The application of target trials with longitudinal targeted maximum likelihood estimation to assess the effect of alcohol consumption in adolescence on depressive symptoms in adulthood.

Time-varying confounding is a common challenge for causal inference in observational studies with time-varying treatments, long follow-up periods, and participant dropout. Confounder adjustment using traditional approaches can be limited by data sparsity, weight instability and computational issues. The Nicotine Dependence in Teens (NDIT) study is a prospective cohort study involving 24 data collection cycles from 1999 to date, among 1,294 students recruited from 10 high schools in Montreal, Canada, including follow-up into adulthood. Our aim is to estimate associations between the timing of alcohol initiation and the cumulative duration of alcohol use on depression symptoms in adulthood. Based on the target trials framework, we define intention-to-treat and as-treated parameters in a marginal structural model with sex as a potential effect-modifier. We then use the observational data to emulate the trials. For estimation, we use pooled longitudinal target maximum likelihood estimation (LTMLE), a plug-in estimator with double robust and local efficiency properties. We describe strategies for dealing with high-dimensional potential drinking patterns and practical positivity violations due to a long follow-up time, including modifying the effect of interest by removing sparsely observed drinking patterns from the loss function and applying longitudinal modified treatment policies to represent the effect of discouraging drinking.

Residential proximity to oil and gas production sites and hematologic malignancies: A case-control study.

BACKGROUND: We investigated the association between residential proximity to oil and gas production sites and hematologic malignancies, due to a cancer cluster in the German state of Lower Saxony. METHODS: A registry-based case-control study was conducted including 3978 cases of hematologic malignancies diagnosed within 2013-2016 and 15,912 frequency-matched controls randomly drawn by population registries. Residential proximity to 5333 oil and gas production sites at the time of diagnosis was calculated. Unconditional logistic regression models were used to estimate the association between living within 1 km of any exposure site and developing a hematologic malignancy. Models were adjusted for matching variables sex, age group, district, and year of diagnosis as well as for proximity to main streets and to agricultural land. RESULTS: We found no association between the development of hematologic malignancies and the proximity to all oil and gas production sites (odds ratio: 0.97; 95% confidence interval: 0.85, 1.11). Focusing on gas production sites increased the odds of developing hematologic cancer (odds ratio: 1.19; 95% confidence interval: 0.97, 1.45). In stratified analyses, associations were stronger in women and for acute myeloblastic leukemia. We also found an association in the district where the initial cluster occurred. CONCLUSIONS: Our results suggest that residential proximity to oil and gas production is not a risk factor for all hematologic malignancies in general. Sporadic and past exposures are the most likely scenarios for mechanisms involving oil and gas production, leading to increased risk for certain subtypes of cancer in certain populations.

From workplace to home environment: spreading of mouse allergens by laboratory animal workers.

PURPOSE: Laboratory animal workers (LAW) working with laboratory mice are exposed to mouse allergens (MA). If MA are spread to home environments, this might increase the risk for allergies in LAW and their families. This study aimed to assess 1. whether spreading of MA from workplace to home environment takes place; 2. which factors increase spreading of MA. METHODS: In a cross-sectional study, dust samples were taken on the mattress and seating in homes of LAW (n = 105) and an unexposed comparison group (n = 13). From 89 LAW, additional dust samples were taken from their workplaces. Samples were analysed using Mus m1 ELISA kits [detection limit (DL) 0.2 ng mus m1/ml]. Sociodemographic data, personal history of allergies and cleaning habits, as well as work-related characteristics (LAW only) were assessed by questionnaire. Latent factors were assessed via factor analysis. Tobit models were fitted to analyse the latent factors' contribution to MA spreading. RESULTS: MA concentration on the seating was significantly higher in home environments of LAW (median = 1.28 ng mus m1/m2) than in the comparison group (median < DL, p = 0.019). The highest workplace MA concentration was found on the floor of the scullery (median = 140,000.00 ng mus m1/m2), followed by hair-covering caps (median = 76.02 ng mus m1/m2). Cage and mouse facility cleaning tasks and infrequent changing of bed linen at home were statistically significantly associated with higher MA concentrations at home. CONCLUSIONS: Spreading of MA from LAW's workplace to their home environment takes place, especially among LAWs involved in cleaning tasks.

