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Decreased appetite is one of the main risk factors of malnutrition. Little is known on how appetite changes during hospitalization and after discharge and how it relates with sarcopenia-related outcomes. We analyzed data of the Hospital-ADL study, a multicenter prospective cohort study that followed 400 acutely hospitalized older adults (≥70 year). Appetite (SNAQ), handgrip strength (Jamar), muscle mass (BIA), mobility (DEMMI), and physical performance (SPPB) were assessed within 48 h of admission, at discharge, and at one and three months post-discharge. The course of decreased appetite was analysed by Generalised Estimating Equations. Linear Mixed Model was used to analyse the associations between decreased appetite and the sarcopenia-related outcomes. Decreased appetite was reported by 51% at hospital admission, 34% at discharge, 28% one month post-discharge, and 17% three months post-discharge. Overall, decreased appetite was associated with lower muscle strength (β = −1.089, p = 0.001), lower mobility skills (β = −3.893, p &lt, 0.001), and lower physical performance (β = −0.706, p &lt, 0.001) but not with muscle mass (β = −0.023, p = 0.920). In conclusion, decreased appetite was highly prevalent among acute hospitalized older adults and remained prevalent, although less, after discharge. Decreased appetite was significantly associated with negative sarcopenia-related outcomes, which underlines the need for assessment and monitoring of decreased appetite during and post hospitalization.

ObjectiveThe clinical course of multiple sclerosis (MS) is variable and largely unpredictable pointing to an urgent need for markers to monitor disease activity and progression. Recent evidence revealed that tissue transglutaminase (TG2) is altered in patient-derived monocytes. We hypothesize that blood cell–derived TG2 messenger RNA (mRNA) can potentially be used as biomarker in patients with MS.MethodsIn peripheral blood mononuclear cells (PBMCs) from 151 healthy controls and 161 patients with MS, TG2 mRNA was measured and correlated with clinical and MRI parameters of disease activity (annualized relapse rate, gadolinium-enhanced lesions, and T2 lesion volume) and disease progression (Expanded Disability Status Scale [EDSS], normalized brain volume, and hypointense T1 lesion volume).ResultsPBMC-derived TG2 mRNA levels were significantly associated with disease progression, i.e., worsening of the EDSS over 2 years of follow-up, normalized brain volume, and normalized gray and white matter volume in the total MS patient group at baseline. Of these, in patients with relapsing-remitting MS, TG2 expression was significantly associated with worsening of the EDSS scores over 2 years of follow-up. In the patients with primary progressive (PP) MS, TG2 mRNA levels were significantly associated with EDSS, normalized brain volume, and normalized gray and white matter volume at baseline. In addition, TG2 mRNA associated with T1 hypointense lesion volume in the patients with PP MS at baseline.ConclusionPBMC-derived TG2 mRNA levels hold promise as biomarker for disease progression in patients with MS.Classification of EvidenceThis study provides Class II evidence that in patients with MS, PBMC-derived TG2 mRNA levels are associated with disease progression.

Objectives: The aims of this study were (1) to quantify and compare the load of a professional football team's training days and matches and (2) to compare training of nonstarters the day after the match with regular training of starters and nonstarters.Methods: On-field training load during in-season training days (categorized as days before match day, i.e., MD minus) and 3 friendly matches were recorded using alocal positioning measurement system.Results: Mixed linear models showed lower load when training approached match day. Relative to match values (100%), training values for running (52 -20%; MD-4 -MD-1) and high-speed running (38 -15%) were lower than for total distance (67 -35%), and all considerably lower than match values. On average, medium and high accelerations and decelerations during training were more similar to match values (90 -39%). Load during nonstarters training was lower than during regular training for almost all variables on MD-4 and several high-intensity variables on MD-3 and MD-2.Conclusions: The results highlight that acceleration and deceleration measures complement more commonly used external load variables based on distance and speed. Furthermore, nonstarters are potentially under-loaded compared to starters, especially in terms of (high-speed) running.

Background The evidence justifying the use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) is limited. We did a prospective randomised trial to compare the safety of IBBR with an ADM immediately after mastectomy with that of two-stage IBBR.Methods We did an open-label, randomised, controlled trial in eight hospitals in the Netherlands. Eligible women were older than 18 years with breast carcinoma or a gene mutation linked with breast cancer who intended to undergo skin-sparing mastectomy and immediate IBBR. Randomisation was done electronically, stratifi ed per centre and in blocks of ten to achieve roughly balanced groups. Women were assigned to undergo one-stage IBBR with ADM (Strattice, LifeCell, Branchburg, NJ, USA) or two-stage IBBR. The primary endpoint was quality of life and safety was assessed by the occurrence of adverse outcomes. Analyses were done per protocol with logistic regression and generalised estimating equations. This study is registered at Nederlands Trial Register, number NTR5446.Findings 142 women were enrolled between April 14, 2013, and May 29, 2015, of whom 59 (91 breasts) in the one-stage IBBR with ADM group and 62 (92 breasts) in the two-stage IBBR group were included in analyses. One-stage IBBR with ADM was associated with signifi cantly higher risk per breast of surgical complications (crude odds ratio 3.81, 95% CI 2.67-5.43, pInterpretation Immediate one-stage IBBR with ADM was associated with adverse events and should be considered very carefully. Understanding of selection of patients, risk factors, and surgical and postsurgical procedures needs to be improved.

Although a broad array of neurocognitive dysfunctions are associated with ADHD, it is unknown whether these dysfunctions play a role in the course of ADHD symptoms. The present longitudinal study investigated whether neurocognitive functions assessed at study-entry (mean age = 11.5 years, SD = 2.7) predicted ADHD symptom severity and overall functioning 6 years later (mean age = 17.4 years, 82.6 % = male) in a carefully phenotyped large sample of 226 Caucasian participants from 182 families diagnosed with ADHD-combined type. Outcome measures were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. Predictors were derived from component scores for 8 domains of neurocognitive functioning: working memory, motor inhibition, cognitive inhibition, reaction time variability, timing, information processing speed, motor control, intelligence. Effects of age, gender, and pharmacological treatment were considered. Results showed that better working memory predicted lower ADHD symptom severity (R 2 = 3.0 %), and less reaction time variability predicted better overall functioning (higher K-GAS-score, R 2 = 5.6 %). Predictors were still significant with baseline behavior included in the models. The role of neurocognitive functioning in the long term outcome of ADHD behavior is discussed. Electronic supplementary material The online version of this article (doi:10.1007/s10802-016-0175-3) contains supplementary material, which is available to authorized users.

Item does not contain fulltext This study intended to investigate the capability of the 4 test items "sprint", "agility", "speed while dribbling" and "throwing a ball" of the Dutch perceptuo-motor skills assessment used at the age of 7-10 years to predict table tennis performance (U13, U15 and U18) in an observational study. Data of 1191 young table tennis players, collected from 1998 to 2013, were analysed in univariable and multivariable logistic and linear regression models. The test items "sprint" and "throwing a ball" showed to be significant predictors for table tennis performance outcomes in boys (P < 0.05). For girls, besides these test items also "speed while dribbling" had a significant contribution (P < 0.05). Since the accuracies of the models were low, it is advised to include other determinants to enhance the predictive value of a model for table tennis performance. Nevertheless, it can be concluded that a perceptuo-motor skills assessment might improve the effectiveness of talent programmes in table tennis as an additional method to objectively estimate a youth players' potential. Future research focusing on the inclusion of test items specifically assessing eye hand coordination and other domains, for example, the psychological and the environmental domain, related to table tennis performance are recommended.

