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1.
Hum Brain Mapp ; 45(5): e26562, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38590154

RESUMEN

The goal of this study was to examine what happens to established associations between attention deficit hyperactivity disorder (ADHD) symptoms and cortical surface and thickness regions once we apply inverse probability of censoring weighting (IPCW) to address potential selection bias. Moreover, we illustrate how different factors that predict participation contribute to potential selection bias. Participants were 9- to 11-year-old children from the Generation R study (N = 2707). Cortical area and thickness were measured with magnetic resonance imaging (MRI) and ADHD symptoms with the Child Behavior Checklist. We examined how associations between ADHD symptoms and brain morphology change when we weight our sample back to either follow-up (ages 9-11), baseline (cohort at birth), or eligible (population of Rotterdam at time of recruitment). Weights were derived using IPCW or raking and missing predictors of participation used to estimate weights were imputed. Weighting analyses to baseline and eligible increased beta coefficients for the middle temporal gyrus surface area, as well as fusiform gyrus cortical thickness. Alternatively, the beta coefficient for the rostral anterior cingulate decreased. Removing one group of variables used for estimating weights resulted in the weighted regression coefficient moving closer to the unweighted regression coefficient. In addition, we found considerably different beta coefficients for most surface area regions and all thickness measures when we did not impute missing covariate data. Our findings highlight the importance of using inverse probability weighting (IPW) in the neuroimaging field, especially in the context of mental health-related research. We found that including all variables related to exposure-outcome in the IPW model and combining IPW with multiple imputations can help reduce bias. We encourage future psychiatric neuroimaging studies to define their target population, collect information on eligible but not included participants and use inverse probability of censoring weighting (IPCW) to reduce selection bias.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Niño , Recién Nacido , Humanos , Sesgo de Selección , Trastorno por Déficit de Atención con Hiperactividad/patología , Probabilidad , Sesgo , Lóbulo Temporal/patología
2.
Brain Behav Immun ; 119: 965-977, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750701

RESUMEN

BACKGROUND: Maternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring's brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. METHODS: We leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring's brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time. RESULTS: We found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. CONCLUSIONS: Our results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , Humanos , Embarazo , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Niño , Masculino , Adolescente , Estudios Longitudinales , Neuroimagen , Desarrollo Infantil , Adulto
3.
Artículo en Inglés | MEDLINE | ID: mdl-38819520

RESUMEN

OBJECTIVES: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. METHODS: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support. RESULTS: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems. CONCLUSIONS: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention.

4.
Alzheimers Dement ; 20(4): 3119-3125, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38380503

RESUMEN

INTRODUCTION: Adverse effects of monoclonal antibodies against amyloid beta are common, and may affect validity of randomized controlled trials (RCTs) through unblinding of participants. METHODS: We used observations from published phase 3 RCTs in Alzheimer's disease to calculate the magnitude of unblinding effects on cognition that would be required to explain observed cognitive benefits in RCTs. RESULTS: In trials of lecanemab, aducanumab, and donanemab, incidence of amyloid-related imaging abnormalities with active treatment ranged from 22% to 44%, the vast majority of which presumably led to unblinding. Effects of unblinding on the Clinical Dementia Rating Sum of Boxes required to fully explain observed drug effects ranged from 1.1 point (95% confidence interval: 0.2-2.0) with aducanumab, to 3.3 points (2.1-4.4) with donanemab and 3.7 points (2.0-5.6) with lecanemab. Infusion-related reactions were common, with potential unblinding effects particularly for lecanemab. Similar patterns were observed for the Alzheimer's Disease Assessment Scale Cognitive subscale. DISCUSSION: Psychological treatment effects due to unblinding may explain a substantial share of observed treatment effects in RCTs.