Long-term effects of asthma medication on asthma symptoms: an application of the targeted maximum likelihood estimation.

BACKGROUND: Long-term effectiveness of asthma control medication has been shown in clinical trials but results from observational studies with children and adolescents are lacking. Marginal structural models estimated using targeted maximum likelihood methods are a novel statistiscal approach for such studies as it allows to account for time-varying confounders and time-varying treatment. Therefore, we aimed to calculate the long-term risk of reporting asthma symptoms in relation to control medication use in a real-life setting from childhood to adulthood applying targeted maximum likelihood estimation. METHODS: In the prospective cohort study SOLAR (Study on Occupational Allergy Risks) we followed a German subsample of 121 asthmatic children (9-11 years old) of the ISAAC II cohort (International Study of Asthma and Allergies in Childhood) until the age of 19 to 24. We obtained self-reported questionnaire data on asthma control medication use at baseline (1995-1996) and first follow-up (2002-2003) as well as self-reported asthma symptoms at baseline, first and second follow-up (2007-2009). Three hypothetical treatment scenarios were defined: early sustained intervention, early unsustained intervention and no treatment at all. We performed longitudinal targeted maximum likelihood estimation combined with Super Learner algorithm to estimate the relative risk (RR) to report asthma symptoms at SOLAR I and SOLAR II in relation to the different hypothetical scenarios. RESULTS: A hypothetical intervention of early sustained treatment was associated with a statistically significant risk increment of asthma symptoms at second follow-up when compared to no treatment at all (RR: 1.51, 95% CI: 1.19-1.83) or early unsustained intervention (RR:1.38, 95% CI: 1.11-1.65). CONCLUSIONS: While we could confirm the tagerted maximum likelihood estimation to be a usable and robust statistical tool, we did not observe a beneficial effect of asthma control medication on asthma symptoms. Because of potential due to the small sample size, lack of data on disease severity and reverse causation our results should, however, be interpreted with caution.

An educational intervention to improve knowledge about prevention against occupational asthma and allergies using targeted maximum likelihood estimation.

PURPOSE: Occupational asthma and allergies are potentially preventable diseases affecting 5-15% of the working population. However, the use of preventive measures is often insufficient. The aim of this study was to estimate the average treatment effect of an educational intervention designed to improve the knowledge of preventive measures against asthma and allergies in farm apprentices from Bavaria (Southern Germany). METHODS: Farm apprentices at Bavarian farm schools were asked to complete a questionnaire evaluating their knowledge about preventive measures against occupational asthma and allergies (use of personal protective equipment, personal and workplace hygiene measures). Eligible apprentices were randomized by school site to either a control or an intervention group. The intervention consisted of a short educational video about use of preventive measures. Six months after the intervention, subjects were asked to complete a post-intervention questionnaire. Of the 116 apprentices (70 intervention group, 46 control group) who answered the baseline questionnaire, only 47 subjects (41%; 17 intervention group, 30 control group) also completed the follow-up questionnaire. We, therefore, estimated the causal effect of the intervention using targeted maximum likelihood estimation. Models were controlled for potential confounders. RESULTS: Based on the targeted maximum likelihood estimation, the intervention would have increased the proportion of correct answers on all six preventive measures by 18.4% (95% confidence interval 7.3-29.6%) had all participants received the intervention vs. had they all been in the control group. CONCLUSIONS: These findings indicate the improvement of knowledge by the educational intervention.

Compatibility of medication with PRISCUS criteria and identification of drug interactions in a large cohort of patients with COPD.