Background Autologous fat grafting (AFG) is increasingly used in cosmetic surgery. However, its efficacy and safety are still ambiguous. Both a comprehensive overview and recapitulation of the relevant literature provide current evidence on the efficacy and outcomes of AFG in cosmetic breast surgery. Objectives This review provides an up-to-date overview of the literature on AFG in cosmetic breast augmentation. Methods A systematic review of the literature on AFG used for cosmetic breast augmentation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This study included selected studies that were published between January 1996 and February 2016 and reported on 10 patients or more who had a minimal mean follow-up period of 1 year. Results In this study, 22 articles that reported on 3565 patients with follow-up periods ranging from 12 to 136 months were included. A complication rate of 17.2% (95% CI 15.9-18.5) was seen. Indurations were the most frequent complication (33.3%, 95% CI 20.4-46.3), followed by persistent pain (25%, 95% CI 0.5-49.5), and hematoma (16.4%, 95% CI 14.5-18.4). Mammograms revealed micro-calcifications (9.0%, 95% CI 6.4-11.5) and macro-calcifications (7.0%, 95% CI 3.8-10.2). The mean volume retention was 62.4% (range, 44.7-82.6%), with a satisfaction rate of 92% in patients and 89% in surgeons. Conclusions AFG is a promising method in achieving autologous cosmetic breast augmentation with satisfactory volume retention and satisfaction rates in eight and six studies, respectively. Complications and radiological findings are comparable to those after implant augmentation. Future studies should focus on cancer occurrence and detection to further substantiate AFG safety. In addition, grafting methods and the use of auxiliary procedures to identify factors leading to better outcomes in terms of volume retention should be investigated. Finally, objective questionnaires are needed to represent patient satisfaction. Level of Evidence 3 ![Graphic][1] Therapeutic [10.1093/asj/sjw119][2] [1]: /embed/inline-graphic-1.gif [2]: /lookup/doi/10.1093/asj/sjw119

Purpose A multifaceted implementation strategy was targeted at supervisors to encourage them to apply a participatory approach (PA) in dealing with employees’ work functioning problems due to health concerns. This paper assesses the effect on employees’ perceived social norms regarding the use of the PA to deal with work functioning problems. Methods Three organizations participated in a cluster randomized controlled trial, with randomization at the department level. Supervisors in the PA intervention departments received the implementation strategy consisting of a working group meeting, supervisor training, and optional coaching. Supervisors in the control departments received written information about the PA only. In two of the organizations, employees were invited to complete surveys at baseline and at 6-month follow-up. The primary outcome was perceived social norms regarding the use of the PA to deal with work functioning problems. Secondary measures included attitudes and self-efficacy, and intention regarding joint problem solving, and sick leave data. Effects were analyzed using multilevel analyses to account for nesting of cases. Results At baseline, 273 employees participated in the survey, with follow-up analyses of 174 employees. There were no statistically significant group effects on employee outcome measures. The intervention group showed a larger reduction in mean sick days (from 4.6 to 2.4 days) versus the control group (from 3.8 to 3.6 days), but this difference did not reach statistical significance (p > .05). Conclusion The multifaceted strategy to implement the participatory approach for supervisors did not show effects on outcomes at the employee level. To gain significant effects at the employee level, may require that an implementation strategy not only targets management and supervisors, but also employees themselves.Trial registration: NTR3733.

Objective: To assess, for people with subacute spinal cord injury, if rehabilitation that is reinforced with the addition of a behavioral intervention to promote physical activity leads to a better health, participation and quality of life. Design: Randomized controlled trial. Setting: Rehabilitation centers. Participants: A total of 39 participants analyzed (45 included), with subacute spinal cord injury in inpatient rehabilitation, dependent on a manual wheelchair (33% tetraplegia, 62% motor complete, 150 ±74 days postinjury). Intervention: A behavioral intervention promoting physical activity after discharge, involving 13 individual sessions delivered by a coach trained in motivational interviewing, beginning two months before and ending six months after discharge from inpatient rehabilitation. Main measures: Physical capacity as determined during a maximal exercise test, body mass index, blood pressure, fasting lipid profile, and social participation (IMPACT-S) and quality of life (SF-36) were determined using questionnaires. Measurements were performed two months before discharge, at discharge, and six and 12 months after discharge from inpatient rehabilitation. B represents the between-group difference. Results: Twelve months after discharge, significant intervention effects were found for diastolic blood pressure (B = –11.35 mmHg, 95% CI = –19.98 to −2.71), total cholesterol (B = –0.89 mmol/L, 95% CI = –1.59 to −0.20), low-density lipoprotein cholesterol (B = −0.63 mmol/L, 95% CI = –1.25 to −0.00) and participation (B = 9.91, 95% CI = 3.34 to 16.48). Conclusions: A behavioral intervention promoting physical activity after discharge from inpatient rehabilitation improves social participation and seems to reduce risk factors for cardiovascular disease in people with subacute spinal cord injury.

Although the average depressed patient benefits moderately from cognitive-behavioral therapy (CBT) or pharmacotherapy, some experience divergent outcomes. The authors tested frequencies, predictors, and moderators of negative and unusually positive outcomes.Sixteen randomized clinical trials comparing CBT and pharmacotherapy for unipolar depression in 1,700 patients provided individual pre- and posttreatment scores on the Hamilton Depression Rating Scale (HAM-D) and/or Beck Depression Inventory (BDI). The authors examined demographic and clinical predictors and treatment moderators of any deterioration (increase ≥1 HAM-D or BDI point), reliable deterioration (increase ≥8 HAM-D or ≥9 BDI points), extreme nonresponse (posttreatment HAM-D score ≥21 or BDI score ≥31), superior improvement (HAM-D or BDI decrease ≥95%), and superior response (posttreatment HAM-D or BDI score of 0) using multilevel models.About 5%-7% of patients showed any deterioration, 1% reliable deterioration, 4%-5% extreme nonresponse, 6%-10% superior improvement, and 4%-5% superior response. Superior improvement on the HAM-D only (odds ratio=1.67) and attrition (odds ratio=1.67) were more frequent in pharmacotherapy than in CBT. Patients with deterioration or superior response had lower pretreatment symptom levels, whereas patients with extreme nonresponse or superior improvement had higher levels.Deterioration and extreme nonresponse and, similarly, superior improvement and superior response, both occur infrequently in randomized clinical trials comparing CBT and pharmacotherapy for depression. Pretreatment symptom levels help forecast negative and unusually positive outcomes but do not guide selection of CBT versus pharmacotherapy. Pharmacotherapy may produce clinician-rated superior improvement and attrition more frequently than does CBT.

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Objective The somatosensory amplification theory considers symptom focusing and somatosensory amplification as important perpetuating factors of persistent physical symptoms. We investigated whether symptom focusing and somatosensory amplification were associated with symptom severity and mental and physical functioning over a three-year period in patients with persistent physical symptoms (PPS). Methods Baseline, 6-, 12-, 24- and 36-months follow-up data from the PROSPECTS study, a prospective cohort consisting of 325 patients with PPS, were used. We applied longitudinal mixed model analyses to investigate if symptom focusing (CBRQ Symptom Focusing Subscale) and somatosensory amplification (Somatosensory Amplification Scale) at baseline were associated with symptom severity (PHQ-15), mental and physical functioning (RAND-36 MCS and PCS) over three years, using all measurements. Results Symptom focusing was associated with increased symptom severity and lower mental and physical functioning over time. Somatosensory amplification at baseline was associated with increased symptom severity and lower mental and physical functioning over time. Effect sizes were small. Associations with baseline symptom focusing decreased over time, associations with baseline somatosensory amplification were more stable. There was no interaction effect of both constructs, but they partly overlapped. Conclusion This is the first study to show that over an extended period, symptom focusing and somatosensory amplification are associated with symptom severity and lower mental and physical functioning in patients with PPS. These results support the impact of both symptom focusing and somatosensory amplification on the perpetuation of symptoms and lowered mental and physical functioning in individuals with PPS.

