Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 µg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 µg/L/h, n = 58) (mean difference, 13.2 µg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Force-Time Characteristics of Repeated Bouts of Depth Jumps and the Effects of Compression Garments.

No studies have reported ground reaction force (GRF) profiles of the repeated depth jump (DJ) protocols commonly used to study exercise-induced muscle damage. Furthermore, while compression garments (CG) may accelerate recovery from exercise-induced muscle damage, any effects on the repeated bout effect are unknown. Therefore, we investigated the GRF profiles of 2 repeated bouts of damage-inducing DJs and the effects of wearing CG for recovery. Nonresistance-trained males randomly received CG (n = 9) or placebo (n = 8) for 72 hours recovery, following 20 × 20 m sprints and 10 × 10 DJs from 0.6 m. Exercise was repeated after 14 days. Using a 3-way (set × bout × group) design, changes in GRF were assessed with analysis of variance and statistical parametric mapping. Jump height, reactive strength, peak, and mean propulsive forces declined between sets (P < .001). Vertical stiffness, contact time, force at zero velocity, and propulsive duration increased (P < .05). According to statistical parametric mapping, braking (17%-25% of the movement) and propulsive forces (58%-81%) declined (P < .05). During the repeated bout, peak propulsive force and duration increased (P < .05), while mean propulsive force (P < .05) and GRF from 59% to 73% declined (P < .001). A repeated bout of DJs differed in propulsive GRF, without changes to the eccentric phase, or effects from CG.

How Safety Culture Surveys Influence the Quality and Safety of Healthcare Organisations.

Objectives Safety culture surveys have been widely used in healthcare for more than two decades predominantly as a tool for measuring the level of safety culture (as defined as the beliefs and attitudes that staff express about how their organisation ought to work and how it does in fact work). However, there is the potential for the survey process itself to influence the safety culture and working practices in departments and organisations. The objective of this study was to identify the mechanism by which these changes might occur. Design, setting and participants Mixed methods combining qualitative semi-structured interviews and quantitative scores from patient safety surveys. This evaluation was conducted across general practice, community and acute hospitals in two NHS regions in England; South West and Greater Manchester. The study was undertaken between 2015 and 2018 during the implementation of a series of Patient Safety Collaboratives. Safety, Communication, Operational Reliability, and Engagement (SCORE) surveys were administered in 15 units, followed by a staff debriefing and a second SCORE survey. Semi-structured interviews were conducted with clinicians (n=61). Results from the first and second surveys were compared in order to test for differences in responses. Sixty-one semi-structured interviews were conducted across participating units and thematically analysed.  Analysis and results Results from the first and second surveys were compared using chi-squared and Fisher's exact tests. Sixty-one semi-structured interviews were conducted across participating units and thematically analysed.  There was little change in responses between the first and second SCORE surveys. Within general practice there was some improvement in responses in three survey domains; however, these differences were not conclusive. The qualitative interview data demonstrated a beneficial effect on safety culture. Staff stated that the survey debriefings created a new safe space where problems could be discussed and improvement plans created.  Conclusions Safety culture surveys can improve safety culture within departments if they are followed by a process that includes debriefing the staff and working with them to develop improvement plans.

The effect of medical grade compression garments on the repeated-bout effect in non-resistance-trained men.

NEW FINDINGS: What is the central question of this study? What are the effects of compression garments on recovery from unaccustomed damaging exercise and subsequent protective adaptations? What is the main finding and its importance? Compression did not influence recovery, but was associated with blunted protective adaptations for isokinetic performance, which were completely absent at high velocities. Based on these findings, the use of compression garments for recovery would not be recommended following unaccustomed exercise, particularly if the maintenance of high-velocity performance following exercise-induced muscle damage is desirable. ABSTRACT: Whilst compression garments (CG) may enhance recovery from exercise-induced muscle damage (EIMD), many recovery strategies can attenuate adaptative responses. Therefore, the effects of CG on recovery from EIMD, and the rapid protective adaptations known as the repeated bout effect (RBE) were investigated. Thirty-four non-resistance-trained males (18-45 years) randomly received class II medical-grade CG or placebo for 72 h following eccentrically-focused lower-body exercise, in a double-blind, randomised controlled trial. Indices of EIMD were assessed at baseline, 0, 24, 48 and 72 h post-exercise, before exercise and testing were repeated after 14 days. Results were analysed using a three-way (time × condition × bout) linear mixed-effects model. Exercise impaired isometric and isokinetic strength, with soreness and thigh circumference elevated for 72 h (P < 0.001). Compression did not enhance recovery (P > 0.05), despite small to moderate effect sizes (ES, reported alongside 90% confidence intervals) for isokinetic strength (ES from 0.2 [-0.41, 0.82] to 0.65 [0.03, 1.28]). All variables recovered faster after the repeated bout (P < 0.005). However, RBE for peak isokinetic force was impaired in CG at 60° s-1 (group × bout interaction: χ2  = 4.24, P = 0.0395; ES = -0.56 [-1.18, 0.07]) and completely absent at 120° s-1 (χ2  = 16.2, P < 0.001, ES = -0.96 [-1.61, -0.32]) and 180° s-1 (χ2  = 10.4, P = 0.001, ES = -0.72 [-1.35, -0.09]). Compression blunted RBE at higher isokinetic velocities without improving recovery in non-resistance-trained males, potentially contraindicating their use following unaccustomed exercise in this population.

