Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models.

BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to €300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393.

Social and physical neighbourhood characteristics and 10-year incidence of depression and anxiety in older adults: Results from the Longitudinal Aging Study Amsterdam.

OBJECTIVE: A growing literature suggests that neighbourhood characteristics are associated with mental health outcomes, but the evidence in older adults is inconsistent. We investigated the association of neighbourhood characteristics, pertaining to demographic, socio-economic, social and physical environment domains, with the subsequent 10-year incidence of depression and anxiety, in Dutch older adults. METHODS: In the Longitudinal Aging Study Amsterdam depressive and anxiety symptoms were assessed four times between 2005/2006 and 2015/2016, using the Center for Epidemiological Studies Depression Scale (n = 1365) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (n = 1420). Neighbourhood-level data on urban density, percent population over 65 years of age, percent immigrants, average house price, average income, percent low-income earners, social security beneficiaries, social cohesion, safety, proximity to retail facilities, housing quality, percent green space, percent water coverage, air pollution (particulate matter (PM2.5)), and traffic noise, were obtained for study baseline years 2005/2006. Cox proportional hazard regression models, clustered within neighbourhood, were used to estimate the association between each neighbourhood-level characteristic and the incidence of depression and anxiety. RESULTS: The incidence of depression and anxiety was 19.9 and 13.2 per 1000 person-years, respectively. Neighbourhood characteristics were not associated with the incidence of depression. However, various neighbourhood characteristics were associated with an increased incidence of anxiety, including: higher urban density level, higher percent immigrants, greater proximity to retail facilities, lower housing quality score, lower safety score, higher PM2.5 levels and less green space. CONCLUSION: Our results indicate that several neighbourhood characteristics are associated with anxiety but not with depression incidence in older age. Several of these characteristics have the potential to be modifiable and thus could serve as a target for interventions at the neighbourhood-level in improving anxiety, provided that future studies replicate our findings and provide further evidence for a causal effect.

Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort.

Background: Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women. Methods: This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation. Results: There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women. Conclusions: There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases.

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

Green spaces, subjective health and depressed affect in middle-aged and older adults: a cross-country comparison of four European cohorts.

BACKGROUND: Studies on associations between urban green space and mental health have yielded mixed results. This study examines associations of green space exposures with subjective health and depressed affect of middle-aged and older adults in four European cohorts. METHODS: Data came from four Western-European and Central-European ageing cohorts harmonised as part of the Mindmap project, comprising 16 189 adults with an average age of 50-71 years. Green space exposure was based on the distance to the nearest green space and the amount of green space within 800 m buffers around residential addresses. Cohort-specific and one-step individual participant data (IPD) meta-analyses were used to examine associations of green space exposures with subjective health and depressed affect. RESULTS: The amount of green spaces within 800 m buffers was lowest for Residential Environment and CORonary heart Disease (Paris, 15.0 hectares) and highest for Health, Alcohol and Psychosocial factors In Eastern Europe (Czech Republic, 35.9 hectares). IPD analyses indicated no evidence of an association between the distance to the nearest green space and depressed affect (OR 0.98, 95% CI 0.96 to 1.00) or good self-rated health (OR 1.01, 95% CI 0.99 to 1.02). Likewise, the amount of green space within 800 m buffers did not predict depressed affect (OR 0.98, 95% CI 0.96 to 1.00) or good self-rated health (OR 1.01, 95% CI 0.99 to 1.02). Findings were consistent across all cohorts. CONCLUSIONS: Data from four European ageing cohorts provide no support for the hypothesis that green space exposure is associated with subjective health or depressed affect. While longitudinal evidence is required, these findings suggest that green space may be less important for older urban residents.

The association of cortisol levels with leukocyte distribution is disrupted in the metabolic syndrome.

BACKGROUND: Leukocyte glucocorticoid sensitivity (GCS) pertains to the responsivity of leukocytes to the regulating actions of glucocorticoids, such as cortisol. Impaired endocrine regulation may link the metabolic syndrome (MetS) to the development of cardiovascular disease. We tested if the physiological association between endogenous cortisol levels and peripheral leukocyte composition becomes disrupted in individuals with MetS. METHODS: MetS was assessed among 689 German industrial employees. The covariance between cortisol levels and hematologic parameters (i.e., proportions of neutrophils and lymphocytes) and their ratio was explored, which has been proposed as a proxy for GCS in vivo. Cortisol level before blood collection was assessed by repeated saliva collection, and the area under the curve was calculated. Linear regression models were adjusted for potential confounders including age, gender, BMI, income, and lifestyle factors. RESULTS: Cortisol levels did not differ between subgroups. Participants without MetS (n = 552) showed the expected association of cortisol with hematologic parameters (ß = 0.207 to 0.216; p values < 0.001). No association (ß = 0.078 to 0.083; p values > 0.10) was found among those with MetS (n = 137), consistent with a reduced GCS. Analyses of separate MetS components showed that reduced GCS was associated specifically with decreased high-density lipoprotein and elevated fasting plasma glucose. CONCLUSIONS: Utilizing a novel statistical approach to infer GCS, this study provided first epidemiological evidence of aberrant physiological regulation of leukocyte distribution by endogenous cortisol levels among individuals with MetS. These findings underline the idea that MetS may involve disruption of endocrine-immune regulation.