Patients with COPD are often of advanced age and have a high number of medications due to their lung disease and comorbidities. Thus they are at risk for unwanted effects from drugs, either due to age or due to interactions between drugs. These issues are not clarified. We therefore assessed the number of medications and potential adverse effects in a large cohort of patients with COPD. The analysis was performed in 2741 patients of the German COPD cohort COSYCONET, using baseline data (visit 1) and follow-up data after about 1.5 years (visit 3). Spirometric GOLD grades 1-4 were found in 8/35/32/9% of patients and GOLD groups ABCD in 7/25/4/48% of patients, while the remaining patients (n = 450, 16.4%) could not be classified according to GOLD criteria. The compatibility of medication with age was evaluated via the PRISCUS list, drug interactions via the AiD clinic system, whereby only drug combinations occurring in at least 10 patients were considered (nine unwanted interactions, one wanted interaction). The median numbers of medications were 5 or more in all patient categories, among them 3 or more non-respiratory medications. In the total population there were 153 patients (10.2%) aged ≥65 years who had any medication of the PRISCUS list with intermediate or low risk. Serious adverse combinations of drugs according to AiD occurred in 114 patients (4.2%), while the number of unwanted but only potentially clinically relevant combinations was 175 (6.4%). The number of wanted combinations was 219 (8.0%). These numbers did not markedly change when restricting the analysis to patients of GOLD grades 1-4. Moreover, the results were similar for visit 1 and visit 3. We conclude that in a large cohort of COPD patients about 10% of patients aged at least 65 years had medications that could interfere with their age and that the proportions of patients with either unwanted or wanted drug interactions were both in the range of 8-10%. These results suggest that problems arising from the high number of medications were not very frequent in the COPD cohort analysed.

Job strain, bullying and violence at work and asthma in Peruvian cleaners-a cross-sectional analysis.

OBJECTIVES: An increased asthma prevalence was found in cleaners. Many of them work in precarious employment conditions, potentially leading to stress, a known risk factor for asthma. We aimed to analyze whether asthma in cleaners might partly be explained by psychosocial working conditions. METHODS: The study population of this cross-sectional study included 199 cleaners employed at regional public health services in Puno Province (Peru). They were compared to 79 unexposed workers from Lima, Peru (response 83%). Both groups answered the short version of the European Working Condition Survey and a modified version of the European Community Respiratory Health screening questionnaire. After multiple imputation, the association between psychosocial working conditions and asthma (wheeze without cold or use of asthma medication) was assessed. RESULTS: The 12-months prevalence of asthma was 22% among cleaners versus 5% among unexposed workers (pChi(2) = .001). Cleaners were more likely than unexposed workers to work with temporary or sub-contracts, have a high employment insecurity, high strain working conditions and low social support (all pChi(2) < .05). Twenty-six percent vs. 10% reported a high bullying score; 39% vs. 8% had experienced violence at work (both pChi(2) < .001). High bullying score (adjusted Odds Ratio 5.6; 95% Confidence Interval 1.5-21.4) and violence (2.4; 1.1-5.4) were the main predictors of asthma. Taking these factors into account, being a cleaner was not statistically significantly associated with the outcome (3.5; 0.9-13.8). CONCLUSIONS: Poor psychosocial working conditions of cleaners may partly explain the high prevalence of asthma. The underlying mechanism might be a stress-induced inflammatory immune response.

Proximity to mining industry and respiratory diseases in children in a community in Northern Chile: A cross-sectional study.

BACKGROUND: In a community in northern Chile, explosive procedures are used by two local industrial mines (gold, copper). We hypothesized that the prevalence of asthma and rhinoconjunctivitis in the community may be associated with air pollution emissions generated by the mines. METHODS: A cross-sectional study of 288 children (aged 6-15 years) was conducted in a community in northern Chile using a validated questionnaire in 2009. The proximity between each child's place of residence and the mines was assessed as indicator of exposure to mining related air pollutants. Logistic regression, semiparametric models and spatial Bayesian models with a parametric form for distance were used to calculate odds ratios and 95 % confidence intervals. RESULTS: The prevalence of asthma and rhinoconjunctivitis was 24 and 34 %, respectively. For rhinoconjunctivitis, the odds ratio for average distance between both mines and child's residence was 1.72 (95 % confidence interval 1.00, 3.04). The spatial Bayesian models suggested a considerable increase in the risk for respiratory diseases closer to the mines, and only beyond a minimum distance of more than 1800 m the health impact was considered to be negligible. CONCLUSION: The findings indicate that air pollution emissions related to industrial gold or copper mines mainly occurring in rural Chilean communities might increase the risk of respiratory diseases in children.

Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management: A PIONEER Analysis Based on Big Data.

BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.

Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.

AIMS: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. METHODS AND RESULTS: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males). CONCLUSION: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.

Risk factors for major gastrointestinal bleeding in the general population in Finland.

BACKGROUND: Data on non-drug related risk-factors for gastrointestinal bleeding (GIB) in the general population are limited, especially for life-style factors, clinical measurements and laboratory parameters. AIM: To identify and investigate non-drug risk factors for major GIB in the general population of Finland. METHODS: We performed a retrospective cohort study using data from the FINRISK health examination surveys, which have been conducted every 5 years across Finland from 1987 to 2007. Participants were adults aged 25 years to 74 years, excluding those with a previous hospitalization for GIB. Follow-up from enrollment was performed through linkage to national electronic health registers and ended at an event of GIB that led to hospitalization/death, death due to any other cause, or after 10 years. Covariates included demographics, socioeconomic and lifestyle factors, clinical measurements, laboratory parameters and comorbidities. Variable selection was undertaken using Least Absolute Shrinkage and Selection Operator (LASSO) and factors associated with GIB were identified using Cox regression. RESULTS: Among 33,508 participants, 403 (1.2%) experienced GIB [256 men (63.5%); mean age, 56.0 years (standard deviation (SD) ± 12.1)] and 33105 who did not experience GIB [15768 men (47.6%); mean age, 46.8 (SD ± 13) years], within 10 years of follow-up. Factors associated with a significantly increased risk of GIB were baseline age [per 10-year increase; hazard ratio (HR) 1.62, 95% confidence interval (CI): 1.42-1.86], unemployment (HR: 1.70, 95%CI: 1.11-2.59), body mass index (BMI) (HR: 1.15, 95%CI: 1.01-1.32), gamma-glutamyl transferase (GGT) (HR: 1.05, 95%CI: 1.02-1.09), precursors of GIB (HR: 1.90, 95%CI: 1.37-2.63), cancer (HR: 1.47, 95%CI: 1.10-1.97), psychiatric disorders (HR: 1.32, 95%CI: 1.01-1.71), heart failure (HR: 1.46, 95%CI: 1.04-2.05), and liver disorders (HR: 3.20, 95%CI: 2.06-4.97). Factors associated with a significantly decreased risk of GIB were systolic blood pressure (SBP) (HR: 0.78, 95%CI: 0.64-0.96), 6-10 cups of coffee a day (HR: 0.67, 95%CI: 0.46-0.99), or > 10 cups (HR: 0.43, 95%CI: 0.23-0.81). CONCLUSION: Our study confirms established risk-factors for GIB and identifies potential risk-factors not previously reported such as unemployment, BMI, GGT, SBP and coffee consumption.

Secondary Treatment for Men with Localized Prostate Cancer: A Pooled Analysis of PRIAS and ERSPC-Rotterdam Data within the PIONEER Data Platform.