Introduction Electroconvulsive therapy (ECT) is an important and effective treatment for depression. However, research on course trajectories of depressive symptoms during ECT is limited. Insight into putative differences in speed of response of depressive symptom dimensions may enable clinicians to optimally inform patients and their relatives. Therefore, we aim to examine course trajectories of depressive symptom dimensions in depressed older persons during ECT.Methods Data were derived from the Mood Disorders in Elderly treated with Electro Convulsive Therapy study, including 110 persons, aged 55 years or more, with a current diagnosis of major depressive disorder and referred for ECT. Exploratory factor analysis was used to identify symptom dimensions, using the 10 depression items of the Montgomery-Åsberg Depression Rating Scale (MADRS). Differences in course trajectories of symptom dimension during 2 weeks were examined by multilevel analyses.Results Three symptom dimensions were identified: a “mood,” “melancholic,” and “suicidal” dimension. Mood showed a significantly greater severity decline as compared with melancholic and suicidal at the 1-week follow-up. At the 2-week follow-up, both mood and melancholic demonstrated a significantly greater decline as compared with suicidal. However, because scores on the suicidality item of the Montgomery-Asberg Depression Rating Scale were already lower at baseline compared with the other items, a floor effect cannot be ruled out.Discussion All symptom dimensions of depression showed a rapid response to ECT. Our findings did not support the general assumption that suicidal symptoms may be the first to improve. However, a floor effect on the suicidality item cannot be ruled out.

Objectives The incidence of children developing metachronous contralateral inguinal hernia (MCIH) is 7–15%. Contralateral groin exploration during unilateral hernia repair can prevent MCIH development and subsequent second surgery and anaesthesia. Preoperative ultrasonography is a less invasive strategy and potentially able to detect contralateral patent processus vaginalis (CPPV) prior to MCIH development. Methods We queried MEDLINE, Embase and Cochrane library to identify studies regarding children aged < 18 years diagnosed with unilateral inguinal hernia without clinical signs of contralateral hernia, who underwent preoperative ultrasonography of the contralateral groin. We assessed heterogeneity and used a random-effects model to obtain pooled estimates of sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Results Fourteen studies (2120 patients) were included, seven (1013 patients) in the meta-analysis. In studies using surgical exploration as reference test (n = 4, 494 patients), pooled sensitivity and specificity were 93% and 88% respectively. In studies using contralateral exploration as reference test following positive and clinical follow-up after negative ultrasonographic test results (n = 3, 519 patients), pooled sensitivity was 86% and specificity 98%. The AUC (0.984) shows high diagnostic accuracy of preoperative ultrasonography for detecting CPPV, although diagnostic ultrasonographic criteria largely differ and large heterogeneity exists. Reported inguinal canal diameters in children with CPPV were 2.70 ± 1.17 mm, 6.8 ± 1.3 mm and 9.0 ± 1.9 mm. Conclusion Diagnostic accuracy of preoperative ultrasonography to detect CPPV seems promising, though may result in an overestimation of MCIH prevalence, since CPPV does not invariably lead to MCIH. Unequivocal ultrasonographic criteria are mandatory for proper diagnosis of CPPV and subsequent prediction of MCIH. Key Points • Diagnostic accuracy of preoperative ultrasonography for detection of CPPV in children with unilateral inguinal hernia is high. • Preoperative ultrasonographic evaluation of the contralateral groin assumedly results in an overestimation of MCIH prevalence. • Unequivocal ultrasonographic criteria are mandatory for proper diagnosis of CPPV and risk factor identification is needed to predict whether CPPV develops into clinically apparent MCIH. Electronic supplementary material The online version of this article (10.1007/s00330-018-5625-6) contains supplementary material, which is available to authorized users.

Background: In patients with rheumatoid arthritis (RA), both high and low forefoot plantar pressures have been reported. Better understanding of pathology in the forefoot associated with altered pressure distribution in patients with RA could help to better formulate and specify goals for treatment with foot orthoses or therapeutic footwear. Objectives: To investigate the association of plantar pressure with disease activity and deformity in the forefoot in patients with rheumatoid arthritis and forefoot symptoms. Methods: A cross sectional study, using data of 172 patients with rheumatoid arthritis and forefoot symptoms, was conducted. Peak pressure (PP) and pressure time integral (PTI) in the forefoot were measured with a pressure platform. Forefoot deformity was assessed using the Platto score. Forefoot disease activity was defined as swelling and/or pain assessed by palpation of the metatarsophalangeal joints. The forefoot was divided in a medial, central and lateral region, in which the following conditions could be present: 1) no pathology, 2) disease activity, 3) deformity or 4) disease activity and deformity. A multilevel analysis was performed using condition per forefoot region as independent variable and PP or PTI in the corresponding region as dependent variable. Results: Statistically significant higher plantar pressures were found in forefoot regions with deformities (RR 1.2, CI 1.1-1.3, P

Purpose Stereotactic ablative body radiation therapy (SABR) for lung tumors ≥5 cm can be associated with more toxicity than that for smaller tumors. We investigated the relationship between dosimetry and toxicity and used a knowledge-based planning solution to retrospectively perform individualized treatment plan quality assurance (QA) with the aim of identifying where planning could have been improved. Methods and Materials Previous retrospective analysis of 53 patients with primary or recurrent non-small cell lung cancer ≥5 cm, treated with 5- or 8-fraction volumetric modulated arc therapy SABR between 2008 and 2014, showed 30% with grade ≥3 toxicity. During this period, several improvements were made to departmental planning protocols. RapidPlan was used to compare dosimetry of patients with or without grade ≥3 toxicity. A model comprising plans from patients without toxicity and compliant with the current planning protocol was used to provide QA for the plans from patients who had toxicity. Results Sixteen of 53 patients had grade ≥3 toxicity, including 10 with radiation pneumonitis (RP), 3 with lung hemorrhage (1 of these also had RP), and 1 with airway stenosis/atelectasis. RP was again shown to be significantly correlated with contralateral and total-lung V5 and mean lung dose. The 4 highest contralateral-lung doses belonged to patients with RP. Five of 10 clinical plans in patients with RP had a contralateral-lung mean dose up to 2.5 times higher than that of the knowledge-based plan. For 2 of 3 patients with lung hemorrhage and 1 with airway stenosis/atelectasis, the clinical plans had the highest proximal bronchial tree doses, which was also higher than in plans from the model. In 8 patients with grade ≥3 toxicity, clinical plans had dosimetry similar to that in the predictions from the model. Conclusions A “no-toxicity” RapidPlan model identified the potential for dosimetric improvement in nearly 50% of historical treatment plans from patients with grade ≥3 toxicity after SABR for lung tumors ≥5 cm. Model-based QA may be useful for benchmarking treatment planning protocols in routine practice and in clinical studies.

