as the need for assistance with at least one essential activity (dressing, bathing, toileting, eating, indoor activities, and continence). Cox proportional hazards models were used to identify factors associated with the trend in the incidence of ADL disability from 2002 to 2014. Results The incidence (per 1,000 person-years) of ADL disability decreased significantly from 64.2 in the 2002 cohort to 46.6 in the 2008 cohort (p < .001), and decreasing trends in the incidence of ADL disability were observed for all sex, age, and residence subgroups (all p < .001), even after adjusting for multiple potential confounding factors. Moreover, we found that adjustment for sociodemographic, lifestyle information, and cardiovascular risk factors (hypertension, diabetes, heart disease, and stroke) explained less of the decline in ADL disability during the period from 2002 to 2014. Conclusion The incidence of ADL disability among the older adults in China appears to have decreased during the study period, and this finding cannot be explained by existing sociodemographic and lifestyle information and cardiovascular risk factors.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3–5 kidney disease who were treated at a public veteran’s hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3–5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b–5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b–5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented.

Cervical cancer is the fourth most common cancer worldwide, but its incidence varies greatly in different countries. Regardless of incidence or mortality, the burden of cervical cancer in China accounts for approximately 18% of the global burden. The Chinese Cervical Cancer Clinical Study is a hospital-based multicenter open cohort. The major aims of this study include (i) to explore the associations of therapeutic strategies with complications as well as mid- and long-term clinical outcomes; (ii) to widely assess the factors which may have an influence on the prognosis of cervical cancer and then guide the treatment options, and to estimate prognosis using a prediction model for precise post-treatment care and follow-up; (iii) to develop a knowledge base of cervical clinical auxiliary diagnosis and prognosis prediction using artificial intelligence and machine learning approaches; and (iv) to roughly map the burden of cervical cancer in different districts and monitoring the trend in incidence of cervical cancer to potentially inform prevention and control strategies. Patients eligible for inclusion were those diagnosed with cervical cancer, whether during an outpatient visit or hospital admission, at 47 different types of medical institutions in 19 cities of 11 provinces across mainland China between 2004 and 2018. In a total, 63 926 patients with cervical cancer were enrolled in the cohort. Since the project inception, a large number of standardized variables have been collected, including epidemiological characteristics, cervical cancer-related symptoms, physical examination results, laboratory testing results, imaging reports, tumor biomarkers, tumor staging, tumor characteristics, comorbidities, co-infections, treatment and short-term complications. Follow-up was performed at least once every 6 months within the first 5 years after receiving treatment and then annually thereafter. At present, we are developing a cervical cancer imaging database containing Dicom files with data of computed tomography/magnetic resonance imaging examination. Additionally, we are also collecting original pathological specimens of patients with cervical cancer. Potential collaborators are welcomed to contact the corresponding authors, and anyone can submit at least one specific study proposal describing the background, objectives and methods of the study.

Context The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. Objective To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. Design, Setting, and Patients This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. Results A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was 7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was Conclusions A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

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.

Background Dementia is a serious and growing health problem, and since most people with dementia live at home, caring responsibilities generally fall on family members. Caregivers are often inadequately supported by formal health services and have poorer psychological and physical health. Our study aimed to compare the contributions of publications from different countries, institutions and authors and present a bibliometric analysis to determine the hotspots and trends in research concerning the health of and interventions for family dementia caregivers. Methods Studies published during 1988–2018 were extracted from the Science Citation Index Expanded of the Web of Science. Each abstract of publications was evaluated to obtain the basic information. A bibliometric analysis was used to evaluate the number or cooperation networks of publications, countries, institutions, journals, citations, authors, references, and keywords. The resulting articles were analyzed descriptively, and the publication keywords were visualized using VOSviewer. Results Five hundred forty-two articles were identified. The annual number of relevant publications has steadily increased since approximately 2006. The USA has the highest number of publications (36.2%), followed by the UK (12.9%). China entered the field late, but research conducted in China has rapidly developed. The most productive institution, journal, and author in this field are University College London, the Journal of the American Geriatrics Society, and Orrell M from the UK, respectively. A co-occurrence analysis of the keywords reveals a mainstream research focus on burden, depression, quality of life, and corresponding interventions for people with dementia caregivers. The keywords “psychosocial intervention”, “long-term”, “e-learning/online”, “communication”, and “qualitative research” reflect the latest hotspots, appearing in approximately 2017–2018. Conclusion Our study details the performance statistics, main topics and trends research on the health of and interventions for dementia caregivers from 1988 to 2018 and provides a comprehensive analysis.

Background Treatments of type B aortic dissection (TBAD) include thoracic endovascular aortic repair (TEVAR), best medical treatment (BMT) and open surgery (OS). This meta-analysis was to compare these three strategies to evaluate which provides best outcomes. Methods We searched clinical trials that compared treatment strategies for TBAD. The outcomes measures were 30-day/in-hospital mortality, long-term survival rate, paraplegia or paraparesis, renal failure, rupture, stroke, late re-intervention, late rupture and aneurismal dilatation/expansion. Results Sixteen control trials covering 10,307 patients were evaluated. Meta-analysis showed that TEVAR provides preferable long-term survival rate (HR=0.71; 95% CI: 0.52–0.95), lower rate of late re-intervention (OR=0.33; 95% CI: 0.13–0.85), late rupture (OR=0.21; 95% CI: 0.10–0.43) and late aneurismal dilatation/expansion (OR=0.15; 95% CI: 0.04–0.63) compared with BMT. However, TEVAR seemed to be associated with higher stroke rate than BMT (OR=1.65; 95% CI: 1.21–2.23). 30-day/in-hospital mortality appeared to be lower in TEVAR (OR=0.49; 95% CI: 0.29–0.81) when compared with OS. In addition, OS induced higher 30-day/in-hospital mortality compared with BMT (OR=3.95, 95% CI: 1.56–10.02). Conclusions Our study shows that TEVAR may be favorable in long-term outcomes and effectively provide morphologic advantages compared to BMT. However, there is a need for prophylactic measures against stroke in TEVAR. OS seems to be inferior to TEVAR both in short-term and long-term outcomes. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy between TEVAR and BMT.

