Between-group Difference In Change Research Articles

Increased knee-extension strength and steps per day after a novel post-hospitalization rehabilitative program in older adults (65+): Secondary analyses of a randomized controlled single-blinded trial using an expanded sample size

IntroductionOlder adults are at risk of developing new or worsened disability when hospitalized for acute medical illness. This study is a secondary analysis of the STAND-Cph trial on the effect of a simple strength training intervention initiated during hospitalization and continued after discharge. We investigated the between-group difference in change in functional performance outcomes, the characteristics of patients who experienced a relevant effect of the intervention, and the characteristics of those who were compliant with the intervention, using an expanded sample size as protocolized. MethodsThe STAND-Cph was a randomized controlled trial conducted at a major Danish university hospital. Acutely admitted older adult patients (65+) from the Emergency Department were randomized to the intervention group receiving progressive strength training and a protein supplement during and after hospitalization (12 sessions over 4 weeks) or control group receiving usual care. The primary outcome was the de Morton Mobility Index assessed at baseline and 4 weeks after discharge. The secondary outcomes were 24-h mobility (assessed by ActivPAL accelerometers), isometric knee-extension strength, 30 s. sit-to-stand performance, and habitual gait speed. ResultsBetween September 2013 and September 2018, a total of 158 patients were included and randomized to either the intervention group (N = 80; mean age 79.9 ± 7.6 years) or the control group (N = 78; mean age 80.8 ± 7.4 years). We found no significant between-group difference in change in our primary outcome (p > 0.05). Both the intention-to-treat (difference in change 0.14 Nm/kg (95 % CI 0.03;0.24), p = 0.01) and the per protocol (difference in change 0.16 Nm/kg (95 % CI 0.04;0.29), p = 0.008) analyses showed that between baseline and 4 weeks, knee-extension strength increased significantly more in the intervention group than in the control group. Also, the per protocol analysis showed that the intervention group increased their daily number of steps significantly more than the control group (difference in change 1088 steps (95 % CI 44; 2132); p = 0.04). When examining subgroups of patients, we found no significant differences neither between those who experienced a clinically relevant improvement in the de Morton Mobility Index and those who did not, nor between those who were compliant and those who were not. ConclusionThis exploratory analysis indicates that while simple progressive strength training and protein supplementation does not improve functional performance assessed by the de Morton Mobility Index, it can benefit specific facets of physical activity and muscle strength among geriatric patients.

Efficacy of Save Medical Corporation (SMC)-01, a Smartphone App Designed to Support Type 2 Diabetes Self-Management Based on Established Guidelines: Randomized Controlled Trial.

Lifestyle modifications are a key part of type 2 diabetes mellitus treatment. Many patients find long-term self-management difficult, and mobile apps could be a solution. In 2010, in the United States, a mobile app was approved as an official medical device. Similar apps have entered the Japanese market but are yet to be classified as medical devices. The objective of this study was to determine the efficacy of Save Medical Corporation (SMC)-01, a mobile app for the support of lifestyle modifications among Japanese patients with type 2 diabetes mellitus. This was a 24-week multi-institutional, prospective randomized controlled trial. The intervention group received SMC-01, an app with functions allowing patients to record data and receive personalized feedback to encourage a healthier lifestyle. The control group used paper journals for diabetes self-management. The primary outcome was the between-group difference in change in hemoglobin A1c from baseline to week 12. The change in hemoglobin A1c from baseline to week 12 was -0.05% (95% CI -0.14% to 0.04%) in the intervention group and 0.06% (95% CI -0.04% to 0.15%) in the control group. The between-group difference in change was -0.11% (95% CI -0.24% to 0.03%; P=.11). There was no statistically significant change in glycemic control. The lack of change could be due to SMC-01 insufficiently inducing behavior change, absence of screening for patients who have high intention to change their lifestyle, low effective usage of SMC-01 due to design issues, or problems with the SMC-01 intervention. Future efforts should focus on these issues in the early phase of developing interventions. Japan Registry of Clinical Trials jRCT2032200033; https://jrct.niph.go.jp/latest-detail/jRCT2032200033.

A multimodal non-pharmacological intervention for persons with dementia in nursing homes: a multicentre randomised controlled trial.

Persons with dementia in nursing homes often experience cognitive decline (e.g., memory and visuospatial/construction problems), behavioural and psychological symptoms of dementia (BPSD), and impaired activities of daily living. Therefore, comprehensive interventions for this population are needed. We assessed whether a multimodal non-pharmacological intervention improved cognitive functions, BPSD, and activities of daily living in persons with dementia in nursing homes. This was a multicentre randomised controlled trial. Participants were 40 persons with dementia (38 women) living in four nursing homes (intervention group = 21; control group = 19). The intervention was conducted for 8 weeks, followed by an 8-week follow-up. Outcome measures were scores on the Japanese version of the Neurobehavioral Cognitive Status Examination Five and the ABC Dementia Scale. In the analysis, parameters were estimated using Bayesian statistics and a mixed-effects linear regression model for the change in each outcome measure. There were significant between-group differences in changes in ABC Dementia Scale BPSD scores (8-week: posteriori median = 1.66, 95% Bayesian confidence interval 0.36-3.01; 16-week: median = 2.37, 95% Bayesian confidence interval 0.05-4.65). There was also a significant between-group difference in changes in Neurobehavioral Cognitive Status Examination Five constructional ability scores (16-week: median = 0.93, 95% Bayesian confidence interval 0.35-1.50). This intervention may have a maintenance and improvement effect on BPSD in persons with dementia in nursing homes, and a sustained effect on constructional ability post-intervention. The intervention may be useful and easy to apply in practice.

A new approach in insulin pump education improves glycemic outcomes: a randomized controlled trial.

To address the scarcity of continued education for insulin pump users, we developed and evaluated a new program (NP) for individuals transitioning to a different insulin pump. In a randomized, controlled 3-month study, adults with type 1 diabetes and suboptimal HbA1c received either NP or usual care program (UC). The NP was designed in collaboration with representatives of the target group and incorporated technical training, case-based learning, and peer experience sharing - encompassing two group sessions, and two follow-up telephone calls. The UC included a single training session led by the pump company with hotline assistance (clinic) but no structured follow-up. The primary endpoint was the difference in time in range (TIR) (70-180mg/dL (3.9-10.0 mmol/L)), measured by continuous glucose monitoring from baseline to 3 months post-course. Psychosocial self-efficacy was measured by the Diabetes Empowerment Scale (DES-SF). Thirty-nine participants (median age 43, 74% female) were included. Mean TIR increased significantly in the NP group and remained unchanged in the UC group (between-group difference in change was 13.5% [95% CI: 4.0 to 22.9], p = 0.0064). Psychosocial self-efficacy improved and HbA1c decreased only significantly in the NP group. Applying a novel education program at pump transition significantly improved glycemic outcomes and self-efficacy.

Combined Physiotherapy and Cognitive Behavioral Therapy for Functional Movement Disorders

Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients' quality of life. To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs. This was a parallel, rater-blinded, single-center, randomized clinical trial. Recruitment took place from June 2022 to April 2023, and follow-up visits were performed at months 3 and 5, concluding in October 2023. Participants were recruited from a national referral center for movement disorders: the Movement Disorders Unit from the Hospital Universitario Virgen Rocio in Seville, Spain. Patients had to be 18 years or older with a confirmed FMD diagnosis and capable of giving consent to participate. Patients who did not meet eligibility criteria or refused to participate were excluded. Any uncontrolled psychiatric disorder was considered an exclusion criterion. Patients were randomly assigned, in a ratio of 1:1 to multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy), or a control intervention (psychological support intervention). Primary outcomes: between-group differences in changes from baseline to month 3 and month 5 in patients' quality of life (EQ-5D-5L score: EQ Index and EQ visual analog scale [EQ VAS]; and 36-Item Short-Form Survey Physical Component Summary [SF-36 PCS] and SF-36 Mental Component Summary [MCS]). Linear mixed models were applied, controlling by baseline severity and applying Bonferroni correction. Of 70 patients screened with an FMD, 40 were enrolled (mean [SD] age, 43.5 [12.8] years; age range, 18-66 years; 32 female [80%]; mean [SD] age at FMD onset, 38.4 [12.1] years), and 38 completed all the follow-up visits and were included in the analysis for primary outcomes. Multidisciplinary treatment improved SF-36 PCS with a mean between-group difference at 3 months of 4.23 points (95% CI, -0.9 to 9.4 points; P = .11) and a significant mean between-group difference at 5 months of 5.62 points (95% CI, 2.3-8.9 points; P < .001), after multiple-comparisons adjustment. There were no significant differences in other quality-of-life outcomes such as SF-36 MCS (mean between-group difference at 3 and 5 months: 0.72 points; 95% CI, -5.5 to 7.0 points; P = .82 and 0.69 points; 95% CI, 2.3-8.9 points; P = .83, respectively), EQ VAS (9.34 points; 95% CI, -0.6 to 19.3 points; P = .07 and 13.7 points; 95% CI, -1.7 to 29.0 points; P = .09, respectively) and EQ Index (0.001 point; 95% CI, -0.1 to 0.1 point; P = .98 and 0.08 points; 95% CI, 0-0.2 points; P = .13, respectively). At months 3 and 5, 42% and 47% of patients, respectively, in the multidisciplinary group reported improved health using the EQ-5D system, compared with 26% and 16% of patients, respectively, in the control group. Results show that multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) effectively improves FMD symptoms and physical aspects of patients' quality of life. Further studies must be performed to evaluate the potential cost-effectiveness of this approach in FMD. ClinicalTrials.gov Identifier: NCT05634486.