Longitudinal studies on the course of neurocognitive functioning of children with ADHD and their unaffected siblings are scarce. Also, it is unclear to what extent that course is related to ADHD outcomes. A carefully phenotyped large sample of 838 Caucasian participants (ADHD-combined type: n = 339, unaffected siblings: n = 271, controls: n = 228; mean age at baseline = 11.4 years, mean age at follow-up = 17.3 years, SD = 3.2) was used to investigate differences in the course of neurocognitive functioning of ADHD affected and unaffected siblings versus controls, and to investigate the relationship between neurocognitive change and ADHD outcomes. At baseline, an aggregated measure of overall neurocognitive functioning and eight neurocognitive measures of working memory, timing (speed/variability), motor control, and intelligence were investigated. Outcomes at follow-up were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. At follow up, affected and unaffected siblings trended to, or fully caught up with performance levels of controls on four (44.4%) and five (55.6%) of the nine dependent variables, respectively. In contrast, performance in remaining key neurocognitive measures (i.e. verbal working memory, variability in responding) remained impaired at follow-up. Change in neurocognitive functioning was not related to ADHD outcomes. Our results question the etiological link between neurocognitive deficits and ADHD outcomes in adolescents and young adults. Electronic supplementary material The online version of this article (10.1007/s10802-018-0449-z) contains supplementary material, which is available to authorized users.

Background The rationale for promoting increased consumption of fruit and vegetables (FV) at an early age is based on results from previous tracking-studies, indicating that dietary habits learned in childhood sustain into adulthood. Previous tracking studies have several limitations (e.g. low study sample, few repeated measurements and/or short a follow-up period). In addition, to our knowledge, no study has shown that a dietary intervention initiated in childhood affects tracking of dietary behaviour. The main objectives in this study were therefore to assess tracking of FV and unhealthy snacks in a large sample with multiple follow-up surveys over 15-years, and whether exposure to free school fruit for one school year modified tracking. Method The longitudinal cohort-study, Fruit and Vegetables Make the Marks, included 38 randomly drawn schools in Norway; nine intervention schools received free fruit (or vegetable) in the school year 2001/2002 and 29 schools severed as control. The baseline sample included 1950 subjects, and 16–92% participated at five follow-up surveys (2002–2016). FV consumption and unhealthy snacks were measured by FFQ. Mixed models were applied to estimate overall tracking coefficients, and to assess whether the intervention modified tracking ((from baseline, from follow-up one (while intervention was running) and from follow-up two (after end of intervention)). Results Overall tracking coefficients were 0.33 for fruit, 0.36 for vegetables and differed by sex for unhealthy snacks: 0.46 males and 0.39 for females (interaction p = 0.065). Most analyses showed no significant difference in tracking between the intervention group and control group. However, from follow-up one, tracking coefficients were different for unhealthy snacks, 0.46 vs. 0.38 (interaction p = 0.036), and from follow-up two for vegetables, 0.35 vs 0.48 (p = 0.036), in the intervention group and control group, respectively. Conclusion Our results indicate low to moderate tracking of FV and unhealthy snacks from childhood to adulthood. We found little evidence that the free fruit intervention modified tracking of fruit, vegetables or unhealthy snacks. More research is needed on if or how we can influence the tracking of fruit, vegetables and unhealthy snacks consumption to improve public health.

BACKGROUND: Both donors and the blood bank rely on the result of the donor health interview. However, survey data suggest that substantial variability in deferral rates among interviewers exist. We studied whether variability remained after adjusting for conditional factors.STUDY DESIGN AND METHODS: The data set included Dutch interview data on whole blood donor visits in 2015, where one of their visits was selected randomly. We applied logistic regression and multilevel regression analyses with the donor visit, with the interviewer representing the levels. We set up four models: 1) all reasons deferral, 2) low-hemoglobin-level deferral, 3) infectious disease risk deferral and 4) other medical reasons deferral.RESULTS: In total, 138,398 visits were included in the study, of which 60,534 (43.7%) related to male donors. The overall deferral rate for men was 7.91% and for women 12.25%. Deferral rates among interviewers ranged from as low as 1.19% up to 28.8%. Models 2 (low hemoglobin level) and particularly 4 (other medical reasons), for both men and women, showed significant intraclass correlation coefficients, implying considerable deferral rate variability among interviewers. Donor age, the number of previous visits, and the season had relatively large effects. However, explained variances of the logistic regression models were relatively low, ranging from 2.53% to 7.35%.CONCLUSION: Deferral appears to be a random process, while substantial variability was found among interviewer deferral rates, suggesting that some interviewers are more cautious than others. Our results suggest heuristic and subjective diagnosing to be prevalent. Steps should be taken to improve interview result validity.

Targeted screening for childhood high blood pressure may be more feasible than routine blood pressure measurement in all children to avoid unnecessary harms, overdiagnosis or costs. Targeting maybe based e.g. on being overweight, but information on other predictors may also be useful. Therefore, we aimed to develop a multivariable diagnostic prediction model to select children aged 9-10 years for blood pressure measurement. Data from 5359 children in a population-based prospective cohort study were used. High blood pressure was defined as systolic or diastolic blood pressure ≥ 95th percentile for gender, age, and height. Logistic regression with backward selection was used to identify the strongest predictors related to pregnancy, child, and parent characteristics. Internal validation was performed using bootstrapping. 227 children (4.2%) had high blood pressure. The diagnostic model included maternal hypertensive disease during pregnancy, maternal BMI, maternal educational level, parental hypertension, parental smoking, child birth weight standard deviation score (SDS), child BMI SDS, and child ethnicity. The area under the ROC curve was 0.73, compared to 0.65 when using only child overweight. Using the model and a cut-off of 5% for predicted risk, sensitivity and specificity were 59% and 76%; using child overweight only, sensitivity and specificity were 47% and 84%. In conclusion, our diagnostic prediction model uses easily obtainable information to identify children at increased risk of high blood pressure, offering an opportunity for targeted screening. This model enables to detect a higher proportion of children with high blood pressure than a strategy based on child overweight only.

BACKGROUND Online contacts with a health professional have the potential to support family caregivers of people with dementia. OBJECTIVE To study the effects of an online self-management support intervention in helping family caregivers to deal with behavior changes of the relative with dementia. The intervention - involving among others personal e-mail contacts with a dementia nurse - was compared to online interventions without these e-mail contacts. METHODS A randomized controlled trial (RCT) was conducted with 81 family caregivers of people with dementia who live at home. Participants were randomly assigned to one of (1) a major self-management support intervention consisting of personal e-mail contacts with a specialist dementia nurse, online videos, and e-bulletins; or (2) a medium intervention consisting only of online videos and e-bulletins; or (3) a minor intervention consisting of only the e-bulletins. The primary outcome was family caregivers’ self-efficacy in dealing with behavior changes of the relative with dementia. Secondary outcomes were family caregivers’ reports of behavior problems in the people with dementia and the quality of the relationship between the family caregiver and the person with dementia. Measurements were performed at the baseline and at six (T1) and twelve weeks (T2) after the baseline. A mixed-model analysis was conducted to compare the outcomes of the three intervention arms. RESULTS Family caregivers participating in the major intervention involving e-mail contacts showed no statistically significant differences in self-efficacy after the intervention compared to the minor intervention involving only e-bulletins (difference -0.02, p-value 0.99). In the adjusted analysis, the medium intervention (involving videos and e-bulletins) showed a negative trend over time (difference -4.21, p=0.09) and at T1 (difference -4.71, p=0.07) compared to the minor intervention involving only e-bulletins. Neither were any statistical differences found between the intervention arms in terms of the reported behavior problems and the quality of the relationship between the family caregiver and the person with dementia. CONCLUSIONS The expectation that an online self-management support intervention involving e-mail contacts would lead to positive effects and be more effective than online interventions without personal e-mail contacts was not borne out. One explanation might be related to the fact that not all family caregivers who were assigned to that intervention actually made use of the opportunity for personal e-mail contact. The online videos were also not always viewed. To obtain more definite conclusions, future research involving extra efforts to reach higher usage rates is required. CLINICALTRIAL Netherlands Trial Registry (NTR): NTR6237; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6237 (Archived by WebCite at http://www.webcitation.org/6v0S4fxTC)

