Search

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]

Simple Summary: This nationwide cohort study evaluated the incidence and severity of immune-related adverse events (irAEs) in melanoma patients receiving adjuvant versus advanced anti-PD-1 therapy. A total of 1465 advanced melanoma patients and 908 adjuvant-treated patients were included. Patients in the adjuvant group were younger, had superior ECOG performance status, and had fewer comorbidities compared to those in the advanced group. No significant difference was observed in the incidence of grade III-IV irAEs between the two groups. However, higher ECOG status (>1) and the presence of any comorbidities were independently associated with an increased risk of irAE development across both treatment settings. Although adjuvant therapy was not linked to a heightened risk of severe irAEs compared to advanced therapy, it was more frequently discontinued due to toxicity in the adjuvant group. These findings provide critical insights for informing patient consultations regarding adjuvant anti-PD-1 treatment. Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment. [ABSTRACT FROM AUTHOR]

This paper provides an overview of the design and cohort characteristics of the Social Spectrum Study: a clinical cohort study that used a two-phase sampling design to identify children at risk for ASD. After screening 1281 children aged 2.5-10 years who had been consecutively referred to one of six mental health services in the Netherlands, children who screened positive for ASD (n = 428) and a random selection of screen negatives (n = 240) were invited to participate in diagnostic assessments and questionnaires regarding the child, family and society. A 1-year follow-up was also conducted. Results from this study may contribute to knowledge of the identification and characterization of children with ASD, family processes, and the impact of ASD on the family and society. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) is increasingly used for various conditions, yet its success and failure remain underexplored. In this multicenter study, we assessed 220 TORS interventions across 211 patients. Success criteria differed by condition, including tumor identification for CUP, resection margins for malignancies, and symptom improvement for benign cases like OSA and chronic lingual tonsillitis. Predictors of success varied, with factors such as patient comorbidity, tumor characteristics, and demographics playing roles. Conversely, failure predictors encompassed postoperative complications and pain, linked to patient health and demographics. These insights into TORS outcomes may aid in patient selection and counseling across different conditions, informing clinical practice and enhancing patient care. Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling. [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]

To evaluate the effect of incorporating calcium advice into early pregnancy counseling on calcium intake during pregnancy in the Netherlands. A multicenter prospective before-after cohort study was conducted introducing risk-based care including calculating individual pre-eclampsia risk. Part of the intervention was to incorporate calcium advice into routine counseling. We calculated individual daily calcium intake and adequacy of calcium intake (≥1,000 mg/day) at 16, 24 and 34 weeks of pregnancy. We performed a multiple logistic regression adjusting for covariates to identify any differences in the risk of inadequate calcium intake between RC and CAC. In regular care (RC, 2013–2015, n=2,477) 60% had inadequate calcium intake, compared to 49% during calcium advice care (CAC, 2017–2018, n=774) (aOR 0.75, 95% CI 0.64–0.88). Specific calcium supplements were used by 2% and 29% in RC and CAC, respectively (OR 25.1, 95% CI 17.8–36.0). Determinants of an inadequate calcium intake were lower age (aOR per additional year 0.96, 95% CI: 0.94–0.98), nulliparity (aOR 1.22, 95% CI: 1.03–1.45) and non-Caucasian origin (aOR 1.83, 95% CI 1.09–3.09). In CAC, risk of inadequate intake decreased with increasing predicted pre-eclampsia risk, which was a trend reversal compared to RC. Incorporating calcium advice into early pregnancy counseling was shown to lead to a decrease in the risk of inadequate calcium intake during pregnancy, but still inadequate intake in half of the women suggesting the need for further study on improving implementation. Awareness of individual increased PE risk had positive effect on calcium intake. [ABSTRACT FROM AUTHOR]

