Impact of post-COVID-19 condition on health status and activities of daily living: the PRIME post-COVID study.

OBJECTIVE: To assess health and activities of daily living (ADL) in SARS-CoV-2-positive adults with and without post-COVID-19 condition (PCC) and compare this with negative tested individuals. Furthermore, different PCC case definitions were compared with SARS-CoV-2-negative individuals. METHODS: All adults tested PCR positive for SARS-CoV-2 at the Public Health Service South Limburg (Netherlands) between June 2020 and November 2021 (n=41 780) and matched PCR negative individuals (2:1, on age, sex, year-quarter test, municipality; n=19 875) were invited by email. Health (five-level EuroQol five-dimension (EQ5D) index and EuroQol visual analogue scale (EQVAS)) and ADL impairment were assessed. PCC classification was done using the WHO case definition and five other common definitions. RESULTS: In total, 8409 individuals (6381 SARS-CoV-2 positive; 53±15 years; 57% female; 9 (7-11) months since test) were included. 39.4% of positives had PCC by the WHO case definition (EQVAS: 71±20; EQ5D index: 0.800±0.191; ADL impairment: 30 (10-70)%) and perceived worse health and more ADL impairment than negatives, that is, difference of -8.50 points (95% CI -9.71 to -7.29; p<0.001) for EQVAS, which decreased by 1.49 points (95% CI 0.86 to 2.12; p<0.001) in individuals with PCC for each comorbidity present, and differences of -0.065 points (95% CI -0.074 to -0.056; p<0.001) for EQ5D index, and +16.72% (95% CI 15.01 to 18.43; p<0.001) for ADL impairment. Health and ADL impairment were similar in negatives and positives without PCC. Replacing the WHO case definition with other PCC definitions yielded comparable results. CONCLUSIONS: Individuals with PCC have substantially worse health and more ADL impairment than negative controls, irrespective of the case definition. Authorities should inform the public about the associated burden of PCC and enable adequate support.

Evaluation of symptomatology and viral load among residents and healthcare staff in long-term care facilities: A coronavirus disease 2019 retrospective case-cohort study.

OBJECTIVES: We evaluated COVID-19 symptoms, case fatality rate (CFR), and viral load among all Long-Term Care Facility (LTCF) residents and staff in South Limburg, the Netherlands (February 2020-June 2020, wildtype SARS-CoV-2 Wuhan strain). METHODS: Patient information was gathered via regular channels used to notify the public health services. Ct-values were obtained from the Maastricht University Medical Centre laboratory. Logistic regression analyses were performed to assess associations between COVID-19, symptoms, CFR, and viral load. RESULTS: Of 1,457 staff and 1,540 residents, 35.1% and 45.2% tested positive for COVID-19. Symptoms associated with COVID-19 for female staff were fever, cough, muscle ache and loss of taste and smell. Associated symptoms for men were cough, and loss of taste and smell. Associated symptoms for residents were subfebrility, fatigue, and fever for male residents only. LTCF residents had a higher mean viral load compared to staff. Male residents had a higher CFR (35.8%) compared to women (22.5%). Female residents with Ct-values 31 or less had increased odds of mortality. CONCLUSIONS: Subfebrility and fatigue seem to be associated with COVID-19 in LTCF residents. Therefore, physicians should also consider testing residents who (only) show aspecific symptoms whenever available resources prohibit testing of all residents. Viral load was higher in residents compared to staff, and higher in male residents compared to female residents. All COVID-19 positive male residents, as well as female residents with a medium to high viral load (Ct-values 31 or lower) should be monitored closely, as these groups have an overall increased risk of mortality.

Design and recruitment of a large-scale cohort study on prevalence, risk factors and impact evaluation of post-COVID-19 condition and its wider long-term social, mental, and physical health impact: The PRIME post-COVID study.

Background: Persistent symptoms, described as long COVID or post-COVID-19 condition, pose a potential public health problem. Here, the design and recruitment of the PRIME post-COVID study is described. PRIME post-COVID is a large-scale population-based observational study that aims to improve understanding of the occurrence, risk factors, social, physical, mental, emotional, and socioeconomic impact of post-COVID-19 condition. Methods: An observational open cohort study was set up, with retrospective and prospective assessments on various health-conditions and health-factors (medical, demographic, social, and behavioral) based on a public health COVID-19 test and by self-report (using online questionnaires in Dutch language). Invited for participation were, as recorded in a public health registry, adults (18 years and older) who were tested for COVID-19 and had a valid Polymerase Chain Reaction (PCR) positive or negative test result, and email address. In November 2021, 61,655 individuals were invited by email to participate, these included all eligible adults who tested PCR positive between 1 June 2020 and 1 November 2021, and a sample of adults who tested negative (2:1), comparable in distribution of age, sex, municipality of residence and year-quarter of testing. New recruitment periods are planned as well. Participants are followed over time by regular follow-up measurements. Data are analyzed using the appropriate data-analyses methods. Discussion: The PRIME post-COVID study will provide insights into various health-related aspects of post-COVID-19 condition in the context of various stages of the COVID-19 pandemic. Results will inform practical guidance for society, clinical and public health practice for the prevention and care for long-term impact of COVID-19. Trial registration ClinicalTrialsgov identifier: NCT05128695.

