Anterior cruciate ligament reconstruction results in alterations in gait variability

Introduction: The temporal structure of gait variability has shown that healthy human gait exhibits long- range correlations and deterministic properties which allow the neuromuscular system to be flexible and adaptable to stresses. Pathology results in deterioration of these properties. We examined structure of gait variability after ACL reconstruction with either BPTB or quadrupled ST/G tendon autografts. Methods: Six patients with BPTB reconstruction, six with ST/G reconstruction and six healthy controls walked on a treadmill at their self-selected pace. Two minutes of continuous kinematic data were recorded with a 6-camera optoelectronic system. The nonlinear measure of the largest Lyapunov Exponent (LyE) was estimated from the knee flexion-extension time series from 100 continuous walking strides to assess the structure of gait variability. Results: The reconstructed limbs in both reconstructed groups exhibited significantly larger LyE values than the control limbs (p \u3c 0.05), even though clinical outcomes indicated complete restoration. No significant differences were found between the two autografts. In addition, the intact contralateral leg produced significant higher LyE values as compared with the ACL-reconstructed leg in both groups. No interaction was found. Discussion: The larger LyE values indicate that the reconstructed knees of both reconstructed groups exhibit more divergence in the movement trajectories during gait. The larger Lye values found in the intact leg in both reconstructed groups could be interpreted as a compensatory mechanism. However, the increased divergence found in both limbs may present an alternative explanation for the impaired neuromuscular performance and increased susceptibility to future pathology, which is supported by the increased amount of osteoarthritis found in ACL-reconstructed patients

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

Background Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. Methods We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. Results Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. Conclusions Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcome

The Effect of Anterior Cruciate Ligament Reconstruction on Stride-to-Stride Variability

Purpose: The purpose of our study was to investigate the functional outcome after anterior cruciate ligament (ACL) reconstruction using bone–patellar tendon– bone (BPTB) and quadrupled semitendinosus and gracilis tendon (ST/G) autografts by evaluating stride-to-stride variability. Methods: Six patients with BPTB and 6 patients with STG ACL reconstruction, 2 years postoperatively, and 6 healthy control subjects walked on a treadmill at a self-selected pace while 2 minutes of continuous kinematic data were recorded with a 6-camera optoelectronic system. Stride-to-stride variability was calculated from the knee flexion/extension data using the nonlinear measure of approximate entropy, which estimates the regularity of movement patterns over time. Results: ACL reconstruction affects stride-to-stride variability. Both the BPTB and the ST/G groups had significantly larger approximate entropy values than the healthy controls. No differences were found between the BPTB and the ST/G approximate entropy values. Conclusions: After ACL reconstruction using either BPTB or quadrupled ST/G, there is increased gait variability as compared to healthy individuals. This could be caused by the altered neuromuscular activity found in ACL-reconstructed limbs. Level of Evidence: Level III, case control study

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes

Evaluation of inconsistency in networks of interventions

Abstract Background The assumption of consistency, defined as agreement between direct and indirect sources of evidence, underlies the increasingly popular method of network meta-analysis. No evidence exists so far regarding the extent of inconsistency in full networks of interventions or the factors that control its statistical detection. Methods In this paper we assess the prevalence of inconsistency from data of 40 published networks of interventions involving 303 loops of evidence. Inconsistency is evaluated in each loop by contrasting direct and indirect estimates and by employing an omnibus test of consistency for the entire network. We explore whether different effect measures for dichotomous outcomes are associated with differences in inconsistency, and evaluate whether different ways to estimate heterogeneity affect the magnitude and detection of inconsistency. Results Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect measure and heterogeneity estimation method. Loops that included comparisons informed by a single study were more likely to show inconsistency. About one-eighth of the networks were found to be inconsistent. The proportions of inconsistent loops do not materially change when different effect measures are used. Important heterogeneity or the overestimation of heterogeneity was associated with a small decrease in the prevalence of statistical inconsistency. Conclusions The study suggests that changing the effect measure might improve statistical consistency, and that an analysis of sensitivity to the assumptions and an estimator of heterogeneity might be needed before reaching a conclusion about the absence of statistical inconsistency, particularly in networks with few studies.</jats:p