INTRODUCTION: Treatment choice for localized prostate cancer is complicated, as each treatment option comes with various pros and cons. It is well established that active surveillance (AS), may be ended with a change to curative treatment at the time of disease progression, but it is less clear whether secondary treatment after initial curative treatment is required. As part of the PIONEER project, we quantified the probabilities of treatment change. METHODS: A cohort study based on PRIAS and ERSPC-Rotterdam data was conducted. Patients were followed up for 10 years or until the 31st of December 2017. The primary outcome was the incidence of treatment change following initial treatment (i.e., a change to curative treatment following AS or secondary treatment after initial RP/RT). RESULTS: Over a period of 1 to 5 years after initial treatment, the cumulative incidence of treatment change ranged from 3.8% to 42.8% for AS, from 7.6% to 12.1% for radical prostatectomy (RP) and from no change to 5.3% for radiation therapy (RT). While the possibility of treatment change in AS is known, the numbers within a five-year period were substantial. For RP and RT, the rate of change to secondary treatment was lower, but still non-neglectable, with 5 (10)-year incidences up to 12% (20%) and 5% (16%), respectively. CONCLUSION: This is one of the first studies comparing the incidence of guideline-recommended treatment changes in men receiving different primary treatments (i.e., AS, RT, or RP) for localized prostate cancer (PCa).

Diagnostic and prognostic factors in patients with prostate cancer: a systematic review.

OBJECTIVES: As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). DESIGN: We performed a systematic review to identify validated and non-validated studies. DATA SOURCES: MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020. ELIGIBILITY CRITERIA: Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded. DATA EXTRACTION AND SYNTHESIS: After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability. CONCLUSION: Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies. ETHICS AND DISSEMINATION: There are no ethical implications.

Prevalence and Risk Factors for Hearing Loss in Chilean Shellfish Divers.

BACKGROUND: Diving within artisanal fishing is a profession carried out by many men in coastal communities of southern Chile. These shellfish divers use surface supplied air for breathing. Among potential health threats are occupational accidents, decompression sickness and barotrauma. Repeated middle and inner ear barotrauma and decompression sickness of the ear may result in hearing loss. OBJECTIVE: To determine the prevalence of hearing loss and related risk factors in artisanal shellfish divers. METHODS: A cross-sectional study including 125 male shellfish divers was carried out in a coastal village in southern Chile. Participants were interviewed using a standard Spanish questionnaire adapted for this population. Hearing loss was assessed through audiometry. Any hearing loss, sensorineural hearing loss and other types of hearing loss (conduction, unilateral and mixed) were used as the outcomes. Bivariate and multiple logistic regression models were carried out to identify risk factors for hearing loss. FINDINGS: Median duration on the job was 25 years (range 1-52), 64% of divers had a low level of schooling and 52% reported not knowing how to use decompression tables. Most (86%) of the divers dove deeper than 30 meters exceeding the 20 meters permitted by law. The majority (80%) reported having experienced several episodes of type II decompression sickness during their working life. The prevalence of any type of hearing loss was 54.4%: 29.0% presented sensorineural hearing loss and 25.6% presented other types of hearing impairment. After adjustment for age and other potential risk factors, diving more than 25 years was the main predictor for all kinds of hearing loss under study. CONCLUSIONS: Hearing loss is frequent in artisanal shellfish divers and safety measures are limited. Although based on small numbers and lacking an unexposed comparison group, our results suggest the need for community-based interventions.

Greenness and job-related chronic stress in young adults: a prospective cohort study in Germany.

OBJECTIVES: We aimed to prospectively study the association between normalised difference vegetation index (NDVI) as a measure of greenness around homes and occupational stress. SETTING: A population-based cohort in Munich and Dresden cities was followed from age 16-18 years to age 20-23 years (n=1632). PARTICIPANTS: At baseline, all participants attended high-school while at follow-up some had started working and others studying at university. At baseline and in each follow-up, we assigned NDVI based on participants' residential geocoded addresses and categorised it by quartiles. OUTCOME MEASURES: School-related, university-related or job-related self-reported chronic stress was assessed at the two follow-ups by the Trier Scale for Assessment of Chronic Stress using work discontent and work overload as outcomes. We modelled the association employing ordinal generalised estimating equations model accounting for changes in sociodemographics, non-job-related stress, job history and environmental covariates. Stratified analysis by each city was performed. RESULTS: NVDI at baseline was higher for participants from Dresden (median=0.36; IQR 0.31-0.41) than Munich (0.31; 0.26-0.34). At follow-up, it decreased only for participants in Dresden (0.34; 0.30-0.40). Higher greenness (quartile 4 vs quartile 1) was associated with less work discontent (OR 0.89; 95% CI 0.80 to 0.99) and less work overload (OR 0.87; 95% CI 0.78 to 0.96). In stratified analyses, results were more consistent for Munich than for Dresden. CONCLUSIONS: Our results suggest that residential green spaces, using the vegetation index as a proxy for exposure, are inversely associated with two types of job-related chronic stress in German young adults transitioning from school to university or working life.