Assessing the role of criminality in neighbourhood safety feelings and self-reported health: results from a cross-sectional study in a Dutch municipality.

BACKGROUND: Neighbourhood safety has repeatedly been shown to be associated with the health and well-being of the residents. Criminality is often seen as one of the key factors affecting neighbourhood safety. However, the relationship between crime, fear of crime and feelings of safety remains underexplored. METHODS: Data on socio-demographic, health and safety perceptions was extracted from the Maastricht municipality survey (the Netherlands) (n = 9656 adults) and merged with data on official neighbourhood crime rates from the Police Registry. Pearson correlation coefficients and multilevel logistic regression models were computed to assess the association between aspects of objective and perceived criminality, individuals' feelings of safety and health. RESULTS: The correlation between the police recorded crime and residents' perceptions of the neighbourhood crime rates was weak (0.14-0.38), with the exception of violent crime (0.59), which indicates that other factors contribute to the perceptions of safety. In turn, the perception of higher rates of violent crime and more nuisance (on the scale 0-10) but not other types of crime or nuisance was positively associated with feeling unsafe (OR 1.27 [1.22;1.32] and 1.39 [1.33;1.46], respectively). Lower general feelings of safety at both the individual and neighbourhood level were consistently associated with worse self-rated health. Among different indicators of safety, the general feelings of safety had the most pronounced association with health, while subjective or objective measures of crime showed limited to no direct relationship with health. CONCLUSIONS: Public health policies targeting safety as a social determinant of health should consider prioritizing areas of violent crime and nuisance to improve general feelings of safety. Further research is needed to understand which factors aside from criminality are driving residents' feelings of safety.

Neighborhood Environment is Associated with Overweight and Obesity, Particularly in Older Residents: Results from Cross-Sectional Study in Dutch Municipality.

We explored whether overweight and obesity were associated with the physical and social environment at neighborhood level. Data from Maastricht municipality survey (The Netherlands) were used (n = 9771 adults). Multinomial regression models were computed (outcome being normal weight, overweight, or obese). We found inconsistent associations between neighborhood social and physical environment characteristics and overweight and obesity in the total sample. The effects were more consistent and stronger for older residents (>65) and obesity as an outcome. Better scores on traffic nuisance, green space, social cohesion, nuisance, and safety were associated with lower odds of obesity among elderly (OR ranged between 0.71 [95% CI 0.44 to 0.93] to 0.85 [95% CI 0.74 to 0.96] for each point of improvement in neighborhood social and physical environment (scale 0-10)). We showed that there are neighborhood-level factors that are associated with obesity, particularly in elderly residents. These could be targeted in preventive strategies outside health care settings.

LucKi Birth Cohort Study: rationale and design.

BACKGROUND: Infancy and childhood are characterized by rapid growth and development, which largely determine health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors in critical periods of life will contribute to the development of effective prevention and intervention strategies. The LucKi Birth Cohort Study was designed and started in 2006 to follow children from birth into adulthood on a wide range of determinants, disorders, and diseases. During preschool and school years, the primary focus is on the etiology and prognosis of atopic diseases (eczema, asthma, and hay fever) and overweight/obesity. METHODS/DESIGN: LucKi is an ongoing, dynamic, prospective birth cohort study, embedded in the Child and Youth Health Care (CYHC) practice of the 'Westelijke Mijnstreek' (a region in the southeast of the Netherlands). Recruitment (1-2 weeks after birth) and follow-up (until 19 years) coincide with routine CYHC contact moments, during which the child's physical and psychosocial development is closely monitored, and anthropometrics are measured repeatedly in a standardised way. Information gathered through CYHC is complemented with repeated parental questionnaires, and information from existing registries of pharmacy, hospital and/or general practice. Since the start already more than 5,000 children were included in LucKi shortly after birth, reaching an average participation rate of ~65 %. DISCUSSION: The LucKi Birth Cohort Study provides a framework in which children are followed from birth into adulthood. Embedding LucKi in CYHC simplifies implementation, leads to low maintenance costs and high participation rates, and facilitates direct implementation of study results into CYHC practice. Furthermore, LucKi provides opportunities to initiate new (experimental) studies and/or to establish biobanking in (part of) the cohort, and contributes relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on www.birthcohorts.net .

Early life growth and the development of preschool wheeze, independent from overweight: the LucKi Birth Cohort Study.

