Platelet-rich plasma induces post-natal maturation of immature articular cartilage and correlates with LOXL1 activation

Platelet-­rich plasma (PRP) is used to stimulate the repair of acute and chronic cartilage damage even though there is no definitive evidence of how this is achieved. Chondrocytes in injured and diseased situations frequently re­ express phenotypic biomarkers of immature cartilage so tissue maturation is a potential pathway for restoration of normal structure and function. We used an in vitro model of growth factor­induced maturation to perform a comparative study in order to determine whether PRP can also induce this specific form of remodeling that is characterised by increased cellular proliferation and tissue stiffness. Gene expression patterns specific for maturation were mimicked in PRP treated cartilage, with chondromodulin, collagen types II/X downregulated, deiodinase II and netrin­1 upregulated. PRP increased cartilage surface cell density 1.5­fold (P < 0.05), confirmed by bromodeoxyuridine incorporation and proportionate increases in proliferating cell nuclear antigen gene expression. Atomic force microscopy analysis of PRP and growth factor treated cartilage gave a 5­fold increase in stiffness correlating with a 10­fold upregulation of lysyl oxidase like­1 gene expression (P < 0.001). These data show PRP induces key aspects of post­natal maturation in immature cartilage and provides the basis to evaluate a new biological rationale for its activity when used clinically to initiate joint repair

Can Transcranial Electrical Stimulation Facilitate Post-stroke Cognitive Rehabilitation? A Systematic Review and Meta-Analysis

BackgroundNon-invasive brain stimulation methods have been widely utilized in research settings to manipulate and understand the functioning of the human brain. In the last two decades, transcranial electrical stimulation (tES) has opened new doors for treating impairments caused by various neurological disorders. However, tES studies have shown inconsistent results in post-stroke cognitive rehabilitation, and there is no consensus on the effectiveness of tES devices in improving cognitive skills after the onset of stroke.ObjectivesWe aim to systematically investigate the efficacy of tES in improving post-stroke global cognition, attention, working memory, executive functions, visual neglect, and verbal fluency. Furthermore, we aim to provide a pathway to an effective use of stimulation paradigms in future studies.MethodsPreferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed. Randomized controlled trials (RCTs) were systematically searched in four different databases, including Medline, Embase, Pubmed, and PsychInfo. Studies utilizing any tES methods published in English were considered for inclusion. Standardized mean difference (SMD) for each cognitive domain was used as the primary outcome measure.ResultsThe meta-analysis includes 19 studies assessing at least one of the six cognitive domains. Five RCTs studying global cognition, three assessing visual neglect, five evaluating working memory, three assessing attention, and nine studies focusing on aphasia were included for meta-analysis. As informed by the quantitative analysis of the included studies, the results favor the efficacy of tES in acute improvement in aphasic deficits (SMD = 0.34, CI = 0.02–0.67, p = 0.04) and attention deficits (SMD = 0.59, CI = −0.05–1.22, p = 0.07), however, no improvement was observed in any other cognitive domains.ConclusionThe results favor the efficacy of tES in an improvement in aphasia and attentive deficits in stroke patients in acute, subacute, and chronic stages. However, the outcome of tES cannot be generalized across cognitive domains. The difference in the stimulation montages and parameters, diverse cognitive batteries, and variable number of training sessions may have contributed to the inconsistency in the outcome. We suggest that in future studies, experimental designs should be further refined, and standardized stimulation protocols should be utilized to better understand the therapeutic effect of stimulation

Joint Consensus Statement on the Vaccination of Adult and Paediatric Haematopoietic Stem Cell Transplant Recipients. Prepared on Behalf of the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT), the Children's Cancer and Leukaemia Group (CCLG), and British Infection Association (BIA).

Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK

Rofecoxib for dysmenorrhoea: meta-analysis using individual patient data

BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in primary dysmenorrhoea. METHODS: Individual patient information was available from three randomised, double blind, placebo and active controlled trials of rofecoxib. Data were combined through meta-analysis. Number-needed-to-treat (NNT) for at least 50% pain relief and the proportion of patients who had taken rescue medication over 12 hours were calculated. Information was collected on adverse effects. RESULTS: For single-dose rofecoxib 50 mg compared with placebo, the NNTs (with 95% CI) for at least 50% pain relief were 3.2 (2.4 to 4.5) at six, 3.1 (2.4 to 9.0) at eight, and 3.7 (2.8 to 5.6) at 12 hours. For naproxen sodium 550 mg they were 3.1 (2.4 to 4.4) at six, 3.0 (2.3 to 4.2) at eight, and 3.8 (2.7 to 6.1) at 12 hours. The proportion of patients who needed rescue medication within 12 hours was 27% with rofecoxib 50 mg, 29% with naproxen sodium 550 mg, and 50% with placebo. In the single-dose trial, the proportion of patients reporting any adverse effect was 8% (4/49) with rofecoxib 50 mg, 12% (6/49) with ibuprofen 400 mg, and 6% (3/49) with placebo. In the other two multiple dose trials, the proportion of patients reporting any adverse effect was 23% (42/179) with rofecoxib 50 mg, 24% (45/181) with naproxen sodium 550 mg, and 18% (33/178) with placebo. CONCLUSIONS: Single dose rofecoxib 50 mg provided similar pain relief to naproxen sodium 550 mg over 12 hours. The duration of analgesia with rofecoxib 50 mg was similar to that of naproxen sodium 550 mg. Adverse effects were uncommon suggesting safety in short-term use of rofecoxib and naproxen sodium. Future research should include restriction on daily life and absence from work or school as outcomes

Unanticipated Insights into Biomedicine from the Study of Acupuncture

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies

The clinical global impression scale and the influence of patient or staff perspective on outcome

<p>Abstract</p> <p>Background</p> <p>Since its first publication, the Clinical Global Impression Scale (CGI) has become one of the most widely used assessment instruments in psychiatry. Although some conflicting data has been presented, studies investigating the CGI's validity have only rarely been conducted so far. It is unclear whether the improvement index CGI-I or a difference score of the severity index CGI-S_difis more valid in depicting clinical change. The current study examined the validity of these two measures and investigated whether therapists' CGI ratings correspond to the view the patients themselves have on their condition.</p> <p>Methods</p> <p>Thirty-one inpatients of a German psychotherapeutic hospital suffering from a major depressive disorder (age M = 45.3, SD = 17.2; 58.1% women) participated. Patients filled in the Beck Depression Inventory (BDI). CGI-S and CGI-I were rated from three perspectives: the treating therapist (THER), the team of therapists involved in the patient's treatment (TEAM), and the patient (PAT). BDI and CGI-S were filled in at admission and discharge, CGI-I at discharge only. Data was analysed using effect sizes, Spearman's <it>ρ </it>and intra-class correlations (ICC).</p> <p>Results</p> <p>Effect sizes between CGI-I and CGI-S _difratings were large for all three perspectives with substantially higher change scores on CGI-I than on CGI-S _dif. BDI_difcorrelated moderately with PAT ratings, but did not correlate significantly with TEAM or THER ratings. Congruence between CGI-ratings from the three perspectives was low for CGI-S _dif(ICC = .37; Confidence Interval [CI] .15 to .59; <it>F</it>_30,60= 2.77, <it>p </it>< .001; mean <it>ρ </it>= 0.36) and moderate for CGI-I (ICC = .65 (CI .47 to .80; <it>F</it>_30,60= 6.61, <it>p </it>< .001; mean <it>ρ </it>= 0.59).</p> <p>Conclusions</p> <p>Results do not suggest a definite recommendation for whether CGI-I or CGI-S _difshould be used since no strong evidence for the validity of neither of them could be found. As congruence between CGI ratings from patients' and staff's perspective was not convincing it cannot be assumed that CGI THER or TEAM ratings fully represent the view of the patient on the severity of his impairment. Thus, we advocate for the incorporation of multiple self- and clinician-reported scales into the design of clinical trials in addition to CGI in order to gain further insight into CGI's relation to the patients' perspective.</p

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluation.

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluatio