Objectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high... Show moreObjectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women. Methods: In this case -control study, cases were women >= 65 years with >= 2 new -onset lower urinary tract symptoms, pyuria, and one uropathogen >= 104 CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen >= 105 CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography -mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves. Results: We included 162 community -dwelling and institutionalized older women. Five urine inflam- matory biomarkers demonstrated high discriminative ability (area under the curve >= 0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C -X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75% -93%] and specificity 89% [95% CI 82%-94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone. Discussion: We identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population. Manu P. Bilsen, Clin Microbiol Infect 2024;30:216 (c) 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
Onychomycosis is the most prevalent nail disease and is frequently encountered in clinical practice. Despite having multiple therapeutic options, of which systemic antifungals are the most... Show moreOnychomycosis is the most prevalent nail disease and is frequently encountered in clinical practice. Despite having multiple therapeutic options, of which systemic antifungals are the most effective, treatment is not always mandatory in all patients. Especially when considering systemic treatment, the risk of adverse reactions may outweigh the potential benefits of treatment. In this case report, we present a clinical case of a 49-year-old male patient with a blank past medical history who experienced a severe drug eruption from terbinafine prescribed for mild onychomycosis that required discontinuation of terbinafine, additional evaluation, and treatment of this adverse reaction. Show less
Background and objectiveEven though children with complex problems frequently need psychosocial care, two thirds does not receive treatment. Various barriers, particularly expectations of barriers,... Show moreBackground and objectiveEven though children with complex problems frequently need psychosocial care, two thirds does not receive treatment. Various barriers, particularly expectations of barriers, can hinder effective access of care. Our aim was to assess the practical barriers expected by parents, and the child, family and need factors associated with these expected barriers.MethodsWe sent web-based questionnaires to parents of a random sample of children known to have or be at risk of having complex problems (response = 77%). We used backward regression analyses to examine which factors were associated with expected barriers for children using psychosocial care, or no care at all.ResultsSeventy-three percent of all parents expected practical barriers. Parents of children using psychosocial care expected more barriers than when using no care at all. For children who used no care, parents of girls expected more barriers (regression coefficient 0.54; 95%-confidence interval 0.16, 0.92) as did families having less social support (-0.30; -0.50, -0.11). When children used psychosocial care, parents expected more barriers when their child was of school-age (0.38; 0.01, 0.75), of non-western origin (vs. native) (0.52; 0.17, 0.88), when parents were older (i.e., 36+ years) (-0.77; -1.12, -0.42), experienced more adverse life events (0.29; 0.13, 0.45) or had less social support (-0.17; -0.34, 0.00).ConclusionEven when their child is already receiving treatment, parents continue to expect practical barriers to psychosocial care. Psychosocial care services and their gatekeepers should address these concerns. Access to psychosocial care can be improved by removing practical barriers, especially if children already receive psychosocial care, or when parents have a limited network or belong to an ethnic minority. Show less
Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy... Show moreNocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of nocebo effects on pressure pain at baseline (N = 69) and 1-month follow-up (N = 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions on the pain-increasing function of a sham transcutaneous electrical nerve stimulation device, then decreased via extinction. One month later, the same procedures were repeated to explore their stability. Results suggest that nocebo effects were induced in the healthy control group during baseline and follow-up. In the patient group, nocebo effects were only induced during follow-up, without clear group differences. Extinction was only observed during baseline in the healthy control group. Further comparisons of nocebo effects and extinction indicated no significant changes across sessions, possibly suggesting their overall magnitudes were stable over time and across groups. In conclusion, contrary to our expectations, patients with fibromyalgia did not have stronger nocebo hyperalgesia; instead, they might be less responsive to nocebo manipulations than healthy controls. Show less
Roos, R.; Pepping, R.M.C.; Aken, M.O. van; Labots, G.; Lahdidioui, A.; Berg, J.M.W. van den; ... ; Nieuwkoop, C. van 2023
Introduction Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as... Show moreIntroduction Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway (‘The Hague RTI Care Bridge’) developed with the aim to treat and coordinate care for these patients outside the hospital.Methods and analysis This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life.Ethics and dissemination The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. Show less