Objectives A few studies of Western populations have found inconsistent results regarding the associations between vitamin D status and physical function. We explored the association between circulating vitamin D status [plasma 25-hydroxyvitamin D, 25(OH)D] and incident activities of daily living (ADL) disability among Chinese older adults. Design Community-based longitudinal cohort study. Setting and Participants A total of 2453 men and women (median age 84.0 years) in 7 Chinese longevity areas were included. Measures Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident ADL, with adjustments for potential sociodemographic, and lifestyle confounders and biomarkers. Because there was a statistically significant interaction between plasma 25(OH)D and sex in relation to incident ADL, men and women were analyzed separately. Results The median concentrations of plasma 25(OH)D were 46.6 nmol/L and 36.4 nmol/L for men and women, respectively. Compared with the lowest quartile in the fully adjusted model, the HR for incident ADL disability for the highest quartile was 0.55 (95% CI 0.36–0.85) for women; for men, a null association was indicated (HRhighest vs lowest 0.61, 95% CI 0.37–1.00). However, when using the recommended circulating 25(OH)D thresholds by the US Institute of Medicine, those with vitamin D sufficiency (≥50 nmol/L) had better ADL disability prognoses than those with vitamin D deficiency ( Conclusions and Implications The relationship between plasma 25(OH)D concentration and incident ADL disability was sex-specific among Chinese older adults. However, participants with recommended vitamin D sufficiency may have better disability prognoses in both sexes, suggesting that the recommended 25(OH)D concentration for bone health may extend to functional outcomes such as ADL disability in Chinese older adults.

BackgroundGenetic factors and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on smoking remains unclear. We aimed to investigate the association of the PRS with COPD and explore whether smoking behaviours could modify such association.MethodsMultivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals for the association of the PRS and smoking with COPD.ResultsThe study included 439 255 participants (mean age 56.5 years; 53.9% female), with a median follow-up of 9.0 years. PRSlasso containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than PRS279 containing 279 genome-wide significance variants. Compared with low genetic risk, the HRs of medium and high genetic risk were 1.39 (95% CI 1.31–1.48) and 2.40 (95% CI 2.24–2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI 10.31–13.10) times that of low genetic risk and never smoking. There were significant interactions between PRSlasso and smoking status for incident COPD (pinteractionConclusionsThe PRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.

// Yue-Lun Zhang 1, 2 , Jin-Qiu Yuan 1, 2 , Kai-Feng Wang 3 , Xiao-Hong Fu 1, 2 , Xiao-Ran Han 1, 2 , Diane Threapleton 1 , Zu-Yao Yang 1, 2 , Chen Mao 1, 2 , Jin-Ling Tang 1, 2 1 Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China 2 Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of The Chinese University of Hong Kong, Shenzhen, Guangdong Province, China 3 Division of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China Correspondence to: Chen Mao, email: maochen@cuhk.edu.hk Jin-Ling Tang, email: jltang@cuhk.edu.hk Keywords: non-small cell lung cancer, epidermal growth factor receptor, prevalence, systematic review, meta-analysis Received: May 17, 2016 Accepted: September 25, 2016 Published: October 12, 2016 ABSTRACT 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.

An ocular jellyfish sting is an ophthalmic emergency and is rarely reported in the medical literature. With the evolution of aquatic activities and entertainment in recent decades, we anticipate that more patients with ocular jellyfish stings may be taken to the emergency department. However, most physicians are unaware of the typical presentations, suitable treatments, prognosis, and possible complications of ocular jellyfish stings. We reported 2 cases with ocular jellyfish stings and collected cases series from literature review. The most common clinical features of ocular jellyfish stings were pain, conjunctival injection, corneal lesion, and photophobia. All patients who sustained ocular stings did so during aquatic activities, and the best management at the scene was proper analgesics and copious irrigation of affected eyes with seawater or saline. The ocular lesions were treated with topical cycloplegics, topical steroids, topical antibiotics, topical antihistamines, and removal of nematocysts. The prognosis was good, and all patients recovered without any permanent sequelae. However, symptoms in some patients may last longer than 1 week. Reported complications included iritis, increased intraocular pressures, mydriasis, decreased accommodation, and peripheral anterior synechiae.

The prognostic value of phosphatase and tensin homolog (PTEN) negativity in breast cancer has been evaluated by many studies but remains controversial. We conducted a meta-analysis to assess the association of PTEN negativity with overall survival and disease-free survival. Thirty-two studies with 4393 patients were identified. PTEN negativity was significantly associated with unfavorable overall survival in breast cancer (hazard ratio=1.89, 95% confidence interval 1.58-2.26), with low heterogeneity among the studies (I(2)=25%, P=0.160) and no evidence for publication bias. Meta-analysis of multivariate hazard ratios and sensitivity analyses did not materially change the results. The data on disease-free survival was heterogeneous (I(2)=61.9%, P

We appreciate the comments by Conway1 on our manuscript which investigated the association of regular glucosamine use with all-cause and cause-specific mortality.2 First, we agree that the underlying mechanisms, including inhibition of nuclear factor-κB thereby reducing inflammation and glucosamine triggering a mimic response of low carbohydrate diet, might partially explain the association between glucosamine use and mortality. Future studies are needed to better understand …