OBJECTIVE: To investigate whether birth weight and postnatal growth rates are independently related to the development of overweight and wheeze up to age 3 years. STUDY DESIGN: Children from the LucKi Birth Cohort Study with complete follow-up for repeated questionnaires (at age 0, 7, and 14 months and 3 years) and informed consent to use height and weight data (measured by trained personnel at age 0, 7, and 14 months and 2 and 3 years) were included (n = 566). Wheeze (parental-reported) and overweight (body mass index [BMI] >85th percentile) were regressed with generalized estimating equations on birth weight and relative growth rates (difference SDS for weight, height, and BMI). RESULTS: Higher birth weight and higher weight and BMI growth rates were associated with increased risk of overweight, but not of wheeze, up to age 3 years. Higher height growth rate was associated with lower risk of wheeze up to 3 years, independent of overweight (aOR, 0.65; 95% CI, 0.53-0.79). In time-lag models, wheeze was associated with subsequently reduced height growth up to age 14 months, but not vice versa. CONCLUSION: Only height growth rate, and not weight and BMI growth rate, is associated with preschool wheeze, independent of overweight. Children who wheeze demonstrate a subsequent reduction in height growth up to age 14 months, but not vice versa. Because height growth rate is not associated with overweight, preschool wheeze and overweight are not associated throughout early life growth.

Living environment matters: relationships between neighborhood characteristics and health of the residents in a Dutch municipality.

Characteristics of an individual alone cannot exhaustively explain all the causes of poor health, and neighborhood of residence have been suggested to be one of the factors that contribute to health. However, knowledge about aspects of the neighborhood that are most important to health is limited. The main objective of this study was to explore associations between certain features of neighborhood environment and self-rated health and depressive symptoms in Maastricht (The Netherlands). A large amount of routinely collected neighborhood data were aggregated by means of factor analysis to 18 characteristics of neighborhood social and physical environment. Associations between these characteristics and self-rated health and presence of depressive symptoms were further explored in multilevel logistic regression models adjusted for individual demographic and socio-economic factors. The study sample consisted of 9,879 residents (mean age 55 years, 48 % male). Residents of unsafe communities were less likely to report good health (OR 0.88 95 % CI 0.80-0.97) and depressive symptoms (OR 0.81 95 % CI 0.69-0.97), and less cohesive environment was related to worse self-rated health (OR 0.81 95 % CI 0.72-0.92). Residents of neighborhoods with more car traffic nuisance and more disturbance from railway noise reported worse mental health (OR 0.79 95 % CI 0.68-0.92 and 0.85 95 % CI 0.73-0.99, respectively). We did not observe any association between health and quality of parking and shopping facilities, facilities for public or private transport, neighborhood aesthetics, green space, industrial nuisance, sewerage, neighbor nuisance or satisfaction with police performance. Our findings can be used to support development of integrated health policies targeting broader determinants of health. Improving safety, social cohesion and decreasing traffic nuisance in disadvantaged neighborhoods might be a promising way to improve the health of residents and reduce health inequalities.

Long-term effects of the RealFit intervention on body composition, aerobic fitness, and behavior.

BACKGROUND: RealFit is a 13-week weight reduction program for youth that focuses on nutrition, physical activity (PA), psychology, and parental participation. The short-term effectiveness of the RealFit intervention, in terms of body composition, aerobic fitness, and dietary and PA behavior, having been proven, the present study evaluated the long-term effects of the intervention. METHODS: The study had a quasi-experimental design. Height, weight, waist circumference, aerobic fitness, and self-reported dietary and PA behavior were assessed at baseline (T(0)), immediately after the 13-week RealFit intervention (T(1)), after 5 months (T(2)), and 1 year (T(3)) of follow-up. A total of 86 adolescents participated in the intervention group. The control group (n=32) comprised overweight adolescents who did not receive any treatment. RESULTS: One year after the RealFit intervention, significant decreases in BMI z-score (mean difference [MD]: -0.39) and waist circumference (MD, -3.24) were found. The comparison between the intervention and control groups, controlling for confounders, resulted in a significant difference (BMI z-score: -0.41; 95% confidence interval [CI]: -0.67 to -0.15; waist circumference: -8.07; 95% CI: -11.58 to -4.56). The results for dietary and PA behavior consistently showed favorable changes in the intervention group. CONCLUSIONS: The RealFit intervention appears to have significant favorable long-term effects on BMI z-score and waist circumference. These changes in body composition obviously represent changes in adolescents' energy balance-related behavior. Taking all results and limitations into account, it may cautiously be concluded that RealFit is an effective weight loss intervention.

Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.

BACKGROUND: The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. METHODS: Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia. RESULTS: HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90). CONCLUSIONS: The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial.

BACKGROUND: Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care. METHODS: Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H(2)-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715. FINDINGS: 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group (euro228 vs euro245; p=0.0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste. INTERPRETATION: Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care.

Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study.

BACKGROUND: Pragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit. DISCUSSION: The first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participant's reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity. SUMMARY: It is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic--explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial.