Testing behaviour and positivity for SARS-CoV-2 infection: insights from web-based participatory surveillance in the Netherlands.

OBJECTIVES: We aimed to identify populations at a high risk for SARS-CoV-2 infection but who are less likely to present for testing, by determining which sociodemographic and household factors are associated with a lower propensity to be tested and, if tested, with a higher risk of a positive test result. DESIGN AND SETTING: Internet-based participatory surveillance data from the general population of the Netherlands. PARTICIPANTS: Weekly survey data collected over a 5-month period (17 November 2020 to 18 April 2021) from a total of 12 026 participants who had contributed at least 2 weekly surveys was analysed. METHODS: Multivariable analyses using generalised estimating equations for binomial outcomes were conducted to estimate the adjusted ORs of testing and of test positivity associated with participant and household characteristics. RESULTS: Male sex (adjusted OR for testing (ORt): 0.92; adjusted OR for positivity (ORp): 1.30, age groups<20 (ORt: 0.89; ORp: 1.27), 50-64 years (ORt: 0.94; ORp: 1.06) and 65+ years (ORt: 0.78; ORp: 1.24), diabetics (ORt: 0.97; ORp: 1.06) and sales/administrative employees (ORt: 0.93; ORp: 1.90) were distinguished as lower test propensity/higher test positivity factors. CONCLUSIONS: The factors identified using this approach can help identify potential target groups for improving communication and encouraging testing among those with symptoms, and thus increase the effectiveness of testing, which is essential for the response to the COVID-19 pandemic and for public health strategies in the longer term.

Ecological momentary assessment study of exposure to radiofrequency electromagnetic fields and non-specific physical symptoms with self-declared electrosensitives.

The main objective of the study is to determine if non-specific physical symptoms (NSPS) in people with self-declared sensitivity to radiofrequency electromagnetic fields (RF EMF) can be explained (across subjects) by exposure to RF EMF. Furthermore, we pioneered whether analysis at the individual level or at the group level may lead to different conclusions. By our knowledge, this is the first longitudinal study exploring the data at the individual level. A group of 57 participants was equipped with a measurement set for five consecutive days. The measurement set consisted of a body worn exposimeter measuring the radiofrequency electromagnetic field in twelve frequency bands used for communication, a GPS logger, and an electronic diary giving cues at random intervals within a two to three hour interval. At every cue, a questionnaire on the most important health complaint and nine NSPS had to be filled out. We analysed the (time-lagged) associations between RF-EMF exposure in the included frequency bands and the total number of NSPS and self-rated severity of the most important health complaint. The manifestation of NSPS was studied during two different time lags - 0-1 h, and 1-4 h - after exposure and for different exposure metrics of RF EMF. The exposure was characterised by exposure metrics describing the central tendency and the intermittency of the signal, i.e. the time-weighted average exposure, the time above an exposure level or the rate of change metric. At group level, there was no statistically significant and relevant (fixed effect) association between the measured personal exposure to RF EMF and NSPS. At individual level, after correction for multiple testing and confounding, we found significant within-person associations between WiFi (the self-declared most important source) exposure metrics and the total NSPS score and severity of the most important complaint in one participant. However, it cannot be ruled out that this association is explained by residual confounding due to imperfect control for location or activities. Therefore, the outcomes have to be regarded very prudently. The significant associations were found for the short and the long time lag, but not always concurrently, so both provide complementary information. We also conclude that analyses at the individual level can lead to different findings when compared to an analysis at group level.

Design of an ecological momentary assessment study of exposure to radiofrequency electromagnetic fields and non-specific physical symptoms.

INTRODUCTION: Idiopathic Environmental Intolerance (IEI) attributed to electromagnetic fields (EMF) refers to self-reported sensitivity mainly characterised by the attribution of non-specific physical symptoms to low-level EMF exposure emitted from sources such as mobile phones. Scientific studies have not provided evidence for the existence of IEI-EMF, but these studies did not resemble the real-life situation or suffered from poor exposure characterisation and biased recall of health symptoms. To improve existing methods for the study of IEI-EMF, an Ecological Momentary Assessment (EMA) study is designed. METHODS AND ANALYSIS: The study is an EMA study in which respondents carry personal exposure metres (exposimeters) that measure radiofrequency (RF) EMF, with frequent assessment of health symptoms and perceived EMF exposure through electronic diary registration during five consecutive days. Participants will be a selection from an epidemiological study who report to be sensitive to RF EMF. The exposimeters measure electric field strength in 12 frequency bands. Diary questions include the occurrence and severity of 10 non-specific physical symptoms, mood states and perceived exposure to (sources of) EMF. The relationship of actual and perceived EMF exposure and mood with non-specific physical symptoms will be analysed using multilevel regression analysis with time-shift models. DISCUSSION: The study has several advantages over previous studies, including assessment of personal EMF exposure and non-specific physical symptoms by an ecological method with a minimised chance of recall bias. The within-person design reduces confounding by time-stable factors (eg, personal characteristics). In the conduct of the study and the analysis and interpretation of its outcomes, some methodological issues including a high participant burden, reactivity, compliance to the study protocol and the potential of chance findings due to multiple statistical testing will be accounted for and limited as much as possible.

Effects of hospital delivery during off-hours on perinatal outcome in several subgroups: a retrospective cohort study.