Using accelerometry to classify physical activity intensity in older adults: What is the optimal wear-site?

Abstract This study aimed to determine the optimal accelerometer wear-site specific cut-points for discrimination of the sedentary time, light physical activity and moderate-to-vigorous physical activity (MVPA) in older adults. Twenty-three adults (14 females) aged 55-77 years wore a GENEActiv accelerometer on their non-dominant wrist, dominant wrist, waist and dominant ankle whilst undertaking eight, five-minute bouts of activity: lay supine, seated reading, slow walking, medium walking, fast walking, folding laundry, sweeping and stationary cycling. VO2 was assessed concurrently using indirect calorimetry. Receiver-operating-characteristic (ROC) analyses were used to derive wear-site specific cut-points for classifying intensity. Indirect calorimetry indicated that being lay supine and seated reading were classified as sedentary (<1.5 METs), laundry as light (1.51-2.99 METs) and sweeping, slow, medium and fast walking and cycling all classified as moderate intensity (>3 METs). Areas under ROC curves indicated that the classification of sedentary activity was good for the non-dominant wrist and excellent for all other wear sites. Classification of MVPA was excellent for the waist and ankle, good for the waist and poor for the dominant and non-dominant wrists. Overall, the ankle location performed better than in other locations. Ankle-worn accelerometry appears to provide the most suitable wear-site to discriminate between sedentary time and MVPA in older adults.

'Being with' or 'doing for'? How the role of an end-of-life volunteer befriender can impact patient wellbeing: interviews from a multiple qualitative case study (ELSA).

PURPOSE: To explore the perspectives of people anticipated to be in their last year of life, family carers, volunteers and staff on the impacts of receiving a volunteer-provided befriending service. Patient participants received up to 12 weeks of a volunteer-provided befriending intervention. Typically, this involved one visit per week from a trained volunteer. Such services complement usual care and are hoped to enhance quality of life. METHODS: Multiple case study design (n = 8). Cases were end-of-life befriending services in home and community settings including UK-based hospices (n = 6), an acute hospital (n = 1) and a charity providing support to those with substance abuse issues (n = 1). Data collection incorporated qualitative thematic interviews, observation and documentary analysis. Framework analysis facilitated within and across case pattern matching. RESULTS: Eighty-four people participated across eight sites (cases), including patients (n = 23), carers (n = 3), volunteers (n = 24) and staff (n = 34). Interview data are reported here. Two main forms of input were described-'being there' and 'doing for'. 'Being there' encapsulated the importance of companionship and the relational dynamic between volunteer and patient. 'Doing for' described the process of meeting social needs such as being able to leave the house with the volunteer. These had impacts on wellbeing with people describing feeling less lonely, isolated, depressed and/or anxious. CONCLUSION: Impacts from volunteer befriending or neighbour services may be achieved through volunteers taking a more practical/goal-based orientation to their role and/or taking a more relational and emotional orientation. Training of volunteers must equip them to be aware of these differing elements of the role and sensitive to when they may create most impact. TRIAL REGISTRATION: ISRCTN12929812.

Standard-Dose Proton Pump Inhibitors in the Initial Non-eradication Treatment of Duodenal Ulcer: Systematic Review, Network Meta-Analysis, and Cost-Effectiveness Analysis.

