People with short symptom duration of knee osteoarthritis benefit more from exercise therapy than people with longer symptom duration: An individual participant data meta-analysis from the OA trial bank.

OBJECTIVE: To investigate whether duration of knee symptoms influenced the magnitude of the effect of exercise therapy compared to non-exercise control interventions on pain and physical function in people with knee osteoarthritis (OA). METHOD: We undertook an individual participant data (IPD) meta-analysis utilising IPD stored within the OA Trial Bank from randomised controlled trials (RCTs) comparing exercise to non-exercise control interventions among people with knee OA. IPD from RCTs were analysed to determine the treatment effect by considering both study-level and individual-level covariates in the multilevel regression model. To estimate the interaction effect (i.e., treatment x duration of symptoms (dichotomised)), on self-reported pain or physical function (standardised to 0-100 scale), a one-stage multilevel regression model was applied. RESULTS: We included IPD from 1767 participants with knee OA from 10 RCTs. Significant interaction effects between the study arm and symptom duration (≤1 year vs >1 year, and ≤2 years vs>2 years) were found for short- (~3 months) (Mean Difference (MD) -3.57, 95%CI -6.76 to -0.38 and -4.12, 95% CI-6.58 to -1.66, respectively) and long-term (~12 months) pain outcomes (MD -8.33, 95%CI -12.51 to -4.15 and -8.00, 95%CI -11.21 to -4.80, respectively), and long-term function outcomes (MD -5.46, 95%CI -9.22 to -1.70 and -4.56 95%CI -7.33 to-1.80, respectively). CONCLUSIONS: This IPD meta-analysis demonstrated that people with a relatively short symptom duration benefit more from therapeutic exercise than those with a longer symptom duration. Therefore, there seems to be a window of opportunity to target therapeutic exercise in knee OA.

Proton dynamics in a spark-plasma sintered BaZr0.7Ce0.2Y0.1O3-δ proton conductor investigated by quasi-elastic neutron scattering.

The thermally activated proton dynamics in the perovskite lattice of spark-plasma sintered BaZr0.7Ce0.2Y0.1O3-δ was investigated by quasi-elastic neutron scattering (QENS) and electrochemical impedance spectroscopy (EIS) in the temperature range from 200-600 °C. The quasi-elastic signal could be resolved into two components corresponding to a translational and rotational motion. From a description of the diffusive movements with the Chudley-Elliot jump diffusion model a jump distance of 3.12 Å and residence time of 13.6 ps were found for the translational protonic diffusion at 600 °C. The diffusion coefficients for QENS and EIS follow an Arrhenius law with activation energies of 0.16 eV, 0.58 eV and 0.88 eV for the microscopic proton self-diffusion, the bulk and grain boundaries, respectively. The rotational motion was analyzed using a two-site jump and a spherical rotation model which resulted in O-H distances of 0.89 Å and 0.71 Å, respectively. The data provided by the two-site jump model evidences the Grotthuss-type mechanism behind the translational proton dynamics.

"Much better than I thought it was going to be": Telehealth delivered group-based education and exercise was perceived as acceptable among people with knee osteoarthritis.

Objective: To understand patient perceived acceptability of participating in a telehealth delivered group-based education and exercise-therapy program for knee osteoarthritis. Design: This qualitative study involved semi-structured, one-on-one interviews with knee osteoarthritis patients who have completed the Good Living with osteoArthritis from Denmark (GLA:D®) program via telehealth or in-person. Interviews were recorded, transcribed verbatim, coded, and analysed using an inductive content analysis approach, focusing on themes related to telehealth. Results: Nineteen participants [12 (63%) female, mean aged 62 years, range 49-72 years] were included. Eleven (58%) received GLA:D® via telehealth and 8 (42%) attended in-person sessions. Two overarching themes (6 sub-themes) related to telehealth perceived acceptability were identified: 1) Perceptions of telehealth acceptability was highly influenced by exposure. Individuals who had received telehealth considered it easy, convenient, and flexible, whereas telehealth was perceived to be inferior and misunderstood by those without exposure. 2) Telehealth participants reported similar program benefits to in-person participants, including reduced fear of pain and joint damage, changed beliefs in value of exercise, and stated improvements in pain and function. Conclusions: Telehealth delivery of group-based education and exercise-therapy for knee osteoarthritis was acceptable for people who had experienced it and provides similar benefits as in-person care for pain and beliefs about the safety and value of exercise. Wider implementation of telehealth group-based education and exercise-therapy may improve access to high value care for people with knee osteoarthritis.

