Musculoskeletal (MS) models should be able to integrate patient-specific MS architecture and undergo thorough validation prior to their introduction into clinical practice. We present a methodology ...to develop subject-specific models able to simultaneously predict muscle, ligament, and knee joint contact forces along with secondary knee kinematics. The MS architecture of a generic cadaver-based model was scaled using an advanced morphing technique to the subject-specific morphology of a patient implanted with an instrumented total knee arthroplasty (TKA) available in the fifth "grand challenge competition to predict in vivo knee loads" dataset. We implemented two separate knee models, one employing traditional hinge constraints, which was solved using an inverse dynamics technique, and another one using an 11-degree-of-freedom (DOF) representation of the tibiofemoral (TF) and patellofemoral (PF) joints, which was solved using a combined inverse dynamic and quasi-static analysis, called force-dependent kinematics (FDK). TF joint forces for one gait and one right-turn trial and secondary knee kinematics for one unloaded leg-swing trial were predicted and evaluated using experimental data available in the grand challenge dataset. Total compressive TF contact forces were predicted by both hinge and FDK knee models with a root-mean-square error (RMSE) and a coefficient of determination (R2) smaller than 0.3 body weight (BW) and equal to 0.9 in the gait trial simulation and smaller than 0.4 BW and larger than 0.8 in the right-turn trial simulation, respectively. Total, medial, and lateral TF joint contact force predictions were highly similar, regardless of the type of knee model used. Medial (respectively lateral) TF forces were over- (respectively, under-) predicted with a magnitude error of M < 0.2 (respectively > -0.4) in the gait trial, and under- (respectively, over-) predicted with a magnitude error of M > -0.4 (respectively < 0.3) in the right-turn trial. Secondary knee kinematics from the unloaded leg-swing trial were overall better approximated using the FDK model (average Sprague and Geers' combined error C = 0.06) than when using a hinged knee model (C = 0.34). The proposed modeling approach allows detailed subject-specific scaling and personalization and does not contain any nonphysiological parameters. This modeling framework has potential applications in aiding the clinical decision-making in orthopedics procedures and as a tool for virtual implant design.
Summary Background Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the ...haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. Methods We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. Findings Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18–3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. Interpretation Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. Funding The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Twin studies show moderate heritability of sleep traits: 40% for insomnia symptoms and 46% for sleep duration. Genome‐wide association studies (GWAS) have identified genetic variants ...involved in insomnia and sleep duration in adults, but it is unknown whether these variants affect sleep during early development. We assessed whether polygenic risk scores for insomnia (PRS‐I) and sleep duration (PRS‐SD) affect sleep throughout early childhood to adolescence.
Methods
We included 2,458 children of European ancestry (51% girls). Insomnia‐related items of the Child Behavior Checklist were reported by mothers at child's age 1.5, 3, and 6 years. At 10–15 years, the Sleep Disturbance Scale for Children and actigraphy were assessed in a subsample (N = 975). Standardized PRS‐I and PRS‐SD (higher scores indicate genetic susceptibility for insomnia and longer sleep duration, respectively) were computed at multiple p‐value thresholds based on largest GWAS to date.
Results
Children with higher PRS‐I had more insomnia‐related sleep problems between 1.5 and 15 years (BPRS‐I < 0.001 = .09, 95% CI: 0.05; 0.14). PRS‐SD was not associated with mother‐reported sleep problems. A higher PRS‐SD was in turn associated with longer actigraphically estimated sleep duration (BPRS‐SD < 5e08 = .05, 95% CI: 0.001; 0.09) and more wake after sleep onset (BPRS‐SD < 0.005 = .25, 95% CI: 0.04; 0.47) at 10–15 years, but these associations did not survive multiple testing correction.
Conclusions
Children who are genetically predisposed to insomnia have more insomnia‐like sleep problems, whereas those who are genetically predisposed to longer sleep have longer sleep duration, but are also more awake during the night in adolescence. This indicates that polygenic risk for sleep traits, based on GWAS in adults, affects sleep already in children.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It is now well established that memories can reactivate during non-rapid eye movement (non-REM) sleep, but the question of whether equivalent reactivation can be detected in rapid eye movement (REM) ...sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep, in this case REM, to trigger reactivation. We then used machine learning classifiers to identify reactivation of task-related motor imagery from wake in REM sleep. Interestingly, the strength of measured reactivation positively predicted overnight performance improvement. These findings provide the first evidence for memory reactivation in human REM sleep after TMR that is directly related to brain activity during wakeful task performance.
Objective
Adolescent psychotic‐like experiences predict the onset of psychosis, but also predict subsequent non‐psychotic disorders. Therefore, it is crucial to better understand the aetiology of ...psychotic‐like experiences. This study examined whether (a) child emotional and behavioural problems at 3 and 6 years, or (b) childhood adversities were associated with psychotic‐like experiences at age 10 years.
Method
This prospective study was embedded in the Generation R Study; 3984 children (mean age 10 years) completed a psychotic‐like experiences questionnaire. Mothers reported problems of their child at ages 3, 6 and 10 years. Additionally, mothers were interviewed about their child's adversities.