Objectives: Dizziness is common in older people. Physicians are often unable to identify a specific cause for dizziness in older people, even after an extensive diagnostic work-up. A prognosis- oriented approach, i.e. treating modifiable risk factors for an unfavourable course of dizziness, may reduce dizziness-related impairment in older people in primary care. Design: Cluster randomized controlled trial. Setting: 45 primary care practices in The Netherlands. Participants 168 participants aged ≥65y who consulted their general practitioner for dizziness and experienced significant dizziness-related impairment (Dizziness Handicap Inventory (DHI) ≥30). Participants were part of to the intervention group (n = 83) or control group (n = 85), depending on whether they were enlisted in an intervention practice or in a control practice. Interventions: The multifactorial intervention consisted of: medication adjustment in case of ≥3 prescribed fall-risk-increasing drugs (FRIDs) and/or stepped mental health care in case of anxiety disorder and/or depression and/or exercise therapy in case of impaired functional mobility. The intervention was compared to usual care. Outcome measures: The primary outcome was dizziness-related impairment. Secondary outcomes were quality of life (QoL), dizziness frequency, fall frequency, anxiety and depression, use of FRIDs. Results: Intention-to-treat analysis showed no significant intervention effect on dizziness-related impairment (DHI score difference -0.69 [95% CI -5.66;4.28]; p = 0.79). The intervention proved effective in reducing the number of FRIDs (FRID difference -0.48 [95% CI -0.89;- 0.06]; p = 0.02). No significant intervention effects were found on other secondary outcomes. The uptake of and adherence to the interventions was significantly lower in patients eligible for ≥2 interventions compared to patients eligible for one intervention (p

ObjectiveInsulin glargine 300 (Gla-300) provides less hypoglycemia risk and more flexibility in injection time. The extent to which these effects translate into improved patient-reported outcomes (PROs) is unknown, and is the subject of this observational study.Research design and methodsAdults with type 2 diabetes treated with basal insulin for at least 6 months initiating Gla-300 were included. Data were collected at baseline (start Gla-300) and at 3-month and 6-month follow-up. Patients and physicians gave reasons for switching to Gla-300 at baseline and the extent to which Gla-300 fulfilled their expectations at 6 months. Mixed model analyses examined PRO changes over time, with emotional well-being (WHO-5 Well-Being Index) as the primary outcome. The secondary outcomes were hypoglycemia incidence, hemoglobin A1c (HbA1c), hypoglycemia worries (worry subscale of the Hypoglycemia Fear Survey), diabetes distress (short form of the Dutch version of the Problem Areas In Diabetes Scale), diabetes medication convenience (Diabetes Medication System Rating Questionnaire (DMSRQ)), sleep quality and duration (Pittsburgh Sleep Quality Index), and adherence (Summary of Diabetes Self-Care Activities).Results162 patients participated: 53.70% were men, the mean age was 65.54 years (9.05), baseline mean HbA1c was 7.87% (1.15) (62.48 mmol/mol (12.61)), and mean diabetes duration was 15.14 years (6.65). Mean WHO-5 Well-Being Index scores improved non-significantly from 61.94 (19.52) at baseline (T0) to 63.83 (19.67) at 6 months (T2). Mean DMSRQ scores improved significantly from 32.96 (9.02) (T0) to 36.70 (8.85) (T2) (pConclusionIn a relatively well-controlled sample of adults with type 2 diabetes, switching to Gla-300 improves diabetes medication convenience.

ObjectiveMedial tibial stress syndrome (MTSS) is a common lower extremity overuse injury often causing long-term reduction of sports participation. This study aimed to investigate the incidence and risk factors of MTSS in first-year Dutch Physical Education Teacher Education (PETE) students.MethodsThis prospective study consisted of physical measures at baseline (height, weight, fat percentage, 3000 m run test, navicular drop test, hip internal and external range of motion, hip adduction and adduction strength, single leg squat and shin palpation), an intake questionnaire at baseline (age, sport participation, presence of MTSS, MTSS history, insole use and use of supportive shoes) and an MTSS registration procedure during the academic year of 2016–2017 (10 months) using a validated questionnaire. In total 221 first-year PETE students were included, of whom 170 (77%) were male and 51 (23%) female. The evaluation of risk factors was conducted with univariable and multivariable logistic generalised estimating equation analyses.ResultsIn total 55 (25%) subjects, 35 (21%) men and 20 (39%) women, developed MTSS during the follow-up period. The associated risk factors were female sex (OR=3.14, 95% CI 1.39 to 7.11), above-average age (OR=0.31, 95% CI 0.13 to 0.76), above-average body mass index (OR=2.29, 95% CI 1.02 to 5.16) and history of MTSS (OR=5.03, 95% CI 1.90 to 13.30).ConclusionThe incidence of MTSS is high in PETE students. Several risk factors were identified. These results demonstrate the need for prevention and may provide direction to preventive intervention design.

PurposeTo investigate the effects of Shared Decision-Making (SDM) using Routine Outcome Monitoring (ROM) primary on patients’ perception of Decisional Conflict (DC), which measures patients’ engagement in and satisfaction with clinical decisions, and secondary on working alliance and treatment outcomes.MethodMulti-centre two-arm matched-paired cluster randomised-controlled trial in Dutch specialist mental health care. SDM using ROM (SDMR) was compared with Decision-Making As Usual (DMAU). Outcomes were measured at baseline (T0) and 6 months (T1). Multilevel regression and intention-to-treat analyses were used. Post hoc analyses were performed on influence of subgroups and application of SDMR on DC.ResultsSeven teams were randomised to each arm. T0 was completed by 186 patients (51% intervention; 49% control) and T1 by 158 patients (51% intervention, 49% control). DC, working alliance, and treatment outcomes reported by patients did not differ significantly between two arms. Post hoc analyses revealed that SDMR led to less DC among depressed patients (p = 0.047, d =− 0.69). If SDMR was applied well, patients reported less DC (SDM: p = 0.000, d = − 0.45; ROM: p = 0.021, d = − 0.32), which was associated with better treatment outcomes.ConclusionExcept for patients with mood disorders, we found no difference between the arms for patient-reported DC. This might be explained by the less than optimal uptake of this generic intervention, which did not support patients directly. Regarding the positive influence of a higher level of applying SDM and ROM on less DC and better treatment outcomes, the results are encouraging for further investments in patient-oriented development and implementation of SDMR.

ObjectiveTo optimally target exercise interventions for patients with cancer, it is important to identify which patients benefit from which interventions.DesignWe conducted an individual patient data meta-analysis to investigate demographic, clinical, intervention-related and exercise-related moderators of exercise intervention effects on physical fitness in patients with cancer.Data sourcesWe identified relevant studies via systematic searches in electronic databases (PubMed, Embase, PsycINFO and CINAHL).Eligibility criteriaWe analysed data from 28 randomised controlled trials investigating the effects of exercise on upper body muscle strength (UBMS) and lower body muscle strength (LBMS), lower body muscle function (LBMF) and aerobic fitness in adult patients with cancer.ResultsExercise significantly improved UBMS (β=0.20, 95% Confidence Interval (CI) 0.14 to 0.26), LBMS (β=0.29, 95% CI 0.23 to 0.35), LBMF (β=0.16, 95% CI 0.08 to 0.24) and aerobic fitness (β=0.28, 95% CI 0.23 to 0.34), with larger effects for supervised interventions. Exercise effects on UBMS were larger during treatment, when supervised interventions included ≥3 sessions per week, when resistance exercises were included and when session duration was >60 min. Exercise effects on LBMS were larger for patients who were living alone, for supervised interventions including resistance exercise and when session duration was >60 min. Exercise effects on aerobic fitness were larger for younger patients and when supervised interventions included aerobic exercise.ConclusionExercise interventions during and following cancer treatment had small effects on UBMS, LBMS, LBMF and aerobic fitness. Demographic, intervention-related and exercise-related characteristics including age, marital status, intervention timing, delivery mode and frequency and type and time of exercise sessions moderated the exercise effect on UBMS, LBMS and aerobic fitness.