Objective Although some people with mild cognitive impairment may not suffer from dementia lifelong, about 5% of them will progress to dementia within 1 year in community settings. However, a general tool for predicting the risk of cognitive impairment was not adequately studied among older adults. Design Prospective cohort study. Setting Community-living, older adults from 22 provinces in China. Participants We included 10,066 older adults aged 65 years and above (mean age, 83.2 ± 11.1 years), with normal cognition at baseline in the 2002–2008 cohort and 9354 older adults (mean age, 83.5 ± 10.8 years) in the 2008–2014 cohort of the Chinese Longitudinal Healthy Longevity Survey. Methods We measured cognitive function using the Chinese version of the Mini-Mental State Examination. Demographic, medical, and lifestyle information was used to develop the nomogram via a Lasso selection procedure using a Cox proportional hazards regression model. We validated the nomogram internally with 2000 bootstrap resamples and externally in a later cohort. The predictive accuracy and discriminative ability of the nomogram were measured by area-under-the-curves and calibration curves, respectively. Results Eight factors were identified with which to construct the nomogram: age, baseline of the Mini-Mental State Examination, activities of daily living and instrumental activities of daily living score, chewing ability, visual function, history of stroke, watching TV or listening to the radio, and growing flowers or raising pets. The area-under-the-curves for internal and external validation were 0.891 and 0.867, respectively, for predicting incident cognitive impairment. The calibration curves showed good consistency between nomogram-based predictions and observations. Conclusions and Implications The nomogram-based prediction yielded consistent results in 2 separate large cohorts. This feasible prognostic nomogram constructed using readily ascertained information may assist public health practitioners or physicians to provide preventive interventions of cognitive impairment.

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, This cohort study uses data from the Chinese Longitudinal Healthy Longevity Study to examine whether body mass index (BMI) is associated with subsequent disability in activities of daily living in Chinese adults 80 years of age or older., Key Points Question Is higher body mass index or overweight or obesity associated with higher risk of subsequent disability in activities of daily living in Chinese adults 80 years of age or older? Findings In this cohort study of 16 022 Chinese adults aged 80 years or older, body mass index was linearly and inversely associated with disability in activities of daily living. When body mass index was categorized by quintiles or categorized by Chinese guidelines, higher body mass index, including being overweight or obese, showed significantly decreased risk of disability in activities of daily living. Meaning The finding suggests that current recommendations for body mass index may need to be revisited; more attention should be paid to underweight rather than overweight or obesity for the prevention of disability in activities of daily living in adults 80 years of age or older.

In this study, two dissolution models were developed to achieve in vitro-in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent solubility and low bioavailability in hypochlorhydric and achlorhydric patients. The dissolution models were designed to approximate the hypo-/achlorhydric and normal fasted stomach conditions after a glass of water was ingested with the drug. The dissolution data from the two models were predictive of the relative in vivo bioavailability of various formulations under the same gastric condition, hypo-/achlorhydric or normal. Furthermore, the dissolution data were able to estimate the relative performance under hypo-/achlorhydric and normal fasted conditions for the same formulation. Together, these biorelevant dissolution models facilitated formulation development for Compound-A by identifying the right type and amount of key excipient to enhance bioavailability and mitigate the negative effect of hypo-/achlorhydria due to drug-drug interaction with acid-reducing agents. The dissolution models use readily available USP apparatus 2, and their broader utility can be evaluated on other BCS 2B compounds with reduced bioavailability caused by hypo-/achlorhydria.

Supplemental Digital Content is available in the text, 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 aim of this study was to estimate the associations between tumor necrosis factor (TNF) gene polymorphisms and type 1 diabetes (T1D) using meta-analysis. Relevant studies were searched using PubMed and Embase up to August 2013. A total of 32 comparisons from 21 studies examining the associations between TNF polymorphisms and T1D were included in the present meta-analysis. Our meta-analysis identified a significant association between TNF -308 A/G polymorphism A allele and T1D in all subjects [odds ratio (OR) 2.001, 95 % confidence interval (CI) 1.732-2.312). Significant associations of AA and AA+AG genotype of TNF -308 A/G polymorphism with genetic susceptibility to T1D were also found (OR 3.203, 95 % CI 2.373-4.324; OR 2.232, 95 % CI 1.881-2.649). After stratification by ethnicity, significant associations of T1D with TNF -308 A/G polymorphism under all genetic models (A allele and AA, AA+AG genotype) were still detected in European (OR 1.952, 95 % CI 1.675-2.274; OR 3.108, 95 % CI 2.169-4.455; OR 2.249, 95 % CI 1.870-2.706, respectively) and non-European populations (OR 2.152, 95 % CI 1.488-3.112; OR 3.439, 95 % CI 2.000-5.914; OR 2.207, 95 % CI 1.496-3.257, respectively). Our meta-analysis also revealed an association of TNF -857 T/C polymorphism T allele with T1D risk (OR 1.647, 95 % CI 1.431-1.896). Furthermore, analysis of TT and TT+TC genotype indicated the same result patterns as shown by the TNF -857 T/C polymorphism T allele (OR 2.206, 95 % CI 1.467-3.317; OR 1.762, 95 % CI 1.490-2.083). In conclusion, our meta-analysis results indicate that TNF -308 A/G and -857 T/C polymorphisms are involved in the genetic background of T1D.

