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Although causal mediation analysis clarifies causal effect estimation, little attention has been devoted to the differences between causal estimation approaches. This paper illustrates the difference between the causal estimation approaches for mediation models with a binary mediator. Using a Monte Carlo simulation study and an empirical data example we show that the regression- and simulation-based approaches provide indirect and total effect estimates that are dependent on the chosen causal contrast, while the imputation- and weighting-based approaches provide overall effect estimates. The results underline the importance of choosing an estimation approach that provides estimates of the causal effect of interest. [ABSTRACT FROM AUTHOR]

Aim: To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. Methodology: This is a prospective case–control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed‐model analyses. Results: A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony‐stimulating factor (p <.001), interleukin (IL)‐1β (p =.03) and IL‐4 (p =.01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL‐10 (p =.03) and IL‐12p70 (p =.01). Conclusions: The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low‐grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis. [ABSTRACT FROM AUTHOR]

There is an increasing awareness that replication should become common practice in empirical studies. However, study results might fail to replicate for various reasons. The robustness of published study results can be assessed using the relatively new multiverse-analysis methodology, in which the robustness of the effect estimates against data analytical decisions is assessed. However, the uptake of multiverse analysis in empirical studies remains low, which might be due to the scarcity of guidance available on performing multiverse analysis. Researchers might experience difficulties in identifying data analytical decisions and in summarizing the large number of effect estimates yielded by a multiverse analysis. These difficulties are amplified when applying multiverse analysis to assess the robustness of the effect estimates from a mediation analysis, as a mediation analysis involves more data analytical decisions than a bivariate analysis. The aim of this paper is to provide an overview and worked example of the use of multiverse analysis to assess the robustness of the effect estimates from a mediation analysis. We showed that the number of data analytical decisions in a mediation analysis is larger than in a bivariate analysis. By using a real-life data example from the Longitudinal Aging Study Amsterdam, we demonstrated the application of multiverse analysis to a mediation analysis. This included the use of specification curves to determine the impact of data analytical decisions on the magnitude and statistical significance of the direct, indirect, and total effect estimates. Although the multiverse analysis methodology is still relatively new and future research is needed to further advance this methodology, this paper shows that multiverse analysis is a useful method for the assessment of the robustness of the direct, indirect, and total effect estimates in a mediation analysis and thereby to inform replication studies. [ABSTRACT FROM AUTHOR]

Background: Physicians' gaze towards their patients may affect patients' trust in them. This is especially relevant considering recent developments, including the increasing use of Electronic Health Records, which affect physicians' gaze behavior. Moreover, socially anxious patients' trust in particular may be affected by the gaze of the physician. Objective: We aimed to evaluate if physicians' gaze towards the face of their patient influenced patient trust and to assess if this relation was stronger for socially anxious patients. We furthermore explored the relation between physicians' gaze and patients' perception of physician empathy and patients' distress. Design: This was an observational study using eye-tracking glasses and questionnaires. Participants: One hundred patients and 16 residents, who had not met before, participated at an internal medicine out-patient clinic. Measures: Physicians wore eye-tracking glasses during medical consultations to assess their gaze towards patients' faces. Questionnaires were used to assess patient outcomes. Multilevel analyses were conducted to assess the relation between physicians' relative face gaze time and trust, while correcting for patient background characteristics, and including social anxiety as a moderator. Analyses were then repeated with perceived empathy and distress as outcomes. Results: More face gaze towards patients was associated with lower trust, after correction for gender, age, education level, presence of caregivers, and social anxiety (β=−0.17, P=0.048). There was no moderation effect of social anxiety nor a relation between face gaze and perceived empathy or distress. Conclusions: These results challenge the notion that more physician gaze is by definition beneficial for the physician-patient relationship. For example, the extent of conversation about emotional issues might explain our findings, where more emotional talk could be associated with more intense gazing and feelings of discomfort in the patient. To better understand the relation between physician gaze and patient outcomes, future studies should assess bidirectional face gaze during consultations. [ABSTRACT FROM AUTHOR]

Objectives To examine whether (a) as people age, accumulation of negative events increases ("sensitizing") or decreases ("steeling") the detrimental effects of subsequent events on depressive symptoms, and (b) how particular psychosocial factors are associated with the strength of these steeling or sensitizing effects. Method We used data from 6 measurement waves from 2,069 adults aged 55–84 (M = 68.0) at baseline in the Longitudinal Aging Study Amsterdam, the Netherlands. We included 18 different life events across the life course. Using hybrid multilevel models, we tested whether the effects of proximate life events (<3 years) on depressive symptoms (measured by the Center for Epidemiologic Studies Depression scale) were moderated by previous cumulative events (childhood until previous measurement wave). Additionally, we tested whether education, mastery, emotional support, neuroticism, having strong faith, and loneliness were associated with the strength of steeling/sensitizing effects. Results Cumulative and proximate life events were independently associated with more depressive symptoms. Interaction effects indicated that the more cumulative life events, the weaker the effects of recent life events, suggesting a "steeling" effect. Unexpectedly, 3-way interaction effects showed that higher mastery and lower neuroticism were associated with weaker steeling effects. These effects were predominantly attributable to within-person changes rather than to fixed between-person differences. Results from analyses with event severity scores were similar. Conclusions As a population, older adults appear to become more resilient against new stressors as they accumulate experience in dealing with negative life events. Findings on mastery tentatively suggest that accepting limits to one's own control over life circumstances may foster a steeling effect. [ABSTRACT FROM AUTHOR]

Background: Confounding bias is a common concern in epidemiological research. Its presence is often determined by comparing exposure effects between univariable- and multivariable regression models, using an arbitrary threshold of a 10% difference to indicate confounding bias. However, many clinical researchers are not aware that the use of this change-in-estimate criterion may lead to wrong conclusions when applied to logistic regression coefficients. This is due to a statistical phenomenon called noncollapsibility, which manifests itself in logistic regression models. This paper aims to clarify the role of noncollapsibility in logistic regression and to provide guidance in determining the presence of confounding bias.Methods: A Monte Carlo simulation study was designed to uncover patterns of confounding bias and noncollapsibility effects in logistic regression. An empirical data example was used to illustrate the inability of the change-in-estimate criterion to distinguish confounding bias from noncollapsibility effects.Results: The simulation study showed that, depending on the sign and magnitude of the confounding bias and the noncollapsibility effect, the difference between the effect estimates from univariable- and multivariable regression models may underestimate or overestimate the magnitude of the confounding bias. Because of the noncollapsibility effect, multivariable regression analysis and inverse probability weighting provided different but valid estimates of the confounder-adjusted exposure effect. In our data example, confounding bias was underestimated by the change in estimate due to the presence of a noncollapsibility effect.Conclusion: In logistic regression, the difference between the univariable- and multivariable effect estimate might not only reflect confounding bias but also a noncollapsibility effect. Ideally, the set of confounders is determined at the study design phase and based on subject matter knowledge. To quantify confounding bias, one could compare the unadjusted exposure effect estimate and the estimate from an inverse probability weighted model. [ABSTRACT FROM AUTHOR]

