Search

The increased demand for organs has led to the increased usage of "higher risk" kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo-, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The number of clinical trials in solid organ transplantation is progressively increasing year on year, but the quality of design and reporting still varies considerably. The constraints on organ availability, improving short-term outcomes, ethics and timescales involved in organ transplantation present unique challenges for trials in this field. An understanding of the methodology and potential pitfalls in clinical research is essential both to interpret trial results and to design robust studies. This review summarizes the scope and quality of reporting in existing transplant clinical trials and details aspects of clinical trial methodology with particular relevance to transplantation. We highlight initiatives designed to improve the quality of this process to ensure that the results of clinical trials are robust, well reported and of use in everyday clinical practice., (© 2016 Steunstichting ESOT.)

Background: Belatacept was intended to provide better outcomes for kidney transplant (KT) recipients by allowing minimization/withdrawal of calcineurin inhibitors (CNI) and steroids., Methods: We searched for randomized controlled trials (RCTs) in adult KT comparing belatacept with CNIs. Methodological quality was assessed. Meta-analyses were performed to calculate odds ratios (OR) and mean differences (MD)., Results: Six RCTs were included. Pooled analyses found no differences for acute rejection at any time point. Renal function [Calculated glomerular filtration rate (cGFR)] was better with belatacept at 12 and 24 months (MD = 11.7 and 13.7 ml/min/1.73 m(2) ). New onset diabetes after transplantation was lower with belatacept at 12 months (OR = 0.43). Systolic and diastolic blood pressures were lower at 12 months (MD -7.2 and -3.1 mmHg) as were triglycerides at 12 and 24 months (MD = -32.9 and -41.7 mg/dl). Total and low-density lipoprotein cholesterol were lower with belatacept at 24 months (MD = -19.8 and -10.6 mg/dl). There were no differences for other outcomes., Conclusion: Limited available data suggest a potential benefit for belatacept by reducing the risk of CNI toxicity, especially renal function, without evidence of increased acute rejection. There were no safety issues apart from a possible risk of post-transplant lymphoproliferative disorder in Epstein-barr virus-seronegative recipients. Further studies are required to confirm this benefit., (© 2015 Steunstichting ESOT.)

The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting quality of randomized controlled trials (RCTs). Our primary aim was to assess to what extent reports of RCTs in solid organ transplantation adhere to the 2010 CONSORT statement. Secondly, we investigated the relationship between CONSORT adherence, methodological quality and some other factors. We included 290 RCTs that were published between 2007 and 2009. We examined to what extent trial reports complied with 30 items of the CONSORT statement. Methodological quality was evaluated using the Jadad scale plus allocation concealment and whether data analysis was by randomized group (intention to treat). On average, trial reports addressed 47% of the CONSORT items. Forty-three per cent of RCTs was considered to be of good quality according to Jadad scale, and the items allocation concealment and data analysis were satisfied in approximately one-third of trials. Good quality RCTs reported on more CONSORT items than poor quality trials. The methodological quality and adherence to the CONSORT statement of RCTs published in journals that endorse the CONSORT statement was superior to those in journals without CONSORT endorsement. Overall compliance with the CONSORT statement and the methodological quality of RCTs in organ transplantation remains unsatisfactory., (© 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

mTOR inhibitors have been associated with wound complications and lymphoceles. We systematically reviewed randomized controlled trials (RCTs) to compare these outcomes for solid organ transplant recipients. Relevant medical databases were searched to identify RCTs in solid organ transplantation comparing mTOR inhibitors with an alternative therapy reporting on wound complications and/or lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty-seven RCTs in kidney, heart, simultaneous pancreas-kidney and liver transplantation were included. Pooled analyses showed a higher incidence of wound complications (OR 1.77, CI 1.31-2.37) and lymphoceles (OR 2.07, CI 1.62-2.65) for kidney transplant recipients on mTOR inhibitors together with calcineurin inhibitors (CNIs). There was also a higher incidence of wound complications (OR 3.00, CI 1.61-5.59) and lymphoceles (OR 2.13, CI 1.57-2.90) for kidney transplant recipients on mTOR inhibitors together with antimetabolites. Heart transplant patients receiving mTOR inhibitors together with CNIs also reported more wound complications (OR 1.82, CI 1.15-2.87). We found a higher incidence of wound complications and lymphoceles after kidney transplantation and a higher incidence of wound complications after heart transplantation for immunosuppressive regimens that included mTOR inhibitors from the time of transplantation., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 (n = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.