ObjectivesLittle is known about the gender and age differences associated with the effects of economic fluctuations on hospitalization for cardiovascular diseases. This paper investigates the impact of economic fluctuations on hospitalization for ischemic heart disease (IHD), stroke, and hypertension by age and gender between January 1996 and December 2012 in Taiwan.MethodsWe adopted a multiple-input time series analysis to examine the strength of the immediate and latent effects of the 17-year quarterly unemployment rates (UR), air pollution exposure (APE), gross domestic product (GDP), per capita consumption expenditure in cigarette and alcohol (ECA), and per capita healthcare expenditure (HE) on the adjusted quarterly incidence rate of hospitalization. The data used in this paper were retrieved from the National Health Insurance Research Database and the website of the Directorate-General of Budget, Accounting and Statistics (DGBAS), Executive Yuan.ResultsOur findings indicate that higher UR increased IHD hospitalization in young men and women and middle-aged women but reduced stroke hospitalization in young men. Higher APE increased IHD hospitalization in young men but reduced it for young women, increased stroke hospitalization in old men and middle-aged women but reduced it for young men, and increased hypertension hospitalization in middle-aged men and young women. Higher ECA reduced IHD hospitalization in middle-aged men, increased stoke hospitalization in middle-aged and old men and middle-aged women. Higher HE reduced IHD hospitalization in old men, young and old women, reduced stroke hospitalization in old women, and reduced hypertension hospitalization in young and middle-aged women.ConclusionsOverall, we found that the economic fluctuations caused increased harmful effects in certain population subgroups but also brought some soothing effects to some groups.

BACKGROUND: Resistance and aerobic exercises are both recommended as effective treatments for people with type 2 diabetes. However, the optimum type of exercise for the disease remains to be determined to inform clinical decision-making and facilitate personalized exercise prescription. OBJECTIVES: Our objective was to investigate whether resistance exercise is comparable to aerobic exercise in terms of effectiveness and safety in people with type 2 diabetes. DATA SOURCES: PubMed, EMBASE, CENTRAL, CINAHL, and SPORTdiscus were systematically searched up to March 2013. The reference lists of eligible studies and relevant reviews were also checked. STUDY SELECTION: We used the following criteria to select studies for inclusion in the review: (i) the study was a randomized controlled trial; (ii) the participants were people with type 2 diabetes aged 18 years or more; (iii) the trial compared resistance exercise with aerobic exercise for a duration of at least 8 weeks, with pre-determined frequency, intensity, and duration; and (iv) the trial provided relevant data on at least one of the following: glycaemic control, blood lipids, anthropometric measures, blood pressure, fitness, health status, and adverse events. STUDY APPRAISAL AND SYNTHESIS METHODS: The assessment of study quality was based on the Cochrane Risk of Bias tool. For effectiveness measures, differences (resistance group minus aerobic group) in the changes from baseline with the two exercises were combined, using a random-effects model wherever possible. For adverse events, the relative risks (resistance group vs. aerobic group) were combined. RESULTS: Twelve trials (n = 626) were included. Following the exercise interventions, there was a greater reduction of glycosylated hemoglobin with aerobic exercise than with resistance exercise (difference 0.18% (1.97 mmol/mol), 95% confidence interval (CI) 0.01, 0.36). This difference became non-significant with sensitivity analysis (p = 0.14). The differences in changes from baseline were also statistically significant for body mass index (difference 0.22, 95% CI 0.06, 0.39), peak oxygen consumption (difference -1.84 mL/kg/min, 95% CI -3.07, -0.62), and maximum heart rate (difference 3.44 beats per minute, 95% CI 2.49, 4.39). Relative risks for adverse events (all) and serious adverse events were 1.17 (95% CI 0.77, 1.79) and 0.89 (95% CI 0.18, 4.39), respectively. LIMITATIONS: Most included trials were short term (8 weeks to 6 months), and seven had important methodological limitations. Additionally, the meta-analyses for some of the secondary outcomes had a small number of participants or substantial statistical heterogeneity. CONCLUSIONS: Although differences in some diabetic control and physical fitness measures between resistance exercise and aerobic exercise groups reached statistical significance, there is no evidence that they are of clinical importance. There is also no evidence that resistance exercise differs from aerobic exercise in impact on cardiovascular risk markers or safety. Using one or the other type of exercise for type 2 diabetes may be less important than doing some form of physical activity. Future long-term studies focusing on patient-relevant outcomes are warranted.

Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter -1082/-819/-592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter -1082/-819/-592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma.Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger's test.A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene -1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and -592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P 0.05), but not with -819 polymorphism (P 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of -1082A/G polymorphism and AC + AA versus CC genotype of -592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for -1082A/G and 1.53 (1.25, 1.87) for -592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for -1082A/G and 1.4 (1.12, 1.64) for -592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for -1082A/G and 1.23 (1.01, 1.48) for -592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected.IL-10 promoter -1028A/G, -592A/C polymorphisms and their haplotypes, but not -819T/C polymorphism, correlate with asthma susceptibility.

The objective of the study was to explore the dynamic effects of socioeconomic status (SES) and lifestyle behaviors on the risks of metabolic syndrome (MS) or cardiovascular disease (CVD) in life course. The data of 12,825 subjects (6616 males and 6209 females) who underwent repeated examinations and answered repeated questionnaires from 2006 to 2014 at the Major Health Screening Center in Taiwan, was collected and analyzed. The trajectory of trends in the subjects&rsquo, SES and lifestyle mobility over time was observed, and the effects of factors with potential impacts on health were tested and analyzed using multiple logistic regression and a generalized estimated equation model. A 10% increase in MS prevalence was observed over the nine-year period. The average Framingham CVD score for people with MS was estimated to be about 1.4% (SD = 1.5%). Except for middle-aged women, marriage was found to raise the risk of CVD, whereas increasing education and work promotions independently reduced CVD risk for the majority of subjects. However, the risk of CVD was raised by half for young men who had a job or lost a job in comparison to continuously unemployed young men. Physical activity was only found to be advantageous for disease prevention in those aged less than 40 years, increased exercise levels were useless for reducing CVD risk among older men. Alcohol drinking and betel chewing caused increased CVD risk in the old and young subjects, respectively, whereas vegetarian diets and vitamin C/E intake were helpful in preventing CVD, even if those habits were ceased in later life. For middle-aged women, getting sufficient sleep reduced CVD risk. We concluded that SES and lifestyle behaviors may have different effects on health over time, among various populations. Accordingly, suggestions can be provided to healthcare workers in designing health promotion courses for people at different life stages.

KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs). However, many patients with KRAS wild-type tumors still do not respond to the treatment. We conducted a systematic review with meta-analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild-type mCRC treated with anti-EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression-free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random-effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67–4.03; HR = 2.52, 95% CI 1.33–4.78 and HR = 1.75, 95% CI 1.19–2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79–4.19; HR = 3.29, 95% CI 1.60–6.75 and HR = 1.85, 95% CI 1.30–2.64, respectively) and lower ORR (RD = −36%, 95% CI −44 to −28%; RD = −38%, 95% CI −51 to −24% and RD = −41%, 95% CI −68 to −14%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of better outcomes in KRAS wild-type mCRC treated with anti-EGFR MoAbs. However, the quality of included studies varied, and some of the meta-analyses were limited by significant between-study heterogeneity. In the future, well-designed large randomized controlled trials conducted in KRAS wild-type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.

Hepatitis B was still a worldwide health problem. This study aimed to conducted a systematic review and meta-analysis to assess a more precise estimation of factors that influence the response to hepatitis B vaccine in adults. Our included studies examined seroprotection rates close to the end of vaccination schedules in healthy adult populations. This meta-analysis including 21053 adults in 37 articles showed that a significantly decreased response to hepatitis B vaccine appeared in adults (age ≥ 40) (RR:1.86, 95% CI:1.55–2.23), male adults (RR:1.40, 95% CI:1.22–1.61), BMI ≥ 25 adults (RR:1.56, 95% CI:1.12–2.17), smoker (RR:1.53, 95% CI:1.21–1.93), and adults with concomitant disease (RR:1.39, 95% CI:1.04–1.86). Meanwhile, we further found a decreased response to hepatitis B vaccine appeared in adults (age ≥ 30) (RR:1.77, 95% CI:1.48–2.10), and adults (age ≥ 60) (RR:1.30, 95% CI:1.01–1.68). However, there were no difference in response to hepatitis B vaccine both in alcoholic (RR:0.90, 95% CI:0.64–1.26) and 0-1-12 vs. 0-1-6 vaccination schedule (RR:1.39, 95% CI:0.41–4.67). Pooling of these studies recommended the sooner the better for adult hepatitis B vaccine strategy. More vaccine doses, supplemental/additional strengthening immunity should be emphasized on the susceptible population of increasing aged, male, BMI ≥ 25, smoking and concomitant disease. The conventional 0-1-6 vaccination schedule could be still worth to be recommended.

Background We conducted a systematic review and meta-analysis to dissect the association between PIK3CA mutations and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) according to PIK3CA exon of mutations in metastatic colorectal cancer (mCRC). Methods We systematically identified studies exploring the association between PIK3CA mutations and clinical outcomes of mCRC patients treated with anti-EGFR MoAbs. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between studies. Results Thirteen studies were considered eligible, with 576 mCRC patients included. In KRAS wild-type mCRC patients, we observed a lower ORR in patients with PIK3CA exon 20 mutations [3 studies, 377 patients; ORR = 0% versus 37%; RR = 0.25; 95% confidence interval (CI) 0.05–1.19; P = 0.082], although the result was not statistically significant because of the small sample size. Only one study provided survival data according to the PIK3CA exon of the mutations, in which PIK3CA exon 20 mutations were statistically significantly associated with shorter PFS (HR = 2.52; 95% CI 1.33–4.78; P = 0.013) and OS (HR = 3.29; 95% CI 1.60–6.74; P = 0.006) in KRAS wild-type mCRC patients treated with anti-EGFR MoAbs. The predictive power of exon 20 mutation is greater than exon 9 mutations and all exons mutations in terms of ORR, PFS, and OS. Conclusion These analyses suggest that PIK3CA exon 20 mutations may be a potential biomarker for resistance to anti-EGFR MoAbs in KRAS wild-type mCRC.

Supplemental Digital Content is available in the text, Hepatitis B and hepatitis C are 2 types of potentially life-threatening liver diseases with high infection rate. Body piercing represents a progressively popular sociocultural phenomenon which is also a potential exposure approach for hepatitis B virus (HBV) and hepatitis C virus (HCV). Conclusions from those researches with statistically risk assessment of body piercing on HBV and HCV transmission are contradictory. Systematically analyze the association between body piercing and the risk of transmitting hepatitis B virus and hepatitis C virus for general population. Make evidence-based recommendations to the current practice and wake up public awareness of this health-threatening behavior. Comprehensive and high sensitivity search strategies were performed to exhaustively search related studies before 15 January 2015 (MEDLINE, EMBASE, WANFANG, CNKI datasets for published literatures, and Google and Google scholars for related grey articles). Two authors identified relevant studies for the review, abstracted data, and assessed literature quality independently and critically according to the selection criteria and quality assessment standard. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate risk of HBV and HCV infection in relation to body piercing status. Subgroup analysis and sensitivity analysis were conducted to examine the source of heterogeneity and test the robust of the results. A total of 40 studies were included in this systematic review (10 for Hep-B, 26 for Hep-C, 4 for both Hep-B and Hep-C), the pooled OR (95% CI) for the association between body piercing and transmission of HBV/HCV is 1.80 (1.18, 2.75) and 1.83 (1.27, 2.64), respectively. Subgroup analysis suggested that highest risk of body piercing related to hepatitis C infection was for former soccer and veterans with OR of 4.63 (2.65, 8.10), while strongest association between body piercing and hepatitis B was for samples derived from students/community with OR of 2.40 (1.44, 4.02). The current systematic review and meta-analysis suggests that body piercing is significantly associated with the transmission of HBV as well as HCV, having body piercing probably can increase the risk of getting infected. Evidence from this study strongly recommends that comprehensive and effective programs should be established to provide safer piercing practice.