Purpose: The SARS-CoV-2 pandemic severely disrupted society and the health care system. In addition to epidemiological changes, little is known about the pandemic's effects on the trauma care chain. Therefore, in addition to epidemiology and aetiology, this study aims to describe the impact of the SARS-CoV-2 pandemic on prehospital times, resource use and outcome. Methods: A multicentre observational cohort study based on the Dutch Nationwide Trauma Registry was performed. Characteristics, resource usage, and outcomes of trauma patients treated at all trauma-receiving hospitals during the first (W1, March 12 through May 11) and second waves (W2, May 12 through September 23), as well as the interbellum period in between (INT, September 23 through December 31), were compared with those treated from the same periods in 2018 and 2019. Results: The trauma caseload was reduced by 20% during the W1 period and 11% during the W2 period. The median length of stay was significantly shortened for hip fracture and major trauma patients (ISS ≥ 16). A 33% and 66% increase in the prevalence of minor self-harm-related injuries was recorded during the W1 and W2 periods, respectively, and a 36% increase in violence-related injuries was recorded during the INT. Mortality was significantly higher in the W1 (2.9% vs. 2.2%) and W2 (3.2% vs. 2.7%) periods. Conclusion: The imposed restrictions in response to the SARS-CoV-2 pandemic led to diminished numbers of acute trauma admissions in the Netherlands. The long-lasting pressing demand for resources, including ICU services, has negatively affected trauma care. Further caution is warranted regarding the increased incidence of injuries related to violence and self-harm. [ABSTRACT FROM AUTHOR]

Background: Activity pacing is a behavioral strategy for coping with fatigue, optimizing physical activity (PA) levels, and achieving a paced approach to lifestyle and sustainable self-regulated exercise practice to optimize health and well-being. Yet little is known about how activity pacing affects PA and health-related quality of life (HRQOL) while controlling for fatigue and demographic characteristics over time in adults with multiple sclerosis (MS). This study examined the natural use of activity pacing and how it is associated with PA and HRQOL over time in adults with MS. Methods: Sixty-eight adults with MS (mean ± SD age, 45.2 ± 10.9 years) completed questionnaires on their activity pacing, fatigue, PA, and HRQOL 14, 33, and 52 weeks after rehabilitation. Associations between the variables were examined using multilevel models. Results: No associations were found between activity pacing and PA ( β = -0.01, P = .89) or between activity pacing and HRQOL ( β = -0.15, P = .09). Conclusions: This study provides an initial understanding of how activity pacing relates to PA and HRQOL in people with MS over time and indicates that there is no clear strategy among adults with MS that is successful in improving PA and HRQOL in the short or long term. Persons with MS may benefit from goal-directed activity pacing interventions to improve longitudinal engagement in PA, and the present study provides a foundation for further intervention development. [ABSTRACT FROM AUTHOR]

Employment of young adults with chronic physical conditions entering the labor market after finishing post-secondary education remains behind compared to typically developing peers. The aim of this study is to evaluate changes in their paid employment levels after following a vocational rehabilitation intervention ('At Work'). Participants aged between 16 and 27 years (n = 90) were recruited via rehabilitation physicians and a jobcoach agency and participated in a vocational rehabilitation program. Cochran's Q and McNemar tests served to test the development of intervention participants' paid employment over time. Chi-square tests were used to compare intervention participants' paid employment level with national reference data selected on age and having a self-reported chronic physical condition. Paid employment level of the intervention cohort significantly increased from 10.0% at baseline to 42.4% at 2-years follow-up (p < 0.001). At 2-years follow-up, their employment rates approached the employment rates of national reference data (42.4% versus 52.9%, p = 0.17). Starting from a disadvantaged position, the paid employment rate of the intervention cohort substantially increased over time, approaching the employment rate of reference data. 'At Work' seems to be appropriate for supporting this specific group who face obstacles to enter the labor market, to find competitive employment. 'At Work' is a vocational rehabilitation intervention for young adults with chronic physical conditions who experience problems with finding and maintaining competitive employment after finishing post-secondary education. The 'At Work' intervention entails a combination of group sessions and individual coaching sessions based on the supported employment methodology. Paid employment rates of the intervention cohort substantially increased on the short- and long term, and approached employment rates of reference data of persons with chronic physical conditions. The 'At Work' intervention seems appropriate to support young adults with chronic physical conditions who experience barriers for work participation, to enter the labor market and find competitive and sustainable employment. [ABSTRACT FROM AUTHOR]