Asunto(s)
Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , Proteínas Amiloidogénicas , Cognición
5.
Eur J Epidemiol ; 38(9): 921-927, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37253997

RESUMEN

Mendelian randomization (MR) is an increasingly popular approach to estimating causal effects. Although the assumptions underlying MR cannot be verified, they imply certain constraints, the instrumental inequalities, which can be used to falsify the MR conditions. However, the instrumental inequalities are rarely applied in MR. We aimed to explore whether the instrumental inequalities could detect violations of the MR conditions in case studies analyzing the effect of commonly studied exposures on coronary artery disease risk.Using 1077 single nucleotide polymorphisms (SNPs), we applied the instrumental inequalities to MR models for the effects of vitamin D concentration, alcohol consumption, C-reactive protein (CRP), triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol on coronary artery disease in the UK Biobank. For their relevant exposure, we applied the instrumental inequalities to MR models proposing each SNP as an instrument individually, and to MR models proposing unweighted allele scores as an instrument. We did not identify any violations of the MR assumptions when proposing each SNP as an instrument individually. When proposing allele scores as instruments, we detected violations of the MR assumptions for 5 of 6 exposures.Within our setting, this suggests the instrumental inequalities can be useful for identifying violations of the MR conditions when proposing multiple SNPs as instruments, but may be less useful in determining which SNPs are not instruments. This work demonstrates how incorporating the instrumental inequalities into MR analyses can help researchers to identify and mitigate potential bias.


Asunto(s)
Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Análisis de la Aleatorización Mendeliana , Bancos de Muestras Biológicas , Colesterol , HDL-Colesterol/genética , Reino Unido , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo
6.
Am J Epidemiol ; 191(8): 1453-1456, 2022 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-35445692

RESUMEN

All else being equal, if we had 1 causal effect we wished to estimate, we would conduct a randomized trial with a protocol that mapped onto that causal question, or we would attempt to emulate that target trial with observational data. However, studying the social determinants of health often means there are not just 1 but several causal contrasts of simultaneous interest and importance, and each of these related but distinct causal questions may have varying degrees of feasibility in conducting trials. With this in mind, we discuss challenges and opportunities that arise when conducting and emulating such trials. We describe designing trials with the simultaneous goals of estimating the intention-to-treat effect, the per-protocol effect, effects of alternative protocols or joint interventions, effects within subgroups, and effects under interference, and we describe ways to make the most of all feasible randomized trials and emulated trials using observational data. Our comments are grounded in the study results of Courtin et al. (Am J Epidemiol. 2022;191(8):1444-1452).


Asunto(s)
Causalidad , Humanos
7.
Eur J Epidemiol ; 37(11): 1171-1180, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36107361

RESUMEN

Dietary trans fatty acids (TFAs) are primarily industrially produced and remain abundant in processed food, particularly in low- and middle-income countries. Although TFAs are a cause of adverse cardiometabolic outcomes, little is known about exposure to TFAs in relation to brain development. We aimed to investigate the effect of maternal TFA concentration during pregnancy on offspring head growth in utero and during childhood. In a prospective population-based study in Rotterdam, the Netherlands, with 6900 mother-child dyads, maternal plasma TFA concentration was assessed using gas chromatography in mid-gestation. Offspring head circumference (HC) was measured in the second and third trimesters using ultrasonography; childhood brain morphology was assessed using magnetic resonance imaging at age 10 years. We performed regression analyses adjusting for sociodemographic and lifestyle confounders and instrumental variable (IV) analyses. Our IV analysis leveraged a national policy change that led to a substantial reduction in TFA and occurred mid-recruitment. After adjusting for covariates, maternal TFA concentration during pregnancy was inversely related to fetal HC in the third trimester (mean difference per 1% wt:wt increase: - 0.33, 95% CI - 0.51, - 0.15, cm) and to fetal HC growth from the second to the third trimester (- 0.04, 95% CI - 0.06, - 0.02, cm/week). Consistent findings were obtained with IV analyses, strengthening a causal interpretation. Association between prenatal TFA exposure and HC in the second trimester or global brain volume at age 10 years was inconclusive. Our findings are of important public health relevance as TFA levels in food remain high in many countries.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Ácidos Grasos trans , Embarazo , Femenino , Humanos , Niño , Ácidos Grasos trans/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Estudios Prospectivos , Feto , Dieta
8.
Am J Epidemiol ; 190(2): 318-321, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32889542