Evaluation of a medical student-delivered smoking prevention program utilizing a face-aging mobile app for secondary schools in Germany: The Education Against Tobacco cluster-randomized controlled trial

BackgroundTo reduce smoking uptake in adolescents, the medical students' network Education Against Tobacco (EAT) has developed a school-based intervention involving a face-aging mobile app (Smokerface). MethodsA two-arm cluster-randomized controlled trial was conducted, evaluating the 2016 EAT intervention, which employed the mobile app Smokerface and which was delivered by medical students. Schools were randomized to intervention or control group. Surveys were conducted at baseline (pre-intervention) and at 9, 16, and 24 months post-intervention via paper & pencil questionnaires. The primary outcome was the difference in within-group changes in smoking prevalence between intervention and control group at 24 months. ResultsOverall, 144 German secondary schools comprising 11,286 pupils participated in the baseline survey, of which 100 schools participated in the baseline and at least one of the follow-up surveys, yielding 7437 pupils in the analysis sample. After 24 months, smoking prevalence was numerically lower in the intervention group compared to control group (12.9 % vs. 14.3 %); however, between-group differences in change in smoking prevalence between baseline and 24-months follow-up (OR=0.83, 95 %-CI: 0.64–1.09) were not statistically significant (p = 0.176). Intention to start smoking among baseline non-smokers declined non-significantly in the intervention group (p = 0.064), and remained essentially unchanged in the control group, but between-group differences in changes at the 24-months follow-up (OR=0.88, 0.64–1.21) were not statistically significant (p = 0.417). ConclusionWhile a trend towards beneficial effects of the intervention regarding smoking prevalence as well as intention to start smoking among baseline non-smokers was observed, our smoking prevention trial demonstrated no significant effect of the intervention.

Hot flashes and sleep disruption in a randomized trial in menopausal women

BackgroundHot flashes, common during menopause, affect up to 80% of Western menopausal women and are reported to contribute to sleep disturbances in midlife. Few prospective data are available to confirm the specific role of hot flashes in disrupting sleep in midlife women, however, or confirm whether changes in hot flashes in response to clinical therapies result in improvement in sleep. ObjectiveTo examine the effects of continuous nitroglycerin therapy on sleep quality in peri- and postmenopausal women with frequent hot flashes (pre-specified secondary trial endpoint), and to examine prospective associations between hot flashes and sleep disruption in this population. Study DesignSleep data were analyzed from a randomized, double-blinded, placebo-controlled trial of continuous transdermal nitroglycerin (NTG) therapy to suppress nitric oxide-mediated vasodilation in peri- or postmenopausal women with hot flashes. Participants were randomized to uninterrupted use of transdermal NTG (0.2-0.6 mg/hour) or placebo for 12 weeks. Nocturnal hot flashes awakening participants from sleep were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks. Sleep disruption (wake time after sleep onset, WASO) was assessed using validated sleep diaries, and global sleep quality was assessed by the validated Pittsburgh Sleep Quality Index (PSQI: range 0 [best] 21 [worst]) questionnaire. Mixed linear models examined changes in sleep quality and disruption, as well as the strength of associations between nocturnal hot flash frequency and sleep outcomes, over 5 and 12 weeks, adjusting for baseline values, age, race, and ethnicity. ResultsAmong the 141 participants (70 to NTG and 71 to placebo, mean age 54.6 [±3.9] years), the mean baseline hot flash frequency was 10.8 (±3.5) per day, including 2.6 (±1.7) nocturnal hot flashes awakening participants. At baseline, hot flashes were the most commonly reported reason for nocturnal awakening, with 62.6% of participants reporting waking due to hot flashes at least twice nightly. Over 5 and 12 weeks, mean frequency of nocturnal hot flashes causing awakenings decreased in both groups (NTG: -0.9 episodes/night, placebo: -1.0 episodes/night). Sleep disruption as measured by average nightly WASO also decreased (NTG: -10.1 minutes, placebo: -7.3 minutes), and mean PSQI score improved (NTG: -1.3 points, placebo: -1.2 points). No significant between-group differences in change in sleep outcomes were detected from baseline to 5 and 12 weeks, including PSQI sleep quality score as a pre-specified secondary trial endpoint (P ≥ .05 for all). Greater improvement in nocturnal hot flash frequency over 5 and 12 weeks was associated with greater improvement in PSQI sleep quality score (β= -0.30, P=.01) and sleep disruption reflected by WASO (β= -1.88, P=.02) in the combined sample. ConclusionAmong menopausal women in a randomized trial of continuous NTG therapy for hot flashes, hot flashes were the most frequently reported cause of nocturnal awakenings. Compared to placebo, continuous NTG therapy did not result in greater improvements in sleep quality from baseline to 5 and 12 weeks. Based on night-by-night symptom diaries and questionnaires, however, greater improvement in nocturnal hot flash frequency in both groups was associated with greater improvement in sleep quality and disruption.