OBJECTIVES: Chest radiograph is considered the first-line diagnostic imaging modality for patients presenting with pulmonary symptoms in the ICU. In this meta-analysis, we aim to evaluate the diagnostic accuracy of chest radiograph, and when concomitantly studied lung ultrasound, in comparison with the gold-standard CT for adult critically ill patients with respiratory symptoms.DATA SOURCES: PubMed, EMBASE, and Gray literature.STUDY SELECTION: Studies comparing chest radiograph, and if performed lung ultrasound, with CT for adult ICU patients with respiratory symptoms.DATA EXTRACTION: Quality was scored with Quality Assessment of Diagnostic Accuracy Studies-2, and study setting, test characteristics, and study design were extracted.DATA SYNTHESIS: In the meta-analysis, we included 10 full-text studies, including 543 patients, and found that chest radiograph has an overall sensitivity of 49% (95% CI, 40-58%) and specificity of 92% (86-95%). In seven studies, where also lung ultrasound was studied, lung ultrasound had an overall sensitivity of 95% (92-96%) and specificity of 94% (90-97%). Substantial heterogeneity was found. A planned subgroup analysis for individual pathologies was performed. The results of four abstract-only studies, included in the systematic review, were considered unlikely to significantly influence results of our meta-analysis. Study limitations were that most studies were of low power combined with methodological limitations.CONCLUSIONS: This meta-analysis demonstrates that chest radiograph has a low sensitivity and reasonable specificity compared with CT for detecting lung pathology in critically ill patients. The studies also investigating lung ultrasound, showed lung ultrasound to be clearly superior to chest radiograph in terms of sensitivity with similar specificity, thereby opting to be the first-line diagnostic tool in these patients.

Insulin glargine-300 (U-300) provides a flatter and more prolonged profile than U-100, with less risk of hypoglycemia. Real-world evidence of the effect of U-300 on Patient Reported Outcomes (PROs) is lacking. Adults with type 2 diabetes (T2DM) using insulin for ≥6 months and initiating U-300 were included. Data were collected at baseline (start U-300; T0)), 3 (T1) and 6 months (T2). Intention-to-treat mixed model analyses examined change over time in HbA1c, self-reported hypoglycemia and PROs: emotional well-being (WHO-5), hypoglycemia worries (HFS-W), diabetes distress (PAID-SF), diabetes medication convenience (DMSRQ), sleep quality and duration (PSQI), and adherence (1 item SDSCA). Also, the extent to which U-300 fulfilled its expectations was measured at T2 both in physicians and patients. P-value threshold was set at .for the WHO-5 and .01 for other outcomes. In total, 162 persons with T2DM participated: 53.7% men, mean age 64.54 years (9.05), baseline mean HbA1c 62.48 mmol/mol (12.61). Hypoglycemia incidence decreased non-significantly: for symptomatic events from 31.5% (T0) to 24.8% (T2), nocturnal events from 6.8% (T0) to 4.1% (T2), severe events from 4.9% (T0) to 0.0% (T2). HbA1c trended towards a decrease to 60.32 mmol/mol (12.09) (T2). Mean WHO-5 scores trended towards improvement, from 61.73 (T0) to 63.93 (T2). Mean DMSRQ scores improved significantly from 32.70 (T0) to 35.80 (T1) (beta T0-T1 = 3.28; p Disclosure T.H. Wieringa: Other Relationship; Self; Sanofi. M. de Wit: Advisory Panel; Self; Sanofi.J. Twisk: None.F.J. Snoek: None.

Diffuse intrinsic pontine glioma (DIPG) is an incurable type of pediatric brainstem cancer that is thought to originate from primitive neural stem cells, and is characterized by the frequent presence of mutations in histone 3 genes. Biopsy studies have shown that a large subset of DIPG possesses a mesenchymal phenotype, likely contributing to the diffuse growth pattern and inherent therapy resistance of these tumors. Recently, the receptor tyrosine kinase AXL has been identified both as an important player in the mesenchymal transition and as a hallmark of neural stem cells. In this study, we demonstrate that AXL is a driver of the mesenchymal and stem-like phenotype of DIPG cells and as such, is a promising therapeutic target. Inhibition of AXL by the small molecule BGB324, in combination with the HDAC inhibitor panobinostat, potently and synergistically decreases cell viability and migration of primary DIPG cultures, and reverses their mesenchymal and stem-like phenotype. Moreover, this combination treatment leads to decreased expression of important genes involved in DNA repair, and a strong radiosensitizing effect on DIPG cultures. Pharmacokinetic studies further reveal that BGB324 is capable of crossing the blood-brain barrier and can reach therapeutic concentrations in mouse brain. Consequently, we demonstrate that treatment of DIPG xenograft bearing mice with BGB324 and panobinostat results in a decrease in tumor load and extended survival. Altogether, our study shows that AXL is an important player in DIPG biology and demonstrates the promising therapeutic potential of the combination of BGB324 and panobinostat for the treatment of DIPG.

Purpose: This study aimed to evaluate the long-term effectiveness and cost-effectiveness of high intensity (HI) versus low-to-moderate intensity (LMI) exercise on physical fitness, fatigue, and health-related quality of life (HRQoL) in cancer survivors. Methods: Two hundred seventy-seven cancer survivors participated in the Resistance and Endurance exercise After ChemoTherapy (REACT) study and were randomized to 12 weeks of HI (n = 139) or LMI exercise (n = 138) that had similar exercise types, durations, and frequencies, but different intensities. Measurements were performed at baseline (4–6 weeks after primary treatment), and 12 (i.e., short term) and 64 (i.e., longer term) weeks later. Outcomes included cardiorespiratory fitness, muscle strength, self-reported fatigue, HRQoL, quality-adjusted life years (QALYs) and societal costs. Linear mixed models were conducted to study (a) differences in effects between HI and LMI exercise at longer term, (b) within-group changes from short term to longer term, and (c) the cost-effectiveness from a societal perspective. Results: At longer term, intervention effects on role (β = 5.9, 95% CI = 0.5; 11.3) and social functioning (β = 5.7, 95%CI = 1.7; 9.6) were larger for HI compared to those for LMI exercise. No significant between-group differences were found for physical fitness and fatigue. Intervention-induced improvements in cardiorespiratory fitness and HRQoL were maintained between weeks 12 and 64, but not for fatigue. From a societal perspective, the probability that HI was cost-effective compared to LMI exercise was 0.91 at 20,000€/QALY and 0.95 at 52,000€/QALY gained, mostly due to significant lower healthcare costs in HI exrcise. Conclusions: At longer term, we found larger intervention effects on role and social functioning for HI than for LMI exercise. Furthermore, HI exercise was cost-effective with regard to QALYs compared to LMI exercise. Trial registration: This study is registered at the Netherlands Trial Register [NTR2153 [http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2153]] on the 5th of January 2010. Implications for Cancer Survivors: Exercise is recommended to be part of standard cancer care, and HI may be preferred over LMI exercise.