Aim: To analyse the effects of different propofol starting doses as premedication for endotracheal intubation on blood pressure in neonates.Methods: Neonates who received propofol starting doses of 1.0 mg/kg (n = 30), 1.5 mg/kg (n = 23) or 2.0 mg/kg (n = 26) as part of a previously published dose-finding study were included in this analysis. Blood pressure in the 3 dosing groups was analysed in the first 60 minutes after start of propofol.Results: Blood pressure declined after the start of propofol in all 3 dosing groups and was not restored 60 minutes after the start of propofol. The decline in blood pressure was highest in the 2.0 mg/kg dosing group. Blood pressure decline was mainly dependent on the initial propofol starting dose rather than the cumulative propofol dose.Conclusion: Propofol causes a dose-dependent profound and prolonged decrease in blood pressure. The use of propofol should be carefully considered. When using propofol, starting with a low dose and titrating according to sedative effect seems the safest strategy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop a prediction model for the prognosis of sick leave due to low back pain (LBP). Methods: This is a cohort study with 103 employees sick-listed due to non-specific LBP and spinal disc herniation. A prediction model was developed based on questionnaire data and registered sick leave data with follow up of 180 days. Results: At follow up 31 (30.1%) employees were still sick-listed due to LBP. Forward selection procedure resulted in a model with: catastrophizing, musculoskeletal work load, and disability. The explained variance was 27.3%, calibration was adequate and discrimination was fair with area under the ROC-curve (AUC) = 0.761 (interquartile range [IQR]: 0.755-0.770). Conclusion: The prediction model of this study can adequately predict LBP sick leave after 180 days and could be used for employees sick listed due LBP. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the relationship of hyposmia in Parkinson's disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression. [ABSTRACT FROM AUTHOR]

Background: Logistic regression is often used for mediation analysis with a dichotomous outcome. However, previous studies showed that the indirect effect and proportion mediated are often affected by a change of scales in logistic regression models. To circumvent this, standardization has been proposed. The aim of this study was to show the relative performance of the unstandardized and standardized estimates of the indirect effect and proportion mediated based on multiple regression, structural equation modeling, and the potential outcomes framework for mediation models with a dichotomous outcome.Methods: We compared the performance of the effect estimates yielded by the three methods using a simulation study and two real-life data examples from an observational cohort study (n = 360).Results: Lowest bias and highest efficiency were observed for the estimates from the potential outcomes framework and for the crude indirect effect ab and the proportion mediated ab/(ab + c') based on multiple regression and SEM.Conclusions: We advise the use of either the potential outcomes framework estimates or the ab estimate of the indirect effect and the ab/(ab + c') estimate of the proportion mediated based on multiple regression and SEM when mediation analysis is based on logistic regression. Standardization of the coefficients prior to estimating the indirect effect and the proportion mediated may not increase the performance of these estimates. [ABSTRACT FROM AUTHOR]

Background: In patients with Prader-Willi syndrome (PWS) body composition is abnormal and alterations in appetite regulating factors, bone mineral density and insulin-like growth factor-1 (IGF-1) levels have been described. Studies in PWS adults are limited. In this study, we investigated body composition, appetite regulating peptides, bone mineral density and markers of bone remodeling in an adult PWS population. Furthermore, we investigated the association between these different parameters and IGF-1 levels because of the described similarities with growth hormone deficient patients. Methods: In this cross-sectional observational cohort study in a university hospital setting we studied fifteen adult PWS patients. Anthropometric and metabolic parameters, IGF-1 levels, bone mineral density and bone metabolism were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR) was calculated. Fourteen healthy siblings served as a control group for part of the measurements. Results: In the adult PWS patients, height, fat free mass, IGF-1 and bone mineral content were significantly lower when compared to controls; body mass index (BMI), waist, waist-to-hip ratio and fat mass were higher. There was a high prevalence of osteopenia and osteoporosis in the PWS patients. Also, appetite regulating peptides and bone remodelling markers were aberrant when compared to reference values. Measurements of body composition were significantly correlated to appetite regulating peptides and high-sensitive C-reactive protein (hs-CRP), furthermore HOMA was correlated to BMI and adipokines. Conclusion: In adults with Prader-Willi syndrome alterations in body composition, adipokines, hs-CRP and bone mineral density were demonstrated but these were not associated with IGF-1 levels. Further investigations are warranted to gain more insight into the exact pathophysiology and the role of these alterations in the metabolic and cardiovascular complications seen in PWS, so these complications can be prevented or treated as early as possible. [ABSTRACT FROM AUTHOR]

Selection for higher education (HE) programs may hinder equal opportunities for applicants and thereby reduce student diversity and representativeness. However, variables which could play a role in inequality of opportunity are often studied separately from each other. Therefore, this retrospective cohort study conducts an innovative intersectional analysis of the inequality of opportunity in admissions to selective HE programs. Using a combination of multivariable logistic regression analyses and descriptive statistics, we aimed to investigate 1) the representativeness of student populations of selective HE programs, as compared to both the applicant pool and the demographics of the age cohort; 2) the demographic background variables which are associated with an applicant's odds of admission; and 3) the intersectional acceptance rates of applicants with all, some or none of the background characteristics positively associated with odds of admission. The study focused on all selective HE programs (n = 96) in The Netherlands in 2019 and 2020, using Studielink applicant data (N = 85,839) and Statistics Netherlands microdata of ten background characteristics. The results show that student diversity in selective HE programs is limited, partly due to the widespread inequality of opportunity in the selection procedures, and partly due to self-selection. Out of all ten variables, migration background was most often (negatively) associated with the odds of receiving an offer of admission. The intersectional analyses provide detailed insight into how (dis)advantage has different effects for different groups. We therefore recommend the implementation of equitable admissions procedures which take intersectionality into account. [ABSTRACT FROM AUTHOR]

Background: Comprehensive insight in the longitudinal development of health-related quality of life (HRQOL) after childhood cancer diagnosis could improve quality of care. Thus, we aimed to study the course and biopsychosocial determinants of HRQOL in a unique national cohort of children with cancer. Methods: HRQOL of 2154 children with cancer was longitudinally reported (median: 3 reports) between diagnosis and 5 years after, using the pediatric quality of life inventory generic core scales (PedsQL). HRQOL was modelled over time since diagnosis using mixed model analysis for children 2–7 years (caregiver-reports) and ≥ 8 years (self-reports). Differences in the course between hematological, solid and central nervous system malignancies were studied. Additional associations of demographics, disease characteristics (age at diagnosis, relapse, diagnosis after the national centralization of childhood cancer care and treatment components) and caregiver distress (Distress thermometer) were studied. Results: Overall, HRQOL improved with time since diagnosis, mostly in the first years. The course of HRQOL differed between diagnostic groups. In children aged 2–7 years, children with a solid tumor had most favorable HRQOL. In children aged ≥ 8 years, those with a hematological malignancy had lower HRQOL around diagnosis, but stronger improvement over time than the other diagnostic groups. In both age-groups, the course of HRQOL of children with a CNS tumor showed little or no improvement. Small to moderate associations (β: 0.18 to 0.67, p < 0.05) with disease characteristics were found. Centralized care related to better HRQOL (β: 0.25 to 0.44, p < 0.05). Caregiver distress was most consistently associated with worse HRQOL (β: − 0.13 to − 0.48, p < 0.01). Conclusions: The HRQOL course presented can aid in identifying children who have not fully recovered their HRQOL following cancer diagnosis, enabling early recognition of the issue. Future research should focus on ways to support children, especially those with a CNS tumor, for example by decreasing distress in their caregivers. [ABSTRACT FROM AUTHOR]

