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1.
Thorax ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653936

RESUMO

OBJECTIVES: To date, only a few studies have investigated the associations between occupational exposures and respiratory outcomes longitudinally in the general population. We investigated the associations between occupational exposures and the development of respiratory symptoms and airway obstruction in the Lifelines Cohort Study. METHODS: We included 35 739 occupationally active subjects with data on chronic cough, chronic phlegm, chronic bronchitis or airway obstruction at baseline and approximately 4.5 years follow-up. Exposures to biological dust, mineral dust, gases/fumes, pesticides, solvents and metals in the current job at baseline were estimated with the ALOHA+job-exposure matrix (JEM). Airway obstruction was defined as FEV1/FVC below the lower limit of normal. Logistic regression analysis adjusted for baseline covariates was used to investigate the associations. RESULTS: At follow-up, 1888 (6.0%), 1495 (4.7%), 710 (2.5%) and 508 (4.5%) subjects had developed chronic cough, chronic phlegm, chronic bronchitis and airway obstruction, respectively. High exposure to biological dust was associated with a higher odds to develop chronic cough and chronic bronchitis. High exposure to pesticides was associated with a higher odds for the development of all respiratory symptoms and airway obstruction. In the multiple exposures analyses, only the association between pesticides exposure and respiratory symptoms remained. CONCLUSIONS: Subjects exposed to high pesticides had a higher odds to develop respiratory symptoms on average 4.5 years later. Control measures should be taken to reduce pesticides exposure among the working population to prevent respiratory symptoms and airway obstruction.

2.
BMJ Open ; 11(3): e044474, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33737436

RESUMO

PURPOSE: The Lifelines COVID-19 cohort was set up to assess the psychological and societal impacts of the COVID-19 pandemic and investigate potential risk factors for COVID-19 within the Lifelines prospective population cohort. PARTICIPANTS: Participants were recruited from the 140 000 eligible participants of Lifelines and the Lifelines NEXT birth cohort, who are all residents of the three northern provinces of the Netherlands. Participants filled out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March 2020, and the cohort consists of everyone who filled in at least one questionnaire in the first 8 weeks of the project. FINDINGS TO DATE: >71 000 unique participants responded to the questionnaires at least once during the first 8 weeks, with >22 000 participants responding to seven questionnaires. Compiled questionnaire results are continuously updated and shared with the public through the Corona Barometer website. Early results included a clear signal that younger people living alone were experiencing greater levels of loneliness due to lockdown, and subsequent results showed the easing of anxiety as lockdown was eased in June 2020. FUTURE PLANS: Questionnaires were sent on a (bi)weekly basis starting in March 2020 and on a monthly basis starting July 2020, with plans for new questionnaire rounds to continue through 2020 and early 2021. Questionnaire frequency can be increased again for subsequent waves of infections. Cohort data will be used to address how the COVID-19 pandemic developed in the northern provinces of the Netherlands, which environmental and genetic risk factors predict disease susceptibility and severity and the psychological and societal impacts of the crisis. Cohort data are linked to the extensive health, lifestyle and sociodemographic data held for these participants by Lifelines, a 30-year project that started in 2006, and to data about participants held in national databases.


Assuntos
/psicologia , Pandemias , Adulto , Ansiedade , Controle de Doenças Transmissíveis , Feminino , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
3.
Clin Transl Allergy ; 10(1): 60, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33303027

RESUMO

BACKGROUND: Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. METHODS: Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA). RESULTS: We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes. CONCLUSION: We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway.

4.
World J Gastroenterol ; 26(38): 5896-5910, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33132643

RESUMO

BACKGROUND: The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM: To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS: A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS: The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION: Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement.

5.
Scand J Work Environ Health ; 46(6): 599-608, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135766

RESUMO

Objectives Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD. Methods For this case-control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix. Results An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR adj) 1.90, 95% confidence interval (CI) 1.01-3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR adj2.68, 95% CI 1.07-6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR adj2.94, 95% CI 1.21-7.13) and pulmonary valve stenosis (OR adj1.99, 95% CI 1.10-3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR adj2.40, 95% CI 1.09-5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR adj3.23, 95% CI 1.14-9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR adj0.32, 95% CI 0.11-0.94). Conclusions Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development.

