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Simple Summary: Recently, nivolumab, pembrolizumab, both immune-checkpoint inhibitors (ICIs) and the combination of dabrafenib plus trametinib (D + T) were registered as adjuvant melanoma treatments, to prevent recurrence. The aim of this paper was to retrospectively review the benefits and risks of these treatments in clinical practice, by extracting data from electronic health records with a text-mining tool. In a population of 122 patients, 55 used nivolumab, 48 used pembrolizumab and 20 used D + T, and we found that the ICIs were better tolerated than D + T. However, the frequent adverse events of D + T are reversible and include pyrexia and fatigue. ICIs show immune-related chronic adverse events, and chronic thyroid-related adverse events occurred frequently. The efficacy results, including the recurrence-free survival, are promising; however, the follow-up was too short for conclusions. This study furthermore showed that the application of text-mining is a valuable method to collect data for the evaluation of adjuvant melanoma treatments. Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods: Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs. [ABSTRACT FROM AUTHOR]

A child's disability, long-term illness, or mental ill-health is known to affect siblings' health, social life, school engagement, and quality of life. This article addresses a research gap by its focus on young sibling carers and the impact of providing care to a sibling. A cross-national survey study was conducted in 2018–2019 (Italy, the Netherlands, Slovenia, Sweden, Switzerland, the UK) to examine the incidence of adolescent sibling carers, the extent of care they provide, and their self-reported health, well-being, and school situation. The survey was completed by 7146 adolescents, aged 15–17, and 1444 of them provided care to family members with health-related conditions. Out of these, 286 were identified as Sibling Carers and 668 as Parent Carers, while 181 had both sibling(s) and parent(s) with health-related conditions, and thus were identified as Sibling–Parent Carers. Sibling Carers and Sibling–Parent Carers carried out higher levels of caring activities compared to Parent Carers. They reported both positive aspects of caring, such as increased maturity, and negative aspects, such as mental ill-health, impact on schooling and a lack of support. To reduce the negative aspects of a sibling carer role, it is important to recognise them and to implement early preventive measures and formal support. [ABSTRACT FROM AUTHOR]

Clinical and research staff who work around magnetic resonance imaging (MRI) scanners are exposed to the static magnetic stray fields of these scanners. Although the past decade has seen strong developments in the assessment of occupational exposure to electromagnetic fields from MRI scanners, there is insufficient insight into the exposure variability that characterizes routine MRI work practice. However, this is an essential component of risk assessment and epidemiological studies. This paper describes the results of a measurement survey of shift-based personal exposure to static magnetic fields (SMF) (B) and motion-induced time-varying magnetic fields (dB/dt) among workers at 15 MRI facilities in the Netherlands. With the use of portable magnetic field dosimeters, >400 full-shift and partial shift exposure measurements were collected among various jobs involved in clinical and research MRI. Various full-shift exposure metrics for B and motion-induced dB/dt exposure were calculated from the measurements, including instantaneous peak exposure and time-weighted average (TWA) exposures. We found strong correlations between levels of static (B) and time-varying (dB/dt) exposure (r = 0.88–0.92) and between different metrics (i.e. peak exposure, TWA exposure) to express full-shift exposure (r = 0.69–0.78). On average, participants were exposed to MRI-related SMFs during only 3.7% of their work shift. Average and peak B and dB/dt exposure levels during the work inside the MRI scanner room were highest among technical staff, research staff, and radiographers. Average and peak B exposure levels were lowest among cleaners, while dB/dt levels were lowest among anaesthesiology staff. Although modest exposure variability between workplaces and occupations was observed, variation between individuals of the same occupation was substantial, especially among research staff. This relatively large variability between workers with the same job suggests that exposure classification based solely on job title may not be an optimal grouping strategy for epidemiological purposes. [ABSTRACT FROM AUTHOR]