Background During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. Objective The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. Methods This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. Results A total of 1,376 patients were included (median age 78 years (interquartile range 74–84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6–9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1–3, patients with CFS 4–5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3–3.0)) and patients with CFS 6–9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8–4.3)). Conclusions The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms. [ABSTRACT FROM AUTHOR]

Aims and objectives: To identify that workarounds (defined as "informal temporary practices for handling exceptions to normal procedures or workflow") by nurses using information technology potentially compromise medication safety. Therefore, we aimed to identify potential risk factors associated with workarounds performed by nurses in Barcode‐assisted Medication Administration in hospitals. Background: Medication errors occur during the prescribing, distribution and administration of medication. Errors could harm patients and be a tragedy for both nurses and medical doctors involved. Interventions to prevent errors have been developed, including those based on information technology. To cope with shortcomings in information technology‐based interventions as Barcode‐assisted Medication Administration, nurses perform workarounds. Identification of workarounds in information technology is essential to implement better‐designed software and processes which fit the nurse workflow. Design: We used the data from our previous prospective observational study, performed in four general hospitals in the Netherlands using Barcode techniques, to administer medication to inpatients. Methods: Data were collected from 2014–2016. The disguised observation was used to gather information on potential risk factors and workarounds. The outcome was a medication administration with one or more workarounds. Logistic mixed models were used to determine the association between potential risk factors and workarounds. The STROBE checklist was used for reporting our data. Results: We included 5,793 medication administrations among 1,230 patients given by 272 nurses. In 3,633 (62.7%) of the administrations, one or more workarounds were observed. In the multivariate analysis, factors significantly associated with workarounds were the medication round at 02 p.m.–06 p.m. (adjusted odds ratio [OR]: 1.60, 95% CI: 1.05–2.45) and 06 p.m.–10 p.m. (adjusted OR: 3.60, 95% CI: 2.11–6.14) versus the morning shift 06 a.m.–10 a.m., the workdays Monday (adjusted OR: 2.59, 95% CI: 1.51–4.44), Wednesday (adjusted OR: 1.92, 95% CI: 1.2–3.07) and Saturday (adjusted OR: 2.24, 95% CI: 1.31–3.84) versus Sunday, the route of medication, nonoral (adjusted OR: 1.28, 95% CI: 1.05–1.57) versus the oral route of drug administration, the Anatomic Therapeutic Chemical classification‐coded medication "other" (consisting of the irregularly used Anatomic Therapeutic Chemical classes [D, G, H, L, P, V, Y, Z]) (adjusted OR: 1.49, 95% CI: 1.05–2.11) versus Anatomic Therapeutic Chemical class A (alimentary tract and metabolism), and the patient–nurse ratio ≥6–1 (adjusted OR: 5.61, 95% CI: 2.9–10.83) versus ≤5–1. Conclusions: We identified several potential risk factors associated with workarounds performed by nurses that could be used to target future improvement efforts in Barcode‐assisted Medication Administration. Relevance to clinical practice: Nurses administering medication in hospitals using Barcode‐assisted Medication Administration frequently perform workarounds, which may compromise medication safety. In particular, nurse workload and the patient–nurse ratio could be the focus for improvement measures as these are the most clearly modifiable factors identified in this study. [ABSTRACT FROM AUTHOR]