Background Muscle weakness is common in patients with knee osteoarthritis (OA). Muscle weakness negatively impacts future functional status, and has been linked to symptomatic and radiographic progression of knee OA. Limited information is available on the course of muscle strength over time in these patients. Objectives The aim of the present study is to (i) analyse the course and (ii) to identify baseline predictors for upper leg muscle strength over time in subjects with knee OA. Methods Data were obtained from the progression cohort of the Osteoarthritis Initiative (OAI) database. Upper leg muscle strength (in N/kg) was measured at baseline, 24 months and 48 months. Potential baseline predictors were demographical factors (age, gender, race, body height, body weight), metabolic factors (body mass index (BMI)), nutrition and vitamin related factors (dietary protein intake, dietary energy intake, vitamin D use, glucosamine use), lifestyle related factors (alcohol consumption, smoking, physical activity), OA-specific factors (KL grade, knee alignment, effusion, pain, pain medication use) and health related factors (comorbidities and depression). Univariable and multivariable mixed model analyses were performed to analyse the course and to identify baseline predictors for muscle strength over time. Results A total of 1390 subjects with knee osteoarthritis were included. The majority of the subjects were female (57.1%), mean ±SD for age was 61.4±9.1 and mean ±SD for body mass index was 30.2±4.9. All subjects had frequent knee symptoms and radiographic tibiofemoral knee OA (Kellgren en Lawrence score ≥2) at baseline. Muscle strength was significantly lower at 24 months and 48 months compared to baseline; there was no difference between 24 and 48 months. Older age, being female, higher BMI, being non-Caucasian, lower protein intake (g/kg bodyweight), higher dietary energy intake, alcohol consumption, less physical activity valgus malalignment, higher score on the WOMAC pain subscale and the use of pain medication at baseline were predictors of lower muscle strength over time. Conclusions Muscle strength decreased over time between baseline and 24 months, but not between 24 and 48 months, which may be attributed to reaching a plateau or to other reasons. In the present study a number of demographic factors, metabolic factors and factors related to nutrition and vitamins, lifestyle and knee OA were found to be predictive for decreased muscle strength over time. This set of baseline factors can be used to identify patients with knee OA at risk for decline of muscle strength over time. External validation of our model is needed. Disclosure of Interest None declared

Physical activity plays an important role in the prevention of chronic lifestyle-related diseases. The development of valid instruments for the assessment of physical activity remains a challenge in field studies. The purpose of the present study was therefore to determine the level of agreement between physical activity objectively measured by the ActiHeart&reg, (Cambridge Neurotechnology Ltd, Cambridge, UK) device and subjectively reported physical activity by means of the International Physical Activity Questionnaire Short Form (IPAQ-SF) among adolescents attending schools in the Tlokwe Local Municipality, South Africa. A cross-sectional study design was used with a total of 63 boys and 45 girls aged 15 years who took part in the Physical Activity and Health Longitudinal Study (PHALS). Stature and weight were measured according to standard International Society for the Advancement of Kinanthropometry (ISAK) protocols. Objective physical activity (PA) was measured by a combined heart rate and accelerometer device (ActiHeart&reg, ) for seven consecutive days. Time spent in moderate-to-vigorous intensity physical activity (MVPA) was assessed. Subjective physical activity was assessed with the self-reported IPAQ-SF. Objective PA indicated that 93% of the participants were inactive and only 6% were highly active. The IPAQ-SF showed that 24% were inactive, with 57% active. A non-significant correlation (r = 0.11, p = 0.29) between the ActiHeart&reg, measure of activity energy expenditure (AEE) and total physical activity (IPAQ-SF) was observed. The Bland&ndash, Altman plot showed no agreement between the two measurement instruments and also a variation in the level of equivalence. When Cohen&rsquo, s kappa (&kappa, ) was run to determine the agreement between the two measurement instruments for estimated physical activity, a poor agreement (&kappa, = 0.011, p &lt, 0.005) between the two was found. The poor level of agreement between the objective measure of physical activity (ActiHeart&reg, ) and the IPAQ-SF questionnaire should be interpreted cautiously. Future physical activity research using a combination of subjective and objective assessment methods in a large-scale cohort in adolescents is recommended.

Background: Randomised controlled trials (RCTs) are the gold standard to estimate treatment effects. When patients receive effective treatment over time they may reach the limit of a certain measurement scale. This phenomenon is known as censoring and leads to skewed distributions of the outcome variable with an excess of either low (floor effect) or high values (ceiling effect). Applying traditional methods such as linear mixed models to analyse these kind of longitudinal RCT data may result in bias of the regression coefficients. To deal with floor effects due to censoring, a tobit mixed model can be used. The objective of this study was to compare the results of longitudinal linear mixed model analyses with longitudinal tobit mixed model analyses. Methods: A simulation study was performed in which several situations of RCTs with floor effects were simulated. From the simulated datasets, which were set up to estimate the interaction between treatment and time, the regression coefficient for this interaction and for the overall treatment effect were estimated. Additionally, data from an empirical RCT were analysed with both methods. Results: Regarding the interaction between treatment and time, the results of the tobit mixed model analysis were the same as the true values in all conditions, while the linear mixed model analysis revealed highly underestimated regression coefficients. However, the overall treatment effect with an increasing number of follow-up measurements in combination with a strong floor effect showed that the estimates from the tobit mixed model were also not accurate. Conclusion: Tobit mixed model analysis should be used to estimate treatments effects in longitudinal RCTs with floor effects due to censoring. © 2018, Prex S.p.A. All rights reserved.

Background: In patients with rheumatoid arthritis (RA), both high and low forefoot plantar pressures have been reported in the literature (1–3). Understanding of contributing factors to forefoot pressure alterations can help to better formulate and specify goals for treatment with foot orthoses or therapeutic footwear. Objectives: Investigate the association of local disease activity and forefoot deformity with plantar pressure in RA patients with forefoot symptoms. Methods: A cross sectional study was conducted in the Amsterdam Foot (AMS-foot) cohort, using data of 172 consecutive patients with RA and forefoot symptoms. Peak pressure (PP) and pressure time integral (PTI) in the forefoot were measured with a pressure platform. Forefoot deformity was measured with the Platto score. Forefoot disease activity was defined as swelling and/or pain measured by palpation of the metatarsophalangeal (MTP) joints. The forefoot was divided in a medial, central and lateral region, in which the following conditions could be present: 1) no abnormality, 2) disease activity, 3) deformity or 4) deformity and disease activity. A multilevel analysis was performed using condition per forefoot region as the independent variable and PP or PTI in the corresponding region as the dependent variable. Results: Statistically significant higher PP and PTI were found in forefoot regions when deformities were present (RR 1.2, CI 1.1–1.3, P Conclusions: Deformities in the medial, central and lateral forefoot regions are related to higher plantar pressures measured in these regions. The absence of an association between local disease activity and plantar pressure might be explained by the low prevalence of MTP pain or swelling as detected by palpation. Future research with ultrasound measurements to detect disease activity is recommended to reveal the effect of forefoot disease activity on plantar pressure. References 1. van der Leeden M, Steultjens M, Dekker JHM, Prins APA, Dekker J. Forefoot joint damage, pain and disability in rheumatoid arthritis patients with foot complaints: The role of plantar pressure and gait characteristics. Rheumatology2006;45(4):465–9. 2. Turner DE, Woodburn J. Characterising the clinical and biomechanical features of severely deformed feet in rheumatoid arthritis. Gait Posture2008;28(4):574–80. 3. Bowen CJ, Culliford D, Allen R, Beacroft J, Gay A, Hooper L, et al. Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months. J Foot Ankle Res. 2011;4(1):25. Disclosure of Interest: None declared