6.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043054

RESUMO

Background: Elevated blood eosinophils have been associated with lower lung function and are believed to be associated with accelerated lung function decline. Method: Blood eosinophils were measured in four cohorts: <45 years cohort within the Vlagtwedde-Vlaardingen (V&V) study, the Uppsala cohort of the European Community Respiratory Health Survey (ECRHS-Uppsala; <45 years), ≥45 years cohort within the V&V study, and the Rotterdam study (≥45 years). Blood eosinophils at baseline were classified as normal (<300 cells·µL-1) or elevated (≥300 cells·µL-1). Lung function was measured at baseline and follow-up with spirometry: forced expiratory volume in 1 s (FEV1), vital capacity (VC) and their ratio FEV1/VC. The association between blood eosinophils and lung function was tested cross-sectionally using linear regression and longitudinally using a mixed model, both adjusted for age, sex, height, pack-years smoking and smoking status. Stratified analyses were done for asthma. Results: Elevated blood eosinophils were associated with lower FEV1 (regression coefficient -147 mL (95% CI -188 to -105 mL)), VC (-120 mL (-165 to -75 mL)) and FEV1/VC (-1.3% (-1.9% to -0.6%)) at baseline in the two <45 years cohorts, and with lower FEV1 (-70 mL (-112 to -27 mL)) and FEV1/VC (-1.8% (-2.6% to -1.0%)) in the two ≥45 years cohorts. Elevated blood eosinophils were associated with an accelerated decline in FEV1 (-5.5 mL·year-1 (95% CI -10.5 to -0.5 mL·year-1)) and VC (-6.4 mL·year-1 (-11.26 to -1.5 mL·year-1)) compared to normal blood eosinophils in the younger asthmatic subjects in the longitudinal studies. Conclusion: Elevated blood eosinophils are associated with lower lung function in the general population and with an accelerated lung function decline among asthmatic individuals.

7.
Ann Am Thorac Soc ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795190

RESUMO

RATIONALE: The association between airborne occupational exposures and lung function level is inconsistent in the general population. Moreover, little is known about the association between occupational exposures and annual lung function decline. OBJECTIVES: We investigated the association between occupational exposures and lung function level and annual lung function decline in the population-based Lifelines cohort study. METHODS: We included 55,631 adults with baseline spirometry and reliable job code-13,759 of these subjects were aged ≥ 30 years and underwent spirometry again after 4.5 years of follow-up. Occupational exposures in the current or last-held job at baseline were estimated with the ALOHA+ job-exposure matrix. Linear regression analyses adjusted for covariates were used to test the association between each occupational exposure-biological dust, mineral dust, gases/fumes, pesticides, solvents, and metals- and lung function level and annual lung function decline. Interactions were used to test effect-modification by sex or smoking. RESULTS: Exposures to biological dust, mineral dust, gases/fumes, insecticides, fungicides, and aromatic solvents were associated with a lower lung function level at baseline. The effects were larger in males and smokers compared to females and non-smokers, respectively. However, no association between occupational exposures and the rate of annual lung function decline was found between baseline and follow-up. CONCLUSIONS: In this study, airborne occupational exposures are associated with lower lung function level but not with a faster lung function decline. These negative effects are more pronounced among males and smokers.