ObjectivesThroughout Europe, many countries offer population-based cancer screening programmes (CSPs). In the Netherlands, two implemented CSPs are targeting people of 50 years and older, aiming at... Show moreObjectivesThroughout Europe, many countries offer population-based cancer screening programmes (CSPs). In the Netherlands, two implemented CSPs are targeting people of 50 years and older, aiming at breast cancer (BC) and colorectal cancer (CRC). In order for a CSP to be (cost-)effective, high participation rates and outreach to the populations at risk are essential. People living in highly urbanised areas and big cities are known to participate less in CSPs. The aim of this study was to gain further insight into the participation patterns of a screening-eligible population of 50 years and over, living in a highly urbanised region, over a longer time period. DesignA retrospective observational study. SettingParticipation data of the regional screening organisation, linked to the cancer incidence data derived from the Netherlands Cancer Registry, concerning the city of The Hague, between 2005 and 2019. Attendance groups were defined as attenders (attending >50% of the invitations) and non-attenders (attending & LE;50% of the invitations), and were mutually compared. ResultsThe databases contained 106 377 unique individuals on the BC screening programme (SP) and 73 669 on the CRC-SP. Non-attendance at both CSPs was associated with living in a lower socioeconomic status (SES) neighbourhood and as a counter effect, also associated with a more unfavourable, relatively late-stage, tumour diagnosis. When combining the results of the two CSPs, our results imply high screening adherence over time. Women who did not participate in both CSPs were older, and more often lived in neighbourhoods with a lower SES score. ConclusionsSince low screening uptake is one of the factors that contribute to increasing inequalities in cancer survival, future outreach strategies should be focused on engaging specific non-attending subgroups. Show less
Improving population health and reducing inequalities through better integrated health and social care services is high up on the agenda of policymakers internationally. In recent years, regional... Show moreImproving population health and reducing inequalities through better integrated health and social care services is high up on the agenda of policymakers internationally. In recent years, regional cross-domain partnerships have emerged in several countries, which aim to achieve better population health, quality of care and a reduction in the per capita costs. These cross-domain partnerships aim to have a strong data foundation and are committed to continuous learning in which data plays an essential role. This paper describes our approach towards the development of the regional integrative population-based data infrastructure Extramural LUMC (Leiden University Medical Center) Academic Network (ELAN), in which we linked routinely collected medical, social and public health data at the patient level from the greater The Hague and Leiden area. Furthermore, we discuss the methodological issues of routine care data and the lessons learned about privacy, legislation and reciprocities. The initiative presented in this paper is relevant for international researchers and policy-makers because a unique data infrastructure has been set up that contains data across different domains, providing insights into societal issues and scientific questions that are important for data driven population health management approaches. Show less
Bulk, S. van den; Petrus, A.H.J.; Willemsen, R.T.A.; Boogers, M.J.; Meeder, J.G.; Rahel, B.M.; ... ; Bonten, T.N. 2023
Introduction Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%-70% of patients with chest pain to the... Show moreIntroduction Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%-70% of patients with chest pain to the emergency department (ED). Only 10%-20% of those referred, are diagnosed with ACS. A clinical decision rule, including a high-sensitive cardiac troponin-I point-of-care test (hs-cTnI-POCT), may safely rule out ACS in primary care. Being able to safely rule out ACS at the GP level reduces referrals and thereby alleviates the burden on the ED. Moreover, prompt feedback to the patients may reduce anxiety and stress.Methods and analysis The POB HELP study is a clustered randomised controlled diagnostic trial investigating the (cost-)effectiveness and diagnostic accuracy of a primary care decision rule for acute chest pain, consisting of the Marburg Heart Score combined with a hs-cTnI-POCT (limit of detection 1.6ng/L, 99th percentile 23ng/L, cut-off value between negative and positive used in this study 3.8ng/L). General practices are 2:1 randomised to the intervention group (clinical decision rule) or control group (regular care). In total 1500 patients with acute chest pain are planned to be included by GPs in three regions in The Netherlands. Primary endpoints are the number of hospital referrals and the diagnostic accuracy of the decision rule 24 hours, 6 weeks and 6 months after inclusion.Ethics and dissemination The medical ethics committee Leiden-Den Haag-Delft (the Netherlands) has approved this trial. Written informed consent will be obtained from all participating patients. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. Show less