Background: Medically unexplained physical symptoms (MUPS) are highly prevalent and may affect work functioning. In this study we aimed to assess the longitudinal association between MUPS and work functioning over 2 years and the influence of job characteristics and depressive and anxiety disorders on this association. Methods: We assessed the longitudinal association between MUPS and work functioning, operationalized in terms of absenteeism and disability at work, in 1887 working participants from the Netherlands Study of Depression and Anxiety (NESDA). The NESDA study population included participants with a current depressive and/or anxiety disorder, participants with a lifetime risk and/or subthreshold symptoms and healthy controls. Absenteeism was assessed with the Health and Labour Questionnaire Short Form and disability with the World Health Organization Disability Assessment Schedule II. MUPS were measured with the Four Dimensional Symptom Questionnaire. Measurements were taken at baseline and at 2 years follow-up. We used mixed model analyses to correct for the dependency of observations within participants. Results: MUPS were positively associated with disability (regression coefficient 0.304; 95 % O 0.281-0.327) and with short and long-term absenteeism over 2 years (OR 1.030, 95 % CI 1.016-1.045; OR 1.099, 95 % CI 1.085-1.114). After adjusting for depressive disorders, anxiety disorders and job characteristics, associations weakened but remained significant. Conclusion: Our results show that MUPS were positively associated with disability and absenteeism over 2 years, even after adjusting for depressive and anxiety disorders and job characteristics. This suggests that early identification of MUPS and adequate management is important. [ABSTRACT FROM AUTHOR]

Background: Medically unexplained physical symptoms (MUPS) are highly prevalent and are associated with frequent health care use (HCU). MUPS frequently co-occur with psychiatric disorders. With this study we examined the longitudinal association between MUPS and HCU over 2 years and the influence of depressive and anxiety disorders and personality traits on this association.Methods: We analysed follow-up data from 2045 to 2981 participants from the Netherlands Study of Depression and Anxiety (NESDA), a multisite cohort study. The study population included participants with a current depressive and/or anxiety disorder, participants with a lifetime risk and/or subthreshold symptoms for depressive and/or anxiety disorders and healthy controls. HCU, measured with the Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness (TIC-P), was operationalized as the number of used medical services and the number of associated contacts. MUPS were measured with the Four Dimensional Symptoms Questionnaire, depressive and anxiety disorders with the Composite International Diagnostic Interview and personality traits with the NEO Five-Factory Inventory. Measurements were taken at baseline, 1 and 2 years follow-up. We used generalized estimating equations (GEE), using HCU at all three measurements as (multivariate) outcome. GEE also takes into account the dependency of observations within participants.Results: MUPS were positively associated with HCU over 2 years (medical services: RR 1.020, 95 % CI 1.017-1.022; contacts: RR 1.037, 95 % CI 1.030-1.044). Neuroticism and depression had the strongest influence on the associations. After adjustment for these factors, the associations between MUPS and HCU weakened, but remained significant (services: RR 1.011, 95 % CI 1.008-1.014; contacts: RR 1.023, 95 % CI 1.015-1.032).Conclusions: Our results show that MUPS were positively associated with HCU over 2 years, even after adjusting for depressive and anxiety disorders and personality traits. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate a novel method for dealing with incomplete scale scores in longitudinal data that result from missing item responses. This method includes item information as auxiliary variables, which is advantageous because it incorporates the observed item-level data while maintaining the scale scores as the focus of the analysis. These auxiliary variables do not change the analysis model, but improve missing data handling. The investigated novel method uses the item scores or some summary of a parcel of item scores as auxiliary variables, while treating the scale scores missing in a latent growth model. The performance of these methods was examined in several simulated longitudinal data conditions and analyzed through bias, mean square error, and coverage. Results show that including the item information as auxiliary variables results in rather dramatic power gains compared with analyses without auxiliary variables under varying conditions. [ABSTRACT FROM PUBLISHER]

Aims Worldwide levels of daily physical activity (PA) in children are low. This has negative health consequences. Schools have been recognised as key settings to promote PA. This study evaluates the effectiveness of the playground programme PLAYgrounds on increasing PA. Methods PLAYgrounds was evaluated by a controlled trial, with a follow-up during one school year (10 months). Accelerometer data were collected on 1500 children in total, divided over 19 sampling moments (every 2 weeks). SOPLAY data were collected at nine sampling moments (once a month). Four intervention and four control schools were matched for playground size, number of pupils and PA levels at baseline. The intervention consisted of restructuring the playground by playground markings and by encouragement of the active use of the playground, through the provision of play equipment and educational measures such as adult encouragement and supporting physical education classes. Multilevel regression analyses were performed to analyse the effects of the intervention. Results PA levels in the intervention group (moderate PA) were significantly different (p<0.001) from the control group (light PA). During the intervention on an average 77.3% of the children engaged in moderate-to-vigorous physical activity in the intervention group and 38.7% in the control group. The effect of the intervention was significantly stronger for girls than for boys (p<0.001). Conclusions The PLAYgrounds programme was effective in increasing PA levels in children during recess over the course of one school year. Thus, the programme could be used to provide structured PA promotion. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the longitudinal associations of person-related factors with physical activity (PA) behavior in young adults. Methods: We analyzed longitudinal self-reported time spent in moderate-intensity PA (MPA; 4-7 METs) and vigorous-intensity PA (VPA; >7 METs) from 499 young adults (49% male) who participated in the Amsterdam Growth and Health Longitudinal Study at the age of 21, 27, 32, and 36 yr. Sociodemographic factors (i.e., marital and employment status), physical factors (i.e., skinfolds, aerobic fitness, neuromotor fitness, back problems, and general health status), psychological factors (i.e., problem and emotion focused coping, mild health complaints, and personality), and behavioral factors (i.e., alcohol consumption, smoking, and energy intake) were assessed at each time point. We performed sex-specific univariable and multivariable generalized estimating equations. Results: Men and women with higher aerobic fitness were more moderately and vigorously active. Not having paid work was associated with more MPA in both men and women. Men with part-time paid work, lower scores on dominance, higher scores on hostility, and above moderate alcohol consumption (i.e., ≥140 g of alcohol per week) were more moderately active. Divorced women and those with better physical flexibility spent more time in MPA. Men having full-time paid work, with a good general health status and nonsmokers, were more vigorously active. Women being married/living together, who had better physical flexibility, lower scores on inadequacy, higher scores on dominance, and low caloric intake (around 2000 kcal•d-1) were more vigorously active. Conclusion: Several sociodemographic, physical, psychological, and behavioral factors were associated with PA in Dutch young adults. Determinants were different for MPA and VPA and for men and women. [ABSTRACT FROM AUTHOR]

Background Sitting is associated with health risks. Factors that influence sitting are however not well understood. The aim was to examine the biological, socio-demographic, work-related and lifestyle determinants of sitting time (including during transport, work and leisure) in young adult Australian women. Methods Self-reported data from 11,676 participants (aged 22-27 years in 2000) in the Australian Longitudinal Study on Women's Health were collected over 9 years in 2000, 2003, 2006 and 2009. Generalised Estimating Equations were used to examine univariable and multivariable associations of body mass index (BMI), country of birth, area of residence, education, marital status, number of children, occupational status, working hours, physical activity, smoking, alcohol intake and stress with week- and weekend-day sitting time. Results Compared with women in the respective referent categories, (1) women with higher BMI, those born in Asia, those with less than University level education, doing white collar work, working 41-48 hours a week, current smokers, non, rare or risky/ high risk drinkers and those being somewhat stressed had significantly higher sitting time; and (2) women living in rural and remote areas, partnered women, those with children, those without a paid job and blue collar workers, those working less than 34 hours a week, and active women had significantly lower sitting time. Conclusions Among young adult Australian women, those with higher BMI, those born in Asia, those with higher level occupations and long working hours, were most at risk of higher sitting time. These results can be used to identify at-risk groups and inform intervention development. [ABSTRACT FROM AUTHOR]