RESUMEN

Case-control studies are an important part of the epidemiologic literature, yet confusion remains about how to interpret estimates from different case-control study designs. We demonstrate that not all case-control study designs estimate odds ratios. On the contrary, case-control studies in the literature often report odds ratios as their main parameter even when using designs that do not estimate odds ratios. Only studies using specific case-control designs should report odds ratios, whereas the case-cohort and incidence-density sampled case-control studies must report risk ratio and incidence rate ratios, respectively. This also applies to case-control studies conducted in open cohorts, which often estimate incidence rate ratios. We also demonstrate the misinterpretation of case-control study estimates in a small sample of highly cited case-control studies in general epidemiologic and medical journals. We therefore suggest that greater care be taken when considering which parameter is to be reported from a case-control study.


Asunto(s)
Estudios de Casos y Controles , Interpretación Estadística de Datos , Oportunidad Relativa , Proyectos de Investigación , Humanos
9.
Hum Brain Mapp ; 42(6): 1583-1593, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33528897

RESUMEN

Individual differences in subcortical brain volumes are highly heritable. Previous studies have identified genetic variants that underlie variation in subcortical volumes in adults. We tested whether those previously identified variants also affect subcortical regions during infancy and early childhood. The study was performed within the Generation R study, a prospective birth cohort. We calculated polygenic scores based on reported GWAS for volumes of the accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus. Participants underwent cranial ultrasound around 7 weeks of age (range: 3-20), and we obtained metrics for the gangliothalamic ovoid, a predecessor of the basal ganglia. Furthermore, the children participated in a magnetic resonance imaging (MRI) study around the age of 10 years (range: 9-12). A total of 340 children had complete data at both examinations. Polygenic scores primarily associated with their corresponding volumes at 10 years of age. The scores also moderately related to the diameter of the gangliothalamic ovoid on cranial ultrasound. Mediation analysis showed that the genetic influence on subcortical volumes at 10 years was only mediated for 16.5-17.6% of the total effect through the gangliothalamic ovoid diameter at 7 weeks of age. Combined, these findings suggest that previously identified genetic variants in adults are relevant for subcortical volumes during early life, and that they affect both prenatal and postnatal development of the subcortical regions.


Asunto(s)
Amígdala del Cerebelo/anatomía & histología , Tronco Encefálico/anatomía & histología , Cuerpo Estriado/anatomía & histología , Estudio de Asociación del Genoma Completo , Herencia Multifactorial/genética , Tálamo/anatomía & histología , Amígdala del Cerebelo/diagnóstico por imagen , Variación Biológica Poblacional , Cohorte de Nacimiento , Tronco Encefálico/diagnóstico por imagen , Niño , Cuerpo Estriado/diagnóstico por imagen , Femenino , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Tálamo/diagnóstico por imagen , Ultrasonografía
10.
Paediatr Perinat Epidemiol ; 35(1): 130-142, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32779786