HIIT at Home: Enhancing Cardiorespiratory Fitness in Older Adults-A Randomized Controlled Trial.

This study aimed to investigate the effectiveness of a 6-month home-based high-intensity interval training (HIIT) intervention to improve peak oxygen consumption (V̇O2peak) and lactate threshold (LT) in older adults. Two hundred thirty-three healthy older adults (60-84 years; 54% females) were randomly assigned to either 6-month, thrice-weekly home-based HIIT (once-weekly circuit training and twice-weekly interval training) or a passive control group. Exercise sessions were monitored using a Polar watch and a logbook for objective and subjective data, respectively, and guided by a personal coach. The outcomes were assessed using a modified Balke protocol combining V̇O2peak and LT measures. General linear regression models assessed between-group differences in change and within-group changes for each outcome. There was a significant between-group difference in the pre-to-post change in V̇O2peak (difference: 1.8 [1.2; 2.3] mL/kg/min; exercise: +1.4 [1.0; 1.7] mL/kg/min [~5%]; control: -0.4 [-0.8; -0.0] mL/kg/min [approximately -1.5%]; effect size [ES]: 0.35). Compared with controls, the exercise group had lower blood lactate concentration (-0.7 [-0.9; -0.4] mmol/L, ES: 0.61), % of peak heart rate (-4.4 [-5.7; -3.0], ES: 0.64), and % of V̇O2peak (-4.5 [-6.1; -2.9], ES: 0.60) at the intensity corresponding to preintervention LT and achieved a higher treadmill stage (% incline) at LT (0.6 [0.3; 0.8]; ES: 0.47), following the intervention. This study highlights the effectiveness of a home-based HIIT intervention as an accessible and equipment-minimal strategy to induce clinically meaningful improvements in cardiorespiratory fitness in older adults. Over 6 months, the exercise group showed larger improvements in all outcomes compared with the control group. Notably, the LT outcome exhibited a more pronounced magnitude of change than V̇O2peak.

Feasibility, acceptability, and efficacy of a positive emotion regulation intervention to promote resilience for healthcare workers during the COVID-19 pandemic: A randomized controlled trial.

Burnout poses a substantial, ongoing threat to healthcare worker (HCW) wellbeing and to the delivery of safe, quality healthcare. While systemic and organization-level changes in healthcare are critically important, HCWs also need individual-level skills to promote resilience. The objective of this trial is to test feasibility, acceptability, and efficacy of PARK, an online self-guided positive affect regulation intervention, in a sample of healthcare workers during the COVID-19 pandemic. In the context of the unprecedented rise in burnout during the COVID-19 pandemic, we conducted a randomized waitlist-controlled trial of the Positive Affect Regulation sKills (PARK) program-a five-week, online, self-guided coping skills intervention nested within an ongoing cohort of HCWs. N = 554 healthcare workers were randomly assigned to receive the intervention immediately or to receive the intervention after approximately 12 weeks. Outcomes included change in burnout, emotional wellbeing (positive affect, meaning and purpose, depression, anxiety) and sleep over approximately 12 weeks. Analyses included mixed-effects linear regression models comparing change over time in outcomes between intervention and control conditions. One third (n = 554) of the participants in the cohort of HCWs consented to participate and enrolled in PARK in April 2022. Compared to those who did not enroll, participants in the trial reported higher burnout, poorer emotional wellbeing, and poorer sleep at baseline (April, 2022; all ps < .05). Intent-to-treat analyses showed that participants randomly assigned to the intervention immediately (PARK-Now) improved significantly on anxiety (within-group change on PROMIS T-score = -0.63; p = .003) whereas those in the waitlist (PARK-Later) did not (within group T-score change 0.04, p = 0.90). The between-group difference in change, however, was not statistically significant (B = -0.67 p = 0.10). None of the other wellbeing outcomes changed significantly in the intervention group compared to the waitlist. Additional as-treated analyses indicated that those participants who completed all 5 of the weekly online lessons (N = 52; 9.4%) improved significantly more on the primary outcome of positive affect compared to those who enrolled in PARK but completed zero lessons (n = 237; 42.8%; B = 2.85; p = .0001). Online self-guided coping skills interventions like PARK can be effective in targeted samples and future work will focus on adaptations to increase engagement and tailor PARK for HCWs who could most benefit.

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.

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,...

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.

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.