Does land-based exercise-therapy improve physical activity in people with knee osteoarthritis? A systematic review with meta-analyses.

PRIMARY OBJECTIVE: Investigate the effects of land-based exercise-therapy on physical activity in people with knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis of randomised or quasi-randomised trials investigating land-based exercise-therapy on physical activity, fitness, and general health in people with KOA. We updated a 2013 Cochrane review search on exercise-therapy for KOA in April 2021 and applied the Cochrane Risk-of-Bias Tool 1.0 to included articles. Standardised mean differences (SMDs) and 95% confidence intervals (CI) were calculated. GRADE was used to assess certainty of the evidence. RESULTS: Twenty-eight randomised controlled trials (2,789 participants) evaluating the effects of resistance-training (n = 10), walking (n = 6) and mixed-exercise programs (n = 7) were identified. Low to moderate certainty evidence indicated small increases in physical activity for exercise-therapy compared to non-exercise interventions in the short-term (SMD, 95% CI = 0.29, 0.09 to 0.50), but not the medium- (0.03, -0.11 to 0.18) or long-term (-0.06, -0.34 to 0.22). Low certainty evidence indicated large increases in physical activity for walking programs (0.53, 0.11 to 0.95) and mixed-exercise programs (0.67, 0.37 to 0.97) compared to non-exercise interventions in the short-term. Low certainty evidence indicated moderate and small increases in physical activity for resistance-training combined with education focused on pain coping skills and self-efficacy compared to education alone at medium-term follow-up (0.45, 0.19 to 0.71). CONCLUSION: Walking and mixed-exercise, but not resistance-training, may improve physical activity in people with KOA in the short-term. Combining resistance-training with education may increase physical activity in the medium-, but not the long-term, highlighting the potential importance of developing more effective longer-term interventions for people with KOA. Future studies evaluating land-based exercise-therapy are encouraged to include physical activity outcomes and longer-term follow-up to increase the certainty of evidence.

Can modifications to how medical imaging findings are reported improve quality of care? A systematic review.

AIM: To synthesise the available evidence about the effects of modifications to diagnostic imaging reports that aim to optimise patient care. MATERIALS AND METHODS: Cochrane methods were used and CENTRAL, MEDLINE, EMBASE, and clinical trials registers were searched from inception to 31 March 2021. Randomised controlled trials of modifications to imaging reports aimed at optimising patient care for any condition were included. Two authors selected studies independently for inclusion, extracted data, assessed risk of bias, and judged certainty of evidence using GRADE. The primary outcome was quality of care (e.g., increased guideline-adherent care, reduced/increased imaging as appropriate). RESULTS: Five trials met eligibility criteria. One tested provision of information about appropriate osteoporosis treatment in bone density reports; two tested provision of criteria and treatment for heart failure in echocardiogram reports; one tested provision of reminders for when routine imaging is not needed in lumbar spine and knee radiography reports; and one tested inclusion of epidemiological data in lumbar spine imaging reports. All trials were susceptible to bias, and four did not blind all participants. Low certainty evidence from two trials found adding information about appropriate care may increase care quality compared to a standard report (RR 1.20 (95% CI 0.96 to 1.50), two trials, 1,548 participants, I2 = 49). This was supported by outcomes of two additional trials that also provided specific clinical guidance. CONCLUSIONS: The present review suggests that providing specific guidance on appropriate clinical intervention in imaging reports may improve patient care. Further high-quality trials are needed to confirm these findings. Prospective PROSPERO registration CRD42020153961.

Effect of cane use on bone marrow lesion volume in people with medial tibiofemoral knee osteoarthritis: randomized clinical trial.

OBJECTIVE: To evaluate effects of daily cane use for 3 months on medial tibiofemoral bone marrow lesion (BML) volumes in people with medial tibiofemoral osteoarthritis (OA). DESIGN: In this randomized controlled trial (RCT), 79 participants with medial tibiofemoral OA were randomized to either a cane group (using a cane whenever walking) or control group (not using any gait aid) for 3 months. The cane group received a single training session by a physiotherapist, using a biofeedback cane to teach optimal technique and body weight support and motor learning principles to facilitate retention of learning. The primary outcome was change in total medial tibiofemoral BML volume (per unit bone volume) measured from magnetic resonance imaging (MRI) at 3 months. Secondary outcomes were BML volumes (per unit bone volume) of the medial tibia and femur, and patient-reported outcomes of overall knee pain, knee pain on walking, physical function, perceived global symptom changes and health-related quality of life. MRI analyses were performed by a blinded assessor. RESULTS: Seventy-eight participants (99%) completed the primary outcome. Mean (standard deviation) daily cane use was 2.3 (1.7) hours over 3 months. No evidence of between-group differences was found for change in total medial tibiofemoral BML volume (mean difference: -0.0010 (95% confidence intervals: -0.0022, 0.0003)). Most secondary outcomes showed minimal differences between groups. CONCLUSION: Daily use of a cane during walking for 3 months aiming to reduce knee joint loading did not change medial tibiofemoral BML volumes compared to no use of gait aids. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12614000909628).