BACKGROUND: Studies have demonstrated a higher risk of adverse outcomes among infants born or admitted during off-hours, as compared to office hours, leading to questions about quality of care provide during off-hours (weekend, evening or night). We aim to determine the relationship between off-hours delivery and adverse perinatal outcomes for subgroups of hospital births. METHODS: This retrospective cohort study was based on data from the Netherlands Perinatal Registry, a countrywide registry that covers 99% of all hospital births in the Netherlands. Data of 449,714 infants, born at 28 completed weeks or later, in the period 2003 through 2007 were used. Infants with a high a priori risk of morbidity or mortality were excluded. Outcome measures were intrapartum and early neonatal mortality, a low Apgar score (5 minute score of 0-6), and a composite adverse perinatal outcome measure (mortality, low Apgar score, severe birth trauma, admission to a neonatal intensive care unit). RESULTS: Evening and night-time deliveries that involved induction or augmentation of labour, or an emergency caesarean section, were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Weekend deliveries were not associated with an increased risk when compared to weekday deliveries. It was estimated that each year, between 126 and 141 cases with an adverse perinatal outcomes could be attributed to this evening and night effect. Of these, 21 (15-16%) are intrapartum or early neonatal death. Among the 3100 infants in the study population who experience an adverse outcome each year, death accounted for only 5% (165) of these outcomes. CONCLUSION: This study shows that for infants whose mothers require obstetric interventions during labour and delivery, birth in the evening or at night, are at an increased risk of an adverse perinatal outcomes.

Predicting the risk of newborn children to become overweight later in childhood: the PIAMA birth cohort study.

OBJECTIVE: To develop a decision rule by which children with a high risk to develop overweight can be distinguished at birth from children at low risk. DESIGN, SETTING AND PARTICIPANTS: Data of 1 687 Dutch children born in 1996/1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) longitudinal birth cohort study were analysed. Perinatal candidate predictors of overweight at 8 years of age were selected and a prediction model was developed using stepwise model selection based on the Akaike Information Criterion (AIC). The prediction model was internally validated using resampling techniques. Outcome measure. Overweight at the age of 8 years. RESULTS: A total of 13.9% (n = 253) of the children were overweight at 8 years of age. Independent positive predictors of overweight were paternal and maternal body mass index, female gender, smoking in the parental house, birth weight and hospital delivery. From the model, a decision rule was derived by which an overweight score could be calculated. Of the children with an overweight score below 89.45, only 2.7% were overweight at the age of 8, whereas in children with an overweight score above 105.02 the prevalence of overweight was 35.4%. CONCLUSION: The risk of overweight at the age of 8 years can be predicted with six characteristics that are available at birth. The decision rule developed in this study may help to target early preventive measures against overweight in high-risk children.

Prediction of the ease of subdivision of scored tablets from their physical parameters.

At present, the ease of subdivision of scored tablets is estimated in vivo. In order to replace such in vivo testing and to develop a surrogate test which uses in vitro techniques, the association between physical parameters of scored tablets and their ease of subdivision was studied. The physical properties of 23 brands of scored tablets of which their ease of subdivision in vivo was known were established. Statistical modeling using a logistic regression model was used to fit the data and estimate the contribution of each physical parameter to the goodness of the fit. For scored oblong tablets, the critical parameters for their ease of subdivision are: diameter; diameter/width ratio; depth of score line and resistance to crushing. Criteria for each of these parameters were derived. All criteria need to be complied with to guarantee sufficient ease of subdivision of scored oblong tablets. For scored round tablets the critical parameters, in decreasing order of importance, for their ease of subdivision, are: resistance to crushing, diameter, score mark (one- or two-sided), and shape (flat or biconvex). A five-parameter predictive model was developed, showing excellent discrimination. For development, the proposed surrogate tests are sufficiently reliable. For release testing and stability studies, resistance to crushing of a scored tablet is a reliable predictor of its ease of subdivision.

Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).

RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown. OBJECTIVES: The objective of this study was to study the dose-effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg (23%). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomised, four-way cross-over study included 24 non-daily male cannabis users (two to nine cannabis cigarettes per month). Participants smoked four cannabis cigarettes containing 0, 29.3, 49.1 and 69.4 mg THC on four exposure days. RESULTS: The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks (simple reaction time, visuo-spatial selective attention, sustained attention, divided attention and short-term memory tasks) and motor control impairment in the motor control task. The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks. Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments. CONCLUSIONS: Response time slowed down and motor control worsened, both linearly, with increasing THC doses. Consequently, cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level.

Simultaneous vaccination with Prevenar and multicomponent vaccines for children: interference or no interference?

Multicomponent vaccines against as many as six infectious diseases are often given simultaneously with monovalent or multivalent vaccines against meningococcus and pneumococcus. Detailed analysis of simultaneous vaccinations, which can lead to suboptimal induced immune responses, should precede their combined use in national immunization programmes. By combining the results of the only two published studies evaluating simultaneous vaccinations with Infanrix hexa and Prevanar in a random-effect meta-analysis, we show that the one-sided 95% confidence interval of the HBV seroconversion rate includes the 95% limit that should be reached in universal programs. We advocate better assessment of potential interferences in immune responses after simultaneous vaccinations. Registration of new vaccines should include this assessment.

High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study.

BACKGROUND: Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke. METHODS AND RESULTS: The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990-1993) were > or = 55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only. CONCLUSIONS: Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

BACKGROUND: Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. OBJECTIVE: To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. DESIGN: Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. SETTING: General population. PARTICIPANTS: A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. MAIN OUTCOME MEASURES: Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. RESULTS: Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. CONCLUSIONS: Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.