Between-group Difference In Change Research Articles

Impact of Time-Restricted Eating and High-Intensity Exercise on Nutrient Intake in Women with Overweight/Obesity: Secondary Analysis of a Randomized Controlled Trial.

Inadequate micronutrient intakes are common in individuals with overweight/obesityand can exacerbate cardiovascular and metabolic disease risk. Diet and exercise are primary strategies for managing overweight and may influence nutrient intakes. In this secondary analysis of dietary data collected in a randomized controlled trial (RCT, ClinicalTrials.gov (NCT04019860), 15 June 2019) of time-restricted eating (TRE), high-intensity interval training (HIIT), a combination (TREHIIT), or a control group (CON), we investigated intervention effects on energy and nutrient intakes in women with overweight/obesity. We randomized 131 women (body mass index (BMI) ≥ 27 kg/m2) to 7 weeks of TRE (≤10-h daily eating window with ad libitum energy intake), HIIT (3 sessions/week, performed at ≥90% maximal heart rate), TREHIIT, or CON. Participants recorded all energy intake in an online food diary during a baseline week (week 0) and at the end of the study (week 6 and week 7). We investigated between-group differences in changes in mean energy, macronutrient, and micronutrient intakes. TRE had reduced intakes of potassium, magnesium, and phosphorus compared with CON (p < 0.01). TREHIIT had non-significant reduced intakes of potassium, thiamine, magnesium, copper, and phosphorus (0.01< p < 0.05). HIIT alone did not negatively impact micronutrient intakes. TRE and TREHIIT induced suboptimal intakes for a greater number of micronutrients compared with HIIT and CON. A ≤10-h TRE window might increase the risk of micronutrient inadequacy in women with overweight/obesity. Future research is needed to investigate the effects of integrating nutritional guidelines with TRE interventions to mitigate the risk of micronutrient inadequacy in individuals with overweight/obesity.

Effect of Cariprazine on Anhedonia in Patients with BipolarI Depression: Post Hoc Analysis of Three Randomized Placebo-Controlled Clinical Trials.

Anhedonic symptoms in bipolarI (BP-I) depression are associated with decreased quality of life and impaired functioning. We evaluated the effects of cariprazine in patients with BP-I depression with lower or higher levels of anhedonia at baseline. Data were pooled from three clinical trials (NCT01396447, NCT02670538, NCT02670551) analyzing the effects of cariprazine 1.5 and 3mg/day in adults with BP-I depression. During post hoc analysis, patients were stratified by baseline median Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor score into a lower (score < median) or higher (score ≥ median) anhedonia subgroup. Outcomes included change from baseline to week6 in MADRS total and anhedonia factor score, with the latter also evaluated after adjusting for other depressive symptoms. Between-group differences in change from baseline to week6 were compared using least-squares mean differences (LSMD) analyzed via a mixed-effect model for repeated measures. Median baseline anhedonia factor score was 19, defining the lower (placebo = 211; cariprazine 1.5mg/day = 200, 3mg/day = 212) and higher (placebo = 249; cariprazine 1.5mg/day = 261, 3mg/day = 250) anhedonia subgroups. In the lower subgroup, cariprazine 1.5mg/day but not 3mg/day was superior to placebo in reducing MADRS total (LSMD [95%CI] 1.5mg/day = - 2.61 [- 4.28, - 0.93], P = .0024) and anhedonia factor scores (- 1.70 [- 2.77, - 0.62], P = .0021) at week6. In the higher subgroup, both cariprazine doses were associated with significantly greater reductions than placebo in MADRS total (1.5mg/day = - 3.01 [- 4.84, - 1.19], P = .0012; 3mg/day = - 3.26 [- 5.12, - 1.40], P = .0006) and anhedonia factor scores (1.5mg/day = - 1.97 [- 3.13, - 0.81], P = .0009; 3mg/day = - 2.07 [- 3.26, - 0.89], P = .0006). Anti-anhedonic effects were preserved after adjusting for other depressive symptoms, suggesting the effect was not pseudospecific. Patients in the higher subgroup had higher baseline depression and therefore the lower subgroup may have had a floor effect. Cariprazine demonstrated antidepressant and specific anti-anhedonic effects regardless of baseline anhedonia symptoms in patients with BP-I depression. ClinicalTrials.gov identifiers, NCT02670538, NCT02670551, NCT01396447.

Personality Feedback With Tailored Self-Care Recommendations Improves Self-Efficacy for Cancer Management: A Randomized Controlled Trial.