INTRODUCTION: There is an ongoing debate on the optimal treatment for stage I NSCLC, with increasing evidence for comparable health outcomes after surgery and stereotactic body radiation therapy (SBRT). For clinical decision making, the experienced quality of life, summarized as health utility, is of importance to choosing between treatments. In this study, we evaluated differences in longitudinal health utility in stage I NSCLC in the first year after surgical resection versus after SBRT before any recurrence of disease. We also assessed the impact of potential prognostic variables on health utility.METHODS: Prospectively collected databases containing data on patients with stage I NSCLC treated with either SBRT or surgery were pooled from two large hospitals in the Netherlands. Quality of life data were measured by the Quality of Life Questionnaire-Core 30 questionnaire at baseline and 3, 6, and 12 months after treatment. Health utility (measured using the European Quality of Life Five-Dimension questionnaire) was calculated from the Quality of Life Questionnaire-Core 30 questionnaire by using a mapping algorithm. Propensity score matching was used to adjust for selection bias. Treatment effects were estimated for the matched patients by using a longitudinal mixed model approach.RESULTS: After correction for Eastern Cooperative Oncology Group score, sex, and age, the difference in 1-year averaged health utility between the SBRT and surgery groups was 0.026 (95% confidence interval: 0.028-0.080). Differences in health utility decreased over time.CONCLUSIONS: A small but not statistically significant difference in health utility was found between patients with stage I NSCLC treated with surgery and those treated with SBRT. Current analysis strengthens existing evidence that SBRT is an equivalent treatment option for early-stage NSCLC. Comparative cost-effectiveness remains to be determined.

BACKGROUND: Insulin resistance after surgery hampers recovery. Oxidative stress is shown to be involved in the occurrence of postoperative insulin resistance. Preoperative carbohydrate-rich oral nutrition supplements reduce but do not prevent insulin resistance. The aim of the present study was to investigate the effect of a carbohydrate-, glutamine-, and antioxidant-enriched preoperative oral nutrition supplement on postoperative insulin resistance.METHODS: A double-blind randomized controlled pilot study in 18 patients with rectal cancer, who received either the supplement (S) or the placebo (P) 15, 11, and 4 hours preoperatively, was conducted. Insulin sensitivity was studied prior to surgery and on the first postoperative day using a hyperinsulinemic euglycemic 2-step clamp.RESULTS: Hepatic insulin sensitivity (insulin-mediated suppression of glucose production) decreased significantly after surgery in both groups, with no differences between the groups. Peripheral insulin sensitivity (glucose rate of disappearance, Rd) was significantly decreased after surgery in both groups (S: 37.2 [19.1-50.9] vs 20.6 [13.9-27.9]; P: 23.8 [15.7-35.5] vs 15.3 [12.6-19.1] µmol/kg·min) but less pronounced in the supplemented group ( P = .04). The percentage decrease in glucose Rd did not differ between the groups. Adipose tissue insulin sensitivity (insulin-mediated suppression of plasma free fatty acids) decreased to the same extent after surgery in both groups.CONCLUSION: Rectal cancer surgery induced profound insulin resistance, affecting glucose and fatty acid metabolism. The preoperative nutrition supplement somewhat attenuated but did not prevent postoperative peripheral insulin resistance.

Previous studies showed that missing data in multi-item scales can best be handled by multiple imputation of item scores. However, when many scales are used, the number of items will become too large for the imputation model to reliably estimate imputations. A solution is to use passive imputation or a parcel summary score that combine and consequently reduce the number of variables in the imputation model. The performance of these methods was evaluated in a simulation study and illustrated in an example. Passive imputation, which updated scale scores from imputed items, and parcel summary scores that use the average over available item scores were compared to using all items simultaneously, imputing total scores of scales and complete-case analysis. Scale scores and coefficient estimates from linear regression were compared to “true” parameters on bias and precision. Passive imputation and using parcel summaries showed smaller bias and more precision than imputing total scores and complete-case analyses. Passive imputation or using parcel summary scores are valid missing data solutions in studies that include many multi-item scales.

Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging. In this postmortem study, we evaluated the correlation between postmortem MRI cortical volume or thickness and the cortical thickness measured on histological sections. Sixteen MS brains were scanned in situ using 3DT1-weighted MRI and these images were used to measure regional cortical volume using FSL-SIENAX, FreeSurfer, and SPM, and regional cortical thickness using FreeSurfer. Subsequently, cortical thickness was measured histologically in 5 systematically sampled cortical areas. Linear regression analyses were used to evaluate the relation between MRI regional cortical volume or thickness and histological cortical thickness to determine which postprocessing technique was most valid. After correction for multiple comparisons, we observed a significant correlation with the histological cortical thickness for FSL-SIENAX cortical volume with manual editing (std. β = 0.345, adjusted R(2) = 0.105, P = 0.005), and FreeSurfer cortical volume with manual editing (std. β = 0.379, adjusted R(2) = 0.129, P = 0.003). In addition, there was a significant correlation between FreeSurfer cortical thickness with manual editing and histological cortical thickness (std. β = 0.381, adjusted R(2) = 0.130, P = 0.003). The results support the use of FSL-SIENAX and FreeSurfer in cases of severe MS pathology. Interestingly none of the methods were significant in automated mode, which supports the use of manual editing to improve the automated segmentation. Hum Brain Mapp 37:2223-2233, 2016. © 2016 Wiley Periodicals, Inc.

Objective In randomized controlled trials (RCTs), outcome variables are often patient-reported outcomes measured with questionnaires. Ideally, all available item information is used for score construction, which requires an item response theory (IRT) measurement model. However, in practice, the classical test theory measurement model (sum scores) is mostly used, and differences between response patterns leading to the same sum score are ignored. The enhanced differentiation between scores with IRT enables more precise estimation of individual trajectories over time and group effects. The objective of this study was to show the advantages of using IRT scores instead of sum scores when analyzing RCTs. Study Design and Setting Two studies are presented, a real-life RCT, and a simulation study. Both IRT and sum scores are used to measure the construct and are subsequently used as outcomes for effect calculation. Results The bias in RCT results is conditional on the measurement model that was used to construct the scores. A bias in estimated trend of around one standard deviation was found when sum scores were used, where IRT showed negligible bias. Conclusion Accurate statistical inferences are made from an RCT study when using IRT to estimate construct measurements. The use of sum scores leads to incorrect RCT results

Significant numbers of involuntary admissions and the fact that compulsory hospitalization is a drastic intervention in a patient’s life justify the introduction of preventive measures. This study looks at the five-year outcome of involuntary admissions after psychiatric emergency consultations in Amsterdam. A cohort of 460 involuntarily admitted patients was investigated prospectively. The annual numbers of involuntary readmissions and the utilization of mental health services were studied, with sociodemographic and clinical characteristics and psychiatric history as predictors. The odds ratios for involuntary readmission during the fourth and fifth follow-up years were 0.71 (95%CI = 0.50–1.01; P = 0.059) and 0.64 (95%CI = 0.45–0.92; P = 0.015), respectively. Readmission was associated with low discontinuity of treatment (Chi2 P ≤ 0.001) and high total consumption of services (Chi2 P ≤ 0.001) during follow-up. It emerged that involuntary readmission could be predicted on the basis of high care c...