8.
Occup Environ Med ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769140

RESUMO

INTRODUCTION: Inflammatory biomarkers are associated with negative health outcomes. In this study, we investigated the associations between airborne occupational exposures and levels and changes in inflammatory biomarkers. METHODS: We included 79 604 adults at baseline from the Lifelines cohort of which 48 403 (60.8%) subjects were followed for a median of 4.5 years. Airborne occupational exposures at the current or last-held job at baseline were estimated with the occupational asthma-specific job-exposure matrix. Both in cross-sectional and longitudinal analyses, we used linear regression models (adjusted for age, sex, education, monthly income, body mass index, smoking, pack-years, asthma and anti-inflammatory medication) to investigate the associations between airborne occupational exposures (allergens, reactive chemicals, pesticides and micro-organisms) and inflammatory biomarkers (C reactive protein (CRP), eosinophils and neutrophils). RESULTS: In the cross-sectional analyses, exposure to allergens, reactive chemicals and micro-organisms was associated with a lower (Log) CRP level (B(95% CI)=-0.05 (-0.08 to -0.02),-0.05(-0.08 to -0.02) and -0.09(-0.16 to -0.02), respectively). Likewise, exposure to allergens, reactive chemicals, pesticides and micro-organisms was associated with a lower (log) neutrophils count (-0.01 (-0.02 to -0.01), -0.01 (-0.02 to -0.01),-0.02 (-0.04 to -0.01) and -0.02(-0.03 to -0.01), respectively). No association between airborne occupational exposures and eosinophils count was found. In the longitudinal analyses, no association between airborne occupational exposures and changes in inflammatory biomarkers was found. CONCLUSIONS: At baseline, airborne occupational exposures are inversely associated with inflammation; no effect of occupational exposures on inflammation was found at follow-up. In the future studies, details of occupational exposures, such as duration of exposures and cumulative exposures, need to be included to investigate the airborne occupational exposures and inflammatory biomarkers.

9.
Sci Rep ; 10(1): 12963, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737337

RESUMO

In this cross-sectional study, we investigated the association between occupational exposures and sickness absence (SA), the mediating role of respiratory symptoms, and whether genetic susceptibility to SA upon occupational exposures exists. Logistic regression was used to examine associations and structural equation modelling was used for mediation analyses. Genetic susceptibility was investigated by including interactions between occupational exposures and 11 candidate single nucleotide polymorphisms (SNPs). Biological dust, mineral dust, and pesticides exposure were associated with a lower prevalence of any SA (OR (95% CI) = 0.72 (0.58-0.89), 0.88 (0.78-0.99), and 0.70 (0.55-0.89), respectively) while gases/fumes exposure was associated with a higher prevalence of long-term SA (1.46 (1.11-1.91)). Subjects exposed to solvents and metals had a higher prevalence of any (1.14 (1.03-1.26) and 1.68 (1.26-2.24)) and long-term SA (1.26 (1.08-1.46) and 1.75 (1.15-2.67)). Chronic cough and chronic phlegm mediated the association between high gases/fumes exposure and long-term SA. Two of 11 SNPs investigated had a positive interaction with exposure on SA and one SNP negatively interacted with exposure on SA. Exposure to metals and gases/fumes showed a clear dose-response relationship with a higher prevalence of long-term SA; contrary, exposure to pesticides and biological/mineral dust showed a protective effect on any SA. Respiratory symptoms mediated the association between occupational exposures and SA. Moreover, gene-by-exposure interactions exist.

10.
Schizophr Res ; 223: 135-147, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32631699

RESUMO

Cross-sectional studies have shown that the polygenic risk score for schizophrenia (PRSSCZ) may influence heterogeneity in cognitive performance although evidence from family-based longitudinal study is limited. This study aimed to identify trajectories of cognitive function and assess whether the PRSSCZ is associated with baseline cognitive performance and predicted six-year trajectories. We included 1119 patients with a schizophrenia spectrum disorder, and 1059 unaffected siblings and 586 unrelated controls who are eligible at baseline. Genotype data were collected at baseline, whereas clinical and sociodemographic data were collected at baseline, three and six years. Group-based trajectory modeling was applied on a weighted standardized composite score of general cognition to unravel cognitive subtypes and explore trajectories over time. We followed a standard procedure to calculate the polygenic risk score. A random-effects ordinal regression model was used to investigate the association between PRSSCZ and cognitive subtypes. Five cognitive subtypes with variable trajectories were found in patients, four in siblings and controls, and six in all combined samples. PRSSCZ significantly predicted poor cognitive trajectories in patients, siblings and all samples. After Bonferroni correction and adjustment for non-genetic factors, only the results in all combined sample remained significant. Cognitive impairment in schizophrenia is heterogeneous and may be linked with high PRSSCZ. Our finding confirmed at least in all combined samples the presence of genetic overlap between schizophrenia and cognitive function and can give insight into the mechanisms of cognitive deficits.

