Mean Between-group Difference Research Articles

Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Intra-Articular Platelet-Rich Plasma Injection After Anterior Cruciate Ligament Reconstruction

Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, -2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Chinese Clinical Trial Registry Identifier: ChiCTR2000040262.

Alternative models to support weight loss in chronic musculoskeletal conditions: effectiveness of a physiotherapist-delivered intensive diet programme for knee osteoarthritis, the POWER randomised controlled trial

ObjectivesTo determine if physiotherapists can deliver a clinically effective very low energy diet (VLED) supplementary to exercise in people with knee osteoarthritis (OA) and overweight or obesity.Methods88 participants with knee...

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage

BackgroundTrials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known.MethodsIn this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients’ assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment.ResultsA total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and −0.013 (95% Bayesian credible interval, −0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration.ConclusionsAmong patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.)

Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials

In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. Novo Nordisk.

Abstract 6290: Effects of a circuit, interval-based exercise program on vascular function among cancer survivors

Abstract Background: Cancer survivors are at an increased risk of cardiovascular comorbidity, including atherosclerosis, hypertension, and heart failure, due to negative impacts of cancer treatments on vascular function. Exercise is recommended in recent cardio-oncology rehabilitation guidelines and has been shown to improve vascular function in clinical populations; however, its effects on vascular function are understudied in clinical oncology settings. Purpose: This pilot study examined whether a circuit, interval-based exercise intervention can improve vascular function, assessed by brachial artery flow-mediated dilation (baFMD) and carotid intima media thickness (cIMT) in breast, prostate, and colorectal cancer survivors. Methods: Overweight or obese (BMI&amp;gt;25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors were randomized to exercise (n=60) or usual care (n=30). Survivors in the 4-month exercise intervention trained three times/week, in a circuit, interval-based supervised moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) program. cIMT and baFMD were measured at baseline and post-intervention via an ultrasound. Paired t-tests and repeated-measures analysis of variance were run to assess within- and between-group differences. Results: The study sample included breast (n=38), prostate (n=24), colorectal (n=28) cancer survivors who were 63.2 ± 10.8 years old, completed chemotherapy and/or radiation (75%) and were obese (87%). Post-intervention, baFMD significantly increased in the exercise group compared to the control group (between-group mean difference: 6.3%; 95% CI: [1.9 to 9.3], p=0.001). There was also a significant reduction in cIMT in the exercise group compared to the control group (between-group mean difference: -0.039mm, 95% CI: [-0.080 to -0.009], p=0.002). Conclusions: Our findings in this pilot study support that a circuit, interval-based aerobic and resistance exercise intervention may improve vascular function in breast, prostate, and colorectal cancer survivors. Future studies are recommended to understand how exercise interventions can be utilized clinically to improve cardiovascular disease risk and co-morbidity among cancer survivors. Citation Format: Cami N. Christopher, Dong-Woo Kang, Paola Gonzalo-Encabo, Rebekah L. Wilson, Amber J. Normann, Mary K. Norris, Christina M. Dieli-Conwright. Effects of a circuit, interval-based exercise program on vascular function among cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6290.

Remotely delivered physiotherapy is as effective as face-to-face physiotherapy for musculoskeletal conditions (REFORM): a randomised trial

QuestionIs remotely delivered physiotherapy as good or better than face-to-face physiotherapy for the management of musculoskeletal conditions? DesignRandomised controlled, non-inferiority trial with concealed allocation, blinded assessors and intention-to-treat analysis. ParticipantsA total of 210 adult participants with a musculoskeletal condition who presented for outpatient physiotherapy at five public hospitals in Sydney. InterventionOne group received a remotely delivered physiotherapy program for 6 weeks that consisted of one face-to-face physiotherapy session in conjunction with weekly text messages, phone calls at 2 and 4 weeks, and an individualised home exercise program delivered through an app. The other group received usual face-to-face physiotherapy care in an outpatient setting. Outcome measuresThe primary outcome was the Patient Specific Functional Scale at 6 weeks with a pre-specified non-inferiority margin of –15 out of 100 points. Secondary outcomes included: the Patient Specific Functional Scale at 26 weeks; kinesiophobia, pain, function/disability, global impression of change and quality of life at 6 and 26 weeks; and satisfaction with service delivery at 6 weeks. ResultsThe mean between-group difference (95% CI) for the Patient Specific Functional Scale at 6 weeks was 2.7 out of 100 points (–3.5 to 8.8), where a positive score favoured remotely delivered physiotherapy. The lower end of the 95% CI was greater than the non-inferiority margin. Whilst non-inferiority margins were not set for the secondary outcomes, the 95% CI of the mean between-group difference ruled out clinically meaningful differences. ConclusionRemotely delivered physiotherapy with support via phone, text and an app is as good as face-to-face physiotherapy for the management of musculoskeletal conditions. Trial registrationACTRN12619000065190.