Background: When study data are clustered, standard regression analysis is considered inappropriate and analytical techniques for clustered data need to be used. For prediction research in which the interest of predictor effects is on the patient level, random effect regression models are probably preferred over standard regression analysis. It is well known that the random effect parameter estimates and the standard logistic regression parameter estimates are different. Here, we compared random effect and standard logistic regression models for their ability to provide accurate predictions. Methods: Using an empirical study on 1642 surgical patients at risk of postoperative nausea and vomiting, who were treated by one of 19 anesthesiologists (clusters), we developed prognostic models either with standard or random intercept logistic regression. External validity of these models was assessed in new patients from other anesthesiologists. We supported our results with simulation studies using intra-class correlation coefficients (ICC) of 5%, 15%, or 30%. Standard performance measures and measures adapted for the clustered data structure were estimated. Results: The model developed with random effect analysis showed better discrimination than the standard approach, if the cluster effects were used for risk prediction (standard c-index of 0.69 versus 0.66). In the external validation set, both models showed similar discrimination (standard c-index 0.68 versus 0.67). The simulation study confirmed these results. For datasets with a high ICC (⩾15%), model calibration was only adequate in external subjects, if the used performance measure assumed the same data structure as the model development method: standard calibration measures showed good calibration for the standard developed model, calibration measures adapting the clustered data structure showed good calibration for the prediction model with random intercept. Conclusion: The models with random intercept discriminate better than the standard model only if the cluster effect is used for predictions. The prediction model with random intercept had good calibration within clusters. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively assess the clinical performance and patient‐reported outcomes of dental implants in dentate patients with primary and secondary Sjögren's syndrome (pSS and sSS, respectively) compared to patients without SS. Materials and Methods: Thirty‐seven implants were placed in 17 patients with pSS/sSS and 26 implants in 17 non‐SS patients to replace missing (pre)molars. Clinical performance, marginal bone‐level changes, patient satisfaction, and oral health‐related quality of life (OHRQoL) were assessed at 1 (T1), 6 (T6), 12 (T12), and 18 (T18) months after placement of the superstructure. Marginal bone‐level changes were measured on standardized dental radiographs. Clinical parameters included implant and crown survival, plaque, bleeding and gingival indices, and probing depth. Patient satisfaction and OHRQoL were assessed with validated questionnaires. Results: Implant survival at T18 was 100% in the patients with pSS/sSS and 96.2% in the non‐SS group. Mean marginal bone loss at T18 did not differ between patients with pSS/sSS and non‐SS patients, 1.10 ± 1.04 and 1.04 ± 0.75 mm, respectively (p =.87). Clinical performance was good with no differences between the groups for all outcome measures (p >.05). OHRQoL in patients with pSS/sSS had improved significantly after placement of implant supported crowns at all measuring moments compared to baseline (p <.05). Nevertheless, patient satisfaction and OHRQoL remained significantly higher for patients without SS at all measuring moments (p <.05). Conclusion: Dental implants can be successfully applied in dentate patients with pSS/sSS and have a positive effect on OHRQoL. [ABSTRACT FROM AUTHOR]

This study is part of the Amsterdam Growth and Health Longitudinal Study, which was undertaken to assess the long-term interrelationships between cumulative frequency of geographic relocation (CFGR) and the development of personality characteristics (i.e., Inadequacy, Rigidity, Social Inadequacy, Dominance, Self-sufficiency, Self-esteem, and Hostility). We found that participants who had more mobility experiences had lower consistency in their personality characteristics (the exception being Rigidity). Residential mobility from different life stages was positively associated with the continuity and change of Inadequacy and Dominance. In addition, young adults with higher Rigidity personality experienced fewer geographic moves during the transition from young adulthood to mid-life. Our study provides evidence that CFGR in different life stages may be associated with the development of personality characteristics from young adulthood to mid-life in different ways. Increased awareness of the potential interrelationships between frequent geographic relocation and personality development may have positive consequences for adult psychological health. [ABSTRACT FROM AUTHOR]

Background: Recently, a three-item screener, derived from the 16-item distress scale of the Four-Dimensional Symptom Checklist (4DSQ), was used to measure psychological distress in sicklisted employees. The aim of the present study was to investigate the ability of the 16-item distress scale and three-item distress screener to identify non-sicklisted employees at risk of sickness absence (SA) due to mental disorders. Methods: Prospective cohort study including 4877 employees working in distribution and transport. The 4DSQ distress scale was distributed at baseline in November 2010. SA diagnosed within the International Classification of Diseases -10 chapter F was defined as mental SA and retrieved from an occupational health register during 2-year follow-up. The area under the receiver operating characteristic curve (AUC) was used to discriminate between workers with ('cases') and without ('non-cases') mental SA during follow-up. Results: A total of 2782 employees (57%) were included in complete cases analysis; 73 employees had mental SA during 2-year follow-up. Discrimination between cases and non-cases was similar for the 16-item distress scale (AUC =0.721; 95% CI, 0.622-0.823) and the three-item screener (AUC = 0.715; 95% CI, 0.615-0.815). Conclusion: Healthcare providers could use the three-item distress screener to identify non-sicklisted employees at risk of future mental SA. [ABSTRACT FROM AUTHOR]

Background: In 1992 a cargo aircraft crashed into apartment buildings in Amsterdam. In the troublesome aftermath rumours emerged on potential toxic exposures and health consequences. The aim of this study is to assess the long-term impact of this disaster on the health-related quality of life (HRQoL) of professional assistance workers.Methods: Historic cohort study, using questionnaires to assess occupational disaster exposure, HRQoL (SF36), and background variables, at on average 8.5 years post-disaster. Participating were the exposed professional firefighters (n = 334) and police officers (n = 834) who reported disaster-related task(s), and their non-exposed colleagues who did not report such tasks (n = 194, and n = 634, respectively).Results: Multivariate logistic regression analysis showed that exposed workers reported a significantly lower physical HRQoL and vitality than non-exposed workers. Exposed police officers also reported a lower mental HRQoL. Among exposed workers, a lower HRQoL was reported significantly more often by workers who had a close one affected by the disaster; by firefighters who rescued people, cleaned-up, or witnessed the immediate disaster scene; and by police officers who supported the injured. Exposed police officers who perceived the disaster as 'not bad' reported a lower HRQoL less often than those to whom it was 'the worst ever'.Conclusions: This study demonstrates that professional disaster assistance workers are at risk for a lower HRQoL, even after years. [ABSTRACT FROM AUTHOR]

The article presents clinical research on the temporal relationship between an enlarged jugular lymphatic sac and increased nuchal translucency thickness in fetuses. Ultrasonography was conducted on the neck region of 34 aneuploid fetuses and 40 euploid fetuses. Weekly examinations were conducted between 11 and 17 weeks of gestational age.