RESUMEN

BACKGROUND: Mendelian randomisation (MR) designs apply instrumental variable techniques using genetic variants to study causal effects. MR is increasingly used to evaluate the role of maternal exposures during pregnancy on offspring health. OBJECTIVES: We review the application of MR to prenatal exposures and describe reporting of methodologic challenges in this area. DATA SOURCES: We searched PubMed, EMBASE, Medline Ovid, Cochrane Central, Web of Science, and Google Scholar. STUDY SELECTION AND DATA EXTRACTION: Eligible studies met the following criteria: (a) a maternal pregnancy exposure; (b) an outcome assessed in offspring of the pregnancy; and (c) a genetic variant or score proposed as an instrument or proxy for an exposure. SYNTHESIS: We quantified the frequency of reporting of MR conditions stated, techniques used to examine assumption plausibility, and reported limitations. RESULTS: Forty-three eligible studies were identified. When discussing challenges or limitations, the most common issues described were known potential biases in the broader MR literature, including population stratification (n = 29), weak instrument bias (n = 18), and certain types of pleiotropy (n = 30). Of 22 studies presenting point estimates for the effect of exposure, four defined their causal estimand. Twenty-four studies discussed issues unique to prenatal MR, including selection on pregnancy (n = 1) and pleiotropy via postnatal exposure (n = 10) or offspring genotype (n = 20). CONCLUSIONS: Prenatal MR studies frequently discuss issues that affect all MR studies, but rarely discuss problems specific to the prenatal context, including selection on pregnancy and effects of postnatal exposure. Future prenatal MR studies should report and attempt to falsify their assumptions, with particular attention to issues specific to prenatal MR. Further research is needed to evaluate the impacts of biases unique to prenatal MR in practice.


Asunto(s)
Variación Genética , Análisis de la Aleatorización Mendeliana , Sesgo , Causalidad , Femenino , Humanos , Embarazo
11.
Optom Vis Sci ; 98(12): 1371-1378, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34759237

RESUMEN

SIGNIFICANCE: Our findings show that non-Dutch background, lower maternal education, and lower net household income level may be new risk factors for myopia development in the Netherlands. Newly introduced physical activity spaces may not be effective enough in increasing outdoor exposure in children to reduce eye growth. PURPOSE: The aims of this study were to evaluate socioeconomic inequalities in myopia incidence, eye growth, outdoor exposure, and computer use and to investigate if newly introduced physical activity spaces can reduce eye growth in school-aged children. METHODS: Participants (N = 2643) from the Dutch population-based birth cohort Generation R were examined at ages 6 and 9 years. Socioeconomic inequalities in myopia incidence, eye growth, and lifestyle were determined using regression analyses. Information on physical activity spaces located in Rotterdam was obtained. Differences in eye growth between those who became exposed to new physical activity spaces (n = 230) and those nonexposed (n = 1866) were evaluated with individual-level fixed-effects models. RESULTS: Myopia prevalence was 2.2% at age 6 years and 12.2% at age 9 years. Outdoor exposure was 11.4 h/wk at age 6 years and 7.4 h/wk at age 9 years. Computer use was 2.1 h/wk at age 6 years and 5.2 h/wk at age 9 years. Myopia incidence was higher in children with non-Dutch background, and families with lower household income and lower maternal education (odds ratio [OR], 1.081 [95% confidence interval, 1.052 to 1.112]; OR, 1.035 [95% confidence interval, 1.008 to 1.063]; OR, 1.028 [95% confidence interval, 1.001 to 1.055], respectively). Children living <600 m of a physical activity space did not have increased outdoor exposure, except those from families with lower maternal education (ß = 1.33 h/wk; 95% confidence interval, 0.15 to 2.51 h/wk). Newly introduced physical activity spaces were not associated with reduction of eye growth. CONCLUSIONS: Children from socioeconomically disadvantaged families became more often myopic than those from socioeconomically advantaged families. We did not find evidence that physical activity spaces protect against myopia for the population at large, but subgroups may benefit.


