Constructing Large Scale Cohort for Clinical Study on Heart Failure with Electronic Health Record in Regional Healthcare Platform:Challenges and Strategies in Data Reuse

Regional healthcare platforms collect clinical data from hospitals in specific areas for the purpose of healthcare management.It is a common requirement to reuse the data for clinical research.However,we have to face challenges like the inconsistence of terminology in electronic health records (EHR) and the complexities in data quality and data formats in regional healthcare platform.In this paper,we propose methodology and process on constructing large scale cohorts which forms the basis of causality and comparative effectiveness relationship in epidemiology.We firstly constructed a Chinese terminology knowledge graph to deal with the diversity of vocabularies on regional platform.Secondly,we built special disease case repositories (i.e.,heart failure repository) that utilize the graph to search the related patients and to normalize the data.Based on the requirements of the clinical research which aimed to explore the effectiveness of taking statin on 180-days readmission in patients with heart failure,we built a large-scale retrospective cohort with 29647 cases of heart failure patients from the heart failure repository.After the propensity score matching,the study group (n=6346) and the control group (n=6346) with parallel clinical characteristics were acquired.Logistic regression analysis showed that taking statins had a negative correlation with 180-days readmission in heart failure patients.This paper presents the workflow and application example of big data mining based on regional EHR data.

Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma

AIM: To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999. METHODS AND RESULTS: Data were retrospectively analyzed by chart review. In 95 cases (72 males and 23 females) sufficient data were available for analysis. Twenty five (29%) of 85 patients were HBsAg or anti HBc positive, 21/85 (25%) were anti HCV positive, and 6/85 (7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV positive patients than in the other two groups. Thirty one (34%) of 90 patients had histories of alcohol abuse. In 79/94 (84%) patients, cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/94 (20%). Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%). According to Okuda 28/94 (30%) were grouped to stage I, 53/94 (56%) were grouped to stage II, and 13/94 (14%) were grouped to stage II. Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8 4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival, though patients with an AFP value greater than 100 microg/L did experience shortened survival. Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage II patients. There was longer survival in those Okuda stage II patients who were treated with percutaneous ethanol injection. CONCLUSION: Even in a low incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival.

Homocysteinemia and Depression in Community-Dwelling Older Adults: The Cohort Longitudinal Study “InveCeAb” (Brain Aging in Abbiategrasso)

Depression is a major health problem, especially for elderly people. According to the “homocysteine hypothesis of depression”, high homocysteine levels may cause depression of mood via cerebrovascular diseases. Whilst biologically plausible, such hypothesis needs yet confirmation. We aimed at: 1) studying the relationships between homocysteinemia (HCY) and depression in a community-dwelling cohort of people aged 70 to 75 years at baseline;2) investigating plasma levels of HCY and 3) comparing these levels between males and females, in the same population. We exploited the data from four waves (2010, 2012, 2014 and 2018) of the longitudinal study “InveCeAb”, with specific regard towards mood assessment, by Geriatric Depression Scale (GDS) scoring, and diagnosis of clinically relevant or subthreshold depression. HCY plasma levels were measured in the waves 2012, 2014 and 2018. Sample attrition was due mainly to death or overall worsening. No statistically significant differences were found in plasma homocysteine levels in each wave, according to depressive symptoms. No correlations were found between plasma HCY levels in each wave with their corresponding GDS scores, even after adjustment for folate and cobalamin blood concentrations. Dichotomized levels of HCY (≤15 vs >15 μM/l) were not associated with dichotomized GDS scores (≤4 vs higher), clinically relevant and subthreshold depression diagnosis and any antidepressive use, in any wave. First (2012) HCY levels increased with participants’ increasing age, cross-sectionally. Listwise HCY concentrations decreased along the 3 waves. HCY levels were always higher in males than in females. Our results may challenge the “homocysteine hypothesis” of depression, whilst supporting the role of high homocysteinemia as a marker of overall bad health.

Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China

Objective To explore the interactions between pre-pregnancy body mass index(BMI) and age on offspring neuropsychological development from 1 to 24 months in China.Methods In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China,between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient(DQ) of children aged from 1 to 24 months.Results Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains(gross motor, fine motor, adaptive, language, and social;P < 0.001).Age × pre-pregnancy BMI ≥ 25 kg/m^2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m^2(P < 0.01). Multiple comparisons showed pre-pregnancy BMI ≥ 25 kg/m^2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months(P < 0.05).Conclusions This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect(from 1 to24 months).

Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwan Residents chronic kidney disease patients acquiring hepatitis B virus infection

AIM To investigate the risk of end-stage renal disease(ESRD) in hepatitis B virus(HBV)-infected patients with chronic kidney disease(CKD) with and without nucleos(t)ide analogue(NA) therapy.METHODS This nationwide cohort study included 103444 Taiwan Residents CKD adults without hepatitis C virus infection from the Taiwan Longitudinal Health Insurance Database 2005 between 1997 and 2012. We identified 2916 CKD patients who acquired HBV infection and did not receive NAs(untreated cohort), and they were propensitymatched 1:4 with 11664 uninfected counterparts. We also identified 442 CKD patients who acquired HBV infection and received NAs(treated cohort), and they were propensity-matched 1:3 with 1326 untreated counterparts. The association between HBV infection, NA use, and ESRD was analyzed using competing risk analysis.RESULTS Multivariable Cox regression analysis showed a 1.67-fold higher risk(P < 0.0001) of ESRD in the untreated cohort(16-year cumulative incidence, 10.1%) than in the matched uninfected cohort(16-year cumulative incidence, 6.6%), which was independent of cirrhosis or diabetes. The treated cohort(16-year cumulative incidence, 2.2%) had an 87% lower ESRD risk(P < 0.0001) compared with the matched untreated cohort(16-year cumulative incidence, 11.9%). The number needed to treat for one fewer ESRD after NA use at 12 years was 12. Multivariable stratified analyses verified these associations in all subgroups.CONCLUSION This study suggests that untreated HBV infection and NA therapy are associated with increased and decreased risk of ESRD, respectively, in CKD patients. Identification of HBV status and targeted monitoring for ESRD development are important in CKD patients living in HBV-endemic areas.

Survival and clinical outcomes in patients with metastatic epidural spinal cord compression after spinal surgery:a prospective,multicenter,observational cohort study

Background:High quality studies have been challenging to undertake in patients with metastatic epidural spinal cord compression.Nonetheless,in the article "Survival and Clinical Outcomes in Surgically Treated Patients With Metastatic Epidural Spinal Cord Compression:Results of the Prospective Multicenter AOSpine Study" recently published in the Journal of Clinical Oncology,our team provided convincing evidence that spinal surgery improves overall quality of life in patients with this potentially devastating complication of cancer.Considering that metastatic spinal lesions treated with surgery have the highest mean cost among all oncological musculo-skeletal issues,it is essential to provide high quality data to optimize the therapeutic approaches and cost-effective use of health care resources.Main body:Although the AOSpine Study provided high quality prospective data,it was primarily limited by the lack of non-operative controls and the relatively small sample size.Given the dearth of medical equipoise and the fundamental difference between patients deemed to be adequate surgical candidates and those who are not amenable to operative intervention,conducting a randomized controlled trial in this patient population was not felt to be ethically or medically feasible.Consequently,the optimal option to overcome limitations of both the lack of controls and the relatively small sample size is through collection of large prospective datasets through rigorously developed and maintained registries.Conclusions:With the alarming increase in the incidence of cancer in China and China's parallel growing cancer control efforts,China would offer a fantastic platform to set up a national metastatic spinal lesion registry.Such registry would not only enhance metastatic epidural spinal cord compression translational research but also optimize patient care.

Measurement Error for Age of Onset in Prevalent Cohort Studies

Prevalent cohort studies involve screening a sample of individuals from a population for disease, recruiting affected individuals, and prospectively following the cohort of individuals to record the occurrence of disease-related complications or death. This design features a response-biased sampling scheme since individuals living a long time with the disease are preferentially sampled, so naive analysis of the time from disease onset to death will over-estimate survival probabilities. Unconditional and conditional analyses of the resulting data can yield consistent estimates of the survival distribution subject to the validity of their respective model assumptions. The time of disease onset is retrospectively reported by sampled individuals, however, this is often associated with measurement error. In this article we present a framework for studying the effect of measurement error in disease onset times in prevalent cohort studies, report on empirical studies of the effect in each framework of analysis, and describe likelihood-based methods to address such a measurement error.