Objectives. We evaluated the effectiveness of a minimal intervention physical activity strategy (physician-based assessment and counseling for exercise [PACE]) applied in general practice settings in the Netherlands. Methods. Randomization took place at the general practice level. Participants were patients aged 18-70 years of age who had been diagnosed with hypertension, hypercholesterolemia, or non-insulin-dependent diabetes and had not been regularly physically active in the past 6 months. Outcome measures were assessed at baseline and at 8-week, 6-month, and 1-year follow-ups. Results. No significant intervention effect over time was observed on physical activity level or stage of change for regular physical activity, and an inverse intervention effect was observed for waist circumference. However, the study population as a whole exhibited a significant increase in physical activity and a borderline significant decrease in body weight at the 1-year follow-up. Conclusions. Positive effects on physical activity level and body weight were observed, but the PACE intervention was not more effective than the standard physical activity advice. (Am J Public Health. 2005;95:1825-1831.) [ABSTRACT FROM AUTHOR]

Study objective: The purpose of this paper is to give an overview and comparison of different easily applicable statistical techniques to analyse recurrent event data. Setting: These techniques include naive techniques and longitudinal techniques such as Cox regression for recurrent events, generalised estimating equations (GEE), and random coefficient analysis. The different techniques are illustrated with a dataset from a randomised controlled trial regarding the treatment of lateral epicondylitis. Main results: The use of different statistical techniques leads to different results and different conclusions regarding the effectiveness of the different intervention strategies. Conclusions: if you are interested in a particular short term or long term result, simple naive techniques are appropriate. However, if the development of a particular outcome is of interest, statistical techniques that consider the recurrent events and additionally corrects for the dependency of the observations are necessary. [ABSTRACT FROM AUTHOR]

This study examines the associations between transitions in paid home care and stress appraisals and psychological well-being of family caregivers of dementia relatives. The sample consisted of 264 caregivers who completed up to 3 interviews during 1 year. Longitudinal analyses (i.e., generalized estimating equations) showed that the onset of paid home care was associated with increases in feelings of worry and strain and a worsening in positive affect. Ending paid home care was strongly associated with a decrease in depressive symptoms, whereas sustained use of paid home care was related to reduced overload. Several possible mechanisms for the complex relationship of paid home care and family caregivers' stress appraisals and well-being are discussed. [ABSTRACT FROM AUTHOR]

Background Among young adults, the metabolic syndrome is an increasingly frequent risk factor for cardiovascular disease. Its determinants are, however, incompletely understood. We investigated the time course, from adolescence (age, 13 years) to young adulthood (age, 36 years), of important potential determinants (body fatness and fat distribution, cardiopulmonary fitness, and lifestyle) in 364 individuals (189 women). Methods Data were derived from the Amsterdam Growth and Health Longitudinal Study and analyzed with the use of generalized estimating equations. Results The prevalence of the metabolic syndrome at the age of 36 years, as identified with a modified National Cholesterol Education Program definition of the syndrome, was 10.4%. Subjects with the metabolic syndrome at the age of 36 years, compared with those without the syndrome, had (from adolescence to the age of 36 years) the following: (1) a more marked increase in total body fatness and in subcutaneous trunk fat; (2) a more marked decrease in cardiopulmonary fitness levels; (3) a more marked increase in physical activities of light-to-moderate intensity, but a more marked decrease in hard physical activities; (4) a trend toward a higher energy intake throughout the years; and (5) a decreased likelihood of drinking alcoholic beverages. Conclusions Fatness, fitness, and lifestyle are important determinants of the metabolic syndrome in young adults. More important, these associations were independent of each other and, therefore, represent separate potential targets for the prevention of the metabolic syndrome. Our study further suggests that intervening early in life (eg, in the period of transition from adolescence to adulthood) may be a fruitful area for prevention of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the agreement between self-reported tobacco consumption and NicCheck 1® (Dynagen Inc. Cambridge, Mass., USA) regarding smoking status and nicotine intake in a population of smokers (20.8%) and non-smokers. NicCheck 1 is a dipstick that changes colour in the presence of urinary nicotine metabolites. Smoking was assessed by self-report and NicCheck 1 in 169 males and 191 females (mean age 36.0 SD 0.7). Self-report and NicCheck 1 agreed highly on smoking status, especially in moderate to heavy smokers. With regard to nicotine intake, there was a large overlap in self-reported tobacco consumption between NicCheck 1 levels, despite a relatively high correlation coefficient between self-report and NicCheck 1 in smokers (i.e. 0.74). No effect modification by gender or BMI was found. When both methods were validated against two blood lipid parameters, self-report seemed to do equally well as NicCheck 1 in assessing nicotine intake. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Little is known regarding the association between smoking and quantitative ultrasound (QUS) parameters. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) are believed to provide information on bone quality besides information on bone mineral density (BMD). The aim of this study was to investigate (1) current tobacco smoking; (2) lifetime tobacco smoking; and (3) years since smoking cessation, in relation to QUS and BMD parameters in 36-year-old men and women. Data came from the ninth measurement of the Amsterdam Growth and Health Longitudinal Study (AGAHLS), in which 165 men (36 smokers and 129 nonsmokers) and 178 women (33 smokers and 145 nonsmokers) participated, with an average age of 36 years (SD=0.7). BUA (dB/MHz) and SOS (m/s) of the calcaneus were assessed by using the CUBA Clinical instrument. BMD of the lumbar spine (L1–L4), total hip, and total body were measured with dual-energy X-ray absorptiometry (DXA). We used multiple linear regression analyses with correction for body weight, physical activity, calcium intake, and alcohol consumption. We found no significant associations between smoking and any of the BMD parameters in 36-year-old men and women. However, both current and lifetime tobacco smoking were significantly and negatively associated with BUA in women but not in men. Lifetime tobacco smoking was significantly and negatively associated with SOS in both sexes. The latter association was independent of body weight, calcium intake, physical activity, and alcohol consumption in women, but not in men. Our results suggest that both current and lifetime tobacco smoking are associated with a deterioration in bone quality but not with a reduction in BMD. However, since BMD parameters and QUS parameters were not measured at the same sites, our results may also simply suggest that the calcaneus is affected by smoking at an earlier stage than the lumbar spine, hip, and total body. [ABSTRACT FROM AUTHOR]

Little is known on the diagnostic characteristics of brief questionnaires on alcohol drinking behaviors. This report investigates the determinants of three short alcohol questionnaires and investigates their diagnostic utility as screening tools for alcohol-related problems in a general population from The Netherlands. This report uses cross-sectional data obtained in the year 2000 from 36-year-old healthy male (N = 166) and female (N = 165) volunteers who reported to drink alcohol at least occasionally. Since they were 13-years-old these volunteers have been members of the Amsterdam Growth And Health Longitudinal Study, which started as a school-based study in 1977. Among many other variables, quantity–frequency questions (QF), the CAGE questionnaire, and a question on the highest number of alcoholic units consumed on one occasion during the previous month (MAX) were asked. The sensitivity, specificity, Cohen's kappa, and diagnostic odds ratio of QF, CAGE, MAX, and combinations of these three brief questionnaires were calculated using a 7-item questionnaire on alcohol-related problems as reference. Both in women and men, the prevalence of most alcohol-related problems and of a high QF, CAGE, and MAX was low. QF, CAGE, and MAX, as well as all possible combinations of the three questionnaires, were poor in detecting last-year alcohol-related problems. The CAGE appeared to perform worse than the even shorter and easier-to-interpret QF and MAX. In this healthy population of 36-year-old men and women, using the QF, MAX, and especially the CAGE questionnaire as screening instruments for alcohol-related problems resulted in many false positive and false negative classifications. [ABSTRACT FROM AUTHOR]