Background: It is unclear to what extent mental health and negative life events (NLEs) contribute to weight change in patients with overweight. This study aimed to evaluate the association of... Show moreBackground: It is unclear to what extent mental health and negative life events (NLEs) contribute to weight change in patients with overweight. This study aimed to evaluate the association of anxiety, depression, NLEs and quality of life (QoL) with weight change over ten years in middle-aged individuals with overweight.Methods: Population-based cohort study of 2889 middle-aged men and women with a body mass index ≥27 kg/m2. Relative weight change over ten years was defined as weight loss (≤- 5 %), stable weight (between >- 5 % and <5 %) or weight gain (≥5 %). At baseline, participants reported anxiety symptoms, depressive symptoms, recent (last year) and distant (lifetime) NLEs, and a mental component summary of QoL. With multinomial logistic regression adjusting for potential confounding, we examined the association of mental health and NLEs with weight change after a median (25th, 75th percentiles) follow-up of 9.7 (9.0-10.5) years.Results: In 51 % participants weight was stable, 33 % participants lost weight and 17 % gained weight. Mild (odds ratio 1.36; 95 % confidence interval 1.05-1.75), and moderate to very severe depressive symptoms (1.43; 0.97-2.12) and four or more distant NLEs (1.35; 1.10-1.67) were associated with weight gain. Anxiety symptoms, the mental component summary of QoL were not associated with either weight gain or weight loss.Limitations: Due to the observational design residual confounding cannot be excluded.Conclusion: Our study suggests that depressive symptoms or having experienced distant NLEs are associated with weight gain over time in middle-aged individuals with overweight. These subgroups might benefit from proactive attention from their health care providers.Keywords: Body weight changes; Life change events; Longitudinal study; Mental health; Overweight. Show less
BackgroundIt is unclear to what extent mental health and negative life events (NLEs) contribute to weight changein patients with overweight. This study aimed to evaluate the association of anxiety... Show moreBackgroundIt is unclear to what extent mental health and negative life events (NLEs) contribute to weight changein patients with overweight. This study aimed to evaluate the association of anxiety, depression, NLEs and quality of life (QoL) with weight change over ten years in middle-aged individuals with overweight.MethodsPopulation-based cohort study of 2889 middle-aged men and women with a body mass index ≥27 kg/m2. Relative weight change over ten years was defined as weight loss (≤− 5 %), stable weight (between >− 5 % and <5 %) or weight gain (≥5 %). At baseline, participants reported anxiety symptoms, depressive symptoms, recent (last year) and distant (lifetime) NLEs, and a mental component summary of QoL. With multinomial logistic regression adjusting for potential confounding, we examined the association of mental health and NLEs with weight change after a median (25th, 75th percentiles) follow-up of 9.7 (9.0–10.5) years.ResultsIn 51 % participants weight was stable, 33 % participants lost weight and 17 % gained weight. Mild (odds ratio 1.36; 95 % confidence interval 1.05–1.75), and moderate to very severe depressive symptoms (1.43; 0.97–2.12) and four or more distant NLEs (1.35; 1.10–1.67) were associated with weight gain. Anxiety symptoms, the mental component summary of QoL were not associated with either weight gain or weight loss.LimitationsDue to the observational design residual confounding cannot be excluded.ConclusionOur study suggests that depressive symptoms or having experienced distant NLEs are associated with weight gain over time in middle-aged individuals with overweight. These subgroups might benefit from proactive attention from their health care providers. Show less
Sijbom, M.; Büchner, F.L.; Saadah, N.H.; Numans, M.E.; Boer, M.G.J. de 2023
ObjectivesThis study aimed to identify determinants of inappropriate antibiotic prescription in primary care in developed countries and to construct a framework with the determinants to help... Show moreObjectivesThis study aimed to identify determinants of inappropriate antibiotic prescription in primary care in developed countries and to construct a framework with the determinants to help understand which actions can best be targeted to counteract development of antimicrobial resistance (AMR).DesignA systematic review of peer-reviewed studies reporting determinants of inappropriate antibiotic prescription published through 9 September 2021 in PubMed, Embase, Web of Science and the Cochrane Library was performed.SettingAll studies focusing on primary care in developed countries where general practitioners (GPs) act as gatekeepers for referral to medical specialists and hospital care were included.ResultsSeventeen studies fulfilled the inclusion criteria and were used for the analysis which identified 45 determinants of inappropriate antibiotic prescription. Important determinants for inappropriate antibiotic prescription were comorbidity, primary care not considered to be responsible for development of AMR and GP perception of patient desire for antibiotics. A framework was constructed with the determinants and provides a broad overview of several domains. The framework can be used to identify several reasons for inappropriate antibiotic prescription in a specific primary care setting and from there, choose the most suitable intervention(s) and assist in implementing them for combatting AMR.ConclusionsThe type of infection, comorbidity and the GPs perception of a patient's desire for antibiotics are consistently identified as factors driving inappropriate antibiotic prescription in primary care. A framework with determinants of inappropriate antibiotic prescription may be useful after validation for effective implementation of interventions for decreasing these inappropriate prescriptions.PROSPERO registration numberCRD42023396225. Show less