11.
Transl Psychiatry ; 10(1): 244, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694510

RESUMO

To tackle the phenotypic heterogeneity of schizophrenia, data-driven methods are often applied to identify subtypes of its symptoms and cognitive deficits. However, a systematic review on this topic is lacking. The objective of this review was to summarize the evidence obtained from longitudinal and cross-sectional data-driven studies in positive and negative symptoms and cognitive deficits in patients with schizophrenia spectrum disorders, their unaffected siblings and healthy controls or individuals from general population. Additionally, we aimed to highlight methodological gaps across studies and point out future directions to optimize the translatability of evidence from data-driven studies. A systematic review was performed through searching PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE and Web of Science electronic databases. Both longitudinal and cross-sectional studies published from 2008 to 2019, which reported at least two statistically derived clusters or trajectories were included. Two reviewers independently screened and extracted the data. In this review, 53 studies (19 longitudinal and 34 cross-sectional) that conducted among 17,822 patients, 8729 unaffected siblings and 5520 controls or general population were included. Most longitudinal studies found four trajectories that characterized by stability, progressive deterioration, relapsing and progressive amelioration of symptoms and cognitive function. Cross-sectional studies commonly identified three clusters with low, intermediate (mixed) and high psychotic symptoms and cognitive profiles. Moreover, identified subgroups were predicted by numerous genetic, sociodemographic and clinical factors. Our findings indicate that schizophrenia symptoms and cognitive deficits are heterogeneous, although methodological limitations across studies are observed. Identified clusters and trajectories along with their predictors may be used to base the implementation of personalized treatment and develop a risk prediction model for high-risk individuals with prodromal symptoms.

12.
BMC Pulm Med ; 20(1): 193, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677943

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis. METHODS: We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach. RESULTS: There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10- 4 in the discovery and OR = 1.30, P = 1.8 × 10- 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52-2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94-1.20). CONCLUSIONS: Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.

13.
PLoS One ; 15(3): e0230483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218582

RESUMO

BACKGROUND: Pre-eclampsia shares pathophysiology with intrauterine growth restriction. OBJECTIVE: To investigate whether delivery of a small for gestational age (SGA) infant in the 1st pregnancy increases the risk of early and late onset pre-eclampsia in the 2nd pregnancy. Conversely, we investigated whether pre-eclampsia in the 1st pregnancy impacts SGA risk in the 2nd pregnancy. STUDY DESIGN: We studied a cohort from the Dutch Perinatal Registry of 265,031 women with 1st and 2nd singleton pregnancies who delivered between 2000 and 2007. We analyzed 2nd pregnancy risks of early and late onset pre-eclampsia-defined by delivery before or after 34 gestational weeks-as well as SGA below the 5th and between the 5th and 10th percentiles risks with multivariable logistic regressions. Interaction terms between 1st pregnancy hypertension, pre-eclampsia, SGA, and delivery before or after 34 gestational weeks were included in the regressions. RESULTS: First pregnancy early onset pre-eclampsia increased risk of SGA <5th percentile (OR 2.1, 95% CI 1.7-2.7) in the 2nd pregnancy. Late onset pre-eclampsia increased the SGA <5th percentile marginally (OR 1.1, 95% CI 1.0-1.3). In the absence of 1st pregnancy hypertensive disorder, women who delivered an SGA infant in their 1st pregnancy were at increased risk of 2nd pregnancy late onset pre-eclampsia (SGA <5th: OR 2.05, 95% CI 1.58-2.66; SGA 5-10th: OR 1.39, 95% CI 1.01-1.93). Early onset 2nd pregnancy pre-eclampsia risk was also increased, but this was only statistically significant for women who delivered an SGA infant below the 5th percentile in the 1st pregnancy (SGA <5th: OR 2.44, 95% CI 1.19-5.00; SGA 5-10th: OR 1.69, 95% CI 0.68-4.24;). CONCLUSION: Women with 1st pregnancy early onset pre-eclampsia have increased risk of SGA <5th percentile in the 2nd pregnancy. SGA in the 1st pregnancy increases pre-eclampsia risk in the 2nd pregnancy even in the absence of hypertensive disorders in the 1st pregnancy, although absolute risks remain low. These findings strengthen the evidence base associating intrauterine growth restriction with early onset pre-eclampsia.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia , Sistema de Registros , Adulto , Fatores Etários , Feminino , Humanos , Países Baixos/epidemiologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Estudos Prospectivos , Fatores de Risco
14.
BMJ Open Respir Res ; 7(1)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32075781