Background: Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual PPI drug is still controversial. The purpose of this study is to compare the efficacy, safety, and cost-effectiveness of standard-dose PPI medications in the initial non-eradication treatment of DU. Methods: We searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, VIP database, and the Wanfang database from their earliest records to September 2017. Randomized controlled trials (RCTs) evaluating omeprazole (20 mg/day), pantoprazole (40 mg/day), lansoprazole (30 mg/day), rabeprazole (20 mg/day), ilaprazole (10 mg/day), ranitidine (300 mg/day), famotidine (40 mg/day), or placebo for DU were included. The outcomes were 4-week ulcer healing rate (4-UHR) and the incidence of adverse events (AEs). A network meta-analysis (NMA) using a Bayesian random effects model was conducted, and a cost-effectiveness analysis using a decision tree was performed from the payer's perspective over 1 year. Results: A total of 62 RCTs involving 10,339 participants (eight interventions) were included. The NMA showed that all the PPIs significantly increased the 4-UHR compared to H2 receptor antagonists (H2RA) and placebo, while there was no significant difference for 4-UHR among PPIs. As to the incidence of AEs, no significant difference was observed among PPIs, H2RA, and placebo during 4-week follow-up. Based on the costs of both PPIs and management of AEs in China, the incremental cost-effectiveness ratio per quality-adjusted life year (in US dollars) for pantoprazole, lansoprazole, rabeprazole, and ilaprazole compared to omeprazole corresponded to $5134.67, $17801.67, $25488.31, and $44572.22, respectively. Conclusion: Although the efficacy and tolerance of different PPIs are similar in the initial non-eradication treatment of DU, pantoprazole (40 mg/day) seems to be the most cost-effective option in China.

How effective are volunteers at supporting people in their last year of life? A pragmatic randomised wait-list trial in palliative care (ELSA).

BACKGROUND: Clinical care alone at the end of life is unlikely to meet all needs. Volunteers are a key resource, acceptable to patients, but there is no evidence on care outcomes. This study aimed to determine whether support from a social action volunteer service is better than usual care at improving quality of life for adults in the last year of life. METHODS: A pragmatic, multi-centre wait-list controlled trial, with participants randomly allocated to receive the volunteer support intervention either immediately or after a 4 week wait. Trained volunteers provided tailored face-to-face support including befriending, practical support and signposting to services, primarily provided within the home, typically for 2-3 hours per week. The primary outcome was rate of change of quality of life at 4 weeks (WHO QOL BREF, a general, culturally sensitive measure). Secondary outcomes included rate of change of quality of life at 8 weeks and Loneliness (De Jong Gierveld Loneliness Scale), social support (mMOS-SS), and reported use of health and social care services at 4 and 8 weeks. RESULTS: In total, 196 adults (61% (n = 109) female; mean age 72 years) were included in the study. No significant difference was found in main or secondary outcomes at 4 weeks. Rate of change of quality of life showed trends in favour of the intervention (physical quality of life domain: b = 3.98, CI, -0.38 to 8.34; psychological domain: b = 2.59, CI, -2.24 to 7.43; environmental domain: b = 3, CI, -4.13 to 4.91). Adjusted analyses to control for hours of volunteer input found significantly less decrease in physical quality of life in the intervention group (slope (b) 4.43, CI, 0.10 to 8.76). While the intervention also favoured the rate of change of emotional (b = -0.08; CI, -0.52 to 0.35) and social loneliness (b = -0.20; CI, -0.58 to 0.18), social support (b = 0.13; CI, -0.13 to 0.39), and reported use of health and social care professionals (b = 0.16; CI, -0.22 to 0.55), these were not statistically significant. No adverse events were reported. CONCLUSIONS: Clinicians can confidently refer to volunteer services at the end of life. Future research should focus on 'dose' to maximise likely impact. TRIAL REGISTRATION: The trial was prospectively registered. ISRCTN Registry: ISRCTN12929812 , registered 20 May 2015.

Insulin--carcinogen or mitogen? Preclinical and clinical evidence from prostate, breast, pancreatic, and colorectal cancer research.

Diabetes mellitus is a chronic disease that affects > 23.6 million Americans, and occurs when the body is unable to produce or becomes resistant to endogenous insulin. This alteration of insulin's action reduces adequate utilization of glucose transporter type 4 (GLUT4) receptors, which are responsible for cellular glucose uptake. Thus, exogenous administration of human insulin and insulin analogs is an important modality used to reduce morbidity and mortality in both type 1 and type 2 diabetes. According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer. To help elucidate the potential interplay between insulin use and cancer, we searched PubMed and MEDLINE to identify articles that assessed the carcinogenic and/or mitogenic potential of diabetes treatments, focusing on insulin specifically. Data from our review suggest that insulin analogs, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers. In conclusion, the positive effects of insulin therapy on reducing morbidity and mortality in diabetes greatly outweigh the risks at this time. However, clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.