Open Reduction Internal Fixation vs Primary Arthrodesis for Displaced Lisfranc Injuries: A Multicenter Randomized Controlled Trial.

There is no consensus whether the primary surgical method should be open reduction and internal fixation (ORIF) or primary arthrodesis (PA) for Lisfranc injuries. The aim of our randomized controlled trial was to compare ORIF and PA for displaced Lisfranc injuries. This study was a national multicenter randomized controlled trial. Altogether 43 displaced Lisfranc injuries were enrolled in this trial. The primary outcome measure was Visual Analogue Scale Foot and Ankle (VAS-FA) at a 24-months follow-up. The secondary outcome measures were VAS-FA pain, function, and other complaints subscales and the American Orthopaedic Foot & Ankle Society (AOFAS) Midfoot Scale. All outcomes were measured at 6, 12, and 24 months. We were unable to reach the planned sample size of 60 patients; thus, the study remains underpowered. The mean VAS-FA Overall score in the ORIF group was 86.5 (95% CI 77.9, 95.1) and 80.1 (95% CI 72.0, 88.1) in the PA group at the 24-month follow-up. We did not find eligible evidence of a difference in VAS-FA Overall scores (mean between-group difference 6.5 [95% CI -5.3, 18.2], Cohen d = 0.100). We did not find evidence of a difference in VAS-FA between ORIF and PA in patients with displaced Lisfranc injuries, and thus both are viable options for the initial surgical method. The trial is underpowered; however, the data may be included in a meta-analysis of similarly designed randomized controlled trials. ClinicalTrials.gov identifier: NCT02953067 24 October 2016. Level I, randomized controlled trial.

The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2 ) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

Weight loss and lifestyle intervention for cardiorespiratory fitness in obstructive sleep apnea: The INTERAPNEA trial

IntroductionAlthough recent trials have shown benefits of weight loss and lifestyle interventions on obstructive sleep apnea (OSA) severity and comorbidities, the effect of these interventions on cardiorespiratory fitness (CRF) remains unknown. This study aimed to investigate the effects of an interdisciplinary weight loss and lifestyle intervention on CRF and self-reported physical fitness in adults with OSA. MethodsEighty-nine men aged 18–65 years with moderate-to-severe OSA and a body mass index ≥25 kg/m2 were randomly assigned to a usual-care group or an 8-week interdisciplinary weight loss and lifestyle intervention. CRF was assessed through the 2-km walking test, and the International Fitness Scale (IFIS) was used to assess self-reported physical fitness. ResultsAs compared with usual-care, the intervention group had greater improvements at intervention endpoint in objective CRF (6% reduction in 2-km walking test total time, mean between-group difference, −1.7 min; 95% confidence interval, −2.3 to −1.1), and self-reported overall physical fitness (18% increase in IFIS total score, mean between-group difference, 2.3; 95% CI 1.2 to 3.3). At 6 months after intervention, the intervention group also had greater improvements in both 2-km walking test total time (10% reduction) and IFIS total score (22% increase), with mean between-group differences of −2.5 (CI 95%, −3.1 to −1.8) and 3.0 (CI 95%, 1.8 to 4.1), respectively. ConclusionsAn 8-week interdisciplinary weight loss and lifestyle intervention resulted in significant and sustainable improvements in CRF and self-reported physical fitness in men with overweight/obesity and moderate-to-severe OSA. Study registrationClinicalTrials.gov registration (NCT03851653)

Treatment of Women With Primary Dysmenorrhea With Manual Therapy and Electrotherapy Techniques: A Systematic Review and Meta-Analysis.