Asunto(s)
Miopía , Niño , Ejercicio Físico , Humanos , Miopía/epidemiología , Miopía/etiología , Miopía/prevención & control , Oportunidad Relativa , Prevalencia , Instituciones Académicas , Factores Socioeconómicos
12.
Neuroimage ; 205: 116258, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31605827

RESUMEN

Physical activity and sedentary behaviors have been linked to a variety of general health benefits and problems. However, few studies have examined how physical activity during childhood is related to brain development, with the majority of work to date focusing on cardio-metabolic health. This study examines the association between physical activity and screen time with white matter microstructure in the general pediatric population. In a sample of 2532 children (10.12 ±â€¯0.58 years; 50.04% boys) from the Generation R Study, a population-based cohort in Rotterdam, the Netherlands, we assessed physical activity and screen time using parent-reported questionnaires. Magnetic resonance imaging of white matter microstructure was conducted using diffusion tensor imaging. Total physical activity was positively associated with global fractional anisotropy (ß = 0.057, 95% CI = 0.016, 0.098, p = 0.007) and negatively associated with global mean diffusivity (ß = -0.079, 95% CI = -0.120, -0.038, p < 0.001), two commonly derived scalar measures of white matter microstructure. Two components of total physical activity, outdoor play and sport participation, were positively associated with global fractional anisotropy (ß = 0.041, 95% CI=(0.000, 0.083), p = 0.047; ß = 0.053, 95% CI=(0.010, 0.096), p = 0.015, respectively) and inversely associated with global mean diffusivity (ß = -0.074, 95% CI= (-0.114, -0.033), p < 0.001; ß = -0.043, 95% CI=(-0.086, 0.000), p = 0.049, respectively). No associations were observed between screen time and white matter microstructure (p > 0.05). This study provides new evidence that physical activity is modestly associated with white matter microstructure in children. In contrast, complementing other recent evidence on cognition, screen time was not associated with white matter microstructure. Causal inferences from these modest associations must be interpreted cautiously in the absence of longitudinal data. However, these data still offer a promising avenue for future work to explore to what extent physical activity may promote healthy white matter development.


Asunto(s)
Conducta Infantil/fisiología , Desarrollo Infantil/fisiología , Imagen de Difusión Tensora , Ejercicio Físico/fisiología , Neuroimagen/métodos , Tiempo de Pantalla , Sustancia Blanca/diagnóstico por imagen , Niño , Femenino , Humanos , Masculino
13.
Epidemiology ; 31(5): 736-744, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32618712

RESUMEN

BACKGROUND: Childhood obesity is a global epidemic, and its prevalence differs by ethnicity. The objective of this study was to estimate the change in ethnic inequalities in child adiposity at age 10 resulting from interventions on diet at age 8 and screen time and sports participation at age 9. METHODS: We conducted a population-based cohort study, the Generation R Study, from 9,749 births in Rotterdam (2002-2006), of which 9,506 children remained in the analysis. We measured ethnicity, diet, screen time, and sports participation through questionnaires; we measured weight, body mass index (BMI), fat mass index, and fat-free mass index directly. We used sequential G-estimation to estimate the reduction in inequality that would result from the interventions. RESULTS: We observed that sociodemographic characteristics, diet, screen time, sports participation, and all adiposity measurements were more favorable in children from Western versus non-Western ethnic backgrounds: weight = -1.2 kg (95% confidence interval [CI] = -1.7, -0.8), BMI = -1.0 kg/m (CI = -1.2, -0.9), and fat mass index = -0.8 kg/m (CI = -0.9, -0.7). We estimated that extreme intervention (maximum diet score of 10, no screen time, and >4 hours/week of sports) reduced ethnic inequalities by 21% (CI = 8%, 35%) for weight, 9% (CI = 4%, 14%) for BMI, and 9% (CI = 6%, 13%) for fat mass index. A diet score ≥5 points, screen time ≤2 hours/day, and sports participation >2 hours/week reduced ethnic inequalities by 17% (CI = 6%, 28%) for weight, 7% (CI = 3%, 11%) for BMI, and 7% (CI = 4%, 10%) for fat mass index. CONCLUSIONS: Our results are consistent with the hypothesis that interventions integrating diet, screen time, and sports participation have a moderate impact on reducing ethnic inequalities in child adiposity.