Resistance exercise training is effective to counteract the adverse effects of androgen deprivation therapy (ADT) on body composition, muscle mass and leg strength in prostate cancer patients (PCa). However, it is unknown whether these effects can be autonomously maintained after cessation of the supervised program. Sixty‐eight PCa patients on ADT were included. The exercise intervention group (EX, n = 37) performed 20 weeks of supervised resistance exercise training. Thereafter, patients were advised to autonomously continue exercise training. The control group (CON, n = 31) only received usual care. Outcome measures were compared between baseline and after 1 year. Changes during the intervention (baseline vs. 20 weeks) and follow‐up period (20 weeks vs. 1 year) were descriptively explored. In EX, 83% reported to have continued exercise training themselves. After 1 year, fat mass gains were attenuated in EX compared to CON (1.2 ± 2.6 and 2.8 ± 1.9 kg, respectively; time × treatment effect p = 0.032). The fat percentage increased, and lean mass and quadriceps muscle cross‐sectional area decreased over time, with no differences between groups (overall 1.6 ± 2.1%, −0.7 ± 2.3 kg and −2.2 ± 2.9 cm2, respectively; time effects, all p < 0.05). For muscle strength, an increase of ∼5% in EX was observed, significantly different from the ∼10% decrease in CON (p < 0.001). Subsequent analyses showed that the initial exercise training‐obtained gains in lean mass, muscle mass and strength in EX compared to CON, declined during the follow‐up period. In conclusion, PCa patients on ADT are not capable to autonomously maintain the exercise‐obtained gains of a 20‐week supervised training program over a subsequent 1‐year period. Highlights: ADT for prostate cancer results in many side effects, including muscle mass lossA supervised resistance exercise training program can counteract many side effectsAfter cessation of the supervised program, exercise benefits are not effectively preservedMore focus on sustainability of exercise programs during ADT is required [ABSTRACT FROM AUTHOR]

Simple Summary: CAR T-cell therapy has emerged as the new standard of care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), but real-world outcomes differ across countries. Additionally, real-world data on health-related quality of life (HR-QoL) are scarce but important, as they reflect the direct experience of patients. In the Netherlands, patients can be referred to the CAR-T tumorboard, a national CAR-T expert panel, who decide whether CAR-T is a feasible treatment option. This multicenter study reports on the favorable outcomes, including the HR-QoL, of axicabtagene ciloleucel (axi-cel) for patients with R/R LBCL after ≥2 lines of systemic therapy in the Netherlands. On the other hand, we show that a substantial proportion of patients are still in need of alternative treatments, including improved CAR-T strategies, as they are unfit for or do not respond to axi-cel. Comparing real-world outcomes between cohorts could help to select best practices and further optimize CAR-T treatment. The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that for over ten years, Lithuanian consumers have been able to report adverse drug reactions (ADR) directly to the competent authority, reporting rates remain low. A comprehensive understanding of consumer perceptions and experiences regarding ADRs is needed to ascertain further factors impacting their engagement in ADR reporting. This study aimed to assess consumer knowledge of, attitude toward, and practice of reporting ADRs. Methods: A questionnaire-guided cross-sectional survey among 404 consumers between October 2021 and June 2022 was conducted. The semi-structured questionnaire comprised open-ended and closed-ended questions to explore the sociodemographic characteristics and general knowledge of ADRs and pharmacovigilance. Other question items evaluated attitudes toward ADR reporting and ADR reporting practice. The data were summarised using descriptive statistics, while the chi-square test was used to assess categorical variables at p < 0.05. The overall percent score in the knowledge and attitude domains was divided into groups of "poor", "moderate", and "good" knowledge, as well as "positive" and "negative" attitudes. Results: While having a generally poor understanding, this study demonstrates that Lithuanian consumers have a favourable attitude toward pharmacovigilance, particularly regarding issues involving the requirement for reporting. The data also revealed the justifications for reporting and not reporting ADRs. Conclusions: The current study provided the first understanding of consumer awareness and ADR reporting intentions, which can help to develop educational campaigns and interventions addressing pharmacovigilance and ADR reporting. [ABSTRACT FROM AUTHOR]

