Between-group Difference In Change Research Articles

Eccentric Muscle Strengthening Using Maximal Contractions Is Deleterious in Knee Osteoarthritis: A Randomized Clinical Trial.

Objectives: To show the superiority of eccentric versus concentric strengthening in terms of improving quadriceps strength in knee osteoarthritis (OA), a randomized controlled study was conducted to perform 12 sessions of either eccentric or concentric isokinetic muscle strengthening over 6 weeks. Methods: We recruited males and females, aged between 40 and 70 years, with predominantly unilateral femorotibial OA. Exclusion criteria were having a prosthesis, inflammatory arthritis or flare-up of OA, symptomatic patellofemoral OA, cardiovascular or pulmonary disease that could be a contraindication to the study treatment, and any pathology that could cause muscle weakness. The primary endpoint was the between-group difference in change in maximum concentric isokinetic knee extension peak torque (PT) at 60°/s on the OA side at 6 weeks. Secondary endpoints were between-group difference in change in concentric hamstring PT at 60°/s; eccentric quadriceps and hamstring PT at 30°/s; 10 m and 200 m walking speeds; pain and functional status (WOMAC score) at 6 weeks and 6 months. Results: The sample consisted of 11 females and 27 males, with a mean age of 57.7 ± 7.52 years and a body mass index (BMI) of 25.95 ± 3.93 kg/m2. Quadriceps strength increased more at 6 weeks in the concentric than the eccentric group with no statistical difference. There was a rate of 25% major adverse events in the eccentric group. Conclusions: Eccentric training resulted in a smaller improvement in quadriceps strength than concentric training and was associated with a high risk of muscle injury, particularly to the hamstring muscles.

Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty

Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population. To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA. A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark. Participants with moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least 1 year after primary TKA were included. Participant recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023. The study included 24 sessions of supervised neuromuscular exercise (2 sessions per week for 12 weeks) and 2 total sessions of pain neuroscience education (6 weeks between each session) or the same pain neuroscience education sessions alone. The interventions were delivered in groups of 2 to 4 participants. The primary outcome was change from baseline to 12 months using the mean score of the Knee Injury and Osteoarthritis Outcome Score, covering the 4 subscales pain, symptoms, activity of daily living, and knee-related quality of life (KOOS4; scores range from 0 to 100, with higher scores indicating better outcomes). The outcome assessors and statistician were blinded. All randomized participants were included in the intention-to-treat analysis. Among the 69 participants (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) included in the study, 36 were randomly assigned to the neuromuscular exercise and pain neuroscience education group, and 33 to the pain neuroscience education-alone group. The intention-to-treat analysis showed no between-group difference in change from baseline to 12 months for the KOOS4 (7.46 [95% CI, 3.04-11.89] vs 8.65 [95% CI, 4.67-12.63] points; mean difference, -1.33 [95% CI, -7.59 to 4.92]; P = .68). Among the 46 participants who participated in the 12-month assessment in the 2 groups, 16 (34.8%) experienced a clinically important improvement (a difference of ≥10 points on the KOOS4) with no between-group difference. No serious adverse events were observed. In this randomized clinical trial, the results demonstrated that neuromuscular exercises and pain neuroscience education were not superior to pain neuroscience education alone in participants with chronic pain after TKA. Approximately one-third of the participants, regardless of intervention, experienced clinically important improvements. Future studies should investigate which patient characteristics indicate a favorable response to exercises and/or pain neuroscience education. ClinicalTrials.gov Identifier: NCT03886259.

Effectiveness of DialBetesPlus, a self-management support system for diabetic kidney disease: Randomized controlled trial

We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group’s change (P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage (P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: −32.3% [95% CI: −49.2%, −9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.

Off- to in-season body composition adaptations in elite male and female endurance and power event athletics competitors: an observational study