The results of recent epidemiological studies suggest that birth weight is related to adult bone mineral status. Since birth weight might also be related to muscle strength and fat-free mass, which are important determinants of bone health, the aim of this study was to investigate the following: is birth weight related to bone mineral content (BMC) and bone mineral density (BMD) at the lumbar level, at the hip and of the total body, and to structural properties of the heel bone, to fat-free mass (FFM) and to muscle strength, at the age of 36 years? Two hundred and eighty-two subjects (162 women) underwent dual X-ray absorptiometry (DEXA) measurement for the assessment of BMC and BMD at different sites and the FFM and/or measurement of the structural properties of the heel bone, which were estimated with speed of sound (H-SOS) and broadband ultrasound attenuation. Muscle strength was assessed with two fitness tests (static arm-pull, and high jump). Information on birth weight was gathered by means of a questionnaire. The data were analyzed by application of multiple linear regression. Birth weight was positively related to FFM. In a crude model, birth weight was found to be positively associated with BMC, but not after adjustment for adult body weight. No significant associations were found between birth weight and muscle strength or birth weight and BMD. Furthermore, birth weight was inversely related to H-SOS. No other relationships were observed. Results support the fetal origins hypothesis that lower birth weight is related to lower BMC and FFM, but not that birth weight is associated with BMD and muscle strength. Furthermore, FFM was not identified as a link between birth weight and musculoskeletal health. [ABSTRACT FROM AUTHOR]

Objective: Better understanding of the relationship between pain and depression in older adults in the community is of particular importance considering the high prevalence of both conditions in these adults. In the present study, the longitudinal relationship between pain and depression in older adults was examined, thereby taking into account the role of physical disability and the possibly modifying effect of sex and age.Methods: The study is based on a sample which at the outset consisted of 325 non-depressed and 327 depressed persons (55-85) drawn from a larger random community-based sample in the Netherlands. Depression (CES-D) and pain (subscale of the Nottingham Health Profile) were measured at eight successive waves over 3 years.Results: Pain was very persistent over time as was to a lesser extent depression. The prognosis of comorbid pain and depression was poor. In longitudinal analyses (Generalized Estimating Equations), pain and depression were strongly associated. At the symptom level, the pain-depression relationship was found to be stronger in men than in women. There was no effect of age on the pain-depression relationship. No support was found for the hypothesis that the pain-depression relationship is mediated by disability.Conclusion: The persistent nature of pain and to a lesser extent depression and the intimate and probably reciprocal association between them stress the need for adequate treatment strategies. [ABSTRACT FROM AUTHOR]

Aims. To investigate the relative validity of retrospectively calculated pack-years (py-retro) by comparing py-retro with prospectively calculated pack-years (py-pro). Design. A 23-year ongoing cohort study (1977-2000). Participants. One hundred and fifty-four males and females, 13 years old in 1977 and 36 years old in 2000. Setting. Amsterdam, the Netherlands. Measurements. To calculate py-pro, current smoking and quitting efforts were investigated nine times in a period of 23 years with the help of an interview or a questionnaire. At the age of 36, subjects filled out a comprehensive questionnaire about their smoking history, to calculate py-retro. Individual differences between py-pro and py-retro were calculated. In addition, Cohen's kappa was calculated after categorising py-pro and py-retro into three groups. Findings. (1) Py-retro does not under- or overestimate life-time tobacco smoking. (2) The relative validity of py-retro was moderate due to large individual differences between py-pro and py-retro. (3) The individual differences between py-pro and py-retro became larger, the higher the number of pack-years. (4) Mean difference (and 95% limits of agreement) between py-pro and py-retro was -0.039 (-5.23, 5.32) when average pack-years was <5.2 and -1.17 (-10.00, 14.65) when pack-years ≥5.2. 5. Cohen's kappa between categorized py-pro and py-retro was 0.79. Conclusions. Future researchers in the field of smoking should be aware of the moderate relative validity of py-retro. Categorizing py-retro into smoking groups results in a misclassification error that is smaller than the quantitative error in continuous py-retro, but goes together with a loss of information. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse longitudinal relationships between resting heart rate and biological risk factors for cardiovascular disease using data from the longitudinal Amsterdam Growth and Health Study (AGHS). In the AGHS, 98 females and 81 males were measured six times between 1977 and 1991. In 1977, the age of the subjects was 13 years. The variables assessed included resting heart rate, diastolic and systolic blood pressure, high-density serum lipoprotein, total serum cholesterol, the sum of four skinfolds, cardiopulmonary fitness (VO 2 max), habitual physical activity and smoking history. To investigate the longitudinal relationships between resting heart rate and diastolic blood pressure, systolic blood pressure, high-density serum lipoprotein, total serum cholesterol, sum of four skinfolds and V O 2 max, generalized estimating equations were used, leading to one standardized longitudinal regression coefficient (beta). Significant univariate relationships were found between resting heart rate and diastolic blood pressure (beta = 0.142; P = 0.00), systolic blood pressure (beta = 0.134; P = 0.00), VO 2 max (beta = -0.091; P = 0.00) and sum of four skinfolds (beta = 0.047; P = 0.021). The relationships between resting heart rate and diastolic blood pressure, systolic blood pressure and VO 2 max did not change substantially when corrected for habitual physical activity and smoking history. The relationship between resting heart rate and sum of four skinfolds was no longer found to be significant when corrected for habitual physical activity and smoking history. For these relationships, no interaction between resting heart rate and sex was found. [ABSTRACT FROM AUTHOR]

Concerns exist about the role of selection in the lack of diversity in health professions education (HPE). In The Netherlands, the gradual transition from weighted lottery to selection allowed for investigating the variables associated with HPE admission, and whether the representativeness of HPE students has changed. We designed a retrospective multi-cohort study using Statistics Netherlands microdata of all 16-year-olds on 1 October 2008, 2012, and 2015 (age cohorts, N > 600,000) and investigated whether they were eligible students for HPE programs (n > 62,000), had applied (n > 14,000), and were HPE students at age 19 (n > 7500). We used multivariable logistic regression to investigate which background variables were associated with becoming an HPE student. HPE students with ≥1 healthcare professional (HP) parent, ≥1 top-10% income/wealth parent, and women are overrepresented compared to all age cohorts. During hybrid lottery/selection (cohort-2008), applicants with ≥1 top-10% wealth parent and women had higher odds of admission. During 100% selection (cohort-2015) this remained the case. Additionally, applicants with ≥1 HP parent had higher odds, those with a migration background had lower odds. Odds of admission are increasingly influenced by applicants' backgrounds. Targeted recruitment and equitable admissions procedures are required to increase matriculation of underrepresented students. [ABSTRACT FROM AUTHOR]