The objective of this study was to evaluate the efficacy of electrotherapy and manual therapy for the treatment of women with primary dysmenorrhea. Systematic searches were conducted in Scopus, Web of Science, PubMed, CINAHL, and MEDLINE. The articles must have been published in the last 10years, had a sample exclusively of women with primary dysmenorrhea, had a randomized controlled trial design, and used interventions that included some form of manual therapy and/or electrotherapy techniques. Two reviewers independently screened articles for eligibility and extracted data. Difference in mean differences and their 95% CIs were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity. Twelve selected studies evaluated interventions, with 5 evaluating electrotherapy techniques and 7 evaluating manual therapy techniques. All studies analyzed identified improvements in pain intensity and meta-analysis confirmed their strong effect. Manual therapy and electrotherapy are effective for the treatment of women with primary dysmenorrhea. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage stands out for its effects on the intensity and duration of pain with the application of a few sessions and their long-term effects. Manual therapy techniques and electrotherapy methods reduce the pain intensity of women with primary dysmenorrhea. Quality of life and degree of anxiety improved significantly with manual therapy interventions. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage are the interventions with which positive effects were achieved with fewer sessions.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. Overweight/obese men (body mass index >25kg/m2 ) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

Physiotherapist-supervised exercises versus unsupervised home-based exercises after nonsurgically treated proximal humerus fracture: a multicenter randomized controlled trial

BackgroundProximal humerus fracture (PHF) is a common fragility fracture in older adults and can have a substantial impact on upper limb function. Although most patients with PHF can be treated non-surgically, it is unknown whether older adults benefit from supervised exercise therapy after PHF. Therefore, the objective of this trial was to investigate whether 10 weeks of physiotherapist-supervised exercises once a week was superior to 10 weeks of non-supervised home-based exercises in older adults with a non-surgically treated displaced 2-part PHF. MethodsThis was designed as an assessor-blinded, prospective, randomized controlled trial and took place in three Nordic countries. In total, 72 patients (≥60 years) with non-surgically treated displaced 2-part PHF were randomized to either physiotherapist-supervised exercises once a week for 10 weeks combined with daily home-based exercises were compared to 10 weeks of daily non-supervised home-based exercises. The primary outcome measure was the Disability of the Arm, Shoulder, and Hand (DASH) with a primary endpoint at 3 months. Secondary outcomes were DASH (at 12 months), Constant-Murley Score, the 15D-instrument, Visual Analog Scale, General Self-Efficacy Scale, and Pain Catastrophizing Scale, with follow-up visits after 3 and 12 months. Non-union and patient death within 3 months were counted as complications. ResultsThe mean age of the patients in both groups was 73 years. At 3 months follow-up, the mean DASH score in the supervised group was 25.9 (SD 16.0) compared to 22.4 (18.9) in the non-supervised group. The mean between-group difference (3.5, 95% CI -5.0 to 12.5) was not clinically relevant. None of the secondary outcome measures presented any clinically relevant or statistically significant between-group differences at 3 or 12 months follow-up. One patient in the supervised group and three in the non-supervised group were diagnosed with non-union. One patient from each group died before 3 months follow-up. ConclusionsThis trial provides no evidence that supervised exercises are superior to non-supervised home-based exercises in improving functional outcome or quality of life in older patients with a non-surgically treated 2-part PHF. Further, our results suggest that most older adults with a non-surgically treated 2-part PHF can perform home-based exercises without the supervision of a physiotherapist.

Long-term effects of lumbar flexion versus extension exercises for chronic axial low back pain: a randomized controlled trial

This study aimed to compare the long-term effects of flexion- and extension-based lumbar exercises on chronic axial low back pain (LBP). This was a 1-year follow-up of a prospective, assessor-blind, randomized controlled trial. Patients with axial LBP (intensity ≥ 5/10) for > 6 months allocated to the flexion or extension exercise group. Patients underwent four sessions of a supervised treatment program and were required to perform their assigned exercises daily at home. Clinical outcomes were obtained at baseline, 1, 3, 6 months, and 1-year. A total of 56 patients (age, 54.3 years) were included, with 27 and 29 in the flexion and extension groups, respectively. Baseline pain and functional scales were similar between both groups. The mean (± standard deviation) baseline average back pain was 6.00 ± 1.00 and 5.83 ± 1.20 in the flexion and extension groups, respectively. At 1-year, the average pain was 3.78 ± 1.40 and 2.26 ± 2.62 (mean between-group difference, 1.52; 95% confidence interval 0.56–2.47; p = 0.002), favoring extension exercise. The extension group tended to have more improvements in current pain, least pain, and pain interference than the flexion group at 1-year. However, there was no group difference in worst pain and functional scales. In this controlled trial involving patients with chronic axial LBP, extension-based lumbar exercise was more effective in reducing pain than flexion-based exercises at 1-year, advocating lumbar extension movement pattern as a component for therapeutic exercise for chronic LBP.Clinical Trial Registration No.: NCT02938689 (Registered on www.clinicaltrial.gov; first registration date was 19/10/2016).