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR = 1.23, 95% CI = 1.11–1.36; CC vs. TT: OR = 1.30, 95% CI = 1.14–1.48; dominant model: OR = 1.25, 95% CI = 1.13–1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR = 1.24, 95% CI = 1.10–1.40; CC vs. TT: OR = 1.31, 95% CI = 1.13–1.52; dominant model: OR = 1.26, 95% CI = 1.12–1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR = 1.15, 95% CI = 1.00–1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR = 1.15, 95% CI = 1.01–1.31; CC vs. TT: OR = 1.30, 95% CI = 1.01–1.68; dominant model: OR = 1.22, 95% CI = 1.00–1.50; and recessive model: OR = 1.11, 95% CI = 1.01–1.23) and lung cancer (CC vs. TT: OR = 1.30, 95% CI = 1.10–1.54; and recessive model: OR = 1.18, 95% CI = 1.02–1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR = 1.30, 95% CI = 1.13–1.49; CC vs. TT: OR = 1.37, 95% CI = 1.14–1.66; dominant model: OR = 1.32, 95% CI = 1.15–1.53) and population-based studies (CC vs. TT: OR = 1.19, 95% CI = 1.06–1.35; dominant model: OR = 1.13, 95% CI = 1.01–1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.

The purpose of this study was to examine the association between psychoactive drug use and motor vehicle crash (MVC) injuries requiring hospitalization in southern Taiwan. A case–control study was conducted in southern Taiwan from January 2009 to December 2009. The cases included car or van drivers who were involved in MVCs and required hospitalization. Demographic and trauma-related data were collected from questionnaires and hospital and ambulance records. Urine and/or blood samples were collected on admission. The controls consisted of drivers who were randomly recruited while driving on public roads. Study subjects were interviewed and asked to provide urine samples. All blood and urine samples were tested for alcohol and a number of other legal and illegal drugs. Only those subjects who provided urine and/or blood specimens were included in the study. During the study period, 254 case patients and 254 control drivers were enrolled. The analysis showed an odds ratio (OR) of 3.41 (95% confidence intervals (95% CI), 1.76–6.70; p < 0.001) for persons taking benzodiazepines, and an OR of 3.50 (95% CI, 1.81–6.85; p < 0.001) for those taking alcohol (blood alcohol concentrations (BAC) ≥ 0.8 g/l) with regard to hospitalizations due to MVCs. For persons taking combinations of benzodiazepines and alcohol, the OR increased to 5.12 (95% CI: 1.77–15.91, p < 0.001). This study concluded that drug use among motor vehicle drivers increases the risk of MVCs that require hospitalization. From a public health perspective, the high risk ratios are concerning, and preventive measures are warranted.

Background and objective: Genetic background may influence susceptibility pulmonary tuberculosis. The evidence for an association between the P2X7 receptor A1513C polymorphism and susceptibility to pulmonary tuberculosis remains inconclusive. In order to provide a more precise estimate of this association, a meta-analysis was performed. Methods: Databases, including PUBMED, OVID, ScienceDirect, SpringerLink, EBSCO and EMBASE were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled OR with 95% CI for the association between susceptibility to pulmonary tuberculosis and the P2X7 receptor A1513C polymorphism. The chi-squared-based Q-test was used to test the heterogeneity hypothesis. Begg's test and Egger's test were used to check publication bias. Results: Six published case–control studies that investigated the association between the P2X7 receptor A1513C polymorphism and susceptibility to pulmonary tuberculosis in 2525 subjects were included in this meta-analysis. The heterogeneity hypothesis test did not reveal any heterogeneity. Begg's test and Egger's test did not detect obvious publication bias among the included studies. This meta-analysis indicated that there was no significant association between the P2X7 receptor A1513C polymorphism and susceptibility to pulmonary tuberculosis (AC vs AA model: OR 1.12, 95% CI: 0.93–1.35; CC vs AA model: OR 1.45, 95% CI: 0.92–2.28; AC + CC vs AA model: OR 1.15, 95% CI: 0.96–1.13; CC vs AC + AA model: OR 1.42, 95% CI: 0.90–2.23). Conclusions: This meta-analysis of six studies involving 2525 subjects suggested that the P2X7 receptor A1531C polymorphism is not associated with susceptibility to pulmonary tuberculosis.

Several polymorphisms of vascular endothelial growth factor (VEGF) such as 936 C/T, -2578 C/A, -406 C/T, and -1154 G/A polymorphism have been identified. Published data on the association between VEGF polymorphisms and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude OR with 95% CI was used to assess the strength of association between them. For VEGF 936C/T polymorphism, a total of 10 studies including 7,685 cases and 7,915 controls were involved in this meta-analysis. Overall, no significant associations were found between VEGF 936C/T polymorphism and breast cancer risk when all studies pooled into the meta-analysis (TC vs. CC: OR = 0.904, 95% CI = 0.797-1.024; TT vs. CC: OR = 0.974, 95% CI = 0.786-1.205; dominant model: OR = 0.911, 95% CI = 0.811-1.024; and recessive model: OR = 0.991, 95% CI = 0.801-1.226). In the subgroup analysis by ethnicity, still no significant associations were found for all comparison models. For -2578 C/A, -406 C/T, and -1154 G/A polymorphism, there were too limited data to perform a meta-analysis. In conclusion, this meta-analysis suggests that the VEGF 936C/T polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