Results
Psychotic‐like experiences were endorsed by ~20% of children and predicted by both emotional and behavioural problems at 3 years (e.g. emotional‐reactive problems: ORadjusted = 1.10, 95% CI: 1.06–1.15, aggressive behaviour: ORadjusted = 1.03, 95% CI: 1.02–1.05) and 6 years (e.g. anxious/depressed problems: ORadjusted = 1.11, 95% CI: 1.06–1.15, aggressive behaviour: ORadjusted = 1.04, 95% CI: 1.04–1.05). Childhood adversities were associated with psychotic‐like experiences (>2 adversities: ORadjusted = 2.24, 95% CI: 1.72–2.92), which remained significant after adjustment for comorbid psychiatric problems.
Conclusion
This study demonstrated associations between early adversities, childhood emotional and behavioural problems and pre‐adolescent psychotic‐like experiences, which will improve the understanding of children at increased risk of severe mental illness.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood ...have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio OR = 1.2; 95% confidence interval CI, 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives We present an overview of the literature between 1997 and 2007 on parental stress reactions following the diagnosis of childhood cancer and we evaluate methodological strengths and ...weaknesses of the studies. Methods PubMed, PsychInfo, and Cinahl databases were used. Sixty-seven were included in the review. Results The conceptualization of parental stress and timing of assessment varies considerably between the studies, which makes comparison difficult. Most emotional stress reactions are seen around the time of diagnosis, with mothers reporting more symptoms than fathers. As a group, parents seem relatively resilient, although a subset of parents reports continuing stress even up to 5 years or more postdiagnosis. Conclusions The authors recommend clear definitions of parental stress, fixed points in time to assess parental stress, and an approach that highlights both parental strengths and weaknesses. Improved assessment can contribute to tailoring psychological care to those parents most in need.
Although Total Hip and Knee Replacements (THR/TKR) improve Health-Related Quality of Life (HRQoL) at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled ...expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA) is related to the improvement in HRQoL after THR or TKR, both at the population and individual level.
In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2-5 years follow-up, using the Short-Form 36 (SF36). Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS). The radiographic severity of OA was classified according to Kellgren and Lawrence (KL) by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score ≥ Minimal Clinically Important Difference) between patients with mild OA (KL Grade 0-2) and severe OA (KL Grade 3+4), whilst adjusting for confounders.
Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients.
Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Introduction Performance status (PS) is an established prognostic factor in patients with advanced cancer and is usually scored by the treating physician. The EORTC QLQ-C30 questionnaire as ...reported by cancer patients is a validated tool to assess quality of life (QoL). Subjectivity plays a role in both assessments, and data on a direct comparison are scarce. Methods We compared the prognostic value for overall survival (OS) of the WHO PS to the baseline physical function scale of the EORTC QLQ-C30 (QLQ-C30 PF) in a prospective randomised phase 3 trial in advanced colorectal cancer (ACC), the CAIRO study. Patients were divided into two groups based on the baseline QLQ-C30 PF. QLQ-C30 PF was considered ‘good’ if the score was more than 66.7% and ‘poor’ if 66.7% or less. Results were validated in a subsequent phase 3 study in ACC, the CAIRO2 study. Results The median OS for patients with a ‘good’ QLQ-C30 PF and a ‘poor’ PF in patients with WHO PS 0 was 20.3 months (n = 300) and 10.4 months (n = 44), in patients with WHO PS 1 16.8 months (n = 125) and 10.1 months (n = 63), and in patients with WHO PS 2 16.2 months (n = 11) and 9.9 months (n = 12), respectively. In a Cox regression model which included other prognostic factors, ‘good’ versus ‘poor’ QLQ-C30 PF was significantly prognostic for OS (0.57 95% confidence interval: 0.46–0.72), but not WHO PS. These results were confirmed in the CAIRO2 study. Conclusions We demonstrate in ACC patients that PF, as assessed by patients using the EORTC QLQ-C30, is superior in terms of prognostic value to WHO PS as scored by physicians. Our data support to include the results of baseline EORTC QLQ-C30 PF instead of WHO PS as a stratification parameter in oncology trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Duchenne muscular dystrophy (DMD) is a muscular condition that leads to muscle loss. Orthotic devices may present a solution for people with DMD to perform activities of daily living (ADL). One such ...device is the active trunk support but it needs a control interface to identify the user's intention. Myoelectric control interfaces can be used to detect the user's intention and consequently control an active trunk support. Current research on the control of orthotic devices that use surface electromyography (sEMG) signals as control inputs, focuses mainly on muscles that are directly linked to the movement being performed (intuitive control). However in some cases, it is hard to detect a proper sEMG signal (e.g., when there is significant amount of fat), which can result in poor control performance. A way to overcome this problem might be the introduction of other, non-intuitive forms of control. This paper presents an explorative study on the comparison and learning behavior of two different control interfaces, one using sEMG of trunk muscles (intuitive) and one using sEMG of leg muscles that can be potentially used for an active trunk support (non-intuitive). Six healthy subjects undertook a 2-D Fitts's law style task. They were asked to steer a cursor into targets that were radially distributed symmetrically in five directions. The results show that the subjects were generally able to learn to control the tasks using either of the control interfaces and improve their performance over time. Comparison of both control interfaces demonstrated that the subjects were able to learn the leg control interface task faster than the trunk control interface task. Moreover, the performance on the diagonal-targets was significantly lower compared to the one directional-targets for both control interfaces. Overall, the results show that the subjects were able to control a non-intuitive control interface with high performance. Moreover, the results indicate that the non-intuitive control may be a viable solution for controlling an active trunk support.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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