Background: Advice and exercise are widely recommended for subacute low back pain, but the effectiveness of these interventions is unclear., Objective: To investigate the effectiveness of physiotherapist-prescribed exercise, advice, or both for subacute low back pain., Design: Factorial randomized, placebo-controlled trial., Setting: 7 university hospitals and primary care clinics in Australia and New Zealand., Patients: 259 persons with subacute low back pain (>6 weeks and <3 months in duration)., Intervention: Participants received 12 physiotherapist-directed exercise or sham exercise sessions and 3 physiotherapist-directed advice or sham advice sessions over 6 weeks., Measurements: Primary outcomes were average pain over the past week (scale, 0 to 10), function (Patient-Specific Functional Scale), and global perceived effect (11-point scale) at 6 weeks and 12 months. Secondary outcomes were disability (Roland-Morris Disability Questionnaire), number of health care contacts, and depression (Depression Anxiety Stress Scales-21)., Results: Exercise and advice were each slightly more effective than placebo at 6 weeks but not at 12 months. The effect of advice on the pain scale was -0.7 point (95% CI, -1.2 to -0.2 point; P = 0.011) at 6 weeks and -0.4 point (CI, -1.0 to 0.3 point; P = 0.27) at 12 months, whereras the effect of exercise was -0.8 point (CI, -1.3 to -0.3 point; P = 0.004) at 6 weeks and -0.5 point (CI, -1.1 to 0.2 point; P = 0.14) at 12 months. The effect of advice on the function scale was 0.7 point (CI, 0.1 to 1.3 points; P = 0.014) at 6 weeks and 0.6 point (CI, 0.1 to 1.2 points; P = 0.023) at 12 months, and the effect of exercise was 0.4 point (CI, -0.2 to 1.0 point; P = 0.174) at 6 weeks and 0.5 point (CI, -0.1 to 1.0 point; P = 0.094) at 12 months. The effect of advice on the global perceived effect scale was 0.8 point (CI, 0.3 to 1.2 points; P < 0.001) at 6 weeks and 0.3 point (CI, -0.2 to 0.9 point; P = 0.24) at 12 months, and the effect of exercise was 0.5 point (CI, 0.1 to 1.0 point; P = 0.017) at 6 weeks and 0.4 point (CI, -0.1 to 1.0 point; P = 0.134) at 12 months. When administered together, exercise and advice had larger effects on all outcomes at 6 weeks (effect on pain, -1.5 [CI -2.2 to -0.7 point; P = 0.001], with similar results for other primary outcomes); however, by 12 months, there was a statistically significant effect only for function (effect, 1.1 points [CI, 0.3 to 1.8 points]; P = 0.005)., Limitation: Physiotherapists were not blinded., Conclusions: In participants with subacute low back pain, physiotherapist-directed exercise and advice were each slightly more effective than placebo at 6 weeks. The effect was greatest when the interventions were combined. At 12 months, the only effect that persisted was a small effect on participant-reported function. AUSTRALIAN CLINICAL TRIALS REGISTRY REGISTRATION NUMBER: 12605000039684.

Aims: Due to their contribution to modulation of intra-abdominal pressure (IAP) and stiffness of the sacroiliac joints, the pelvic floor muscles (PFM) have been argued to provide a contribution to control of the lumbar spine and pelvis. Furthermore, as IAP is modulated during respiration this is likely to be accompanied by changes in PFM activity., Methods: In order to evaluate the postural and respiratory function of the PFM, recordings of anal and vaginal electromyographic activity (EMG) were made with surface electrodes during single and repetitive arm movements that challenge the stability of the spine. EMG recordings were also made during respiratory tasks: quiet breathing and breathing with increased dead-space to induce hypercapnoea., Results: EMG activity of the PFM was increased in advance of deltoid muscle activity as a component of the pre-programmed anticipatory postural activity. This activity was independent of the direction of arm movement. During repetitive movements, PFM EMG was tonic with phasic bursts at the frequency of arm movement. This activity was related to the peak acceleration of the arm, and therefore the amplitude of the reactive forces imposed on the spine. Respiratory activity was observed for the anal and vaginal EMG and was primarily expiratory. When subjects moved the arm repetitively while breathing, PFM EMG was primarily modulated in association with arm movement with little respiratory modulation., Conclusions: This study provides evidence that the PFM contribute to both postural and respiratory functions.

Study Design: Cohort study., Objective: To conduct a head-to-head comparison of the responsiveness of pain, disability, and physical impairment measures in patients with low back pain., Summary of Background Data: Pain, disability, and physical impairment measures are routinely measured in clinical practice and clinical research. However, to date, a head-to-head comparison has not been performed., Methods: A numerical pain scale (0-10), the 24-item and 2 modified 18-item versions of the Roland Morris questionnaire, the patient specific functional scale, and physical impairment measures were completed by 155 patients with low back pain at baseline and then again after 6 weeks together with an 11-point global perceived effect scale. Responsiveness was evaluated by using effect sizes and t tests, correlating the change scores for each outcome with the global perceived effect score and by calculating the Guyatt responsiveness index., Results: The most responsive outcome proved to be the patient specific functional scale (effect size = 1.6), followed by the numerical pain scale (effect size = 1.3) and 24-item Roland Morris questionnaire (effect size = 0.8). The responsiveness of the two 18-item Roland Morris versions was equal to the 24-item version. However, the physical impairment measures were not very responsive (effect size 0.1-0.6). The ranking of the responsiveness indices was consistent across all statistical analyses., Conclusions: Physical impairments are routinely measured in clinical practice and clinical research, but the lower responsiveness indicates that this approach is not optimal. Our findings suggest that more emphasis should be placed on change in pain and disability scores than on change in physical impairments.

Objectives: To describe the course of acute low back pain and sciatica and to identify clinically important prognostic factors for these conditions., Design: Systematic review., Data Sources: Searches of Medline, Embase, Cinahl, and Science Citation Index and iterative searches of bibliographies., Main Outcome Measures: Pain, disability, and return to work., Results: 15 studies of variable methodological quality were included. Rapid improvements in pain (mean reduction 58% of initial scores), disability (58%), and return to work (82% of those initially off work) occurred in one month. Further improvement was apparent until about three months. Thereafter levels for pain, disability, and return to work remained almost constant. 73% of patients had at least one recurrence within 12 months., Conclusions: People with acute low back pain and associated disability usually improve rapidly within weeks. None the less, pain and disability are typically ongoing, and recurrences are common.

To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine-wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles.