Systematic reviews and meta-analysis of time-to-event outcomes are frequently published within the Cochrane Database of Systematic Reviews (CDSR). However, these outcomes are handled differently ...across meta-analyses. They can be analysed on the hazard ratio (HR) scale or can be dichotomized and analysed as binary outcomes using effect measures such as odds ratios (OR) or risk ratios (RR). We investigated the impact of reanalysing meta-analyses from the CDSR that used these different effect measures.
We extracted two types of meta-analysis data from the CDSR: either recorded in a binary form only ("binary"), or in binary form together with observed minus expected and variance statistics ("OEV"). We explored how results for time-to-event outcomes originally analysed as "binary" change when analysed using the complementary log-log (clog-log) link on a HR scale. For the data originally analysed as HRs ("OEV"), we compared these results to analysing them as binary on a HR scale using the clog-log link or using a logit link on an OR scale.
The pooled HR estimates were closer to 1 than the OR estimates in the majority of meta-analyses. Important differences in between-study heterogeneity between the HR and OR analyses were also observed. These changes led to discrepant conclusions between the OR and HR scales in some meta-analyses. Situations under which the clog-log link performed better than logit link and vice versa were apparent, indicating that the correct choice of the method does matter. Differences between scales arise mainly when event probability is high and may occur via differences in between-study heterogeneity or via increased within-study standard error in the OR relative to the HR analyses.
We identified that dichotomising time-to-event outcomes may be adequate for low event probabilities but not for high event probabilities. In meta-analyses where only binary data are available, the complementary log-log link may be a useful alternative when analysing time-to-event outcomes as binary, however the exact conditions need further exploration. These findings provide guidance on the appropriate methodology that should be used when conducting such meta-analyses.
The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of ...early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network’s core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network’s data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.
Systematic reviews and meta-analysis of time-to-event outcomes can be analysed on the hazard ratio (HR) scale but are very often dichotomised and analysed as binary using effect measures such as odds ...ratios (OR). This thesis investigates the impact of using these different scales by re-analysing meta-analyses from the Cochrane Database of Systematic Reviews (CDSR), using individual participant data (IPD) and a comprehensive simulation study. For the CDSR and IPD, the pooled HR estimates were closer to 1 than the OR estimates in most meta-analyses. Important differences in between-study heterogeneity between the HR and OR analyses were observed. These caused discrepant conclusions between the OR and HR scales in some meta-analyses. Situations under which the clog-log link outperformed the logit link and vice versa were apparent, indicating that the correct method choice does matter. Differences between scales occurred mainly when event probability was high and could occur via differences in between-study heterogeneity or via increased within-study standard error in OR relative to HR analyses. In many simulation scenarios, analysing time-to-event data as binary using the logit link did not substantially affect bias and coverage apart from those where large percentage random censoring and long follow-up time was present. The method though lacks precision particularly for small meta-analyses. Analysing the data as binary using the clog-log link consistently produced more bias, low coverage and low power. If a HR estimate cannot be obtained per trial to perform a meta-analysis of time-to-event data, a meta-analysis using the OR scale (using the logit link) could be conducted but with awareness that this would provide less precise estimates in the analysis. Investigators should avoid performing meta-analyses on the OR scale in the presence of high event probability, large percentage random censoring and therefore longer follow-up times assuming of large event rates of the trials included.
Background
In England, nearly one child in ten lives in overcrowded housing. Crowding is likely to worsen with increasing population size, urbanisation, and the ongoing concerns about housing ...shortages. Children with behavioural difficulties are at increased risk of mental and physical health problems and poorer employment prospects.
Objective
To test the association between the level of crowding in the home and behavioural problems in children, and to explore what factors might explain the relationship.
Methods
Mothers of 2576 children from the Southampton Women's Survey population‐based mother‐offspring cohort were interviewed. Crowding was measured at age 2 years by people per room (PPR) and behavioural problems assessed at age 3 years with the Strengths and Difficulties Questionnaire (SDQ). Both were analysed as continuous measures, and multivariable linear regression models were fitted, adjusting for confounding factors: gender, age, single‐parent family, maternal education, receipt of benefits, and social class. Potential mediators were assessed with formal mediation analysis.
Results
The characteristics of the sample were broadly representative of the population in England. Median (IQR) SDQ score was 9 (6‐12) and PPR was 0.75 (0.6‐1). In households that were more crowded, children tended to have more behavioural problems (by 0.20 SDQ points (95% CI 0.08, 0.32) per additional 0.2 PPR, adjusting for confounding factors). This relationship was partially mediated by greater maternal stress, less sleep, and strained parent‐child interactions.
Conclusions
Living in a more crowded home was associated with a greater risk of behavioural problems, independent of confounding factors. The findings suggest that improved housing might reduce childhood behavioural problems and that families living in crowded circumstances might benefit from greater support.
Abstract
Introduction
There has been little focus on sleep and its relation to behavior and cognition in preschool-aged children. We aimed to investigate the association between sleep duration in ...early preschoolers (» 3.5 years of age) and later behavioral and cognitive outcomes (» 5 years of age) in European children.