The published data on the predictive and prognostic value of KRAS mutations in metastatic colorectal cancer (mCRC) treated with cetuximab seemed inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Systematic computerised searches of the PubMed, EMBase, BIOSIS, and SCOPUS were performed. A total of 22 studies were identified. Random-effects model or fix-effects model was used according to between-study heterogeneity. A total of 2188 mCRC patients were included in the final meta-analysis. The rate of KRAS mutations was 38% (829/2188). The overall response rate (ORR) of mutant KRAS patients was 14% (119/829), whereas the ORR of wild-type KRAS patients was 39% (529/1359). The overall pooled relative ratio (RR) for ORR was 0.24 (95% confidence intervals (CI): 0.16-0.38; P

Epidemiologic studies have evaluated the association between BRAF mutations and resistance to the treatment of anti-EGFR monoclonal antibodies (MoAb) in patients with metastatic colorectal cancer (mCRC). However, the results are still inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. A total of 11 studies were included in the final meta-analysis. There were seven studies for unselected mCRC patients and four studies for patients with wild type KRAS mCRC. Among unselected mCRC patients, BRAF V600E mutation was detected in 48 of 546 primary tumors (8.8%). The objective response rate (ORR) of patients with mutant BRAF was 29.2% (14/48), whereas the ORR of patients with wild-type BRAF was 33.5% (158/472).The overall RR for ORR of mutant BRAF patients over wild-type BRAF patients was 0.86 (95% CI = 0.57–1.30; P = 0.48). For patients with KRAS wild-type mCRC, BRAF V600E mutation was detected in 40 of 376 primary tumors (10.6%). The ORR of patients with mutant BRAF was 0.0% (0/40), whereas the ORR of patients with wild-type BRAF was 36.3% (122/336). The pooled RR of mutant BRAF patients over wild-type BRAF patients was 0.14 (95% CI = 0.04–0.53; P = 0.004). In conclusion, this meta-analysis provides evidence that BRAF V600E mutation is associated with lack of response in wild-type KRAS mCRC treated with anti-EGFR MoAbs. BRAF mutation may be used as an additional biomarker for the selection of mCRC patients who might benefit from anti-EGFR MoAbs therapy.

Epidemiological studies have evaluated the association between ATM C.1066-6T > G (IVS10-6T > G) mutation and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of 11 studies including 8,831 cases and 4,957 controls were identified. The carrier frequency of the ATM C.1066-6T > G mutation was 0.5% (45/8,831) in patients with breast cancer and 0.7% (38/4,957) in healthy controls. When all the 11 studies were pooled into the meta-analysis, there was no evidence for significant association between C.1066-6T > G mutation and breast cancer risk (OR 0.87, 95% CI 0.55–1.37). In the subgroup analyses by source of controls and family history with BRCA1/2 status, no significant association were found in any subgroup of population. When sensitivity analyses were performed, all the results were not materially altered. In summary, the meta-analysis strongly suggests that ATM C.1066-6T > G mutation is not associated with increased breast cancer risk.

Published data on the association between MnSOD Val16Ala polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981-1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934-1.083; dominant model: OR = 1.013, 95% CI = 0.962-1.066; and recessive model: OR = 0.985, 95% CI = 0.931-1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Published data on the association between BRCA2 N372H polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97-1.05; HH versus NN: OR = 1.05, 95% CI = 0.97-1.13; dominant model: OR = 1.01, 95% CI = 0.98-1.05; and recessive model: OR = 1.05, 95% CI = 0.98-1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01-1.21; dominant model: OR = 1.05, 95% CI = 1.00-1.10; recessive model: OR = 1.09, 95% CI = 1.00-1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

Published data on the association between XRCC3 5'-UTR and IVS5-14 polymorphisms and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between these polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. A total of four studies were involved in the meta-analysis with 6,303 cases and 6,563 controls for XRCC3 5'-UTR polymorphism and with 6,270 cases and 6,682 controls for XRCC3 IVS5-14 polymorphism. For XRCC3 5'-UTR A/G polymorphism, significantly elevated breast cancer risk was associated with variant genotype when all studies were pooled into the meta-analysis (AG vs. AA: OR = 1.11, 95% CI = 1.03-1.19; dominant model: OR = 1.09, 95% CI = 1.01-1.17). For XRCC3 IVS5-14 A/G polymorphism, significantly decreased breast cancer risk was associated with variant genotype (GG vs. AA: OR = 0.86, 95% CI = 0.77-0.96). In conclusion, this meta-analysis suggests that the variant G allele of XRCC3 5'-UTR polymorphism is a low-penetrant risk factor for developing breast cancer, while the variant G allele of XRCC3 IVS5-14 polymorphism has a protective effect on breast cancer development.

Epidemiological studies have evaluated the association between CYP17 MspA1 polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 35 studies including 22,090 cases and 28,498 controls were identified. Genotype distributions of CYP17 in the controls of all studies were in agreement with Hardy-Weinberg equilibrium (HWE) except for three studies. When all 35 studies were pooled into the meta-analysis, there was no evidence for significant association between CYP17 MspA1 polymorphism and breast cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96-1.04; for A2/A2 vs. A1/A1: OR = 1.03, 95% CI = 0.97-1.08; for dominant model: OR = 1.01, 95% CI = 0.97-1.05; for recessive model: OR = 1.03, 95% CI = 0.98-1.08). In the subgroup analyses by ethnicity, menopausal status and source of controls, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1 polymorphism is not associated with increased breast cancer risk.