RESUMO

INTRODUCTION: Although bacteria contribute significantly to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), the added value of antibiotics remains controversial, especially in outpatient settings. Age may affect antibiotic effectiveness, but real-world evidence is lacking. We aimed to assess the influence of age on the effectiveness of doxycycline for AECOPD. METHODS: A retrospective cohort study among outpatients with the first recorded AECOPD treated with oral corticosteroids was conducted using a large pharmacy dispensing database. The primary outcome was treatment failure within 15-31 days after treatment start. Secondary outcome was time to second exacerbation. All analyses were stratified by age groups. RESULTS: We identified 6300 outpatients with the first AECOPD. 2261 (36%) received doxycycline and 4039 (64%) did not receive any antibiotic (reference group). Overall, there was no difference in treatment failure (adjusted OR: 0.97, 95% CI: 0.84 to 1.12) between two groups. Similarly, no difference in treatment failure was observed in younger groups. However, in patients with advanced age (≥75 years), treatment failure was significantly reduced by doxycycline compared with reference (16% vs 20%, adjusted OR: 0.77, 95% CI: 0.62 to 0.97). Overall, median time to second exacerbation was 169 days (95% CI: 158 to 182 days) in doxycycline group compared with 180 days (95% CI: 169 to 191 days) in reference group (adjusted HR: 1.06, 95% CI: 0.99 to 1.12). Although in older patients there was a trend within 3 months towards longer time of next exacerbation by doxycycline, it did not achieve statistical significance. CONCLUSIONS: Our findings showed short-term treatment benefit of doxycycline added to oral corticosteroids for chronic obstructive pulmonary disease patients with advanced age. This value remains unclear for persons aged under 75 years in current primary care. Long-term preventive benefits of doxycycline for the next exacerbation were not observed, irrespective of age.

15.
Occup Environ Med ; 77(3): 172-178, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31949041

RESUMO

OBJECTIVES: The aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring. METHODS: We used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk. RESULTS: Among 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age. CONCLUSION: Our study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis.


Assuntos
Gastrosquise/epidemiologia , Exposição Materna/estatística & dados numéricos , Exposição Ocupacional/estatística & dados numéricos , Solventes/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Idade Materna , Análise Multivariada , Gravidez , Medição de Risco , Fatores de Risco , Autorrelato , Estados Unidos/epidemiologia , Adulto Jovem
17.
Obes Rev ; 21(2): e12936, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31833645

RESUMO

Evidence on the association between physical activity (PA) and adiposity in young children is inconclusive. A systematic review and meta-analyses were conducted to examine associations between accelerometer-derived PA and varying adiposity outcomes in preschool children. Searches were conducted in Embase, MEDLINE and Web of Science to identify studies on the association between total PA, sedentary behaviour or different PA intensities and adiposity in children aged 2 to 7 years. Separate random effects meta-analyses were performed for varying PA intensities and adiposity outcomes. Fifty-six articles were included in the review and 48 in the meta-analyses. There was substantial evidence of an inverse association between moderate-to-vigorous- or vigorous PA and body fat percentage (stdß [SE] = -0.162[0.041]; 5 studies), weight status (r = -0.120, P<.001; 11 studies), fat mass (stdß [SE] = -0.103[0.051]; 5 studies), fat mass index (stdß [SE] = -0.121[0.036]; 2 studies) and skinfold thickness (stdß [SE] = -0.145[0.036]; 4 studies). However, total PA, sedentary behaviour, and different PA intensities were not associated with body mass index (BMI) or waist circumference. Adiposity levels were lower among preschool children engaged in more (moderate-to-) vigorous PA compared with their peers, but no associations between PA and BMI or waist circumference were found.