To test whether a personality feedback intervention improves three domains of cancer self-management: self-awareness, self-efficacy, and positive affect. From 11/2020-02/2021, 372 adults diagnosed with cancer participated in a randomized controlled trial (RCT) of an intervention that entailed reading a brief personality-related excerpt during an online survey. Eligibility included self-reported age ≥ 18years, current or past cancer diagnosis, and ability to read English. The survey included a baseline assessment with a personality questionnaire, then randomized participants to one of two groups. The intervention group (n=184) received a personality feedback report with tailored self-care tips, whereas the control group (n=188) received a generic reading on personality theory. At the end of the survey, participants completed outcome measures of self-awareness (primary), self-efficacy for illness management, and positive affect. General linear models tested between-group differences in changes from baseline to post-test on each outcome. There was no intervention effect on self-awareness (primary outcome) or positive affect. However, compared to controls, intervention participants experienced a greater increase in self-efficacy for illness management (d=0.33, p=0.002), including in 2 of 3 constituent domains: self-efficacy for managing symptoms (d=0.36, p<0.001) and self-efficacy for managing treatments/medication (d=0.22, p=0.035). Despite the primary outcome's null results, this was the first RCT of a personality feedback intervention to show improvements in self-efficacy for managing chronic illness. Given the important role of self-efficacy in self-management, the intervention has implications for other cancer outcomes. Follow-up studies on longer-term outcomes such as health behaviors and quality of life should be explored. NCT04625439.

Impact of prior knee surgery on change in knee pain, quality of life, and walking speed following supervised education and exercise therapy: an analysis of 30,545 people with knee osteoarthritis

To investigate the impact of prior knee surgery on changes in outcomes following an 8-week supervised patient education and exercise therapy program in patients with knee osteoarthritis. Patients were classified according to knee surgery in the most affected knee joint (yes/no) prior to enrolment in the Good Life with osteoArthritis in Denmark (GLA:D®) program. Between-group differences in outcome changes from baseline to 3 months follow-up were evaluated using linear regression stratified by sex. Outcomes were knee pain intensity (VAS, 0–100 mm), joint related quality of life (Knee Injury and Osteoarthritis Outcome Score Quality of Life subscale score (KOOS QOL, 0–100)) and walking speed (40-m fast-paced walk test). To evaluate clinically relevant between-group differences, proportions of patients reaching a threshold of minimal important change in the surgery and non-surgery groups were compared. Among 30,545 patients, 27% (n, 8254) had prior surgery in the most affected knee. The prior surgery and the non-surgery group experienced improvements in all outcomes with minor between-group differences in change in pain intensity (males, 0.03 95% CI − 0.9 to 1.0; females, 1.3 95% CI 0.6 to 2.1); KOOS QOL (males, 0.3 95% CI − 0.4 to 0.9; females 0.02 95% CI − 0.5 to 0.5); and walking speed (males, 0.01 95% CI − 0.01 to 0.02; females 0.01 95% CI 0.003 to 0.02). The responder analysis showed no clinically relevant between-group differences in improvements. Previous knee surgery does not seem to modify the clinical outcome following exercise therapy and patient education in patients with knee osteoarthritis.Key Points• About one in four patients with knee osteoarthritis participating in an 8-week supervised patient education and exercise therapy program had previous knee joint surgery in the most affected knee.• Those with prior knee surgery were more likely to be males, to have prior knee injury, to have a longer symptom duration, and to have a high physical activity level compared to those without previous knee surgery.• Patients with prior knee surgery did not experience clinically relevant less change in knee pain, joint related quality of life, and walking speed after participation in the intervention, compared to those without previous knee surgery.• Patients with previous knee surgery can expect clinical outcomes following exercise therapy and patient education similar to patients without prior knee joint surgery.

A phase 2, randomized, double-blind, placebo-controlled study to assess the tolerability and pharmacodynamic effects of CRD-740, a PDE9 inhibitor, in participants with chronic heart failure