Objective: We investigated methotrexate safety and the influence of dose on efficacy outcomes in combination with three different biologic treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). Methods: This post hoc analysis included 812 treatment‐naïve patients with early RA who were randomized (1:1:1:1) in the NORD‐STAR trial to receive methotrexate in combination with ACT, certolizumab‐pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment. Results: Compared with ACT, the prevalence of methotrexate‐associated side effects was higher when methotrexate was combined with tocilizumab (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.20–1.84) but not with certolizumab‐pegol (HR 0.99, 95% CI 0.79–1.23) or with abatacept (HR 0.93, 95% CI 0.75–1.16). With ACT as the reference, the methotrexate dose was significantly lower when used in combination with tocilizumab (β −4.65, 95% CI −5.83 to −3.46; P < 0.001) or abatacept (β −1.15, 95% CI −2.27 to −0.03; P = 0.04), and it was numerically lower in combination with certolizumab‐pegol (β −1.07, 95% CI −2.21 to 0.07; P = 0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations. Conclusion: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/wk, and these were more frequent in combination with tocilizumab versus ACT. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks. [ABSTRACT FROM AUTHOR]

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose–response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5–13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose–response curves were examined. Mixed model analysis showed positive linear dose–response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73–88%) children, but not all, showed positive linear dose–response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose–response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose–response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121). [ABSTRACT FROM AUTHOR]

Background When resources are limited, occupational health survey participants are usually invited to consultations based on an occupational health provider's subjective considerations. This study aimed to find health survey participants at risk of long-term (i.e. ≥ 42 consecutive days) sickness absence (LTSA) for consultations with occupational health providers (OHPs). Methods The data of 64 011 non-sicklisted participants in occupational health surveys between 2010 and 2015 were used for the study. In a random sample of 40 000 participants, 27 survey variables were included in decision tree analysis (DTA) predicting LTSA at 1-year follow-up. The decision tree was transferred into a strategy to find participants for OHP consultations, which was then tested in the remaining 24 011 participants. Results In the development sample, 1358 (3.4%) participants had LTSA at 1-year follow-up. DTA produced a decision tree with work ability as first splitting variable; company size and sleep problems were the other splitting variables. A strategy differentiating by company size would find 75% of the LTSA cases in small (≤99 workers) companies and 43% of the LTSA cases in medium-sized (100–499 workers) companies. For large companies (≥500 workers), case-finding was only 25%. Conclusions In small and medium-sized companies, work ability and sleep problems can be used to find occupational health survey participants for OHP consultations aimed at preventing LTSA. Research is needed to further develop a case-finding strategy for large companies. [ABSTRACT FROM AUTHOR]

Worrisome sexual behavior (WSB) is often described as an outcome specific to child sexual abuse (CSA). Therefore, it is highly relevant to study WSB in relation to sexual abuse, especially in very young children, as it is hard to recognize sexual abuse in children who have limited verbal capacities of disclosing. Over time, literature describing WSB following CSA has gradually broadened. However, a gap remains regarding the long-term development of WSB in children who were sexually abused during infancy or very early childhood. To our knowledge, our study is the first to examine developmentally-related sexual behavior versus sexual abuse-specific behavior longitudinally in children who were sexually abused at a very young age. In total, we examined the sexual behavior, as reported by parents of 45 children who experienced early-age sexual abuse for a period of more than five years. Overall, we found that WSB is likely to be a CSA-specific and potentially long-term outcome for children who were sexually abused at a very young age. Despite the decrease in sexual abuse-specific behavior over time, the level of this behavior was still significantly high 8 years after the sexual abuse. This finding supports long-term monitoring and assessment and intervention for WSB over time. Despite these findings, it is important to note that WSB does not serve as proof of sexual abuse in children; likewise, when a child does not present with WSB, it does not indicate the absence of a substantiated history of sexual abuse. [ABSTRACT FROM AUTHOR]

Study Question: Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs.Summary Answer: Reproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs; fewer ongoing pregnancies and live births are achieved with a prolonged time to a live birth.What Is Known Already: The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance.Study Design, Size, Duration: This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8-12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization.Participants/materials, Setting, Methods: Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Additionally, the medical files of all participants were reviewed. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded.Main Results and the Role Of Chance: In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value <0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups.Limitations, Reasons For Caution: In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol; the influence of IUAs on reproductive outcome may therefore be underestimated. Women undergoing a recurrent D&C for miscarriage were included, a specific group likely to generate clinically significant adhesions. The findings should therefore not be generalized to all women undergoing D&C for miscarriage.Wider Implications Of the Findings: As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered.Study Funding/competing Interest(s): The original PAPA study (NTR 3120) was an investigator initiated study that was funded by the Foundation for scientific investigation in Obstetrics and Gynaecology of the Saint Lucas Andreas Hospital (currently renamed OLVG Oost), SWOGA. The syringes containing ACP gel were received from Anika Therapeutics, the manufacturer of Hyalobarrier® Gel Endo. The current follow-up study was also an investigator-initiated study without funding. The funder and sponsor had no role in the design of this follow-up study, data collection, data analysis, data interpretation, trial design, patient recruitment, writing of the report or any aspect pertinent to the study. ABH, RAL, JAFH and JWRT have no conflict to declare. HAMB reports being a member of safety board research Womed.Trial Registration Number: Netherlands Trial Register NTR 3120. [ABSTRACT FROM AUTHOR]

Purpose: Since food banks have a strong influence on recipients' diets, and seem to have difficulties in supporting healthy diets, improving the dietary quality of food parcels is important. The aim of our study was to assess whether improving the dietary quality of food parcels, using different strategies, can positively impact the actual dietary intake of Dutch food bank recipients. Methods: This randomized cross-over controlled trial (Trial ID: ISRCTN40554133) with four intervention conditions [(1) Control (standard food parcel), (2) snacks– (standard food parcel with replacement of unhealthy snacks by staple foods), (3) FV+ (standard food parcel plus the recommended daily amount of fruit and vegetables), (4) snacks– + FV+ (standard food parcel with replacement of unhealthy snacks by staple foods plus the recommended daily amount of fruit and vegetables)] included 163 food bank recipients, from three food banks. At baseline, participants filled in a questionnaire. Dietary intake data were collected through 24-h recalls after both intervention conditions at 4 and 8 weeks follow-up. Primary outcome was daily fruit and vegetable intake, secondary outcomes were daily dietary intakes of food groups and nutrients. Results: Multi-level linear regression analysis, using a two-level model, showed a higher mean daily fruit intake in participants in the FV+ condition than in participants in the Control condition (delta (δ): 74 [40.3;107.6] g). Both mean daily fruit and vegetable intake were higher in participants in the Snacks– + FV+ condition than in participants in the Control condition (fruit δ: 81.3 [56.5;106.2] g; vegetables δ: 46.2 [17.5;74.9] g), as well as in the Snacks– condition (fruit δ: 70.0 [38.8;101.1] g; vegetables δ: 62.2 [26.2; 98.2] g). Conclusions: This study shows that improving the dietary quality of food parcels can positively impact the dietary intake of Dutch food bank recipients. With this information we can further develop effective strategies that can be easily applied by food banks, to improve dietary intake of food bank recipients. [ABSTRACT FROM AUTHOR]