Background Decision aids can be used to support shared decision making ( SDM). A patient-oriented treatment decision aid ( DA) was developed for type 2 diabetes but its use by general practice staff appeared to be limited. Objectives To explore views of practice staff towards SDM and the DA. Design A mixed-methods study within the Dutch PORTDA-diab trial. Setting and participants Included were 17 practices with staff members who were responsible for routine diabetes care and had worked with the DA, and 209 of their patients. Methods Interviews were conducted focusing on applicability, usefulness and feasibility of the DA. Interviews were tape-recorded, transcribed verbatim and subjected to content analysis for identifying and classifying views. Patient-reported data about the use of the DA were collected. Associations between specific views and use of the DA were tested using Pearson point-biserial correlation. Results The majority of practice staff expressed positive views towards SDM, which was associated with making more use of the DA. Most of the staff expressed that the DA stimulated a two-way conversation. By using the DA, several became aware of their paternalistic approach. Some staff experienced a conflict with the content of the DA, which was associated with making less use of the DA. Conclusions The DA was considered useful by practice staff to support SDM. A positive view towards SDM was a facilitator, whereas experiencing a conflict with the content of the DA was a barrier for making use of the DA. [ABSTRACT FROM AUTHOR]

Objective. To determine whether MRI features are associated with development of radiographic knee OA and can be used as a predictive tool in early knee OA. Methods. In 148 participants of the Cohort Hip and Cohort Knee study (mean age 56 years, 78% women), with a Kellgren Lawrence (KL) score ≤1, we obtained semi-quantitatively scored knee MRI scans and radiographs at baseline. After 5 years, we determined the development of radiographic knee OA (KL 52). We calculated odds ratios (ORs), with 95% CIs adjusted for age, sex and BMI, to identify MRI features associated with OA development. With these MRI features, we constructed an internally validated prediction model, for which we measured the area under the receiver operating characteristics curve, sensitivity and specificity. Results. Radiographic OA developed in 28% of the participants after 5 years. Statistically significant associations were: cartilage defects OR = 1.7 (95% CI: 1.1, 2.6), osteophytes OR = 3.1 (1.7, 5.7), bone marrow lesions OR = 2.0 (1.2, 3.4), effusion OR = 2.1 (1.2, 3.5) and meniscal pathology OR = 2.8 (1.3, 6.3). With the combined MRI features in a prediction model, the sensitivity was 66%, the specificity 67% and the optimism-corrected area under the receiver operating characteristics curve 0.685. Conclusion. In early knee OA, MRI depicts significantly associated pathology in cartilage, bone and menisci, whereas the radiograph fails to detect these changes. Although MRI has potential for identifying patients at risk for developing radiographic knee OA, it cannot be used as an absolute diagnostic tool in early knee OA due to its low discriminative ability. [ABSTRACT FROM AUTHOR]

As restructuring a negative cognitive style is a central skill taught in many depression prevention programs, we tested whether a universal prevention program evoked a change in negative cognitive style in adolescents. In addition, we examined distinct developmental trajectories of negative cognitive styles and assessed whether research condition (intervention versus control) predicted these trajectories. Young adolescents (n=1343; Mean age=13.4 years; SD=0.77; 52.3%girls) were randomly allocated to a cognitive behavioral therapy (CBT)-based depression prevention program or a care as usual control condition. A negative cognitive style was assessed at baseline, post-treatment and 6- and 12-months follow-up. Adolescents who received the intervention did not differ in their negative cognitive style from the control group at any time-point. We found four distinctive trajectories of negative cognitive style: normative, increasing, decreasing and stable high, which were not predicted by intervention condition and were not moderated by gender. Yet, the results revealed a trend, which indicated that adolescents who followed the program tended to show an increasing than a normative developmental pattern. We concluded that the CBTbased depression prevention program did not reduce or prevent an increase in negative cognitive style. [ABSTRACT FROM AUTHOR]