Purpose Three out of ten patients do not return to work after total knee arthroplasty (TKA). Patient expectations are suggested to play a key role. What are patients' expectations regarding the ability to perform work-related knee-demanding activities 6 months after TKA compared to their preoperative status? Methods A multi-center cross-sectional study was performed among 292 working patients listed for TKA. The Work Osteoarthritis or joint-Replacement Questionnaire (WORQ, range 0–100, minimal important difference 13) was used to assess the preoperatively experienced and expected ability to perform work-related knee-demanding activities 6 months postoperatively. Differences between the preoperative and expected WORQ scores were tested and the most difficult knee-demanding work-related activities were described. Results Two hundred thirty-six working patients (81%) completed the questionnaire. Patients' expected WORQ score (Median = 75, IQR 60–86) was significantly (p < 0.01) higher than their preoperative WORQ score (Median = 44, IQR 35–56). A clinical improvement in ability to perform work-related knee-demanding activities was expected by 72% of the patients, while 28% of the patients expected no clinical improvement or even worse ability to perform work-related knee-demanding activities 6 months after TKA. Of the patients, 34% expected severe difficulty in kneeling, 30% in crouching and 17% in clambering 6 months after TKA. Conclusions Most patients have high expectations, especially regarding activities involving deep knee flexion. Remarkably, three out of ten patients expect no clinical improvement or even a worse ability to perform work-related knee-demanding activities 6 months postoperatively compared to their preoperative status. Therefore, addressing patients expectations seems useful in order to assure realistic expectations regarding work activities. [ABSTRACT FROM AUTHOR]

Background: There is a high need for evidence-based psychosocial treatments for adult attention-deficit hyperactivity disorder (ADHD) to offer alongside treatment as usual (TAU). Mindfulness-based cognitive therapy (MBCT) is a promising psychosocial treatment. This trial investigated the efficacy of MBCT + TAU v. TAU in reducing core symptoms in adults with ADHD. Methods: A multicentre, single-blind, randomised controlled trial (ClinicalTrials.gov: NCT02463396). Participants were randomly assigned to MBCT + TAU (n = 60), an 8-weekly group therapy including meditation exercises, psychoeducation and group discussions, or TAU only (n = 60), which reflected usual treatment in the Netherlands and included pharmacotherapy and/or psychoeducation. Primary outcome was ADHD symptoms rated by blinded clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. Outcomes were assessed at baseline, post-treatment, 3- and 6-month follow-up. Post-treatment effects at group and individual level, and follow-up effects were examined. Results: In MBCT + TAU patients, a significant reduction of clinician-rated ADHD symptoms was found at post-treatment [ M difference = −3.44 (−5.75, −1.11), p = 0.004, d = 0.41]. This effect was maintained until 6-month follow-up. More MBCT + TAU (27%) than TAU participants (4%) showed a ⩽30% reduction of ADHD symptoms (p = 0.001). MBCT + TAU patients compared with TAU patients also reported significant improvements in ADHD symptoms, mindfulness skills, self-compassion and positive mental health at post-treatment, which were maintained until 6-month follow-up. Although patients in MBCT + TAU compared with TAU reported no improvement in executive functioning at post-treatment, they did report improvement at 6-month follow-up. Conclusions: MBCT might be a valuable treatment option alongside TAU for adult ADHD aimed at alleviating symptoms. [ABSTRACT FROM AUTHOR]

The aim of this qualitative study was to identify barriers and facilitators to the adoption and particularly the implementation of a web-based computer-tailored obesity prevention intervention by occupational health centers. Participants were directors of Dutch occupational health centers who had adopted and implemented the intervention for the corresponding efficacy study (n = 8) as well as non-adopters (n = 12). Individual semi-structured interviews were carried out to study barriers and facilitators related to the intervention, the user, the organization, and the socio-political environment. All interviews were carried out by telephone, audio-recorded and transcribed verbatim. The transcripts were analyzed using a directed-content approach and coded by two persons. There were important differences in perceptions between adopters and non-adopters, particularly on barriers and facilitators related to the intervention and the personal beliefs of the implementer. The relative advantages of the intervention were considered to be most important. Participants also indicated that their personal attitudinal and self-efficacy beliefs influenced their implementation efforts. Regarding the organization, the possibilities to increase profits and integrate the intervention within the organization were considered to be important facilitators for the implementation. Participants mentioned few implementation barriers and facilitators related to the socio-political environment. Strategies to improve the implementation of web- based computer-tailored interventions by occupational health centers should be tailored to implementers' unique perceptions and particularly address the perceived advantages and disadvantages of the intervention, attitudinal and self-efficacy beliefs, and the potential to increase organizations' profits and competitiveness. [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]