Asunto(s)
Adiposidad , Etnicidad , Disparidades en el Estado de Salud , Obesidad Infantil , Adiposidad/etnología , Índice de Masa Corporal , Niño , Estudios de Cohortes , Dieta , Etnicidad/estadística & datos numéricos , Humanos , Obesidad Infantil/etnología , Obesidad Infantil/prevención & control , Tiempo de Pantalla , Deportes/estadística & datos numéricos , Factores de Tiempo
14.
Eur J Epidemiol ; 35(6): 557-565, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31863226

RESUMEN

Cancer diagnoses which are not confirmed by pathology are often under-registered in cancer registries compared to pathology-confirmed diagnoses. It is unknown how many patients have a non pathology-confirmed cancer diagnosis, and whether their characteristics and survival differ from patients with a pathology-confirmed diagnosis. Participants from the prospective population-based Rotterdam Study were followed between 1989 and 2013 for the diagnosis of cancer. Cancer diagnoses were classified into pathology-confirmed versus non pathology-confirmed (i.e., based on imaging or tumour markers). We compared participant characteristics and the distribution of cancers at different sites. Furthermore, we investigated differences in overall survival using survival curves adjusted for age and sex. During a median (interquartile range) follow-up of 10.7 (6.3-15.9) years, 2698 out of 14,024 participants were diagnosed with cancer, of which 316 diagnoses (11.7%) were non pathology-confirmed. Participants with non pathology-confirmed diagnoses were older, more often women, and had a lower education. Most frequently non pathology-confirmed cancer sites included central nervous system (66.7%), hepato-pancreato-biliary (44.5%), and unknown primary origin (31.2%). Survival of participants with non pathology-confirmed diagnoses after 1 year was lower compared to survival of participants with pathology-confirmed diagnoses (32.6% vs. 63.4%; risk difference of 30.8% [95% CI 25.2%; 36.2%]). Pathological confirmation of cancer is related to participant characteristics and cancer site. Furthermore, participants with non pathology-confirmed diagnoses have worse survival than participants with pathology-confirmed diagnoses. Missing data on non pathology-confirmed diagnoses may result in underestimation of cancer incidence and in an overestimation of survival in cancer registries, and may introduce bias in aetiological research.


Asunto(s)
Neoplasias/mortalidad , Neoplasias/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Evaluación del Resultado de la Atención al Paciente , Estudios Prospectivos , Sistema de Registros/estadística & datos numéricos , Tasa de Supervivencia
16.
Am J Epidemiol ; 188(1): 231-238, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30239571

RESUMEN

Mendelian randomization (MR) is used to answer a variety of epidemiologic questions. One stated advantage of MR is that it estimates a "lifetime effect" of exposure, though this term remains vaguely defined. Instrumental variable analysis, on which MR is based, has focused on estimating the effects of point or time-fixed exposures rather than "lifetime effects." Here we use an empirical example with data from the Rotterdam Study (Rotterdam, the Netherlands, 2009-2013) to demonstrate how confusion can arise when estimating "lifetime effects." We provide one possible definition of a lifetime effect: the average change in outcome measured at time t when the entire exposure trajectory from conception to time t is shifted by 1 unit. We show that MR only estimates this type of lifetime effect under specific conditions-for example, when the effect of the genetic variants used on exposure does not change over time. Lastly, we simulate the magnitude of bias that would result in realistic scenarios that use genetic variants with effects that change over time. We recommend that investigators in future MR studies carefully consider the effect of interest and how genetic variants whose effects change with time may impact the interpretability and validity of their results.