Methods
We used harmonized data from five cohorts from the EU Child Cohort Network, established by the LifeCycle Project (n=16.444 children): ALSPAC and SWS from UK, EDEN and ELFE from France and INMA from Spain. Within all cohorts, total sleep duration per day and behavioral and cognitive information were reported by parents. Internalizing and externalizing behaviors were measured with the Strengths and Difficulties Questionnaire and treated as percentile scores. Verbal and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or with the McCarthy Scales of Children’s Abilities depending on the cohort and treated as standardized scores. All scores were cohort specific. Associations between sleep duration during early preschool age and later behavior and/or cognition were estimated using linear regression and pooled with two-stage individual participant data meta-analysis adjusted for child, maternal and household information. Analyses were done in DataSHIELD.
Results
Global mean sleep duration was 11h54 ± 1h00 per day at mean age 3.5 years but differed by country, with children from France showing longer sleep duration than children from the UK or Spain. In multivariate meta-analysis, 1 hour of additional sleep duration per day at mean age 3.5 years was associated with reduced internalizing and externalizing behavior percentile scores at mean age 5.1 years (internalizing behavior: badjusted= -1.05, 95%-CI -1.93, -0.18, I2: 30.3%; externalizing behavior: badjusted= -2.12, 95%-CI -2.78, -1.47, I2: 0.0%). No association was observed between sleep duration and subsequent verbal or non-verbal intelligence
Conclusion
Longer sleep duration in early preschool age (» 3.5 years of age) was associated with subsequent lower internalizing and externalizing behavior scores (» 5 years of age), but not with verbal or non-verbal intelligence. Adequate sleep duration at an early age is important for children’s later mental health.
Support (If Any)
KG was granted a LifeCycle fellowship.
Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to ...developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.
We examined associations between different chronic morbidities and help-seeking for possible cancer symptoms.
Postal survey of individuals aged >50 years in England. Participants could report prior ...morbidities in respect of 12 pre-defined conditions. Among patients experiencing possible cancer symptoms we examined associations between specific morbidities and self-reported help-seeking (i.e. contacted versus not contacted a GP) for each alarm symptom using regression analyses.
Among 2042 respondents (42% response rate), 936 (46%) recently experienced 1 of 14 possible cancer symptoms considered in our analysis. Of them, 80% reported one or more morbidities, most frequently hypertension/hypercholesterolemia (40%), osteomuscular (36%) and heart diseases (21%). After adjustment for socio-demographic characteristics, patients with hypertension/hypercholesterolemia were more likely to report help-seeking for possible cancer symptoms, such as unexplained cough (OR = 2.0; 95% confidence interval (CI) 1.1-3.5), pain (OR = 2.2; 95% CI 1.0-4.5) and abdominal bloating (OR = 2.3; 95% CI 1.1-4.8). Urinary morbidity was associated with increased help-seeking for abdominal bloating (OR = 5.4; 95% CI 1.2-23.7) or rectal bleeding (OR = 5.8; 95% CI 1.4-23.8). In contrast, heart problems reduced help-seeking for change in bowel habits (OR = 0.4; 95% CI 0.2-1.0).
Comorbidities are common and may facilitate help-seeking for possible cancer symptoms, but associations vary for specific symptom-comorbidity pairs. The findings can contribute to the design of future cancer symptom awareness campaigns.
•Advanced stage at diagnosis was strongly associated with lower satisfaction with cancer care.•Emergency presentation was associated with the lowest ratings of care and screening with the best.•The ...findings argue for improvements in the care of emergency presenters.
Whether diagnostic route (e.g. emergency presentation) is associated with cancer care experience independently of tumour stage is unknown.
We analysed data on 18 590 patients with breast, prostate, colon, lung, and rectal cancers who responded to the 2014 English Cancer Patient Experience Survey, linked to cancer registration data on diagnostic route and tumour stage at diagnosis. We estimated odds ratios (OR) of reporting a negative experience of overall cancer care by tumour stage and diagnostic route (crude and adjusted for patient characteristic and cancer site variables) and examined their interactions with cancer site.
After adjustment, the likelihood of reporting a negative experience was highest for emergency presenters and lowest for screening-detected patients with breast, colon, and rectal cancers (OR versus two-week-wait 1.51, 95% confidence interval CI 1.24–1.83; 0.88, 95% CI 0.75–1.03, respectively). Patients with the most advanced stage were more likely to report a negative experience (OR stage IV versus I 1.37, 95% CI 1.15–1.62) with little confounding between stage and route, and no evidence for cancer-stage or cancer-route interactions.
Though the extent of disease is strongly associated with ratings of overall cancer care, diagnostic route (particularly emergency presentation or screening detection) exerts important independent effects.
Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of ...pet, timing, and degree of exposure.
Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization.
We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis.
The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio OR = 0.97 95% CI = 0.87-1.09 and 0.92 95% CI = 0.85-1.01, respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 95% CI = 0.75-1.13 and 0.93 95% CI = 0.57-1.54, respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 95% CI = 4.91-9.10 and 5.98 95% CI = 3.14-11.36, respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization.
Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.
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Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association ...between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children’s Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: − 1.27, 95% CI − 2.22, − 0.32 / − 2.39, 95% CI − 3.04, − 1.75). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: − 0.28, 95% CI − 0.83, 0.27 / − 0.42, 95% CI − 0.99, 0.15). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children’s later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.
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