Background Prediction models for risk of cardiovascular events generally do not include young adults, and cardiovascular risk factors differ between women and men. Therefore, this study aimed to... Show moreBackground Prediction models for risk of cardiovascular events generally do not include young adults, and cardiovascular risk factors differ between women and men. Therefore, this study aimed to develop prediction models for first-ever cardiovascular event risk in men and women aged 30 to 49 years.Methods and Results We included patients aged 30 to 49 years without cardiovascular disease from a Dutch routine care database. Outcome was defined as first-ever cardiovascular event. Our reference models were sex-specific Cox proportional hazards models based on traditional cardiovascular predictors, which we compared with models using 2 predictor subsets with the 20 or 50 most important predictors based on the Cox elastic net model regularization coefficients. We assessed the C-index and calibration curve slopes at 10 years of follow-up. We stratified our analyses based on 30- to 39-year and 40- to 49-year age groups at baseline. We included 542 141 patients (mean age 39.7, 51% women). During follow-up, 10 767 cardiovascular events occurred. Discrimination of reference models including traditional cardiovascular predictors was moderate (women: C-index, 0.648 [95% CI, 0.645-0.652]; men: C-index, 0.661 [95%CI, 0.658-0.664]). In women and men, the Cox proportional hazard models including 50 most important predictors resulted in an increase in C-index (0.030 and 0.012, respectively), and a net correct reclassification of 3.7% of the events in women and 1.2% in men compared with the reference model.Conclusions Sex-specific electronic health record-derived prediction models for first-ever cardiovascular events in the general population aged <50 years have moderate discriminatory performance. Data-driven predictor selection leads to identification of nontraditional cardiovascular predictors, which modestly increase performance of models. Show less
Pepping, R.M.C.; Aken, M.O. van; Vos, R.C.; Numans, M.E.; Berg, J.M.W. van den; Kroon, I.; Nieuwkoop, C. van 2023
Introduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated... Show moreIntroduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated care is associated with unnecessary hospital referral and admission with potential iatrogenic harm. Therefore, we aimed to co-create a regional integrated care pathway (ICP), including a hospital at home journey. Developing the ICP: Tasked with using design thinking methodology, stakeholders from regional healthcare facilities, together with patient representatives, were assigned to different focus groups based on their expertise. The focus of each session was to co-create ideal patient journeys suitable for embedding in the ICP. Results: Based on these sessions, a regional cross-domain ICP was developed that comprises three patient journeys. The first journey included a hospital at home track, the second a tailored visit, with priority assessment, to regional emergency departments, and the third concerned referral to readily available nursing home ‘recovery-beds’ under the supervision of an elderly care medicine specialist. Conclusion: Using design thinking and involving end-users during the whole process, we created an ICP for community-dwelling frail older people with moderate-severe acute respiratory infections. This resulted in three realistic patient journeys, including a hospital at home track, which will be implemented and evaluated in the near future. Show less
Background Socioeconomic status and ethnicity are not explicitly incorporated as risk factors in the four SCORE2 cardiovascular disease (CVD) risk models developed for country-wide implementation... Show moreBackground Socioeconomic status and ethnicity are not explicitly incorporated as risk factors in the four SCORE2 cardiovascular disease (CVD) risk models developed for country-wide implementation across Europe (low, moderate, high and very-high model). The aim of this study was to evaluate the performance of the four SCORE2 CVD risk prediction models in an ethnic and socioeconomic diverse population in the Netherlands.Methods The SCORE2 CVD risk models were externally validated in socioeconomic and ethnic (by country of origin) subgroups, from a population-based cohort in the Netherlands, with GP, hospital and registry data. In total 155,000 individuals, between 40 and 70 years old in the study period from 2007 to 2020 and without previous CVD or diabetes were included. Variables (age, sex, smoking status, blood pressure, cholesterol) and outcome first CVD event (stroke, myocardial infarction, CVD death) were consistent with SCORE2. Findings 6966 CVD events were observed, versus 5495 events predicted by the CVD low-risk model (intended for use in the Netherlands). Relative underprediction was similar in men and women (observed/predicted (OE-ratio), 1.3 and 1.2 in men and women, respectively). Underprediction was larger in low socioeconomic subgroups of the overall study population (OE-ratio 1.5 and 1.6 in men and women, respectively), and comparable in Dutch and the combined "other ethnicities" low socioeconomic subgroups. Underprediction in the Surinamese subgroup was largest (OE-ratio 1.9, in men and women), particularly in the low socioeconomic Surinamese subgroups (OE-ratio 2.5 and 2.1 in men and women). In the subgroups with underprediction in the low-risk model, the intermediate or high-risk SCORE2 models showed improved OE-ratios. Discrimination showed moderate performance in all subgroups and the four SCORE2 models, with C-statistics between 0.65 and 0.72, similar to the SCORE2 model development study.Interpretation The SCORE 2 CVD risk model for low-risk countries (as the Netherlands are) was found to underpredict CVD risk, particularly in low socioeconomic and Surinamese ethnic subgroups. Including socioeconomic status and ethnicity as predictors in CVD risk models and implementing CVD risk adjustment within countries is desirable for adequate CVD risk prediction and counselling. Show less
