Efficacy of MSC for steroid-refractory acute GVHD associates with MSC donor age and a defined molecular profile

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Ankles back in randomized controlled trial (ABrCt): braces versus neuromuscular exercises for the secondary prevention of ankle sprains. Design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Ankle sprains are the most common sports and physical activity related injury. There is extensive evidence that there is a twofold increased risk for injury recurrence for at least one year post injury. In up to 50% of all cases recurrences result in disability and lead to chronic pain or instability, requiring prolonged medical care. Therefore ankle sprain recurrence prevention in athletes is essential. This RCT evaluates the effect of the combined use of braces and neuromuscular training (e.g. proprioceptive training/sensorimotor training/balance training) against the individual use of either braces or neuromuscular training alone on ankle sprain recurrences, when applied to individual athletes after usual care.</p> <p>Methods/Design</p> <p>This study was designed as three way randomized controlled trial with one year follow-up. Healthy individuals between 12 and 70 years of age, who were actively participating in sports and who had sustained a lateral ankle sprain in the two months prior to inclusion, were eligible for inclusion. After subjects had finished ankle sprain treatment by means of usual care, they were randomised to any of the three study groups. Subjects in group 1 received an eight week neuromuscular training program, subjects in group 2 received a sports brace to be worn during all sports activities for the duration of one year, and group 3 received a combination of the neuromuscular training program and a sports brace to be worn during all sports activities for the duration of eight weeks. Outcomes were assessed at baseline and every month for 12 months therafter. The primary outcome measure was incidence of ankle sprain recurrences. Secondary outcome measures included the direct and indirect costs of recurrent injury, the severity of recurrent injury, and the residual complaints during and after the intervention.</p> <p>Discussion</p> <p>The ABrCt is the first randomized controlled trial to directly compare the secondary preventive effect of the combined use of braces and neuromuscular training, against the use of either braces or neuromuscular training as separate secondary preventive measures. This study expects to identify the most effective and cost-efficient secondary preventive measure for ankle sprains. The study results could lead to changes in the clinical guidelines on the prevention of ankle sprains, and they will become available in 2012.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2157">NTR2157</a></p

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG) A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402

The Knight of Malta

BACKGROUND: For most women, participation in decision-making during maternity care has a positive impact on their childbirth experiences. Shared decision-making (SDM) is widely advocated as a way to support people in their healthcare choices. The aim of this study was to identify quality criteria and professional competencies for applying shared decision-making in maternity care. We focused on decision-making in everyday maternity care practice for healthy women. METHODS: An international three-round web-based Delphi study was conducted. The Delphi panel included international experts in SDM and in maternity care: mostly midwives, and additionally obstetricians, educators, researchers, policy makers and representatives of care users. Round 1 contained open-ended questions to explore relevant ingredients for SDM in maternity care and to identify the competencies needed for this. In rounds 2 and 3, experts rated statements on quality criteria and competencies on a 1 to 7 Likert-scale. A priori, positive consensus was defined as 70% or more of the experts scoring >/=6 (70% panel agreement). RESULTS: Consensus was reached on 45 quality criteria statements and 4 competency statements. SDM in maternity care is a dynamic process that starts in antenatal care and ends after birth. Experts agreed that the regular visits during pregnancy offer opportunities to build a relationship, anticipate situations and revisit complex decisions. Professionals need to prepare women antenatally for unexpected, urgent decisions in birth and revisit these decisions postnatally. Open and respectful communication between women and care professionals is essential; information needs to be accurate, evidence-based and understandable to women. Experts were divided about the contribution of professional advice in shared decision-making and about the partner's role. CONCLUSIONS: SDM in maternity care is a dynamic process that takes into consideration women's individual needs and the context of the pregnancy or birth. The identified ingredients for good quality SDM will help practitioners to apply SDM in practice and educators to prepare (future) professionals for SDM, contributing to women's positive birth experience and satisfaction with care