BackgroundMonitoring elite athletes’ body composition (BC) is vital for health and optimizing performance in sports emphasizing leanness, such as athletics. This study aims to investigate and compare sex- and event-specific off-to in-season BC changes in endurance and power event athletics competitors.MethodsElite male and female endurance athletes (> 800 m runners; n = 21) and power event athletes (sprinters, jumpers; n = 32) underwent dual-energy X-ray absorptiometry (DXA) scans for whole and regional lean mass (LM), fat mass (FM), bone mineral content (BMC), and density (BMD) during off-season (September-October) and in-season (April-May). Linear mixed models tested between-group off-season differences in BC, within-group off-season to in-season changes, and between-group differences in change. To assess meaningful or least significant changes (LSC) in BC, DXA precision errors were determined from two consecutive total body scans in a subsample of athletes (n = 30).ResultsMale athletes (n = 26) gained significantly (p < 0.05) more body mass (BM; mean difference 1.5 [95% confidence interval (CI):0.5–2.4] kg), LM (843 [95% CI:-253:1459] g), and trunk LM (756 [-502:1156] g) than female athletes (n = 27). The proportion of changes in athlete’s BC exceeding the LSC threshold for LM and trunk LM were 70% and 65% in males, and 48% and 26% in females. Significant (p < 0.05) within-group off-season to in-season increases in LM were found for male endurance and power athletes, and female power athletes. All groups significantly increased BMD (p < 0.05). Only male and female power athletes had significant in- to-off-season increases in BMC. 80% of all athletes who had a meaningful increase in BMC belonged to the power event group. No significant within- or between group change in FM was observed.ConclusionsThe present study found that male athletes gained more BM, LM and trunk LM than females. Within-group increases in regional and whole-body LM and BMC were predominantly found among power event competitors. Incorporating individual meaningful changes alongside traditional statistics provided additional insights into sex and event-group differences. Future research on elite athletic event groups should include DXA measurements closer to major outdoor-season competitions, coupled with site-specific measures (ultrasound, MRI) for better detection of subtle changes in LM and FM.

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition

Many patients with post-COVID condition (PCC) experience persistent fatigue, muscle pain, and cognitive problems that worsen after exertion (referred to as postexertional malaise). Recommendations currently advise against exercise in this population to prevent symptom worsening; however, prolonged inactivity is associated with risk of long-term health deterioration. To assess postexertional symptoms in patients with PCC after exercise compared with control participants and to comprehensively investigate the physiologic mechanisms underlying PCC. In this randomized crossover clinical trial, nonhospitalized patients without concomitant diseases and with persistent (≥3 months) symptoms, including postexertional malaise, after SARS-CoV-2 infection were recruited in Sweden from September 2022 to July 2023. Age- and sex-matched control participants were also recruited. After comprehensive physiologic characterization, participants completed 3 exercise trials (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order. Symptoms were reported at baseline, immediately after exercise, and 48 hours after exercise. The primary outcome was between-group differences in changes in fatigue symptoms from baseline to 48 hours after exercise, assessed via the visual analog scale (VAS). Questionnaires, cardiopulmonary exercise testing, inflammatory markers, and physiologic characterization provided information on the physiologic function of patients with PCC. Thirty-one patients with PCC (mean [SD] age, 46.6 [10.0] years; 24 [77%] women) and 31 healthy control participants (mean [SD] age, 47.3 [8.9] years; 23 [74%] women) were included. Patients with PCC reported more symptoms than controls at all time points. However, there was no difference between the groups in the worsening of fatigue in response to the different exercises (mean [SD] VAS ranks for HIIT: PCC, 29.3 [19.5]; controls, 28.7 [11.4]; P = .08; MICT: PCC, 31.2 [17.0]; controls, 24.6 [11.7]; P = .09; ST: PCC, 31.0 [19.7]; controls, 28.1 [12.2]; P = .49). Patients with PCC had greater exacerbation of muscle pain after HIIT (mean [SD] VAS ranks, 33.4 [17.7] vs 25.0 [11.3]; P = .04) and reported more concentration difficulties after MICT (mean [SD] VAS ranks, 33.0 [17.1] vs 23.3 [10.6]; P = .03) compared with controls. At baseline, patients with PCC showed preserved lung and heart function but had a 21% lower peak volume of oxygen consumption (mean difference: -6.8 mL/kg/min; 95% CI, -10.7 to -2.9 mL/kg/min; P < .001) and less isometric knee extension muscle strength (mean difference: -37 Nm; 95% CI, -67 to -7 Nm; P = .02) compared with controls. Patients with PCC spent 43% less time on moderate to vigorous physical activity (mean difference, -26.5 minutes/d; 95% CI, -42.0 to -11.1 minutes/d; P = .001). Of note, 4 patients with PCC (13%) had postural orthostatic tachycardia, and 18 of 29 (62%) showed signs of myopathy as determined by neurophysiologic testing. In this study, nonhospitalized patients with PCC generally tolerated exercise with preserved cardiovascular function but showed lower aerobic capacity and less muscle strength than the control group. They also showed signs of postural orthostatic tachycardia and myopathy. The findings suggest cautious exercise adoption could be recommended to prevent further skeletal muscle deconditioning and health impairment in patients with PCC. ClinicalTrials.gov Identifier: NCT05445830.

Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Individuals with knee osteoarthritis show few limitations in balance recovery responses after moderate gait perturbations

BackgroundKnee osteoarthritis causes structural joint damage. The resultant symptoms can impair the ability to recover from unexpected gait perturbations. This study compared balance recovery responses to moderate gait perturbations between individuals with knee osteoarthritis and healthy individuals. MethodsKinematic data of 35 individuals with end-stage knee osteoarthritis, and 32 healthy individuals in the same age range were obtained during perturbed walking on a treadmill at 1.0 m/s. Participants received anteroposterior (acceleration or deceleration) or mediolateral perturbations during the stance phase. Changes from baseline in margin of stability, step length, step time, and step width during the first two steps after perturbation were compared between groups using a linear regression model. Extrapolated center of mass excursion was descriptively analyzed. FindingsAfter all perturbation modes, extrapolated center of mass trajectories overlapped between individuals with knee osteoarthritis and healthy individuals. Participants predominantly responded to mediolateral perturbations by adjusting their step width, and to anteroposterior perturbations by adjusting step length and step time. None of the perturbation modes yielded between-group differences in changes in margin of stability and step width during the first two steps after perturbation. Small between-group differences were observed for step length (i.e. 2 cm) of the second step after mediolateral and anteroposterior perturbations, and for step time (i.e. 0.01–0.02 s) of first step after mediolateral perturbations and the second step after outward and belt acceleration perturbations. InterpretationDespite considerable pain and damage to the knee joint, individuals with knee osteoarthritis showed comparable balance recovery responses after moderate gait perturbations to healthy participants.

One-year effectiveness of high-load compared with low-load strengthening exercise on self-reported function in patients with hypermobile shoulders: a secondary analysis from a randomised controlled trial

ObjectivesTo investigate the long-term effectiveness of high-load versus low-load strengthening exercise on self-reported function in patients with hypermobility spectrum disorder (HSD) and shoulder symptoms.MethodsA secondary analysis of a superiority, parallel-group,...

Evaluation of a Modified Mindfulness-Based Stress Reduction Intervention for Adults with Cerebral Palsy and Anxiety and/or Emotion Regulation Difficulties-A Randomised Control Trial.

Mindfulness-Based Stress Reduction (MBSR) has not yet been evaluated for people with cerebral palsy (CP). The aims of this randomised control trial were to investigate whether a modified telehealth MBSR program could improve mindfulness and reduce depression, anxiety, and emotion regulation difficulties among adults with CP with elevated anxiety and/or emotional regulation difficulties. Participants (n = 31) with elevated anxiety and/or emotion regulation difficulties and no/mild intellectual impairment were randomised to a modified telehealth MBSR program (90 min weekly, 9 weeks) group or a wait-list group. Measurements were collected prior to (T1), after (T2), and 8 weeks post-intervention (T3). The primary outcome was the mean between-group difference in the change in Cognitive and Affective Mindfulness Scale-R (CAMS-R) scores in T1-T2. The secondary outcomes included mean within-group differences over time for the CAMS-R total scores, Depression Anxiety and Stress Scale-21 subscales, and Difficulties in Emotion Regulation Scale (DERS) total t-score. We found no statistically significant between-group difference in mean change in mindfulness scores for T1-T2 (primary outcome). Secondary outcomes: The MBSR intervention group had improved CAMS-R scores with respect to T1-T2 and T1-T3; improved mean scores for Depression and Stress subscales for T1-T2; and improved DERS t-scores for T1-T2 and T1-T3. In conclusion, this study found no significant between-group difference for the primary outcome of mindfulness. The MBSR program was successfully modified for adults with CP and was effective in improving depression, stress, and emotion regulation. ACTRN12621000960853.

Health-related quality of life with pembrolizumab plus chemotherapy vs placebo plus chemotherapy for advanced triple-negative breast cancer: KEYNOTE-355.

In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).

Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (-0.23 ± 0.08 pg/mL) and improvements in cholesterol (-0.31 ± 0.18 mmol/L) and LDL (-0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (-190.8 ± 106.40 kcal LCS restriction, -245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (-8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.