Social and physical neighbourhood characteristics and loneliness among older adults: results from the MINDMAP project.

BACKGROUND: Loneliness is associated with several adverse mental and physical health outcomes in older adults. Previous studies have shown that a variety of individual-level and perceived area-level characteristics are associated with loneliness. This study examined the associations of objectively measured social and physical neighbourhood characteristics with loneliness. METHODS: We used cross-sectional data from 1959 older adults (63-98 years) who participated in the Longitudinal Ageing Study Amsterdam (LASA; wave 2011/12) and the Health and Living Conditions of the Population of Eindhoven and Surroundings study (GLOBE; wave 2014) in the Netherlands. Study-specific loneliness scores were harmonised across both cohort studies and divided into tertiles denoting low, medium and high levels of loneliness. Objectively measured neighbourhood characteristics, including area-level percentages of low educated residents, social security beneficiaries and unoccupied dwellings, average income, crime levels and land use mix, were linked to individual-level data. Multinomial logistic regression analyses were conducted to examine the associations of interest. RESULTS: There was no statistical evidence for an association of the included neighbourhood characteristics with loneliness. Although not statistically significant, the observed associations suggested that participants living in neighbourhoods with more heterogeneous land use mix were less likely to have a medium and high level of loneliness than those living in more homogeneous neighbourhoods in terms of land use mix (ORmedium=0.54, 95% CI=0.18-1.67; ORhigh=0.67, 95% CI=0.21-2.11). CONCLUSION: The results indicate that the included objectively measured social and physical neighbourhood characteristics are not associated with loneliness in old age.

Overview of retrospective data harmonisation in the MINDMAP project: process and results.

BACKGROUND: The MINDMAP project implemented a multinational data infrastructure to investigate the direct and interactive effects of urban environments and individual determinants of mental well-being and cognitive function in ageing populations. Using a rigorous process involving multiple teams of experts, longitudinal data from six cohort studies were harmonised to serve MINDMAP objectives. This article documents the retrospective data harmonisation process achieved based on the Maelstrom Research approach and provides a descriptive analysis of the harmonised data generated. METHODS: A list of core variables (the DataSchema) to be generated across cohorts was first defined, and the potential for cohort-specific data sets to generate the DataSchema variables was assessed. Where relevant, algorithms were developed to process cohort-specific data into DataSchema format, and information to be provided to data users was documented. Procedures and harmonisation decisions were thoroughly documented. RESULTS: The MINDMAP DataSchema (v2.0, April 2020) comprised a total of 2841 variables (993 on individual determinants and outcomes, 1848 on environmental exposures) distributed across up to seven data collection events. The harmonised data set included 220 621 participants from six cohorts (10 subpopulations). Harmonisation potential, participant distributions and missing values varied across data sets and variable domains. CONCLUSION: The MINDMAP project implemented a collaborative and transparent process to generate a rich integrated data set for research in ageing, mental well-being and the urban environment. The harmonised data set supports a range of research activities and will continue to be updated to serve ongoing and future MINDMAP research needs.

Associations between dietary factors and obesity-related biomarkers in healthy children and adolescents - a systematic review.