Background: Promoting adaptation, improving well-being and maintaining an optimal quality of life (QOL) is an important aspect in dementia care. The purpose of this study was to identify determinants of QOL in young onset dementia, and to assess differences in QoL domains between people with Alzheimer's disease (AD) and frontotemporal dementia (FTD). Methods: In total 135 persons with AD and 58 persons with FTD were included from two prospective cohort studies. QOL was assessed with the proxy reported quality of life in Alzheimer's disease questionnaire (QoL-AD). Possible determinants were explored using multiple linear regression and included sociodemographic variables, diagnosis, dementia severity, disease awareness, neuropsychiatric symptoms, met and unmet needs and hours of personal and instrumental care. Differences between QOL domains in people with AD and FTD were calculated using Mann-Whitney U tests. Results: Lower QOL was associated with more depressive symptoms, lower disease awareness, and a higher amount of needs, both met and unmet. People with AD scored lower on the memory and higher on the friends' subscale. No differences were found for the other items. Conclusion: This study demonstrates a unique set of determinants of QOL in AD and FTD. Interventions directed towards these specific factors may improve QOL. [ABSTRACT FROM AUTHOR]

Objective: To assess the degree of fatigue in children and youth after traumatic and non-traumatic brain injury (TBI and NTBI) and related factors. Method: Follow-up study including patients with a hospital-based diagnosis of acquired brain injury (ABI), aged 4–20 years at onset and their parents. Parents and children (dependent on age) completed the Paediatric Quality of Life Inventory™ Multidimensional Fatigue Scale (PedsQL™ MFS), which measures general fatigue (GF), sleep/rest fatigue (SRF) and cognitive fatigue (CF). Additional assessments included the Child & Family Follow-up Survey (CFFS) and PedsQL™ 4.0 General Core Scales and sociodemographic and disease characteristics. Results: Eighty-eight parents completed the PedsQL™ MFS 24–30 months after diagnosis, with 49/88 patients (56%) completing the child version. The median age of the patients was 11 years (interquartile range [IQR] = 7). There were 69 patients with TBI (16% moderate/severe TBI) and 19 patients with NTBI (16% moderate/severe NTBI). The median parent-reported and child-reported PedsQL™ MFS Total Scale Scores were 76.5 (SD = 16.4) and 78.5 (12.9), respectively (Spearmanr= 0.450,p= 0.001). Apart from NTBI, increasing age and a single-parent household were significantly associated with more fatigue according to the parent-reported PedsQL™ MFS Total Score (and/or one or more sub-scale scores). Conclusion: Two years after onset, in particular, the parent-reported fatigue after NTBI was considerable. Moreover, older children and children from a single-parent household were found to have higher fatigue levels. [ABSTRACT FROM PUBLISHER]