Effectiveness of an Intensive, Functional, and Gamified Rehabilitation Program on Upper Limb Function in People With Stroke (EnteRtain): A Multicenter Randomized Clinical Trial

Background1 Despite a growing interest in gaming rehabilitation for upper limb (UL) recovery post-stroke, studies investigating the effects of game-based rehabilitation incorporating functional games are lacking. Objective To investigate the efficacy of an intensive, functional, gamified rehabilitation program compared to task-based training on UL motor function in acute/sub-acute stroke survivors. Methods This randomized, multicenter, single-blind, clinical trial comprises 120 participants with unilateral stroke who were randomized to receive either gamified training (n = 64) using the ArmAble™ [experimental group (EG)] or task-based training (n = 56) in conjunction with conventional therapy for 2 hours per day, 6 days per week for 2 weeks, followed by UL rehabilitation for another 4 weeks at home. Primary outcomes evaluated by a blinded assessor included the Fugl-Meyer Assessment-Upper Extremity (FM-UE), and Action Research Arm Test (ARAT). Data were analyzed using a linear mixed-effect regression model. Results The mean (standard deviation) age of the participants was 54.4 ± 11.7 years (78.1% men) in the EG and 57.7 ± 10.9 years (73.2% men) in the comparator group (CG). The median (interquartile range) time since stroke was 30.0 (54.0) days in the EG and 22.5 (45.0) days in the CG. Following the 2-week intervention, a statistically significant improvement was observed in the EG for the FM-UE [between-group mean differences (95% confidence interval): −3.9 (−6.5, −1.3); P = .003]; but not for the ARAT [−2.9 (−5.8, 0.0); P = .051]. Gains at 6 weeks were significantly greater in the EG for both FM-UE [−3.9 (−6.5, −1.3); P = .003]; and ARAT [−3.0 (−5.9, −0.0); P = .046]. Conclusion Gamified rehabilitation using the ArmAble™ device has shown immediate and short-term improvement in UL function after acute/sub-acute stroke. Clinical Trials Registry Number: CTRI/2020/09/027651

Effectiveness of an eHealth-Delivered Program to Empower People With Musculoskeletal Pain in Rural Australia: A Randomized Controlled Trial.

Our objective was to evaluate the effectiveness of a three-month physiotherapist-delivered eHealth physical activity program compared with usual care to improve function in adults with low back pain or knee osteoarthritis in rural Australia. This was a parallel, two-group, pragmatic, superiority, randomized controlled trial involving three- and six-month posttreatment follow-ups. There was a total of 156 adults with chronic nonspecific low back pain (n=97) or knee osteoarthritis (n=59) from rural Australia. The intervention involved an eHealth physical activity and an exercise program that included five to eight teleconsultations with a physiotherapist (primary time point three months) or usual care (eg, general practitioner, physiotherapy, and pain medication). The primary outcome was the Patient-Specific Functional Scale (0-30), with a three-point difference between groups being considered the minimum clinically important difference. Participants receiving the eHealth intervention (n=78) reported significantly greater and clinically worthwhile improvements in function (mean between-group difference 3.6; 95% confidence interval [CI] 1.3-5.9) compared to participants receiving usual care (n=78). Small but statistically significantly greater improvements in disability (7.2 of 100; 95% CI 2.1-12.3) and quality of life (4.5 of 100; 95% CI 0.0-9.0) also favored the eHealth group. No clinical or statistical differences between groups were found for the secondary outcomes of pain, coping skills, and physical activity levels. A physiotherapist-delivered eHealth intervention is effective and provides clinically meaningful improvements in function compared to usual care for people with musculoskeletal pain in rural communities. These findings highlight the potential for eHealth-based programs to improve access to evidence-based exercise interventions for people with musculoskeletal pain in rural communities.

Cost-utility analysis of Dexcom G6 real-time continuous glucose monitoring versus FreeStyle Libre 1 intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in Belgium.