Diversity of Cl− Channels

Cl− channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl− channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca2+-activated Cl− channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl− channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl− channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl−-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles

Economic optimization of full-sib test group size and genotyping effort in a breeding program for Atlantic salmon

Background: Breeding companies may want to maximize the rate of genetic gain from their breeding program within a limited budget. In salmon breeding programs, full-sibs of selection candidates are subjected to performance tests for traits that cannot be recorded on selection candidates. While marginal gains in the aggregate genotype from phenotyping and genotyping more full-sibs per candidate decrease, costs increase linearly, which suggests that there is an optimum in the allocation of the budget among these activities. Here, we studied how allocation of the fixed budget to numbers of phenotyped and genotyped test individuals in performance tests can be optimized. Methods: Gain in the aggregate genotype was a function of the numbers of full-sibs of selection candidates that were (1) phenotyped in a challenge test for sea lice resistance (2) phenotyped in a slaughter test (3) genotyped in the challenge test, and (4) genotyped in the slaughter test. Each of these activities was subject to budget constraints. Using a grid search, we optimized allocation of the budget among activities to maximize gain in the aggregate genotype. We performed sensitivity analyses on the maximum gain in the aggregate genotype and on the relative allocation of the budget among activities at the optimum. Results: Maximum gain in the aggregate genotype was €386/ton per generation. The response surface for gain in the aggregate genotype was rather flat around the optimum, but it curved strongly near the extremes. Maximum gain was sensitive to the size of the budget and the relative emphasis on breeding goal traits, but less sensitive to the accuracy of genomic prediction and costs of phenotyping and genotyping. The relative allocation of budget among activities at the optimum was sensitive to costs of phenotyping and genotyping and the relative emphasis on breeding goal traits, but was less sensitive to the accuracy of genomic prediction and the size of the budget. Conclusions: There is an optimum allocation of budget to the numbers of full-sibs of selection candidates that are phenotyped and genotyped in performance tests that maximizes gain in the aggregate genotype. Although potential gains from optimizing group sizes and genotyping effort may be small, they come at no extra cost.</p

Derivation of the economic value of R₀ for macroparasitic diseases and application to sea lice in salmon

Background: Macroparasites, such as ticks, lice, and helminths, are a concern in livestock and aquaculture production, and can be controlled by genetic improvement of the host population. Genetic improvement should aim at reducing the rate at which parasites spread across the farmed population. This rate is determined by the basic reproduction ratio, i.e. R 0, which is the appropriate breeding goal trait. This study aims at providing a method to derive the economic value of R 0. Methods: Costs of a disease are the sum of production losses and expenditures on disease control. Genetic improvement of R 0 lowers the loss-expenditure frontier. Its economic effect depends on whether the management strategy is optimized or not. The economic value may be derived either from the reduction in losses with constant expenditures or from the reduction in expenditures with constant losses. Results: R 0 ≤ 1, the economic value of a further reduction is zero because there is no risk of a major epidemic. When R 0 > 1 and management is optimized, the economic value increases with decreasing values of R 0, because both the mean number of parasites per host and frequency of treatments decrease at an increasing rate when R 0 decreases. When R 0 > 1 and management is not optimized, the economic value depends on whether genetic improvement is used for reducing expenditures or losses. For sea lice in salmon, the economic value depends on a reduction in expenditures with constant losses, and is estimated to be 0.065€/unit R 0 /kg production. Discussion: Response to selection for measures of disease prevalence cannot be predicted from quantitative genetic theory alone. Moreover, many studies fail to address the issue of whether genetic improvement results in reduced losses or expenditures. Using R 0 as the breeding goal trait, weighed by its appropriate economic value, avoids these issues. Conclusion: When management is optimized, the economic value increases with decreasing values of R 0 (until the threshold R 0 = 1, where it drops to zero). When management is not optimized, the economic value depends on whether genetic improvement is used for reduced expenditures or production losses. For sea lice in salmon, the economic value is estimated to be 0.065 €/unit R 0 /kg production.</p