A 12-year cohort study on the efficacy of plasmaderived hepatitis B vaccine in rural newborns

AIM To understand the anti-HBs persistenceand the long-term preventive efficacy in ruralnewborns after vaccination with plasma-derivedhepatitis B vaccine.METHODS In the time of expanded program onimmunization(EPI),the newborns werevaccinated with 10μg×3 doses of hepatitis Bvaccine and 762 newborns who were HBsAgnegative after primary immunization wereselected for cohort observation from 1986 to1998.Their serum samples were detectedqualitatively and quantitatively for hepatitis Binfecting markers,including HBsAg,anti-HBsand anti-HBc by SPRIA Kits.The annual HBsAgpositive conversion rate was counted by life-table method.RESULTS①The anti-HBs positive rate was94.44% for the babies born to HBsAg negativemothers and 84.21% for those born to HBsAgpositive mothers in the 1st year afterimmunization,and dropped to 51.31% and52.50% in the 12th year respectively.GMT valuewas dropped from 31.62 to 3.13 and 23.99 to 3.65in the 2nd to the 12th year respectively.Therewas a marked drop in GMT at the 3rd to the 5thyear,and in anti-HBs positive rate at the 9th tothe 10th year.②In the period of 12 yearsobservation,the person-year HBsAg positive conversion rates were 0.12%(5/4150.0)innewborns born to HBsAg negative mothers and0.20%(1/508.0)in those born to HBsAgpositive mothers,and none of the HBsAgpositive converted children became HBsAgchronic carriers.Compared with the baselinebefore immunization,the protective rates were97.19% and 95.32% respectively.CONCLUSION The protective efficacy ofplasma-derived hepatitis B vaccine persisted atleast 12 years,and a booster dose seems notnecessary within at least 12 years after theprimary three-doses immunization to newbornsborn to HBsAg negative mothers.

Silicosis in Automobile Foundry Workers: A 29-Year Cohort Study

Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.

Effect of 7 and 13-Valent Pneumococcal Conjugate Vaccines Different Number of Doses for Pneumonia Control in 2008 and 2010 Birth Cohort Children

The 7-valent pneumococcal conjugate vaccine (PCV) was introduced in Uruguay in March 2008. In April 2010, it was replaced by PCV13. Surveillance of both vaccines was performed on hospitalized children with consolidated pneumonia. The effect of different number of vaccine doses was evaluated in 2008 and 2010 birth cohorts vaccinated with PCV7 and PCV13 respectively. The study aims to estimate the effects of PCV7 and PCV13 different number of doses on consolidated pneumonia, through the study of hospitalized children from 2008 and 2010 birth cohorts. Vaccination records of every child were available providing precise vaccination data;therefore a new approach was used to estimate PCVs effect. Incidence rate was calculated for each year of the study and for the different number of vaccine doses used each year. Exposure was calculated as person per year and rate ratio values determined the decrease of consolidated pneumonias. This decrease in percentage was estimated as the difference between the incidence with no vaccine and the incidence of every one of the doses. Incidence rate ratio revealed significant values for the three vaccine doses of PCVs for both cohorts. Upon comparing incidences, significant reduction percentages of consolidated pneumonia admissions were found. The reduction percentage of consolidated pneumonia for fully vaccinated (3 doses) patients was 69.3% and 84.6 % for PCV7 and PCV13, respectively. These results confirm that PCV7 and PCV13 are highly effective for reducing pediatric hospitalizations due to consolidated pneumonia, as reported by other national publications and demonstrated by international researchers.

Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China:a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.

Low selenium and reduced cognitive function in a cohort elderly study

Cognitive function in the elderly is affected by various environmental,social,and individual factors.Studies show that chemical trace elements are closely related to cognitive function.As a protective factor,selenium promotes cognition in the elderly.However,study results into the effects of selenium on cognition have varied.By eliminating unstable environmental and other related factors,the present study selected elderly individuals from rural areas of the Shandong province to verify whether low selenium exposure is a risk factor for decreased cognitive function.Results demonstrated that age,sex,education,occupation,hypertension,stroke,and body selenium levels were factors affecting cognitive function in the elderly,and that selenium was an important protective factor.Moreover,results supported the hypothesis that a lifelong low selenium level is associated with low cognitive function.