Comparing the Effect of Repetitive Transcranial Magnetic Stimulation Therapy and Aerobic Exercise as an Add-on Therapy on the Cognitive Function of Patients with Depression

Background: Cognitive disturbances are a major cause of disability in depression. The antidepressant medication effectively improves cognitive function. However, its adverse effect limits its use, so add-on treatment is needed to support its effectiveness. Aim: This study aims to compare the efficacy of aerobic exercise and repetitive transcranial magnetic stimulation (rTMS) as an add-on treatment for improving cognitive function. Material and Methods: Twenty-seven patients with first episodes of moderate and severe depression were recruited from the outpatient psychiatry clinic to join this randomized controlled trial. Participants were allocated to three groups: antidepressant only, antidepressant with add-on aerobic exercise, and antidepressant with add-on rTMS therapy. All participants received 2 weeks of intervention. Cognitive functions were assessed using Montreal Cognitive Assessment (MOCA). Results: No differences were found in baseline characteristic data between groups. Total MOCA score increased after intervention in a group with no add-on treatment (p=0.007), with add-on aerobic exercise (p=0.011), and with add-on rTMS therapy (p=0.017). Hence, there was no between-group difference (p=0.222). The MOCA subtest analysis revealed between-group differences in changes in delayed recall subtest score (p=0.01). The group with add-on rTMS therapy improved better than the group with antidepressants only (p=0.005). Conclusion: The addition of rTMS therapy resulted in better improved delayed recall function than the addition of aerobic exercise or without any add-on treatment. This finding supports the application of rTMS therapy as an add-on treatment to improve the cognitive function of patients with depression.

A six-month low-carbohydrate diet high in fat does not adversely affect endothelial function or markers of low-grade inflammation in patients with type 2 diabetes: an open-label randomized controlled trial

BackgroundWhile a low-carbohydrate diet (LCD) reduces HbA1c in patients with type 2 diabetes (T2D), the associated high intake of fat may adversely affect cardiovascular risk factors. To address this, we examined the effect of a non-calorie-restricted LCD high in fat on endothelial function and markers of low-grade inflammation in T2D over 6 months.MethodsIn an open-label randomized controlled trial, 71 patients with T2D were randomized 2:1 to either a LCD (< 20 E% carbohydrates, 50–60 E% fat) or a control diet (50–60 E% carbohydrates, 20–30 E% fat) for six months. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were assessed by ultrasound in the brachial artery together with plasma interleukin-6 (IL-6) and serum high-sensitivity C-reactive protein (hsCRP) in the participants at baseline (n = 70) and after six months (n = 64).ResultsThe FMD and NID were unaltered in both groups after six months, and there were no between-group differences in change of either FMD (p = 0.34) or NID (p = 0.53) in response to the interventions. The circulating hsCRP and IL-6 levels decreased only in response to LCD (both p < 0.05). However, comparing changes over time with the control diet, the LCD did not reduce either IL-6 (p = 0.25) or hsCRP (p = 0.07) levels. The lack of changes in FMD and NID in response to LCD persisted after adjustment for cardiovascular risk factors.ConclusionA LCD high in fat for six months does not adversely affect endothelial function or selected markers of low-grade inflammation, which suggests that this nutritional approach does not increase the risk of cardiovascular disease.Trial registration ClinicalTrials.gov (NCT03068078).

The Effects of Exercise Training on Exercise Capacity and Vascular Function after Transcatheter Aortic Valve Implantation-A Pilot Study.

Transcatheter aortic valve implantation (TAVI) improves event-free survival in patients with severe aortic stenosis, but patients' exercise capacity remains poor after the procedure. Therefore, we sought to compare the effects of a supervised center-based exercise training program and unsupervised exercise routine on exercise capacity and vascular function in patients after TAVI. Patients were randomized to either center-based exercise training (12-24 sessions of combined aerobic and low-weight resistance training twice weekly for 8-12 weeks) or an unsupervised home-based exercise routine (initial appraisal with detailed recommendations and monthly follow-up). Exercise capacity (cardiopulmonary testing) and vascular function (ultrasonographic measurement of flow-mediated vasodilation (FMD) and arterial stiffness) were assessed at the baseline and after the study period. We included 23 patients (mean age of 81 years, 61% women), with higher-than-expected drop-out rates (41%) because of the coronavirus-19 pandemic outbreak. Exercise capacity improved over time, irrespective of the intervention group: 0.09 mL/min/kg increase in peak oxygen uptake (95% CI [0.01-0.16]; p = 0.02), 8.2 Watts increase in workload (95% CI [0.6-15.8]; p = 0.034), and 47 s increase in cumulative exercise time (95% CI [5.0-89.6]; p = 0.029). A between-group difference in change over time (treatment effect) was detected only for FMD (4.49%; 95% CI [2.35; 6.63], p < 0.001), but not for other outcome variables. Both supervised and unsupervised exercise training improve exercise capacity and vascular function in patients after TAVI, with supervised exercise training possibly yielding larger improvements in vascular function, as determined by FMD.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