Novel approaches for the design, delivery and administration of vaccine technologies.

It is easy to argue that vaccine development represents humankind's most important and successful endeavour, such is the impact that vaccination has had on human morbidity and mortality over the last 200 years. During this time the original method of Jenner and Pasteur, i.e. that of injecting live-attenuated or inactivated pathogens, has been developed and supplemented with a wide range of alternative approaches which are now in clinical use or under development. These next-generation technologies have been designed to produce a vaccine that has the effectiveness of the original live-attenuated and inactivated vaccines, but without the associated risks and limitations. Indeed, the method of development has undoubtedly moved away from Pasteur's three Is paradigm (isolate, inactivate, inject) towards an approach of rational design, made possible by improved knowledge of the pathogen-host interaction and the mechanisms of the immune system. These novel vaccines have explored methods for targeted delivery of antigenic material, as well as for the control of release profiles, so that dosing regimens can be matched to the time-lines of immune system stimulation and the realities of health-care delivery in dispersed populations. The methods by which vaccines are administered are also the subject of intense research in the hope that needle and syringe dosing, with all its associated issues regarding risk of injury, cross-infection and patient compliance, can be replaced. This review provides a detailed overview of new vaccine vectors as well as information pertaining to the novel delivery platforms under development.

A transfusion prescription template and other human factor interventions to improve balanced transfusion delivery in major haemorrhage due to trauma.

OBJECTIVES: The aim of this study is to improve practice in the management of major haemorrhage, particularly in red cell to plasma transfusion ratios. BACKGROUND: A review of the management of major haemorrhage in trauma in Newcastle Hospitals Trust in 2012-2013 showed good mortality outcomes but found that red cell : plasma transfusion ratios could be improved. Human factors techniques transferable from industry and the military were identified, and a package of interventions was implemented, including an intensive multidisciplinary team training programme and a new major haemorrhage prescription template. METHODS/MATERIALS: We reviewed the management of all 243 adult trauma patients admitted with major haemorrhage to the Emergency Department in the Newcastle Hospitals Trust in the 4-year period from April 2012. We analysed clinical details, blood components transfused and patient outcomes and used Trauma Audit and Research Network data to correlate with injury severity and predicted survival. RESULTS: Mean transfusion ratios of red cells to plasma improved from 1·5 : 1 and 1·6 : 1 in the first 2 years to 1·1 : 1 in the 2 years following implementation of the new measures. There was a statistically significant improvement in the delivery of a balanced transfusion, defined as a red cell : plasma ratio of <1·3 : 1 following the changes. CONCLUSION: Simple changes to procedures, specifically implementation of a new major haemorrhage prescription template and multidisciplinary team training, have resulted in marked improvement in the ratio of red cells to plasma transfused to trauma patients with major haemorrhage or requiring emergency blood. The package of changes could be easily replicated in other health-care settings.

A walking program for people with severe knee osteoarthritis did not reduce pain but may have benefits for cardiovascular health: a phase II randomised controlled trial.

OBJECTIVE: The primary aim was to evaluate the effect of a dosed walking program on knee pain for patients with severe knee osteoarthritis (OA). Secondary aims evaluated the effects on cardiovascular health, function and quality of life. DESIGN: Participants with severe knee OA and increased cardiovascular risk were randomly assigned to a 12-week walking program of 70 min/week of at least moderate intensity, or to usual care. The primary outcome was knee pain (0-10). Secondary outcomes were of cardiovascular risk including physical activity, blood pressure, blood lipid and glucose levels, body mass index and waist circumference; WOMAC Index scores; physical function; and quality of life. RESULTS: Forty-six participants (23 each group) were recruited. Sixteen participants (70%) adhered to the walking program. Intention to treat analysis showed no between-group difference in knee pain. The walking group had increased odds of achieving a healthy systolic blood pressure (OR = 5.7, 95% CI 1.2-26.9), and a faster walking speed (Mean Difference (MD) = 0.12 m/s, 95% CI 0.02-0.23). Per protocol analysis based on participant adherence showed the walking group had more daily steps (MD = 1345 steps, 95% CI 365-2325); more time walking (MD = 18 min/day, 95% CI 5-31); reduced waist circumference (MD = -5.3 cm, 95% CI -10.5 to -0.03); and increased knee stiffness (MD = 0.9 units, 95% CI 0.07-1.8). CONCLUSIONS: Patients with severe knee OA prescribed a 12-week walking program of 70 min/week may have had cardiovascular benefits without decreasing knee pain. Australian New Zealand Clinical Trials Registry ACTRN12615000015549.