19.
Respir Res ; 20(1): 268, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791327

RESUMO

BACKGROUND: Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers. METHODS: We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Illumina 450 K) in blood of never smokers in four independent cohorts, LifeLines COPD&C (N = 903), LifeLines DEEP (N = 166), Rotterdam Study (RS)-III (N = 150) and RS-BIOS (N = 206). We meta-analyzed the cohort-specific methylation results to identify differentially methylated CpG-sites with FEV1/FVC. Expression Quantitative Trait Methylation (eQTM) analysis was performed in the Biobank-based Integrative Omics Studies (BIOS). RESULTS: A total of 36 CpG-sites were associated with FEV1/FVC in never smokers at p-value< 0.0001, but the meta-analysis did not reveal any epigenome-wide significant CpG-sites. Of interest, 35 of these 36 CpG-sites have not been associated with lung function before in studies including subjects irrespective of smoking history. Among the top hits were cg10012512, cg02885771, annotated to the gene LTV1 Ribosome Biogenesis factor (LTV1), and cg25105536, annotated to Kelch Like Family Member 32 (KLHL32). Moreover, a total of 11 eQTMS were identified. CONCLUSIONS: With the identification of 35 CpG-sites that are unique for never smokers, our study shows that DNA methylation is also associated with FEV1/FVC in subjects that never smoked and therefore not merely related to smoking.


Assuntos
Metilação de DNA/genética , Epigênese Genética/genética , Estudo de Associação Genômica Ampla/métodos , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Estudos de Coortes , Ilhas de CpG/genética , Feminino , Volume Expiratório Forçado/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Valores de Referência , Fumantes , Fumar/genética
20.
Eur J Cancer ; 121: 113-122, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31569066

RESUMO

AIM: Intensive treatment regimens have contributed to a marked increase in childhood cancer survival rates. Death due to treatment-related adverse effects becomes an increasingly important area to further improve overall survival. In this study, we examined 5-year survival in children with cancer to identify risk factors for treatment-related mortality (TRM). METHODS: All children (aged <18 years at diagnosis) diagnosed with cancer in 2 Dutch university hospitals between 2003 and 2013 were included, survival status was determined and causes of death were analysed. Various demographic and treatment factors were evaluated, for which a multivariable competing risks analysis was performed. RESULTS: A total of 1764 patients were included; overall 5-year survival was 78.6%. Of all 378 deaths, 81 (21.4%) were treatment-related, with infection being responsible for more than half of these deaths. Forty percent of TRM occurred in the first three months after initial diagnosis. Factors associated with TRM in the multivariable competing risks analysis were diagnosis of a haematological malignancy, age at diagnosis <1 year and receipt of allogeneic haematopoietic stem cell transplantation. In children suffering from haematological malignancies, TRM accounted for 56.3% of 103 deaths. CONCLUSION: Over one in five deaths in children with cancer death was related to treatment, mostly due to infection. In children suffering from a haematological malignancy, more children died due to their treatment than due to progression of their disease. To further increase overall survival, clinical and research focus should be placed on lowering TRM rates without compromising anti-tumour efficacy. The findings presented in this study might help identifying areas for improvement.


Assuntos
Protocolos Antineoplásicos , Causas de Morte , Mortalidade da Criança , Neoplasias/mortalidade , Neoplasias/terapia , Adolescente , Protocolos Antineoplásicos/classificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasias/patologia , Países Baixos/epidemiologia , Prevalência , Fatores de Risco , Taxa de Sobrevida
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