The median eating duration in the U.S. is 14.75h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Eighty-one adults with overweight or obesity (age 18-50years, BMI 25-45kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2±6.9years, BMI 33.8±5.7kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p=0.03). There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab

BackgroundTocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and...

Effect of 6-week treatment with topical betamethasone dipropionate in patients with symptomatic hand osteoarthritis: A randomized double-blind, placebo-controlled trial

ObjectiveTo examine the efficacy and safety of topical corticosteroid over 6 weeks in patients with symptomatic hand osteoarthritis. DesignIn a randomized, double-blind, placebo-controlled trial, community-based participants with hand osteoarthritis were randomly assigned (1:1) to topical Diprosone OV (betamethasone dipropionate 0.5 ​mg/g in optimised vehicle, n=54) or placebo (plain paraffin, n=52) ointment to painful joints 3 times daily for 6 weeks. Primary outcome was pain reduction [assessed by 100 ​mm visual analogue scale (VAS)] at 6 weeks. Secondary outcomes included changes in pain and function using the Australian Canadian Osteoarthritis Hand Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA), and Michigan Hand Outcomes Questionnaire (MHQ) at 6 weeks. Adverse events were recorded. ResultsOf 106 participants (mean age 64.2 years, 85.9% female), 103 (97.2%) completed the study. Change in VAS at 6 weeks was similar in the Diprosone OV and placebo groups (−19.9 vs. −20.9, adjusted difference 0.6, 95% CI -8.9 to 10.2). There were no significant between-group differences in change in AUSCAN pain [adjusted difference 25.8 (−16.0 to 67.5)], AUSCAN function [21.2 (−55.0 to 97.4)], FIHOA [-0.1 (−1.7 to 1.5)], or MHQ [-1.2 (−6.0 to 3.6)]. Incidence of adverse events was 16.7% in Diprosone OV and 19.2% in placebo group. ConclusionsTopical Diprosone OV ointment, although well-tolerated, was no better than placebo in improving pain or function over 6 weeks in patient with symptomatic hand osteoarthritis. Future studies should consider examining joints with synovitis and whether delivery approaches enhancing transdermal penetration of corticosteroids into joints are effective in hand osteoarthritis. Trial registrationACTRN 12620000599976. Registered May 22, 2020.

Minimally important differences for interpreting EORTC QLQ-C30 change scores over time: A synthesis across 21 clinical trials involving nine different cancer types

IntroductionEarly guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can vary by scale, direction of change, cancer type and estimation method has raised doubt about a single global standard. This paper identifies MID patterns for interpreting group-level change in EORTC QLQ-C30 scores across nine cancer types. MethodsData were obtained from 21 published EORTC Phase III trials that enroled 13,015 patients across nine cancer types (brain, colorectal, advanced breast, head/neck, lung, mesothelioma, melanoma, ovarian, and prostate). Anchor-based MIDs for within-group change and between-group differences in change over time were obtained via mean change method and linear regression, respectively. Separate MIDs were estimated for improvements and deteriorations. Distribution-based estimates were derived and compared with anchor-based MIDs. ResultsAnchor-based MIDs mostly ranged from 5 to 10 points. Differences in MIDs for improvement vs deterioration, for both within-group and between-group, were mostly within a 2-points range. Larger differences between within-group and between-group MIDs were observed for several scales in ovarian, lung and head/neck cancer. Most anchor-based MIDs ranged between 0.3 SD and 0.5 SD distribution-based estimates. ConclusionsOur results reinforce recent claims that no single MID can be applied to all EORTC QLQ-C30 scales and disease settings. MIDs varied by scale, improvement/deterioration, within/between comparisons and by cancer type. Researchers applying commonly used rules of thumb must be aware of the risk of dismissing changes that are clinically meaningful or underpowering analyses when smaller MIDs apply.

Electrically assisted cycling for individuals with type 2 diabetes mellitus: a pilot randomized controlled trial

BackgroundType 2 diabetes mellitus (T2DM) and its associated complications puts considerable strain on healthcare systems. With the global incidence of T2DM increasing, effective disease management is essential. Physical activity (PA) is a key component of T2DM management; however, rates of PA engagement are low in this population. Developing effective and sustainable interventions that encourage PA is a high priority. Electrically assisted bicycles are becoming increasingly popular and may increase PA in healthy adults. This study aimed to provide evidence of the feasibility of conducting a randomized controlled trial to evaluate the efficacy of an e-cycling intervention to increase PA and improve health in individuals with T2DM.MethodsA parallel-group two-arm randomized, waitlist-controlled pilot study was conducted. Individuals were randomized to either an e-bike intervention or standard care. The intervention incorporated two one-to-one e-bike skills training and behavioural counselling sessions delivered by a community-based cycling charity, followed by a 12-week e-bike loan with two further sessions with the instructors. Feasibility was assessed via measures related to recruitment, retention and intervention implementation. Post-intervention interviews with instructors and participants explored the acceptability of the study procedures and intervention. Clinical, physiological and behavioural outcomes were collected at baseline and post-intervention to evaluate the intervention’s potential.ResultsForty participants (Mage = 57) were randomized, of which 34 were recruited from primary care practices. Thirty-five participants were retained in the trial. The intervention was conducted with high fidelity (> 80% content delivered). E-bike training provided participants with the skills, knowledge and confidence needed to e-bike independently. Instructors reported being more confident delivering the skills training than behavioural counselling, despite acknowledging its importance. The study procedures were found to be acceptable to participants. Between-group differences in change during the intervention were indicative of the interventions potential for improving glucose control, health-related quality of life and cardiorespiratory fitness. Increases in overall device measured moderate-to-vigorous PA behaviour following the intervention were found, and there was evidence that this population self-selected to e-cycle at a moderate intensity.ConclusionsThe study’s recruitment, retention, acceptability and potential efficacy support the development of a definitive trial subject to identified refinements.Trial registrationISRCTN, ISRCTN67421464. Registered 17/12/2018.

Effects of Controlled Supramaximal High-Intensity Interval Training on Cardiorespiratory Fitness and Global Cognitive Function in Older Adults: The Umeå HIT Study-A Randomized Controlled Trial.

This study examined the effects of regulated and controlled supramaximal high-intensity interval training (HIT) adapted for older adults, compared to moderate-intensity training (MIT), on cardiorespiratory fitness; cognitive, cardiovascular, and muscular function; and quality of life. Sixty-eight nonexercising older adults (66-79 years, 44% males) were randomized to 3 months of twice-weekly HIT (20-minute session including 10 × 6-second intervals) or MIT (40-minute session including 3 × 8-minute intervals) on stationary bicycles in an ordinary gym setting. Individualized target intensity was watt controlled with a standardized pedaling cadence and individual adjustment of the resistance load. Primary outcomes were cardiorespiratory fitness (V̇o2peak) and global cognitive function (unit-weighted composite). V̇o2peak increased significantly (mean 1.38 mL/kg/min, 95% CI [0.77, 1.98]), with no between-group difference (mean difference 0.05 [-1.17, 1.25]). Global cognition did not improve (0.02 [-0.05, 0.09]), nor differed between groups (0.11 [-0.03, 0.24]). Significant between-group differences in change were observed for working memory (0.32 [0.01, 0.64]), and maximal isometric knee extensor muscle strength (0.07 N·m/kg [0.003, 0.137]), both in favor of HIT. Irrespective of the group, there was a negative change in episodic memory (-0.15 [-0.28, -0.02]), a positive change in visuospatial ability (0.26 [0.08, 0.44]), and a decrease in systolic (-2.09 mmHg [-3.54, -0.64]) and diastolic (-1.27 mmHg [-2.31, -0.25]) blood pressure. In nonexercising older adults, 3 months of watt-controlled supramaximal HIT improved cardiorespiratory fitness and cardiovascular function to a similar extent as MIT, despite half the training time. In favor of HIT, there was an improvement in muscular function and a potential domain-specific effect on working memory. NCT03765385.