Asunto(s)
Causalidad , Análisis de la Aleatorización Mendeliana/métodos , Sesgo , Interpretación Estadística de Datos , Humanos , Mutación , Obesidad/genética , Factores de Tiempo
19.
Milbank Q ; 96(3): 434-471, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30277601

RESUMEN

Policy Points: Historically, reforms that have increased the duration of job-protected paid parental leave have improved women's economic outcomes. By targeting the period around childbirth, access to paid parental leave also appears to reduce rates of infant mortality, with breastfeeding representing one potential mechanism. The provision of more generous paid leave entitlements in countries that offer unpaid or short durations of paid leave could help families strike a balance between the competing demands of earning income and attending to personal and family well-being. CONTEXT: Policies legislating paid leave from work for new parents, and to attend to individual and family illness, are common across Organisation for Economic Co-operation and Development (OECD) countries. However, there exists no comprehensive review of their potential impacts on economic, social, and health outcomes. METHODS: We conducted a systematic review of the peer-reviewed literature on paid leave and socioeconomic and health outcomes. We reviewed 5,538 abstracts and selected 85 published papers on the impact of parental leave policies, 22 papers on the impact of medical leave policies, and 2 papers that evaluated both types of policies. We synthesized the main findings through a narrative description; a meta-analysis was precluded by heterogeneity in policy attributes, policy changes, outcomes, and study designs. FINDINGS: We were able to draw several conclusions about the impact of parental leave policies. First, extensions in the duration of paid parental leave to between 6 and 12 months were accompanied by attendant increases in leave-taking and longer durations of leave. Second, there was little evidence that extending the duration of paid leave had negative employment or economic consequences. Third, unpaid leave does not appear to confer the same benefits as paid leave. Fourth, from a population health perspective, increases in paid parental leave were consistently associated with better infant and child health, particularly in terms of lower mortality rates. Fifth, paid paternal leave policies of adequate length and generosity have induced fathers to take additional time off from work following the birth of a child. How medical leave policies for personal or family illness influence health has not been widely studied. CONCLUSIONS: There is substantial quasi-experimental evidence to support expansions in the duration of job-protected paid parental leave as an instrument for supporting women's labor force participation, safeguarding women's incomes and earnings, and improving child survival. This has implications, in particular, for countries that offer shorter durations of job-protected paid leave or lack a national paid leave entitlement altogether.


Asunto(s)
Salud Infantil , Política de Salud/legislación & jurisprudencia , Organización para la Cooperación y el Desarrollo Económico , Permiso Parental/legislación & jurisprudencia , Ausencia por Enfermedad/legislación & jurisprudencia , Femenino , Humanos , Organización para la Cooperación y el Desarrollo Económico/legislación & jurisprudencia , Organización para la Cooperación y el Desarrollo Económico/estadística & datos numéricos , Embarazo , Factores Socioeconómicos , Equilibrio entre Vida Personal y Laboral/legislación & jurisprudencia
20.
Eur J Epidemiol ; 33(10): 947-952, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30039250

RESUMEN

Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a causal effect of the exposure on the outcome. Complications arise with a binary exposure that is a dichotomization of a continuous risk factor (for example, hypertension is a dichotomization of blood pressure). This can lead to violation of the exclusion restriction assumption: the genetic variant can influence the outcome via the continuous risk factor even if the binary exposure does not change. Provided the instrumental variable assumptions are satisfied for the underlying continuous risk factor, causal inferences for the binary exposure are valid for the continuous risk factor. Causal estimates for the binary exposure assume the causal effect is a stepwise function at the point of dichotomization. Even then, estimation requires further parametric assumptions. Under monotonicity, the causal estimate represents the average causal effect in 'compliers', individuals for whom the binary exposure would be present if they have the genetic variant and absent otherwise. Unlike in randomized trials, genetic compliers are unlikely to be a large or representative subgroup of the population. Under homogeneity, the causal effect of the exposure on the outcome is assumed constant in all individuals; rarely a plausible assumption. We here provide methods for causal estimation with a binary exposure (although subject to all the above caveats). Mendelian randomization investigations with a dichotomized binary exposure should be conceptualized in terms of an underlying continuous variable.


Asunto(s)
Variación Genética , Análisis de la Aleatorización Mendeliana/métodos , Modelos Genéticos , Presión Sanguínea , Humanos , Hipertensión , Funciones de Verosimilitud , Modelos Estadísticos , Distribución Aleatoria , Factores de Riesgo
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