Conditions of Non-Unique Identifiers in Record Linkage Using Japanese Cohort Dataset

The applications of unique identifiers such as name, home address and social security number to link different datasets have been commonly used and well-published. Also, the theoretical concepts of probabilistic algorithm in record linkage have been well-defined in the literature. However, few studies have reported the applications of its probabilistic algorithm using non-unique identifiers. In this paper, we investigate several variables (weight, height, waist, age, sex, smoking and alcohol habit) as non-unique identifiers using Japanese cohort dataset with three-year baseline of 1989-1991 to observe how effectively these identifiers can be used and what influence those may have on record linkage. Moreover, we modify the conditions of these identifiers and estimate the sensitivity, specificity and accuracy for comparison. We further investigate this by using extended ten-year baseline of 1989-1999 as well. As a result, we conclude that the combination of age, sex, weight and height predicts better estimation with regards to the sensitivity, specificity and accuracy than other combinations in both men and women in case of using three-year baseline, whereas the combination of age, sex and height predicts better in both men and women in case of using ten-year baseline.

Trends and risk factors of elderly-onset Crohn’s disease: A nationwide cohort study

BACKGROUND The incidence of inflammatory bowel disease(IBD)is increasing in Asia.Numerous risk factors associated with IBD development have been investigated.AIM To investigate trends and environmental risk factors of Crohn’s disease(CD)diagnosed in persons aged≥40 years in South Korea.METHODS Using the National Health Insurance Service database,a total of 14060821 persons aged>40 years who underwent national health screening in 2009 were followed up until December 2017.Patients with newly diagnosed CD were enrolled and compared with non-CD cohort.CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database.The mean follow-up periods was 7.39 years.Age,sex,diabetes,hypertension,smoking,alcohol consumption,regular exercise,body mass index,anemia,chronic kidney disease(CKD)and dyslipidemia were adjusted for in the multivariate analysis model.RESULTS During the follow-up,1337(1.33/100000)patients developed CD.Men in the middle-aged group(40-64 years)had a higher risk than women[adjusted hazard ratio(aHR)1.46,95%confidence interval(CI):1.29-1.66];however,this difference tended to disappear as the age of onset increases.In the middle-aged group,patients with a history of smoking[(aHR 1.46,95%CI:1.19-1.79)and anemia(aHR 1.85,95%CI:1.55-2.20)]had a significantly higher CD risk.In the elderly group(age,≥65 years),ex-smoking and anemia also increased the CD risk(aHR 1.68,95%CI:1.22-2.30)and 1.84(95%CI:1.47-2.30,respectively).Especially in the middle-aged group,those with CKD had a statistically elevated CD risk(aHR 1.37,95%CI:1.05-1.79).Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups.[Middle-aged:aHR 0.77(95%CI:0.66-0.89)and aHR 0.73(95% CI:0.63-0.84),respectively][Elderly-group:aHR 0.57(95% CI:0.42-0.78)and aHR 0.84(95%CI 0.67-1.04),respectively].For regular physical activity and dyslipidemia,negative correlation between CD incidences was proved only in the middle-aged group[aHR 0.88(95%CI:0.77-0.89)and aHR 0.81(95%CI:0.68-0.96),respectively].CONCLUSION History of cigarette smoking,anemia,underweight and CKD are possible risk factors for CD in Asians aged>40 years.

Assessment of Retreatment Tuberculosis Cases amongst All Tuberculosis Cases Notification in District Swat 2015-2017: A Retrospective Cohort Review

Retreatment Tuberculosis (TB) has long been a neglected area in global TB control. To determine the notification of re-treatment Tuberculosis TB cases among all enrolled TB patients, we conducted a retrospective cohort review of routine program data from 2015-2017. A total of 8663 tuberculosis cases (all new and old forms) were registered at the study site. Of these, 1916 (22%) were pulmonary bacteriological confirmed;3498 (40.37%) were pulmonary clinical diagnosed and 3396 (39.20%) were clinically or bacteriological confirmed extra-pulmonary tuberculosis cases. Retreatment cases trend was found to be increased from 1% in 2015 to 1.6% in 2017. Majority of re-treatment cases were in the age group 18 - 43 years and only 7 patients were under the age of 15 years. This concludes that notification of re-treatment cases is very low among all enrolled TB patients and this could be possibly due to the fact that most of the re-treatment cases were registered as new cases or misdiagnosed. There is need and space to increase retreatment cases. Most of the re-treatment cases were usually converted to MDR-TB (Multi-Drug Resistant Tuberculosis) as noted in PMDT (Programmatic management of Drugs resistant tuberculosis) site. Therefore, proper history and diagnosis should be encouraged at the time of case notification.