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The influence of graft choice on isokinetic muscle strength 4-24 months after anterior cruciate ligament reconstructio

Role of glycine and GLYT-1 transporter in intestinal cell protection

Glycine has been shown to protect a broad range of tissues and cell types against oxidative stress. In the intestine, these effects have been observed against Ischaemia-Reperfusion injury, hypothermic ischaemia and chemically induced colitis. The process by which glycine exerts its protective effects remain uncertain. In this thesis, the ability of glycine to protect human intestinal cells against tert-butyl hydroperoxide (t-BuOOH) induced cell death, and the requirement for GLYT-1 in the protective mechanism were explored. The human i1eo-caecal adenocarcinoma cell line, HCT-8, was chosen as an in vitro mfldel of human intestinal epithlium. RT-PCR with mRNA from HCT-8 cells and the human enterocytic Caco-2 cells was used to determine exwession of a range of amino acid transporters. Immunohistochemistry techniques using a GLYT-1 specific antibody were employed to determine the localisation of GLYT-1 in this cell line and human large intestine. Uptake of glycine in HCT-8 cell monolayers was measured using radio-labelled uptake experiments. For cytoprotection studies, the MIT assay and the ApoGSH assay were used to determine cell viability and glutathione concentration respectively, following t-BuOOH treatment. Expression of GLYT-1 and other specific amino acid transporters known to be expressed in the small and large intestine was determined, confirming the suitability of this cell line as a model for the study of amino acid absorption. GLYT-1 protein was shown to be localised along the apical and basolateral membranes of both human colon and HCT-8 cells. A proportion of Na+/Cr -,.dependent glycine uptake in HCT-8 cells was inhibited by sarcosine and the GLYT-1 inhibitor .ALX-5407, at both apical and basolateral membranes, and was attributed to GLYT-1. Exogenous glycine supplementation, prior to t·BuOOH treatment, protected HCT-8 cells against cell death and preserved intracellular glutathione concentration. Protection was specific to glycine and dependent on GLYT-1 activity. Glycine cytoprotection requires GLYT-1 activity, supporting a requirement for intracellular glycine accumulation. Maintained intracellular glutathione content is indicated as a mechanism through which the protective effect may in part be mediated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Characteristics of networks of interventions: a description of a database of 186 published networks.

Systematic reviews that employ network meta-analysis are undertaken and published with increasing frequency while related statistical methodology is evolving. Future statistical developments and evaluation of the existing methodologies could be motivated by the characteristics of the networks of interventions published so far in order to tackle real rather than theoretical problems. Based on the recently formed network meta-analysis literature we aim to provide an insight into the characteristics of networks in healthcare research. We searched PubMed until end of 2012 for meta-analyses that used any form of indirect comparison. We collected data from networks that compared at least four treatments regarding their structural characteristics as well as characteristics of their analysis. We then conducted a descriptive analysis of the various network characteristics. We included 186 networks of which 35 (19%) were star-shaped (treatments were compared to a common comparator but not between themselves). The median number of studies per network was 21 and the median number of treatments compared was 6. The majority (85%) of the non-star shaped networks included at least one multi-arm study. Synthesis of data was primarily done via network meta-analysis fitted within a Bayesian framework (113 (61%) networks). We were unable to identify the exact method used to perform indirect comparison in a sizeable number of networks (18 (9%)). In 32% of the networks the investigators employed appropriate statistical methods to evaluate the consistency assumption; this percentage is larger among recently published articles. Our descriptive analysis provides useful information about the characteristics of networks of interventions published the last 16 years and the methods for their analysis. Although the validity of network meta-analysis results highly depends on some basic assumptions, most authors did not report and evaluate them adequately. Reviewers and editors need to be aware of these assumptions and insist on their reporting and accuracy

Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE I

Methods employed to synthesise data in full and star networks published until 12/2012.

<p>For a description of the network meta-analysis methods see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086754#pone-0086754-t001" target="_blank">Table 1</a>. The table shows the number of networks and the respective percentage in parenthesis.</p