BACKGROUND: The obesity prevalence in children and adolescents has increased worldwide during the past 30 years. Although diet has been identified as one risk factor for developing obesity in this age group, the role of specific dietary factors is still unclear. One way to gain insight into the role of these factors might be to detect biomarkers that reflect metabolic health and to identify the associations between dietary factors and these biomarkers. This would enable nutrition-related metabolic changes to be detected early in life, which might be a promising strategy to prevent childhood obesity. However, existing literature offers only inconclusive evidence for diet and some of these obesity-related biomarkers (e.g., blood lipids). We thus conducted a systematic literature review to further examine eligible studies that investigate associations between dietary factors and 12 obesity-related biomarkers in healthy children and adolescents aged 3-18 years. METHODS: We searched the scientific databases PubMed/Medline and Web of Science Core Collection for potentially eligible articles. Our final literature search resulted in 2727 hits. After the selection process, we included 81 articles that reported on 1111 single observations on dietary factors and any of the obesity-related biomarkers. RESULTS: Around 81% of the total observations showed nonsignificant results. For many biomarkers we did not find enough observations to draw clear conclusions on possible associations between a dietary factor and the respective biomarker. In cases where we identified enough observations, the results were contradictory. Since these nonsignificant and inconclusive findings may impede the development of effective strategies against childhood obesity, this article takes a closer look at possible reasons for such findings. In addition, it provides action points for future research efforts. CONCLUSIONS: In conclusion, current evidence on associations between dietary factors and obesity-related biomarkers is inconclusive. We thus provided an overview on which specific limitations may impede current research. Such knowledge is necessary to enable future research efforts to better elucidate the role of diet in the early stages of obesity development.

Association of household cleaning agents and disinfectants with asthma in young German adults.

OBJECTIVES: We scrutinised the association of private use of household sprays and disinfectants with asthma incidence in young adults in the transition from school to working life. METHODS: Between 2007 and 2009,2051 young adults aged 19-24 years living in two major German cities took part in the Study on Occupational Allergy Risks II. Self-reported exposure to household sprays and disinfectants was characterised according to a composite score for frequency of use as no use (score=0), low use (score between 1 and the median), medium use (score between the median and the 90th percentile) and high use (score above the 90th percentile). Two outcome variables (current asthma and current wheezing) with four mutually exclusive categories (never, incident, persistent and remittent) were used for the risk analyses. Multinomial logistic regression models examined the association between the frequency of using household sprays and disinfectants with asthma and wheezing adjusting for potential confounders. RESULTS: Compared with no use, high use of disinfectants was associated with a more than twofold increased odds of incident asthma (OR 2.79, 95% CI 1.14 to 6.83). In addition, low/medium use of disinfectants was associated with remittent asthma (OR 2.39, 95% CI 1.29 to 4.47). The evidence for an association between high usage of household sprays and asthma incidence was weak (OR 2.79, 95% CI 0.84 to 9.20). CONCLUSION: Our results support the hypothesis of an association between the use of cleaning products and elevated risks for asthma and wheezing in young adults at the start of working life.

[The role of iridectomy in glaucoma surgery]. / Rolul iridectomiei periferice în chirurgia antiglaucomatoasa.

PURPOSE: analysis of the influence of peripheral iridectomy on the efficiency and safety of trabeculectomy and phacotrabeculectomy in patients with open-angle glaucoma. METHODS: interventional, prospective, randomized and comparative study with two groups: 44 eyes with trabeculectomy (group 1) and 24 eyes with phacotrabeculectomy (group 2). Each of the two groups was divided into two main subgroups (with and without iridectomy), compared with each other in terms of efficacy and safety of surgical procedure. RESULTS: Iridectomy was performed on 22 eyes in group 1 (subgroup 1A) and on 12 eyes in group 2 (subgroup 2A), the remaining cases in each group forming subgroups without peripheral iridectomy (subgroup 1B, 2B respectively). Statistical analysis reveals that iridectomy does not seem to influence the efficiency of filtration procedure, regardless of the postoperative moment of analysis (early or final). In all four subgroups at 1 year was a significant decreasing of intraocular pressure, with a low rate of complications. CONCLUSIONS: A proper selection of open-angle glaucoma cases allows the abandonment of peripheral iridectomy in trabeculectomy and phacotrabeculectomy.

[Retinitis pigmentosa--clinical and genetic aspects with low vision]. / Retinitis pigmentosa--clinica, genetica si low-vision.

PURPOSE: Clinical and genetic study of a case of retinitis pigmentosa following the vision and the quality of life in this disease. METHOD: This paper presents a female periodically reevaluated in our clinic from the first diagnosis of retinitis pigmentosa which was established ten years ago, with many relatives with the diagnosis of retinitis pigmentosa, has also high hyperopia and optic disc drusen. A particular aspect--she is student at English Faculty and she want to become professor in a school for children with low vision. Clinical evaluation included complete ophthalmic and general examination, family history and also some additional lab and imaging study, In genetic evaluation of this case were used the basic rules of genetics to diagnose the genetic form of retinitis pigmentosa in order to offer a correct genetic counseling. CONCLUSIONS: Retinitis pigmentosa needs a broad clinical evaluation and a careful socio-professional rehabilitation of these low-vision patients.

[Daily and nightly fluctuation of intraocular pressure and blood pressure in glaucoma and non-glaucoma patients]. / Fluctuatiile diurne si nocturie ale presiunii intraoculare si tensiunii arteriale sistemice la pacientii glaucomatosi si nongla'ucomatosi.