Occupational determinants of continued smoking during pregnancy. INMA Valencia cohort study

To describe the smoking habits of the mothers participating in the INMA (INfancia y Medio Ambiente or Childhood and the Environment) cohort of Valencia and to determine which occupational factors are associated with smoking cessation during pregnancy. Cohort study comprising 855 pregnant women from Health Service Areas 6 and 7 was set up in the Autonomous Region of Valencia, Spain. Data on smoking and smoking cessation during pregnancy, and on sociodemographic and work related variables were collected through structured questionnaires at the first and third trimester of pregnancy. Multivariate logistic regression models were constructed to assess factors related to smoking at the beginning of the pregnancy and to continued smoking. 787 women followed in the project and completed all the data. Among them 40.9% smoked at the beginning of pregnancy and 56.2% continued until gestational week 32. Time and effort spent on housework was associated with smoking at the beginning of pregnancy while stress in the workplace related variables contributed to both the prevalence of smoking at the beginning of the pregnancy and the persistence in the habit throughout pregnancy. We found a high prevalence of smoking among the pregnant mothers. Both, conditions in the workplace, as well as the burden of housework were found to be risk factors for smoking and not quitting during pregnancy. These factors should be taken into account when developing health programs designed to encourage the incorporation of healthy habits into the lives of pregnant women.

Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: Results from a 14-year cohort study

BACKGROUND The risk of developing prediabetes based on the metabolic/obesity phenotypes has been poorly investigated. AIM To examine the association of baseline metabolic/obesity phenotypes and their changes over time with the risk of prediabetes development. METHODS In a population-based cohort study, 1741 adults (aged > 19 years) with normal blood glucose were followed for 14 years. Anthropometric and biochemical measures were evaluated regularly during the follow-up period. According to body mass index and metabolic health status, participants were categorized into four groups: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Multivariable Cox regression analysis was used to measure the risk of prediabetes according to the baseline metabolic/obesity phenotype and their changes during the follow-up. RESULTS In the whole population with a mean (95CCI for mean) follow up duration of 12.7 years (12.6-12.9), all three MUNW, MHO, MUO groups were at higher risk for developing prediabetes compared to the MHNW group (P = 0.022). The MUNW group had the highest risk for developing prediabetes (hazard ratio (HR): 3.84, 95%CI: 1.20, 12.27). In stratified analysis by sex, no significant association was found in men, while women in the MUNW group were at the greatest risk for prediabetes (HR: 6.74, 95%CI: 1.53, 29.66). Transforming from each phenotype to MHNW or MHO was not related to the risk of prediabetes development, whereas transforming from each phenotype to MUO was associated with an increased risk of prediabetes (HR > 1;P < 0.05). CONCLUSION Our findings indicate that MHO is not a high risk, unless it transforms into MUO over time. However, people in the MUNW group have the greatest risk for developing prediabetes, and therefore, they should be screened and treated.

Effect of tumor necrosis factor inhibitors on rheumatoid arthritis-induced peripheral neuropathy A cohort study

In this historical cohort study, 236 patients with primary rheumatoid arthritis were treated with the tumor necrosis factor inhibitors, etanercept or infliximab （n = 80）, or by conventional methods （n = 156）. Results revealed that 11 patients developed varying types of peripheral neuropathy at 1-2 years post-treatment （mean 16 months）. The incidence of peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 8.8% （7/80）, which was significantly higher than the conventional treatment group （2.6%; 4/156）. The relative risk of developing peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 3.41 （95% confidence interval： 1.03 11.31）. Comparison of the tumor necrosis factor inhibitors revealed that etanercept and infliximab had no significant difference in terms of inducing peripheral neuropathy. Experimental findings indicate that tumor necrosis factor inhibitors may increase the risk of peripheral neuropathy.

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Effect of exposure to ambient PM2.5 pollution on the risk of respiratory tract diseases： a meta-analysis of cohort studies

The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter 〈 2.5 gm （PM2.5）, as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter （PM2.5） and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 （3.1%） were included in this meta-analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic-related than non-traffic-related air pollution. In children, the pooled relative risk （RR） represented significant increases in wheezing （8.2%）, cough （7.5%）, and lower respiratory illness （15.3%）. The pooled RRs in children were 1.091 （95%CI： 1.049, 1.135） for exposure to 〈 25 gg/m3 PM2.5, and 1.126 （95%CI： 1.067, l. 190） for exposure to 〉 25 gg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.