Published data on the association between manganese superoxide dismutase (MnSOD) Val(16)Ala polymorphism and prostate cancer (PCA) risk are inconclusive. To derive a more precise estimate of the association between them, a meta-analysis was performed.PubMed and Embase were searched. All eligible studies were retrieved. The pooled odds ratio (OR) with 95% confidence interval (CI) for PCA risk associated with Val/Ala versus Val/Val, Ala/Ala versus Val/Val, dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val) were estimated, respectively.A total of 12 studies including 8,962 subjects were involved in this meta-analysis. Overall, the meta-analysis indicated that significantly elevated cancer risk was associated with Ala variant genotype when all the eligible studies were pooled into the meta-analysis (for Val/Ala vs. Val/Val: OR = 1.11, 95% CI = 1.00-1.24; for Ala/Ala vs. Val/Val: OR = 1.22, 95% CI = 1.00-1.49; for dominant model: OR = 1.14, 95% CI = 1.03-1.26). In the subgroup analysis by ethnicity, statistically significant increased risks were found among Caucasians with Ala allele (for Val/Ala vs. Val/Val: OR = 1.12, 95% CI = 1.00-1.25; for dominant model: OR = 1.14, 95% CI = 1.02-1.26). However, no significant associations were found in Africans.This meta-analysis suggests that the Ala allele of the MnSOD gene was a low-penetrance susceptible gene in PCA development, especially in Caucasians.

Epidemiological studies have evaluated the association between catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 41 studies including 25,627 cases and 34,222 controls were identified. Genotype distributions of COMT in the controls of all studies were in agreement with the Hardy-Weinberg equilibrium (HWE) except for three studies. When all 41 studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val108/158Met polymorphism and breast cancer risk (for Val/Met vs. Val/Val: OR = 0.99, 95% CI = 0.93-1.04; for Met/Met vs. Val/Val: OR = 0.96, 95% CI = 0.88-1.04; for dominant model: OR = 0.97, 95% CI = 0.92-1.03; for recessive model: OR = 0.97, 95% CI = 0.90-1.04). In the subgroup analyses by ethnicity, menopausal status, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that COMT Val108/158Met polymorphism is not associated with increased breast cancer risk.

Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03-1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01-1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01-1.15; for dominant model: OR = 1.08; 95% CI = 1.02-1.15; for recessive model: OR = 1.29; 95% CI = 1.00-1.68). In the subgroup analysis by cancer types, significant associations were found in breast cancer (for allelic effect: OR = 1.16; 95% CI = 1.01-1.34) and ovarian cancer (for allelic effect: OR = 1.24; 95% CI = 1.00-1.54; for 6A/6A vs. 9A/9A: OR = 2.34; 95% CI = 1.03-5.33). However, no significant associations were found in colorectal cancer, bladder cancer, prostate cancer and lung cancer for all genetic models. In summary, this meta-analysis suggests that the TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer.

Published data on the association between STK15 F31I polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, Web of Science, and Chinese Biomedicine Database were searched. Crude ORs with 95% CIs were used to assess the strength of association between the STK15 F31I polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (FI vs. FF; II vs. FF), dominant model (FI + II vs. FF), and recessive model (II vs. FI + FF), respectively. A total of 10 studies including 10,537 cases and 14,477 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with II variant genotype in homozygote comparison and recessive genetic model when all studies were pooled into the meta-analysis (for II vs. FF: OR = 1.23, 95% CI = 1.10–1.37; for recessive model: OR = 1.21, 95% CI = 1.05–1.40). In the subgroup analysis by ethnicity, significantly increased risks were found for II allele carriers among Caucasians (for II vs. FF: OR = 1.24, 95% CI = 1.08–1.43; for recessive model: OR = 1.21, 95% CI = 1.00–1.45); significantly increased risks were also found among Asians for II versus FF (OR = 1.21; 95% CI = 1.01–1.45). In conclusion, this meta-analysis suggests that the STK15 31II allele is a low-penetrant risk factor for developing breast cancer.

The aim of this study to determine whether serum p53 protein and antibodies are associated with malignant tumors. A case-control study was conduct in 569 patients with various types of malignant tumors and 879 healthy controls. Serum p53 protein and antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA).The rate of positive p53 protein in patients with various malignant tumors was 4.22% compared with 0.34% in healthy controls (P < 0.001). The rate of anti-p53 antibodies in patients with various malignant tumors was 14.59% compared with 1.02% in healthy controls (P < 0.001). The adjusted odd ratio (OR) for p53 protein was 17.55 (95% CI = 4.98-61.94). The adjusted odd ratio for anti-p53 antibodies was 14.27 (95% CI = 6.75-30.16). The study strongly suggested that serum p53 protein and antibody are associated with increased cancer risk and can be used as early serological markers in the diagnosis of malignancies tumors.

To explore the real association between p53 codon 72 polymorphism and lung cancer risk, a pooled analysis of 32 case-control studies involving 19,255 subjects was conducted. When all 32 studies were pooled into the analysis, significantly elevated lung cancer risks were associated with variant genotypes in all genetic models (for Pro/Arg vs. Arg/Arg: OR 1.21, 95% CI 1.01-1.23; for Pro/Pro vs. Arg/Arg: OR 1.20, 95% CI 1.03-1.39; for Pro/Pro + Pro/Arg vs. Arg/Arg: OR 1.14, 95% CI 1.03-1.25; for Pro/Pro vs. Arg/Arg + Pro/Arg: OR 1.06, 95% CI 1.01-1.12). In the subgroup analysis by ethnicity, histological type, or smoking status, significantly increased risks were found in subgroups such as Asians, Caucasians, lung adenocarcinoma patients, or smokers, respectively. In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development.