Objective. To study for the first time in a randomized controlled trial the feasibility, safety and efficacy of an exercise training programme in children and adolescents with JDM. Methods. Patients were randomly assigned to the Intervention Group (IG; n = 14) or Waiting Control Group (WCG; n = 12). The intervention comprised an individually tailored 12-week home-based exercise programme of treadmill interval training and strength exercises. The efficacy of the IG over usual care (WCG) was examined with mixed linear regression (intention-to-treat). Effect sustainability during 12 weeks follow-up was also examined. Results. Seventy-five percent of the participants completed the intervention. Reasons for discontinuation were motivation/fatigue, recurrent infections and increasing physical complaints. No hospitalizations occurred and immune suppressive therapy remained stable or decreased in the patients who participated in the intervention. The estimated marginal means after the intervention period were significantly in favour of the IG compared with the WCG for standing long jump distance [difference between groups (95% CI): 13cm (2-23)], the 30-s number of push-ups [8 (3-13)] and sit-ups [4 (0.4-8)], and the parent Childhood Health Assessment Questionnaire 30 + 8 score [-0.13 (-0.24 to-0.01)] and effects sustained at follow-up. A trend was seen for the maximal oxygen uptake divided by body mass during maximal exercise treadmill testing; the IG scored 3.0ml/kg/min (-1.3 to 7.3) higher compared with the WCG. Other outcomes (e.g. isometric muscle strength and perception of fatigue) did not differ between IG and WCG. Conclusion. Exercise training is of value in the clinical management of JDM. [ABSTRACT FROM AUTHOR]

Objective. To monitor whether biologic DMARD (bDMARD) home storage temperatures comply with the manufacturers' Summary of Product Characteristics (SmPC) recommendations. Methods. This observational study included consenting adult patients from eight Dutch pharmacies who received their bDMARDs with a validated temperature logger. Patients were instructed to store their packages according to standard label instructions and to return the temperature logger(s) after use. Primary outcome was defined as the proportion of patients that stored their bDMARDs within the SmPC recommended temperature range. In addition, the proportion of patients storing bDMARDs below 0°C or above 25 °C for longer than two consecutive hours was estimated. Results. A total of 255 (87.0%) patients (mean age 53.2 (S.D.; 13.1) years, 51.4% female) returned their temperature logger(s) to the pharmacy. Of these, 17 patients (6.7%) stored their bDMARD within the recommended temperature range. The proportion of the patients that stored their bDMARD for more than 2 h consecutive time below 0°C or above 25°C was respectively 24.3% (median duration: 3.7 h (IQR 2.2 h; range 2.0-1,097.1 h) and 2.0% (median duration: 11.8 h (IQR 44.3 h; range 2.0-381.9 h). Conclusion. The majority of patients do not store their bDMARDs within the SmPC-recommended temperature range. [ABSTRACT FROM AUTHOR]

Background: Children's fussy eating behavior has been related to both underweight and overweight in cross-sectional studies, but the direction of these associations and the relation with more detailed measures of body composition remains unclear. We aimed to examine whether fussy eating at age 4 years is longitudinally related to body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI) at 6 years of age. Methods: This study was embedded in Generation R, a population-based, prospective cohort. Data were available for 4191 children. The Children's Eating Behaviour Questionnaire (CEBQ), administered at age 4 years, was used to derive a fussy eating profile. This profile is characterized by high scores on food avoidant scales and low scores on food approach scales. At age 6 years, height and weight were measured at our research center. Body fat and fat-free mass were measured using Dual-energy-X-ray absorptiometry. We used age- and sex-specific standard deviation scores (SDS) for all outcomes. Results: After adjustment for confounders, the fussy eating profile was related to lower BMI-SDS (B = -0.37, 95 % CI: -0.47;-0.26), lower FMI-SDS (B = -0.22, 95 % CI: -0.33;-0.12) and lower FFMI-SDS (B = -0.41, 95 % CI: -0.54;-0.29). When adjusting for baseline BMI at 4 years, the fussy eating profile predicted a 0.11 lower BMI-SDS at age 6 (95 % CI: -0.19;-0.04). This change in BMI was mainly due to a decrease in FFMI (B = -0.19, 95 % CI: -0.29;-0.09). Fussy eaters also had a higher risk of becoming underweight than non-fussy eaters (OR = 2.28, 95 % CI: 1.34;3.87). Conclusions: Our findings suggest that young fussy eaters are at risk of having a lower fat free mass and of becoming underweight over a 2-year period. This implies that fussy eaters may benefit from careful monitoring to prevent an adverse growth development. [ABSTRACT FROM AUTHOR]

Background: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. Methods: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results: We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. Limitations: The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. Conclusion: These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: screening for frailty might help to prevent adverse outcomes in hospitalised older adults.Objective: to identify the most predictive and efficient screening tool for frailty.Design and setting: two consecutive observational prospective cohorts in four hospitals in the Netherlands.Subjects: patients aged ≥70 years, electively or acutely hospitalised for ≥2 days.Methods: screening instruments included in the Dutch Safety Management Programme [VeiligheidsManagementSysteem (VMS)] on four geriatric domains (ADL, falls, undernutrition and delirium) were used and the Identification of Seniors At Risk, the 6-item Cognitive Impairment Test and the Mini-Mental State Examination were assessed. Three months later, adverse outcomes including functional decline, high-healthcare demand or death were determined. Correlation and regression tree analyses were performed and predictive capacities were assessed.Results: follow-up data were available of 883 patients. All screening instruments were similarly predictive for adverse outcome (predictive power 0.58–0.66), but the percentage of positively screened patients (13–72%), sensitivity (24–89%) and specificity (35–91%) highly differed. The strongest predictive model for frailty was scoring positive on ≥3 VMS domains if aged 70–80 years; or being aged ≥80 years and scoring positive on ≥1 VMS domains. This tool classified 34% of the patients as frail with a sensitivity of 68% and a specificity of 74%. Comparable results were found in the validation cohort.Conclusions: the VMS-tool plus age (VMS+) offers an efficient instrument to identify frail hospitalised older adults at risk for adverse outcome. In clinical practice, it is important to weigh costs and benefits of screening given the rather low-predictive power of screening instruments. [ABSTRACT FROM PUBLISHER]

Introduction: Construction workers are at risk of developing occupational contact dermatitis. Gloves, when used properly, may protect against chemicals and coarse materials. We investigated the prevalence and determinants of contact dermatitis in a population of Dutch construction workers and aimed at validating questionnaire items on hand hygiene. Methods: A cross-sectional study was conducted at 13 construction sites, yielding data of 177 subjects (95% response rate). A questionnaire covering questions on hand hygiene and contact dermatitis symptoms was used. Agreement between workplace observations and a number of questionnaire items was assessed by calculating Cohen’s kappa. Log-binomial regression analysis was used to assess the association between contact dermatitis and various hand hygiene-related determinants. Results: The 1-year prevalence of self-reported contact dermatitis in our study sample was 46.9%. Multiple regression analysis showed a positive association with difficulties with hand cleaning (prevalence ratio [PR]: 1.26, 95% confidence interval [CI]: 1.05–1.52), hand contamination at the end of the working day (PR: 2.30, 95% CI: 1.14–4.65), and intensive hand cream use (PR: 2.07, 95% CI: 1.42–3.01). Observations of hand contamination, glove use, and glove types were found to agree well with the self-reported data from the questionnaire (Cohen’s kappa’s 0.75, 0.97, and 0.88). Conclusions: Self-reported contact dermatitis prevalence in construction workers was high and related to hand hygiene. A strong agreement was found between workplace observations and self-reported questionnaire data. [ABSTRACT FROM PUBLISHER]