PURPOSE: To determine and compare 24-hour fluctuations of intraocular pressure (IOP) and systemic blood pressure (BP) in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG) versus non-glaucoma patients. METHODS: Applanation IOP and BP were measured every 2 hours by one observer for 24 hours in 102 patients. The patients were classified: group 1 - 21 patients with OHT and POAG without treatment, group 2 - 40 patients with OHT and POAG with a satisfactory diurnal therapeutic control of IOP (daytime IOP ? 21 mmHg), group 3 - 13 patients with POAG with unsatisfactory control of IOP under maximal tolerated medication (daytime IOP > 21 mmHg), and group 0-28 non-glaucoma patients (control group). RESULTS: In all glaucoma patients groups 24-hour IOP fluctuations were greater than in the control group (group 0 - 3.62 +/- 0.82 mmHg, ANOVA p < 0.001). Untreated OHT/POAG had 24-hour IOP fluctuations significantly greater than those with good therapeutic control (group 1 - 5.66 +/- 1.66 mmHg versus group 2 - 4.27 +/- 1.86 mmHg, p = 0.0001). POAG with uncontrolled IOP under maximal tolerated medication had the 24-hour IOP fluctuations significantly greater than the other groups (group 3 - 8.38 +/- 3.78 mmHg, p?0.0001). In these patients there was an evident nocturnal mean IOP peak between 0-2 am which temporally correlates with nocturnal systemic BP "dip". Nocturnal IOP peaks (between 11 pm-7 am) were found more frequently in treated glaucoma patients (45.28% - groups 2 and 3 versus 10.2% - groups 0 and 1, p < 0.0001). CONCLUSIONS: Circadian lOP fluctuations in glaucoma patients, even with a satisfactory diurnal therapeutic control, are greater than in the age-matched control subjects. Patients with uncontrolled lOP under topical maximal tolerated medication had the greatest 24-hour lOP fluctuations. Nocturnal lOP peaks occur more often in medically treated patients and 24-hour monitoring of lOP may be useful in this patients.

[Concordance of nictemeral IOP variations between fellow eyes in glaucoma and non glaucoma patients]. / Concordanta fluctuatiilor nictemerale ale presiunii intraoculare între ochii congeneri la pacienti glaucomatosi si non-glaucomatosi.

PURPOSE: To study the concordance of nictemeral IOP variations between fellow eyes in patients with treated and untreated OHT/POAG versus non-glaucoma patients. Also, we evaluate the symmetry or asymmetry level of mean, peak and IOP fluctuations between fellow eyes in glaucoma patients compared with normal controls. DESIGN: Cross-sectional study. METHODS: Applanation IOP and blood pressure were measured every 2 hours by one observer for 24 hours in 124 patients. The patients were classified: group 1--36 non-glaucoma patients (control group), group 2--32 patients with OHT and POAG without treatment, group 3--43 patients with OHT and POAG with a satisfactory diurnal therapeutic control of IOP (daytime IOP>21 mmHg) and group 4--13 patients with POAG with unsatisfactory control of IOP under maximal tolerated medication (daytime IOP>21 mmHg). RESULTS: The nictemeral curves of fellow eyes exhibited parallel profiles; according to the paired t-test there were no significant differences between fellow eyes throughout all measurement intervals. There is a high correlation of 24 h IOP between fellow eyes in all our study groups (r=0.8632, p<0.0001). There were no significant differences between fellow eyes in moment or value of peak IOP (paired t-test p=0.53). Comparing the mean absolute differences in IOP between fellow eyes throughout all 12 measurement points, the smallest differences between fellow eyes were found in groups 1 and 3 (0.85 mmHg, respectively 0.90 mmHg, p=0.47). The differences between fellow eyes were significantly greater in groups 2 and 4 (1.28 mmHg, respectively 2.6 mmHg, p<0.0001). The greatest probability of IOP differences to be in +/- 3 mmHg interval was found in normal patients (97.91%) and in patients with therapeutic control of IOP (97.26%). The greatest asymmetry of IOP was found in the group with therapeutically uncontrolled IOP (over 1/5 measurements were outside the +/- 3 mmHg interval). CONCLUSIONS: The nictemeral variation of IOP in glaucoma patients were largely concordant between fellow eyes and the 24-hour IOP curves of fellow eyes exhibited parallel profiles. There were no significant differences between fellow eyes in mean, peak and IOP fluctuations. The asymmetry over +/- 3 mmHg between fellow eyes varied from 2.09% in normals to 20.53% in patients with therapeutically uncontrolled IOP.