Derivation of the economic value of R₀ for macroparasitic diseases and application to sea lice in salmon

Background: Macroparasites, such as ticks, lice, and helminths, are a concern in livestock and aquaculture production, and can be controlled by genetic improvement of the host population. Genetic improvement should aim at reducing the rate at which parasites spread across the farmed population. This rate is determined by the basic reproduction ratio, i.e. R 0, which is the appropriate breeding goal trait. This study aims at providing a method to derive the economic value of R 0. Methods: Costs of a disease are the sum of production losses and expenditures on disease control. Genetic improvement of R 0 lowers the loss-expenditure frontier. Its economic effect depends on whether the management strategy is optimized or not. The economic value may be derived either from the reduction in losses with constant expenditures or from the reduction in expenditures with constant losses. Results: R 0 ≤ 1, the economic value of a further reduction is zero because there is no risk of a major epidemic. When R 0 > 1 and management is optimized, the economic value increases with decreasing values of R 0, because both the mean number of parasites per host and frequency of treatments decrease at an increasing rate when R 0 decreases. When R 0 > 1 and management is not optimized, the economic value depends on whether genetic improvement is used for reducing expenditures or losses. For sea lice in salmon, the economic value depends on a reduction in expenditures with constant losses, and is estimated to be 0.065€/unit R 0 /kg production. Discussion: Response to selection for measures of disease prevalence cannot be predicted from quantitative genetic theory alone. Moreover, many studies fail to address the issue of whether genetic improvement results in reduced losses or expenditures. Using R 0 as the breeding goal trait, weighed by its appropriate economic value, avoids these issues. Conclusion: When management is optimized, the economic value increases with decreasing values of R 0 (until the threshold R 0 = 1, where it drops to zero). When management is not optimized, the economic value depends on whether genetic improvement is used for reduced expenditures or production losses. For sea lice in salmon, the economic value is estimated to be 0.065 €/unit R 0 /kg production.</p

Feasibility of a home-based exercise intervention with remote guidance for patients with stable grade II and III gliomas: a pilot randomized controlled trial

OBJECTIVE: In this pilot study, we investigated the feasibility of a home-based, remotely guided exercise intervention for patients with gliomas. DESIGN: Pilot randomized controlled trial (RCT) with randomization (2:1) to exercise or control group. SUBJECTS: Patients with stable grade II and III gliomas. INTERVENTION: The six-month intervention included three home-based exercise sessions per week at 60%-85% of maximum heart rate. Participants wore heart rate monitors connected to an online platform to record activities that were monitored weekly by the physiotherapist. MAIN MEASURES: Accrual, attrition, adherence, safety, satisfaction, patient-reported physical activity, VO2 peak (by maximal cardiopulmonary exercise testing) and body mass index (BMI) at baseline and at six-month follow-up. RESULTS: In all, 34 of 136 eligible patients (25%) were randomized to exercise training ( N = 23) or the control group ( N = 11), of whom 19 and 9, respectively, underwent follow-up. Mean adherence to prescribed sessions was 79%. Patients' experiences were positive. There were no adverse events. Compared to the control group, the exercise group showed larger improvements in absolute VO2 peak (+158.9 mL/min; 95% CI: -44.8 to 362.5) and BMI (-0.3 kg/m²; 95% CI: -0.9 to 0.2). The median increase in physical activity was 1489 metabolic equivalent of task (MET) minutes higher in the exercise group. The most reported reasons for non-participation were lack of motivation or time. CONCLUSION: This innovative and intensive home-based exercise intervention was feasible in a small subset of patients with stable gliomas who were interested in exercising. The observed effects suggest that the programme may improve cardiorespiratory fitness. These results support the need for large-scale trials of exercise interventions in brain tumour patients