The aim of this study was to assess the long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring (rtCGM) with alert functionality compared with FreeStyle Libre1 intermittently scanned continuous glucose monitoring (isCGM) without alerts in adults with type 1 diabetes in Belgium. The IQVIA CORE Diabetes Model was used to estimate cost-effectiveness. Input data for the simulated baseline cohort were sourced from the randomised ALERTT1 trial (ClinicalTrials.gov. NCT03772600). The age of the participants was 42.9 ± 14.1 years (mean ± SD), and the baseline HbA1c was 57.8 ± 9.5 mmol/mol (7.4 ± 0.9%). Participants using rtCGM showed a reduction in HbA1c of 3.6 mmol/mol (0.36 percentage points) based on the 6-month mean between-group difference. In the base case, both rtCGM and isCGM were priced at €3.92/day (excluding value-added tax [VAT]) according to the Belgian reimbursement system. The analysis was performed from a Belgian healthcare payer perspective over a lifetime time horizon. Health outcomes were expressed as quality-adjusted life years. Probabilistic and one-way sensitivity analyses were used to account for parameter uncertainty. In the base case, rtCGM dominated isCGM, resulting in lower diabetes-related complication costs and better health outcomes. The associated main drivers favouring rtCGM were lower HbA1c, fewer severe hypoglycaemic events and reduced fear of hypoglycaemia. The results were robust under a wide range of one-way sensitivity analyses. In models where the price of rtCGM is €5.11/day (a price increase of 30.4%) or €12.34/day (a price increase of 214.8%), rtCGM was cost-neutral or reached an incremental cost-effectiveness ratio of €40,000 per quality-adjusted life year, respectively. When priced similarly, Dexcom G6 rtCGM with alert functionality has both economic and clinical benefits compared with FreeStyle Libre1 isCGM without alerts in adults with type 1 diabetes in Belgium, and appears to be a cost-effective glucose monitoring modality. Trial registration ClinicalTrials.gov NCT03772600.

Effect of a home-based isometric handgrip training programme on systolic blood pressure in adults: A randomised assessor-blinded trial

ABSTRACT Objectives To evaluate the effects of 20 weeks of home-based isometric handgrip training (IHT) compared with usual care on systolic blood pressure (SBP) in adults. Design and participants This was a randomised, controlled, assessor-blinded trial. Participants were randomised to either IHT (intervention group) or usual care (control group). Interventions Participants randomised to the intervention group performed a session of 16 min of effective workout home-based IHT three times per week for 20 weeks. Participants randomised to the control group were asked to continue their daily activities as usual. Outcomes The primary outcome was the difference in SBP between groups over 20 weeks. Secondary outcomes were diastolic blood pressure, heart rate, handgrip strength, and self-administered home blood pressure measures. Results Forty-eight adults (mean [SD] age, 64 [8] years) were included in this trial. The adjusted between-group mean difference in SBP was 8.12 mmHg (95% CI 0.24 to 16.01, p = 0.04) – favouring the usual care group. No differences between groups were found in any of the home blood pressure measurements. Conclusions This trial showed that 20 weeks of home-based isometric handgrip training was not superior compared to the usual care in lowering SBP.

Effectiveness of a Preschool Motor Skill Intervention on Body Mass Index and Movement Behavior: 6-, 18-, and 30-Month Findings From a Cluster Randomized Controlled Trial.

To study the effectiveness of a preschool staff-delivered motor skills intervention on body composition and physical activity over a 2.5-year time frame. In this pragmatic parallel cluster randomized controlled trial (16 preschools), outcome data were collected after 6 (body composition only), 18, and 30months of intervention. The main physical activity outcomes were accelerometer behavior measures summarizing the total percentage of child daily movement (walk, run, cycle, and standing that included minor movements) and preschool movement during preschool attendance. To estimate between-group mean differences in outcomes, mixed-linear regression analyses including baseline value of the selected outcome and a treatment × time interaction term as a fixed effect were applied. In addition, the baseline preschool and child were included as a random effect. For body mass index, a total of 437 children (90%) had at least one valid baseline and one follow-up assessment. The corresponding numbers for preschool movement and daily movement were 163 (55%) and 146 (49%), respectively. No significant between-group mean difference was identified for body mass index, waist-to-height ratio, or any physical activity outcomes. Overall, this preschool motor skills intervention had no effect on either child anthropometry or physical activity, consistent with previous studies.