Purpose: A previously developed prediction model and decision tree were externally validated for their ability to identify occupational health survey participants at increased risk of long-term sickness absence (LTSA) due to mental disorders. Methods: The study population consisted of N = 3415 employees in mobility services who were invited in 2016 for an occupational health survey, consisting of an online questionnaire measuring the health status and working conditions, followed by a preventive consultation with an occupational health provider (OHP). The survey variables of the previously developed prediction model and decision tree were used for predicting mental LTSA (no = 0, yes = 1) at 1-year follow-up. Discrimination between survey participants with and without mental LTSA was investigated with the area under the receiver operating characteristic curve (AUC). Results: A total of n = 1736 (51%) non-sick-listed employees participated in the survey and 51 (3%) of them had mental LTSA during follow-up. The prediction model discriminated (AUC = 0.700; 95% CI 0.628–0.773) between participants with and without mental LTSA during follow-up. Discrimination by the decision tree (AUC = 0.671; 95% CI 0.589–0.753) did not differ significantly (p = 0.62) from discrimination by the prediction model. Conclusion: At external validation, the prediction model and the decision tree both poorly identified occupational health survey participants at increased risk of mental LTSA. OHPs could use the decision tree to determine if mental LTSA risk factors should be explored in the preventive consultation which follows after completing the survey questionnaire. [ABSTRACT FROM AUTHOR]

Background: Foot problems are highly prevalent in patients with rheumatoid arthritis. Treatment of foot problems related to rheumatoid arthritis often consists of custom made foot orthoses. One of the assumed working mechanisms of foot orthoses is redistribution of plantar pressure by creating a larger weight bearing area. Overall, the reported treatment effect of foot orthoses on foot pain in rheumatoid arthritis is small to medium. Therefore, we developed a foot orthoses optimization protocol for evaluation and adaptation of foot orthoses by using the feedback of in-shoe plantar pressure measurements. The objectives of the present study were: 1) to evaluate the 3-months outcomes of foot orthoses developed according to the protocol on pain, physical functioning and forefoot plantar pressure in patients with foot problems related to rheumatoid arthritis, and 2) to determine the relationship between change in forefoot plantar pressure and change in pain and physical functioning.Methods: Forty-five patients with foot problems related to rheumatoid arthritis were included and received foot orthoses developed according to the protocol. Outcome measures were assessed at baseline and after three months of wearing foot orthoses in 38 patients. Change scores and effect sizes (ES) were calculated for pain, physical functioning and plantar pressure. In a subgroup of patients with combined forefoot pain and high plantar pressure, the relationship between change in plantar pressure and change in pain and physical functioning was analyzed.Results: In the total group of 38 patients, statistically significant changes in pain (ES 0.69), physical functioning (ES 0.82) and forefoot plantar pressure (ES 0.35) were found. In the subgroup (n = 23) no statistically significant relationships were found between change in plantar pressure and change in pain or physical functioning.Conclusion: Foot orthoses developed according to a protocol for improving the plantar pressure redistribution properties lead to medium to large improvements in pain and physical functioning. The hypothesis that more pressure reduction would lead to better clinical outcomes could not be proven. [ABSTRACT FROM AUTHOR]

Background: To enable successful inclusion of electroencephalography (EEG) outcome measures in Alzheimer's disease (AD) clinical trials, we retrospectively mapped the progression of resting-state EEG measures over time in amyloid-positive patients with mild cognitive impairment (MCI) or dementia due to AD. Methods: Resting-state 21-channel EEG was recorded in 148 amyloid-positive AD patients (MCI, n = 88; dementia due to AD, n = 60). Two or more EEG recordings were available for all subjects. We computed whole-brain and regional relative power (i.e., theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-13 Hz), beta (13-30 Hz)), peak frequency, signal variability (i.e., theta permutation entropy), and functional connectivity values (i.e., alpha and beta corrected amplitude envelope correlation, theta phase lag index, weighted symbolic mutual information, inverted joint permutation entropy). Whole-group linear mixed effects models were used to model the development of EEG measures over time. Group-wise analysis was performed to investigate potential differences in change trajectories between the MCI and dementia subgroups. Finally, we estimated the minimum sample size required to detect different treatment effects (i.e., 50% less deterioration, stabilization, or 50% improvement) on the development of EEG measures over time, in hypothetical clinical trials of 1- or 2-year duration. Results: Whole-group analysis revealed significant regional and global oscillatory slowing over time (i.e., increased relative theta power, decreased beta power), with strongest effects for temporal and parieto-occipital regions. Disease severity at baseline influenced the EEG measures' rates of change, with fastest deterioration reported in MCI patients. Only AD dementia patients displayed a significant decrease of the parieto-occipital peak frequency and theta signal variability over time. We estimate that 2-year trials, focusing on amyloid-positive MCI patients, require 36 subjects per arm (2 arms, 1:1 randomization, 80% power) to detect a stabilizing treatment effect on temporal relative theta power. Conclusions: Resting-state EEG measures could facilitate early detection of treatment effects on neuronal function in AD patients. Their sensitivity depends on the region-of-interest and disease severity of the study population. Conventional spectral measures, particularly recorded from temporal regions, present sensitive AD treatment monitoring markers. [ABSTRACT FROM AUTHOR]

Parenting programs are effective for children with externalizing problems, but not always easily accessible for parents. In order to facilitate accessibility, we developed a self-help parenting program, consisting of a manual and online part. The efficacy of the program in reducing children's externalizing problems was compared to waitlist in a randomized controlled trial. In addition, two versions of the program were exploratively compared, one with and one without biweekly telephonic support. Candidate moderators (child and parent factors) and parental satisfaction were also examined. We randomly assigned 110 families to one of the following three conditions: the support condition, the no support condition, or the waitlist condition. Intervention duration was 15 weeks. Outcomes were collected at baseline (T0), 8 weeks (T1), 15 weeks (T2), and 28 weeks (T3) and included daily telephonic measurements of parent-rated externalizing behavior and the Intensity scale of the parent-rated Eyberg Child Behavior Inventory (ECBI). Main analyses compared outcomes at T2, using longitudinal regressions with T0 as fixed factor. Results showed that children improved significantly more on both outcomes in the intervention condition compared to waitlist, with small to medium effect sizes. Parental satisfaction was high. Neither differences in efficacy nor in parental satisfaction were found between the support and no support condition. No moderators were detected. The newly developed self-help parenting program is effective in reducing children's externalizing behavior problems and may help improve access to evidence-based care. [ABSTRACT FROM AUTHOR]

Background: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. Methods: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. Results: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [ B = −0.49, 95% confidence interval (CI) −0.61 to −0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = −0.68, 95% CI −1.31 to −0.05, p = 0.03) and than 1–2 years (B = −0.86, 95% CI −1.66 to −0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. Conclusions: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression. [ABSTRACT FROM AUTHOR]

Introduction: Vincristine is an integral component of treatment for children with cancer. Its main dose‐limiting side effect is vincristine‐induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1‐hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short‐term outcomes (median follow‐up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1‐hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow‐up 20 months), which includes treatment outcome as a secondary objective (follow‐up 3 years). Methods: VIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric‐modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed. Results: Forty‐five participants per randomization group were included. There was no significant effect of 1‐hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one‐hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one‐hour group and one patient in the push group relapsed. Two patients in the one‐hour group died. Conclusion: 1‐hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1‐hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile. Vincristine is an integral component of treatment for children with cancer. Its main dose‐limiting side effect is vincristine‐induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of one‐hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. We found that in patients receiving concurrent azoles, one‐hour infusion may be less toxic. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the 'Plants for Joints' (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s. d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P  < 0.0001). The PFJ intervention led to greater decreases in body weight (difference –3.9 kg), fat mass (–2.8 kg), waist circumference (–3 cm), HbA1c (–1.3 mmol/mol) and low-density lipoprotein (–0.32 mmol/l), whereas patient-reported outcome measures, blood pressure, glucose and other lipids did not change. Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform ; NL7800. [ABSTRACT FROM AUTHOR]