Spotlight on platelets: summary of BBTS combined special interest group autumn meeting, November 2015.

This conference first addressed aspects of component quality, highlighting the role of pathogen inactivation, the role of PAS or plasma in prolonging platelet viability and acceptable storage deviations. A series of talks on the medical use of platelets covered the role of platelet transfusion in preventing intracranial haemorrhage, platelet prophylaxis in haematological patients and the new trial of the HLA Matchmaker programme to provide epitope-matched platelets. The session on the surgical use of platelets considered the role of platelet transfusions in patients on anti-platelet agents, major trauma and interventional procedures and also the scope for tests of platelet function to direct therapy. The conference concluded with a panel discussion highlighting key areas of general interest, including the clinical use of platelets and near patient platelet function tests.

The maximum tolerated dose of walking for people with severe osteoarthritis of the knee: a phase I trial.

OBJECTIVE: To determine how much physical activity, in the form of walking, can be safely and feasibly tolerated for people with severe knee osteoarthritis (OA). DESIGN: Phase I dose response trial with escalating walking doses of 10, 20, 35, 50, 70, and 95 min over 1 week, were prescribed non-randomly to people with severe knee OA. The primary stopping rule was a substantial increase in knee pain. The primary outcomes were an estimation of the maximum tolerated dose of walking; and the proportion of people who did not complete the dose for feasibility reasons. The secondary outcomes were pain, stiffness and activity limitation Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Twenty-four participants (13 women) aged 53-83 years, and average body mass index (BMI) of 34 kg/m(2) (SD 9) were recruited. Three participants were assigned to each dose between 10 and 70 min, and nine participants assigned to the 95-min dose. The trial was stopped at 95 min due to the maximum number of adverse events occurring at this dose. Therefore, the maximum tolerated dose was 70 min. No participant stopped due to reasons related to feasibility. There was a moderate association between dose and increased activity (linear R(2) = 0.31, cubic R(2) = 0.69) and reduced stiffness (linear R(2) = 0.20, cubic R(2) = 0.52), with increased benefits at moderate to higher doses. CONCLUSIONS: There is preliminary evidence that 70 min per week of moderate intensity supervised walking was safe and feasible for people with severe OA of the knee; for higher doses there was a risk of exacerbating knee pain levels.

Where did platelets go in 2012? A survey of platelet transfusion practice in the North of England.

OBJECTIVES: To record the fate of transfused platelet doses in the North of England, and thereby assist with demand-planning and help target teaching on appropriate use. BACKGROUND: Platelet use has risen recently to the extent that donation practice has changed to meet demand. Two national comparative audits have shown inappropriate use and the 2010 audit concluded that current U.K. guidelines for platelet usage should be completely implemented at a local level. It is necessary to know how platelets are used and by whom in order to facilitate guideline concordance. METHODS: All hospital trusts in the North East and Cumbria recorded data on all platelet doses transfused in two separate 4-week periods in 2012. Data were entered onto an electronic survey tool. RESULTS: One thousand and five hundred and seventy-four reports were received, documenting 1937 transfused doses--96% of total issues for the study periods. One thousand and forty-five platelet doses (54%) were given for haematological indications. The second commonest indication was cardiac surgery (201 doses, 10% of the total) followed by non-haematological oncology (127 doses, 6.5%), critical care (106 doses, 5%) and liver disease (50 doses, 2.5%). The commonest haematological indication was acute myeloid leukaemia, 310 doses, (16% of all platelet use), followed by stem cell transplantation, 271 doses (14%). Seventy-two percent of platelet doses were given prophylactically, the majority without any planned procedure. CONCLUSION: The commonest indication for platelet use, where reinforcement of guidelines will be productive, is prophylaxis in haematological disease. Use of platelets in cardiac surgery is also worthy of close scrutiny.

