Per- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular... Show morePer- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular risk profile, the distribution of levels and relations with cardio-metabolic risk markers in the general population have not been fully characterized. We assessed the association between blood levels of perfluorooctaneic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) and a range of lipoproteins and metabolites as well as clinical lipid measurements. We used data from participants of the Netherlands Epidemiology of Obesity study (NEO) (n = 584) and the Rhineland Study (n = 1962), jointly spanning an age range of 30 to 89 years. PFAS were measured with the Metabolon HD4 platform, and lipoprotein and metabolite profiles were measured using Nightingale's nuclear magnetic resonance-spectroscopy platform, and mainly comprised lipoprotein markers. Using linear regression analyses, we quantified age-, sex-, and education-adjusted associations of PFOA, PFOS, and PFHxS with clinical lipid measurements and 224 lipoproteins and metabolites. Higher levels of PFAS, particularly PFOS and PFHxS, were associated with higher concentrations of total lipid, cholesterol and phospholipid content in most HDL, IDL, LDL, and VLDL subclasses. The effect sizes were age-dependent for the majority of the associations, with the deleterious effects of PFAS being generally stronger in people below compared to those above median age. Our observation that in the general population even low PFAS concentrations are associated with an unfavorable lipid profile, calls for further critical regulation of PFAS substances. Show less
Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the... Show moreDepression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as a total indicator for depression severity. The present dissertation aimed to expand our knowledge of depression by researching its symptom-specific longitudinal characteristics, its predictive factors, and methods for predicting depression and anxiety while taking individual symptoms into account. We demonstrated that individual depressive symptoms are not synchronized over time within patients and in groups of patients. We found that individual symptoms of depression are associated to different risk factors, as preceding chronicity, neuroticism, and inflammation were related to individual symptoms with vastly different magnitudes. Taken these findings together we have demonstrated that depressive disorder can not be characterized as an unified syndrome. Addressing depression at the syndrome level may obscure insights into both patient and symptom-specific characteristics. Our findings strengthen the idea that employing a symptom-focused approach in both clinical care and research is of value. With this dissertation, we hope to have contributed to the development of alternative ways to define and study depression and its symptoms. Show less
Background Visual impairment frequently occurs amongst older people. Therefore, the aim of this study was to investigate the predictive value of visual impairment on functioning, quality of life... Show moreBackground Visual impairment frequently occurs amongst older people. Therefore, the aim of this study was to investigate the predictive value of visual impairment on functioning, quality of life and mortality in people aged 85 years. Methods From the Leiden 85-plus Study, 548 people aged 85 years were eligible for this study. Visual acuity was measured at baseline by Early Treatment Diabetic Retinopathy Study charts (ETDRS). According to the visual acuity (VA) three groups were made, defined as no (VA > 0.7), moderate (0.5 <= VA <= 0.7) or severe visual impairment (VA < 0.5). Quality of life, physical, cognitive, psychological and social functioning were measured annually for 5 years. For mortality, participants were followed until the age of 95. Results At baseline, participants with visual impairment scored lower on physical, cognitive, psychological and social functioning and quality of life (p < 0.001). Compared to participants with no visual impairment, participants with moderate and severe visual impairment had an accelerated deterioration in basic activities of daily living (respectively 0.27-point (p = 0.017) and 0.35 point (p = 0.018)). In addition, compared to participants with no visual impairment, the mortality risk was 1.83 (95% CI 1.43, 2.35) for participants with severe visual impairment. Discussion In very older adults, visual impairment predicts accelerated deterioration in physical functioning. In addition, severely visually impaired adults had an increased mortality risk. A pro-active attitude, focussing on preventing and treating visual impairment could possibly contribute to the improvement of physical independence, wellbeing and successful aging in very old age. Show less
BACKGROUND CONTEXT: Defining clinically meaningful success criteria from patientreported outcome measures (PROMs) is crucial for clinical audits, research and decision-making.PURPOSE: We aimed to... Show moreBACKGROUND CONTEXT: Defining clinically meaningful success criteria from patientreported outcome measures (PROMs) is crucial for clinical audits, research and decision-making.PURPOSE: We aimed to define criteria for a successful outcome 3 and 12 months after surgery for cervical degenerative radiculopathy on recommended PROMs.STUDY DESIGN: Prospective cohort study with 12 months follow-up.PATIENT SAMPLE: Patients operated at one or two levels for cervical radiculopathy included in the Norwegian Registry for Spine Surgery (NORspine) from 2011 to 2016.OUTCOME MEASURES: Neck disability index (NDI), Numeric Rating Scale for neck pain (NRS-NP) and arm pain (NRS-AP), health-related quality-of-life EuroQol 3L (EQ-5D), general health status (EQ-VAS).METHODS: We included 2,868 consecutive cervical degenerative radiculopathy patients operated for cervical radiculopathy in one or two levels and included in the Norwegian Registry for Spine Surgery (NORspine). External criterion to determine accuracy and optimal cut-off values for success in the PROMs was the global perceived effect scale. Success was defined as "much better" or "completely