Aims and objectives To explore which factors determine successful intermittent catheterisation. Background Intermittent catheterisation is a safe, effective treatment and is associated with improved quality of life, although negative issues are reported. Factors which determine adherence are largely unknown. An additional qualitative study was conducted to gain insight into patient's experience with intermittent catheterisation in everyday life. Design A prospective multicentre study was conducted between March 2012-March 2013 with one year follow-up. Methods Patients with a variety of diagnoses referred to the outpatient clinic, ≥18 years, performed catheterisation at least once a day for ≥3 months were included. Data were obtained by patients' specific questionnaire Visual Analog Scale of quality of life regarding voiding problems, a questionnaire about catheterisation in daily practice, King's Health questionnaire, and a short questionnaire after one year. Results Of the 129 (72 male) patients, mean age 62 (22-86) years, seven died and 63 stopped, 32/63 (50%) due to recovered bladder function. Fifty-nine (47%) continued to perform catheterisation after one year. Forty-seven (86%) patients reported catheterisation had become part of their life or had a positive effect on their life. A weak correlation was found between increasing age and cessation of catheterisation. Visual Analogue Scale - score on quality of life improved for the total group. The King's Health questionnaire identified in the total group that the impact of the bladder problem in daily life, limitations in daily activities and negative emotions decreased over time. Conclusion Adherence of successful intermittent catheterisation can be influenced negatively by increasing age. However, we think catheterisation should be considered as an option for older patients. We could not conform that if intermittent catheterisation was beneficial for the patient, it would positively influence adherence. Further prospective studies on adherence of intermittent catheterisation in larger groups need to be undertaken. Relevance to Clinical Practice After implementation of the national guideline in 2008, we were able to perform a multicentre study. This prospective study gives insight into patients who were undertaking intermittent catheterisation and which factors determine successful intermittent catheterisation adherence. After following the national guideline, we found no factors for additional interventions in assessment or coaching intermittent catheterisation. Post void residual volume turned out to be not a predictor for the necessity of intermittent catheterisation. A large group of patients could discontinue intermittent catheterisation during follow-up due to bladder function recovery. Although a weak correlation was found between increasing age and ceasing of catheterisation, we think the older can benefit from intermittent catheterisation. In the first period, additional support, for example given by a district nurse, may be necessary for this group to achieve better outcomes. [ABSTRACT FROM AUTHOR]

BackgroundCD64 is expressed on the surface membrane of neutrophils (nCD64) in the presence of bacterial infection. Although initial studies in intensive care settings have been promising, only two small, methodologically flawed studies have been performed in feverish children presenting to the emergency departement (ED), both of which were showing a moderate diagnostic value of nCD64 to detect a serious bacterial infection (SBI). This study aimed to determine the diagnostic value of nCD64 in children presenting with fever to the ED for detecting SBI.MethodsIn this prospective observational multi-centre study previously healthy children aged 1 month–16 years with fever, presenting to the ED of two hospitals in the Netherlands in 2011–2012 were included. Standardised information on clinical features were collected and nCD64 and CRP were measured routinely. Multivariable logistic regression was used to determine the discriminative ability to detect SBI (ROC-area) of nCD64 compared with CRP. Diagnostic performance measures including sensitivity, specificity and likelihood ratios were calculated.ResultsIn 392 children (45%) with both CRP and nCD64 determined, 52 children (13%) had an SBI. The AUC of the ROC curve for CD64 was 0.62 (95% CI = 0.54–0.70) and 0.75 (95% CI = 0.67-0.83) for CRP. Neither duration of fever nor deviated vital signs influenced the diagnostic performance of nCD64.ConclusionNCD64 expression has poor discriminative value to detect children with an SBI in a general population of febrile children at the ED. It has no superior value compared to CRP in this setting, neither in total nor in sub-populations. [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.In head and neck cancer (HNC) patients, long-term treatment-related complications include radiotherapy (RT)-induced carotid vasculopathy and stroke. The current study investigated the magnetic resonance imaging (MRI) characteristics of the carotid wall in long-term HNC survivors treated with RT. Methods.MRI of the carotid arteries was performed within a prospective cohort of 42 HNC patients on average 7 years after RT. Two independent radiologists assessed maximal vessel wall thickness of common and internal carotid arteries. In case of wall thickening (≥ 2 mm) the MRI signals as well as length of the thickened segment were assessed. Results.Mean (SD) age of the 42 patients at baseline was 53 (13) years and mean (SD) follow-up time after RT was 6.8 (1.3) years. In total 62% were men and 60% had one or more cerebrovascular risk factors. Mean (SD) dose of RT on the common carotid arteries and internal carotid arteries was 57 Gy (11) and 61 Gy (10), respectively. Wall thickening was observed in 58% of irradiated versus 27% of non-irradiated common carotid arteries and 24% of irradiated versus 6% of non-irradiated internal carotid arteries (p < 0.05). Mean (SD) thickness of the irradiated and non-irradiated common carotid arteries was 2.5 (0.9) and 2 (0.7) mm (p = 0.02). Mean thickness of the irradiated and non-irradiated internal carotid arteries was 1.8 (0.8) and 1.5 mm (0.3) (n.s.). Mean length of the thickened vessel wall was 48 mm versus 36 mm in the irradiated versus non-irradiated common carotid arteries (p = 0.03) and 20 mm versus 15 mm in the irradiated versus non-irradiated internal carotid arteries (n.s.). No significant differences were observed for signal intensities of the vessel walls. Conclusions.Our study showed significantly more vessel wall thickening in irradiated versus non-irradiated carotid arteries years after RT for HNC, while no differences in signal intensities were observed. [ABSTRACT FROM AUTHOR]

Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging--derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD. [ABSTRACT FROM AUTHOR]

The article presents the results of a 10-year follow-up of a randomized multicenter trial that compared surgical treatment with ambulatory compression therapy for venous leg ulcers. Disease specific and generic quality-of-life (QoL) as well as current ulcer state and recurrence during the follow-up period were assessed. The results indicate that surgical treatment was more effective in increasing patients' chances of being ulcer-free.

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]

Purpose: The aim of this study is to evaluate the effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine. Methods: Between 2001 and 2007, 164 medical students took part in the prospective explorative study during their clinical clerkship in internal medicine at the VU University Medical Center, Amsterdam, The Netherlands. In a fixed order, each student had to formulate a treatment plan for a real patient in three situations of increasing realism: a minimal level (studying a patient record), medium level (preparing for a therapeutic consultation), and optimal level (preparing for and performing a therapeutic consultation with the patient). Results: In comparison to studying a patient record (minimal context level), preparing a therapeutic consultation (medium context) improved four of the six steps of the WHO six-step plan. Preparing and performing a therapeutic consultation with a real patient (optimal context) further improved three essential prescribing competencies, namely checking for contraindications and interactions, prescription writing, and instructions to the patient. Conclusion and recommendations: The results of this first explorative study suggest that enrichment of the learning context (responsibility for patient care) might be an important factor to improve the training of rational prescribing skills of medical students during their clinical clerkship in internal medicine. Clinical (pharmacology) teachers should be aware that seemingly small adaptations in the learning context of prescribing training during clinical clerkships (i.e., with or without involvement with and responsibility for patient care) may have relatively large impact on the development of prescribing competencies of our future doctors. [ABSTRACT FROM AUTHOR]

Background: Many people with dementia die in long-term care settings. These patients may benefit from a palliative care goal, focused on comfort. Admission may be a good time to revisit or develop care plans. Objective: To describe care goals in nursing home patients with dementia and factors associated with establishing a comfort care goal. Design: We used generalized estimating equation regression analyses for baseline analyses and multinomial logistic regression analyses for longitudinal analyses. Setting: Prospective data collection in 28 Dutch facilities, mostly nursing homes (2007-2010; Dutch End of Life in Dementia study, DEOLD). Results: Eight weeks after admission (baseline), 56.7% of 326 patients had a comfort care goal. At death, 89.5% had a comfort care goal. Adjusted for illness severity, patients with a baseline comfort care goal were more likely to have a religious affiliation, to be less competent to make decisions, and to have a short survival prediction. Their families were less likely to prefer life-prolongation and more likely to be satisfied with family-physician communication. Compared with patients with a comfort care goal established later during their stay, patients with a baseline comfort care goal also more frequently had a more highly educated family member. Conclusions: Initially, over half of the patients had a care goal focused on comfort, increasing to the large majority of the patients at death. Optimizing patient-family-physician communication upon admission may support the early establishing of a comfort care goal. Patient condition and family views play a role, and physicians should be aware that religious affiliation and education may also affect the (timing of) setting a comfort care goal. [ABSTRACT FROM AUTHOR]