Estimating the Causal Impact of Proximity to Gold and Copper Mines on Respiratory Diseases in Chilean Children: An Application of Targeted Maximum Likelihood Estimation.

In a town located in a desert area of Northern Chile, gold and copper open-pit mining is carried out involving explosive processes. These processes are associated with increased dust exposure, which might affect children's respiratory health. Therefore, we aimed to quantify the causal attributable risk of living close to the mines on asthma or allergic rhinoconjunctivitis risk burden in children. Data on the prevalence of respiratory diseases and potential confounders were available from a cross-sectional survey carried out in 2009 among 288 (response: 69 % ) children living in the community. The proximity of the children's home addresses to the local gold and copper mine was calculated using geographical positioning systems. We applied targeted maximum likelihood estimation to obtain the causal attributable risk (CAR) for asthma, rhinoconjunctivitis and both outcomes combined. Children living more than the first quartile away from the mines were used as the unexposed group. Based on the estimated CAR, a hypothetical intervention in which all children lived at least one quartile away from the copper mine would decrease the risk of rhinoconjunctivitis by 4.7 percentage points (CAR: - 4.7 ; 95 % confidence interval ( 95 % CI): - 8.4 ; - 0.11 ); and 4.2 percentage points (CAR: - 4.2 ; 95 % CI: - 7.9 ; - 0.05 ) for both outcomes combined. Overall, our results suggest that a hypothetical intervention intended to increase the distance between the place of residence of the highest exposed children would reduce the prevalence of respiratory disease in the community by around four percentage points. This approach could help local policymakers in the development of efficient public health strategies.

Chronic Stress in Young German Adults: Who Is Affected? A Prospective Cohort Study.

We aimed to prospectively assess changes in chronic stress among young adults transitioning from high school to university or working life. A population-based cohort in Munich and Dresden (Germany) was followed from age 16-18 (2002-2003) to age 20-23 (2007-2009) (n = 1688). Using the Trier Inventory for the Assessment of Chronic Stress, two dimensions of stress at university or work were assessed: work overload and work discontent. In the multiple ordinal generalized estimating equations, socio-demographics, stress outside the workplace, and job history were additionally considered. At follow-up, 52% of the population were university students. Work overload increased statistically significantly from first to second follow-up, while work discontent remained constant at the population level. Students, compared to employees, reported a larger increase in work overload (adjusted odds ratio (OR): 1.33; 95% confidence interval (95% CI): 1.07, 1.67), while work discontent did not differ between the groups. In conclusion, work overload increases when young adults transition from school to university/job life, with university students experiencing the largest increase.

Systematic Analysis of Self-Reported Comorbidities in Large Cohort Studies - A Novel Stepwise Approach by Evaluation of Medication.