recovered." Cut-off values were assessed by analyzing the area under the receiver operating curves for follow-up scores, mean change scores, and percentage change scores.RESULTS: All PROMs showed high accuracy in defining success and nonsuccess and only minor differences were found between 3- and 12-month scores. At 12 months, the area under the receiver operating curves for follow-up scores were 0.86 to 0.91, change scores were 0.74 to 0.87, and percentage change scores were 0.74 to 0.91. Percentage scores of NDI and NRS-AP showed the best accuracy. The optimal cut-off values for each PROM showed considerable overlap across those operated due to disc herniation and spondylotic foraminal stenosis.CONCLUSIONS: All PROMs, especially NDI and NRS-AP, showed good to excellent discriminative ability in distinguishing between a successful and nonsuccessful outcome after surgery due to cervical radiculopathy. Percentage change scores are recommended for use in research and clinical practice. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
Barele, M. van; Heemskerk-Gerritsen, B.A.M.; Doorn, H.C. van; Schmidt, M.K.; Hooning, M.J.; Jager, A. 2020
Introduction: Hormone replacement therapy can diminish hormone depletion -related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Re-... Show moreIntroduction: Hormone replacement therapy can diminish hormone depletion -related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Re- covery of menstruation after chemotherapy -induced amenorrhea in young hormone receptor -negative BC patients however, is accepted. To determine the safety of this strategy, we investigated the effect of recovery of menstruation on disease -free survival (DFS) and overall survival (OS) in young hormone receptor -negative BC patients treated with (neo)adjuvant chemotherapy. Methods: We selected 636 patients from a single -center cohort with early stage hormone receptor - negative BC and under the age of 50 years when treated with chemotherapy. Suf ficient data on course of menstruation in medical records was retrospectively found for 397 patients, of whom 299 patients (75%) had a recovery of menstruation after chemotherapy. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recovery of menstruation on DFS and OS. Results: Patients with recovery of menstruation after chemotherapy less frequently had lymph node involvement at diagnosis (45% vs 66%, p = 0.001). After a median follow-up of 6.7 years, the adjusted hazard ratios were 1.45 (95% CI: 0.83-2.54) for DFS and 1.19 (95% CI: 0.71-1.98) for OS. Conclusion: No signi ficantly increased recurrence risk was found for hormone receptor -negative BC patients with recovery of menstruation after chemotherapy. However, the outcome of the multivariable model is not reassuring and a potentially increased recurrence risk cannot be excluded. The results need to be validated in a larger prospective study for a more de finitive answer. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury.Study Design and Setting: We... Show moreObjective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury.Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified.Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study.Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations. (C) 2020 The Authors. Published by Elsevier Inc. Show less
Matthijssen, X.M.E.; Wouters, F.; Boeters, D.M.; Boer, A.C.; Dakkak, Y.J.; Niemantsverdriet, E.; Helm-van Mil, A.H.M. van der 2019
Studies in this thesis were performed in a secondary care cohort of patients with hand osteoarthritis. Several factors were investigated for their association with disease status and disease... Show moreStudies in this thesis were performed in a secondary care cohort of patients with hand osteoarthritis. Several factors were investigated for their association with disease status and disease progression after two years. These factors included comorbidity, illness perceptions and MRI-defined inflammatory features such as bone marrow lesions, synovitis and joint effusion. In the MRI studies we found that these MRI-features have a clinically relevant role for their association with pain (at the same moment and after two years) and progression of radiographic damage after two years. In the second part of this thesis we evaluated the clinimetric properties of two new instruments: self-reported painful joint count and semi-automatic joint space width measurements. Show less
Similarities and differences in the (short-term) psychosocial development of children in foster care, family-style group care, and residential care were investigated in a sample of 121 Dutch... Show moreSimilarities and differences in the (short-term) psychosocial development of children in foster care, family-style group care, and residential care were investigated in a sample of 121 Dutch children (M age = 8.78 years; SD = 2.34 years; 47% female; 59% Caucasian) one year after their initial placement. Pretest and posttest measurements were carried out at the substitute caregivers using the CBCL. The results were examined at group level and case level. At group level, the findings showed no evidence for higher effectiveness in favor to the family-oriented settings (foster care, and family-style group care), as hypothesized. By contrast, some small differences were found between foster care and family-style group care, in favor of the latter. At individual level, a more or less equal number of children (18%) with a clinical pretest score on psychosocial functioning clinically significant improved (behavioral normalization). An important concern is that a number of children without clinical psychosocial problems at the time of admission clinically significant deteriorated (behavioral aberration) in psychosocial functioning (20%). This might indicate a poor match between the risks, needs and responsivity of the child on the one hand and the chosen intervention on the other. Future research on factors that (prior and during placement) positively as well as negatively affect the child’s psychosocial development is needed to further clarify this finding. Show less
Jansen, M.A.E.; Heuvel, D. van den; Jaddoe, V.W.V.; Zelm, M.C. van; Moll, H.A. 2017
