•The National Lung Screening Trial only performed 3 annual CT screening rounds.•Effects of 3 additional screening rounds were microsimulated using original data.•Additional screening may have led to ...substantial further LC mortality reduction.
To microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST).
We used multiple imputation to model the effect of additional screening in the full NLST cohort on the time to LC diagnosis and on LC death in those participants who were diagnosed with LC by the end of NLST. Nodule growth models were derived from a Dutch in-vivo study. Microsimulations were repeated 500 times. The method was validated by simulating three rounds of CT screening in the original chest radiography (CXR) cohort. The times up to which the simulations remained within the 95 % confidence bands of the CT cohort’s original results were used to estimate the validity of the results in the CT cohort with three additional simulated screening rounds.
Validation of the simulation approach on the CXR cohort resulted in a LC mortality reduction which remained well within the 95 % confidence intervals of the original CT cohort up to 6.5 years after the start of simulations. Simulating additional CT screening in the CT cohort led to LCs being diagnosed earlier than originally, resulting in a relative risk reduction in LC mortality of 11 % (95 % confidence bands, 7 %–14 %) at 6.5 years. This is equivalent to preventing 71 % (48 %–94 %) more LC deaths than the original CT cohort achieved in comparison to the original CXR cohort.
Three additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.
Abstract
Background
Periconceptional use of oral contraceptives (OCs) has been reported to increase risks of pregnancy complications and adverse birth outcomes, but risks are suggested to differ ...depending on the timing of discontinuation, amount of oestrogen and progestin content.
Methods
Prospective cohort study among 6470 pregnancies included in the PRegnancy and Infant DEvelopment (PRIDE) Study in 2012–19. Exposure was defined as any reported use of OCs within 12 months pre-pregnancy or after conception. Outcomes of interest were gestational diabetes, gestational hypertension, pre-eclampsia, pre-term birth, low birthweight and small for gestational age (SGA). Multivariable Poisson regression using stabilized inverse probability weighting estimated relative risks (RRs) with 95% CIs.
Results
Any periconceptional OC use was associated with increased risks of pre-eclampsia (RR 1.38, 95% CI 0.99–1.93), pre-term birth (RR 1.38, 95% CI 1.09–1.75) and low birthweight (RR 1.45, 95% CI 1.10–1.92), but not with gestational hypertension (RR 1.09, 95% CI 0.91–1.31), gestational diabetes (RR 1.02, 95% CI 0.77–1.36) and SGA (RR 0.96, 95% CI 0.75–1.21). Associations with pre-eclampsia were strongest for discontinuation 0–3 months pre-pregnancy, for OCs containing ≥30 µg oestrogen and for first- or second-generation OCs. Pre-term birth and low birthweight were more likely to occur when OCs were discontinued 0–3 months pre-pregnancy, when using OCs containing <30 µg oestrogen and when using third-generation OCs. Associations with SGA were observed for OCs containing <30 µg oestrogen and for third- or fourth-generation OCs.
Conclusions
Periconceptional OC use, particularly those containing oestrogen, was associated with increased risks of pre-eclampsia, pre-term birth, low birthweight and SGA.
This study examines longitudinal associations of air pollution and green space with cardiometabolic risk among children in the Netherlands.
Three Dutch prospective cohorts with a total of 13,822 ...participants aged 5 to 17 years were included: (1) the Amsterdam Born Children and their Development (ABCD) study from Amsterdam (n = 2,547), (2) the Generation R study from Rotterdam (n = 5,431), and (3) the Lifelines study from northern Netherlands (n = 5,844). Air pollution (PM2.5, PM10, NO2, and elemental carbon (EC)) and green space exposures (density in multiple Euclidean buffer sizes) from 2006 to 2017 at home address level were used. Cardiometabolic risk factor clustering was assessed by a MetScore, which was derived from a confirmatory factor analysis of six cardiometabolic risk factors to assess the overall risk. Linear regression models with change in Metscore as the dependent variable, adjusted for multiple confounders, were conducted for each cohort separately. Meta-analyses were used to pool cohort-specific estimates.
Exposure to higher levels of NO2 and EC was significantly associated with increases in MetScore in Lifelines (per SD higher exposure: βNO2 = 0.006, 95 % CI = 0.001 to 0.010; βEC = 0.008, 95 % CI = 0.002 to 0.014). In the other two cohort studies, these associations were in the same direction but these were not significant. Higher green space density in 500-meter buffer zones around participants’ residential addresses was not significantly associated with decreases of MetScore in all three cohorts. Higher green space density in 2000-meter buffer zones was significantly associated with decreases of MetScore in ABCD and Lifelines (per SD higher green space density: βABCD = -0.008, 95 % CI = -0.013 to −0.003; βLifelines = -0.002, 95 % CI = -0.003 to −0.00003). The pooled estimates were βNO2 = 0.003 (95 % CI = -0.001 to 0.006) for NO2, βEC = 0.003 (95 % CI = -0.001, 0.007) for EC, and β500m buffer = -0.0014 (95 % CI = -0.0026 to −0.0001) for green space.
More green space exposure at residence was associated with decreased cardiometabolic risk in children. Exposure to more NO2 and EC was also associated with increased cardiometabolic risk.
A baseline computed tomography (CT) scan for lung cancer (LC) screening may reveal information indicating that certain LC screening participants can be screened less, and instead require dedicated ...early cardiac and respiratory clinical input. We aimed to develop and validate competing death (CD) risk models using CT information to identify participants with a low LC risk and a high CD risk.
Participant demographics and quantitative CT measures of LC, cardiovascular disease and chronic obstructive pulmonary disease were considered for deriving a logistic regression model for predicting 5-year CD risk using a sample from the National Lung Screening Trial (n=15 000). Multicentric Italian Lung Detection data were used to perform external validation (n=2287).
Our final CD model outperformed an external pre-scan model (CD Risk Assessment Tool) in both the derivation (area under the curve (AUC) 0.744 (95% CI 0.727-0.761) and 0.677 (95% CI 0.658-0.695), respectively) and validation cohorts (AUC 0.744 (95% CI 0.652-0.835) and 0.725 (95% CI 0.633-0.816), respectively). By also taking LC incidence risk into consideration, we suggested a risk threshold where a subgroup (6258/23 096 (27%)) was identified with a number needed to screen to detect one LC of 216 (
23 in the remainder of the cohort) and ratio of 5.41 CDs per LC case (
0.88). The respective values in the validation cohort subgroup (774/2287 (34%)) were 129 (
29) and 1.67 (
0.43).
Evaluating both LC and CD risks post-scan may improve the efficiency of LC screening and facilitate the initiation of multidisciplinary trajectories among certain participants.
Summary
Objective
To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across ...European regions.
Methods
Data were harmonised between the European multi‐centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0–9.9 and 5.0–7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child.
Results
The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar‐sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years.
Conclusions
Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.
Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development ...are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging.
Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH.
IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH.
In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.
PDF