Cardiopulmonary exercise testing before and after blood transfusion: a prospective clinical study.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is used to risk-stratify patients undergoing major elective surgery, with a poor exercise capacity being associated with an increased risk of complications and death. Patients with anaemia have a decreased exercise capacity and an increased risk of morbidity and mortality after major surgery. Blood transfusion is often used to correct anaemia in the perioperative period but the effect of this intervention on exercise capacity is not well described. We sought to measure the effect of blood transfusion on exercise capacity measured objectively with CPET. METHODS: Patients with stable haematological conditions requiring blood transfusion underwent CPET before and 2-6 days after transfusion. RESULTS: Twenty patients were enrolled and completed both pre- and post-transfusion tests. The mean (sd) haemoglobin (Hb) concentration increased from 8.3 (1.2) to 11.2 (1.4) g dl(-1) after transfusion of a median (range) of 3 (1-4) units of packed red cells. The anaerobic threshold increased from a mean (sd) of 10.4 (2.4) to 11.6 (2.5) ml kg(-1) min(-1) (P=0.018), a mean difference of 1.2 ml kg(-1) min(-1) (95% confidence interval (CI)=0.2-2.2). When corrected for the change in Hb concentration, the anaerobic threshold increased by a mean (sd) of 0.39 (0.74) ml kg(-1) min(-1) per g dl(-1) Hb. CONCLUSIONS: Transfusion of allogeneic packed red cells in anaemic adults led to a significant increase in their capacity to exercise. This increase was seen in the anaerobic threshold, and other CPET variables.

What proportion of people with hip and knee osteoarthritis meet physical activity guidelines? A systematic review and meta-analysis.

OBJECTIVE: To determine the proportion of people with hip and knee osteoarthritis that meet physical activity guidelines recommended for adults and older adults. METHOD: Systematic review with meta-analysis of studies measuring physical activity of participants with hip and knee osteoarthritis using an activity monitor. Physical activity levels were calculated using the mean average [95% confidence interval (CI)] weighted according to sample size. Meta-analyses determined the proportion of people meeting physical activity guidelines and recommendations of (1) ≥150 min per week of moderate to vigorous physical activity (MVPA) in bouts of ≥10 min; (2) ≥150 min per week of MVPA in absence of bouts; (3) ≥10,000 steps per day and ≥7000 steps per day. The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of the evidence. RESULTS: For knee osteoarthritis, 21 studies involving 3266 participants averaged 50 min per week (95% CI = 46, 55) of MVPA when measured in bouts of ≥10 min, 131 min per week (95% CI = 125, 137) of MVPA, and 7753 daily steps (95% CI = 7582, 7924). Proportion meta-analyses provided high quality evidence that 13% (95% CI = 7, 20) completed ≥150 min per week of MVPA in bouts of ≥10 min, low quality evidence that 41% (95% CI = 23, 61) completed ≥150 min per week of MVPA in absence of bouts, moderate quality evidence that 19% (95% CI = 8, 33) completed ≥10,000 steps per day, and low quality evidence that 48% (95% CI = 31, 65) completed ≥7000 steps per day. For hip osteoarthritis, 11 studies involving 325 participants averaged 160 min per week (95% CI = 114, 216) of MVPA when measured in bouts of ≥10 min, 189 min per week (95% CI = 166, 212) of MVPA, and 8174 daily steps (95% CI = 7670, 8678). Proportion meta-analyses provided low quality evidence that 58% (95% CI = 18, 92) completed ≥150 min per week of MVPA in absence of bouts, low quality evidence that 30% (95% CI = 13, 50) completed ≥10,000 steps per day, and low quality evidence that 60% (95% CI = 47, 73) completed ≥7000 steps per day. CONCLUSION: A small to moderate proportion of people with knee and hip osteoarthritis met physical activity guidelines and recommended daily steps. Future research should establish the effects of increasing physical activity in this population to meet the current physical activity guidelines.

Strategies to reduce transfusion acquired vCJD.

Variant Creutzfeldt-Jakob disease (vCJD) can be transmitted by transfusion. The risk depends on the number of infected donors in the community. An estimate of these numbers in a less genetically susceptible population, based on the epidemic seen so far, suggests a maximum of 300 more cases. From this, it is possible to predict a maximum of one transfusion acquired case in 3 years from plasma transfusion. Importation of plasma from outside the UK has been advocated to prevent these cases and would cost around £30 million per year. An alternative measure is to use the observed susceptibility and exposure to dietary vCJD by age, and to target low risk donors for the production of components such as fresh frozen plasma (FFP) and platelets. This will reduce the possible cases of plasma transfusion-acquired vCJD at little or no extra cost to the health service.