OBJECTIVE: In large cohort studies comorbidities are usually self-reported by the patients. This way to collect health information only represents conditions known, memorized and openly reported by the patients. Several studies addressed the relationship between self-reported comorbidities and medical records or pharmacy data, but none of them provided a structured, documented method of evaluation. We thus developed a detailed procedure to compare self-reported comorbidities with information on comorbidities derived from medication inspection. This was applied to the data of the German COPD cohort COSYCONET. METHODS: Approach I was based solely on ICD10-Codes for the diseases and the indications of medications. To overcome the limitations due to potential non-specificity of medications, Approach II was developed using more detailed information, such as ATC-Codes specific for one disease. The relationship between reported comorbidities and medication was expressed by a four-level concordance score. RESULTS: Approaches I and II demonstrated that the patterns of concordance scores markedly differed between comorbidities in the COSYCONET data. On average, Approach I resulted in more than 50% concordance of all reported diseases to at least one medication. The more specific Approach II showed larger differences in the matching with medications, due to large differences in the disease-specificity of drugs. The highest concordance was achieved for diabetes and three combined cardiovascular disorders, while it was substantial for dyslipidemia and hyperuricemia, and low for asthma. CONCLUSION: Both approaches represent feasible strategies to confirm self-reported diagnoses via medication. Approach I covers a broad spectrum of diseases and medications but is limited regarding disease-specificity. Approach II uses the information from medications specific for a single disease and therefore can reach higher concordance scores. The strategies described in a detailed and reproducible manner are generally applicable in large studies and might be useful to extract as much information as possible from the available data.

Working Conditions, Workplace Violence, and Psychological Distress in Andean Miners: A Cross-sectional Study Across Three Countries.

BACKGROUND: Psychosocial working conditions are well-known determinants of poor mental health. However, studies in mining populations where employment and working conditions are frequently precarious have, to our knowledge, only focused on occupational accidents and diseases. OBJECTIVES: The aim of this study was to assess psychosocial working conditions and psychological distress in Andean underground miners. METHODS: The study population consisted of 153 Bolivian miners working in a silver mining cooperative, 137 Chilean informal gold miners, and 200 formal Peruvian silver miners employed in a remote setting. High work demands, minimal work control, minimal social support at work, and workplace exposure to violence and bullying were assessed using the Spanish short form of the European Working Condition Survey. A general health questionnaire score >4 was used as cutoff for psychological distress. Associations between psychosocial work environment and psychological distress were tested using logistic regression models controlling for potential confounding and effect modification by country. FINDINGS: Prevalence of psychological distress was 82% in the Bolivian cooperative miners, 29% in the Peruvian formal miners, and 22% in the Chilean informal miners (pχ(2) < 0.001). 55% of the miners had suffered violence during the 12-months before the survey. Workplace demands were high (median 12.5 on a scale from 7-14), as was social support (median 5.5 on a scale from 3-6). After adjustment for country and other relevant exposure variables and considering interactions between country and job strain, miners in active (odds ratio [OR], 6.8; 95% confidence interval [CI] 2.1-22.7) and high strain jobs (OR, 7.2; 95% CI, 1.7-29.9) were at increased odds of distress compared with those in low strain jobs. Violence at work also contributed to increased odds of distress (OR, 1.86; 95% CI, 1.1-3.1). CONCLUSIONS: Psychological distress is associated with the psychosocial work environment in Andean underground miners. Interventions in mining populations should take the psychosocial work environment into account.

La experiencia peruana dentro de un estudio multicentrico Internacional para evaluar la eficacia de altas dosis de simvastatina

Los resultados obtenidos demuestran una significativa mayor reducción de los niveles de LDL colesterol y colesterol total en el grupo de pacientes tratados con 80 mg. de simvastina con respecto al grupo tratado con simvastatina 40 mg.. También es remarcable el fuerte incremento del HDL colesterol con respecto a niveles basales que se presento tanto en el grupo de simvastina 40 mg. como el de 80 mg. contrastado con los resultados observados en los estudios con otras elastinas como atorvastatina. Asi mismo es de notar que la adherencia al tratamiento y los eventos adversos clinicos y de lapratorio fueron semejantes en mabos grupos de estudio. El uso de una dosis mayor de simvastina no influyo negativamente en estos pacientes luego de 24 semanas de tratamiento. En conclusión el uso de simvastatina a dos de 80 mg. al día es bien tolerado, con efectos secundarios comparables a las dosis convencionales y provee una significativa mayor reducción del LDL colesterol de hasta 54.4 por ciento que podría se útil en pacientes con o sin enfermedad coronaria que no responden adecuadamente a dosis convencionales de estatinas