Abstract Background Natriuretic peptide (NP) receptor activation has a beneficial role in the treatment of heart failure (HF). The enzyme phosphodiesterase (PDE) 9 breaks down cGMP, the second messenger stimulated by natriuretic peptides. PDE9 inhibition may increase intracellular cGMP signaling and, potentially, have beneficial effects in HF. We examined the effects of the selective PDE9 inhibitor CRD-740 on the NP signaling pathway in HF. Purpose The objectives of this early phase 2 trial were to assess the tolerability of CRD-740 and its effects on plasma and urinary cGMP (markers of potential clinical effiacy) in patients with HFrEF, including those receving background treatment with sacubitril/valsartan. Methods Key inclusion criteria were patients with a history of HFrEF of &amp;gt; 6 mos, NYHA II or III, EF &amp;lt; 40% and NT-proBNP ≥600 pg/ml at screening (≥1000 pg/mL if in atrial fibrillation), on treatment with stable guideline-directed therapy for a minimum of 4 weeks. Patients were randomized 2:1 double-blind to CRD-740 (10mg twice daily for 2 weeks, then 25mg twice daily for 10 weeks) or placebo. Tolerability and safety were assessed. The primary pharmacodynamic endpoint was the between-group change from baseline in plasma cGMP at Week 4. Exploratory endpoints included urine cGMP levels, KCCQ and biomarkers. Results 60 patients were randomized to CRD-740 (n=40) or placebo (n=20). Baseline characteristics included age 67+13 yrs, 85% men, EF 28+7%, BMI 30+10, with 73% of patients taking sacubitril/valsartan, and 47% on SGLT2 inhibitors. The primary endpoint was positive, with placebo-corrected change in plasma cGMP significantly increased at all time points at week 4 in those treated with CRD-740 (see Table). cGMP levels were also increased on day 1 (Table) and week 2. A significant increase in urinary cGMP also was observed with CRD-740 vs placebo (Figure) in 6-hour collections at day 1 (p=0.012) and week 2 (p=0.014). In this small study, not powered for exploratory endpoints, directionally favorable placebo-corrected, baseline-adjusted changes also were seen in the KCCQ Clinical (+7.1 [95%CI, -1.6, +15.7], p=0.11) and Overall Summary Scores (+7.4 [-0.8, +15.5], p=0.075) for patients on CRD-740. No significant changes in NT-proBNP were observed between treatment groups. Adverse events (AEs) were observed in 62% and 50% of CRD-740 and placebo-treated patients, with discontinuation in 5% and 10% respectively, with no between-group difference in change in BP. There were no hypotension AEs, and no treatment-related serious adverse events. Conclusions In this early phase 2 trial, PDE9 inhibition with CRD-740 was well-tolerated and resulted in substantial elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan. These results support the potential of PDE9 inhibition to further activate the beneficial effects of the NP receptor-cGMP pathway incrementally to that achieved by existing HF treatments.Changes in Plasma cGMP over Time (ng/mL)Changes in Urinary cGMP over Time

Possible Glycemic Effects of Vagus Nerve Stimulation Evaluated by Continuous Glucose Monitoring in People with Diabetes and Autonomic Neuropathy: A Randomized, Sham-Controlled Trial.

Objective: Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. Methods: We randomized 145 individuals with type 1 diabetes (T1D) (n = 70) or type 2 diabetes (T2D) (n = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS (n = 68) or sham (n = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. Results: For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups (P = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group (P = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, P = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Conclusions: Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.

Free Summer Programming and Body Mass Index Among Schoolchildren From Low-Income Households

Children experience accelerated gains in body mass index (BMI) during the summer months when school is not in session. Children from low-income households are most susceptible. Accelerated BMI gain in summer may be due to the removal of the health-promoting structure provided by schools. During summer, a common form of health-promoting structure is summer day camps (SDCs). Summer day camps are predominately fee for service, which creates a financial barrier for children from low-income households. One solution to mitigate accelerated BMI gain is providing free access to an existing SDC. To investigate whether providing free access to an existing community SDC can mitigate accelerated BMI z score (zBMI) gain in elementary school-age children. This randomized clinical trial was conducted during the summers of 2021, 2022, and 2023 in the southeastern United States. Participants were children (kindergarten through fourth grade) from predominantly low-income households who were randomized to attend an SDC operated by a parks and recreation commission or continue summer as usual (control). Free SDC every weekday (Monday through Friday) for 8 to 10 weeks. The primary outcome was between-group differences in change of zBMI measured before school ended (May) and on return to school from summer (late August). Secondary analyses examined the dose response of zBMI change with parent-reported child attendance at SDCs during the summer for all children (intervention and control). A total of 422 children (mean [SD] age, 8.2 [1.5] years; 202 [48%] female, 220 [52%] male, 292 [69%] at or below 200% federal poverty level, 127 [30%] with food insecurity) were randomized to 1 of 2 conditions: summer as usual (control, n = 199) or free SDC (n = 223). Intent-to-treat analysis indicated mean (SE) change in zBMI at the end of the summer was 0.046 (0.027) for the control and -0.048 (0.025) for the intervention group, representing a significant between-group difference of -0.094 (95% CI, -0.166 to -0.022). Dose-response analyses indicated that every 1 day per week increase in attending an SDC resulted in a -0.034 to -0.018 zBMI reduction, which translates to a gain of 0.046 to 0.080 zBMI for children never attending summer programming vs -0.09 to -0.04 zBMI reduction for children attending summer programming every weekday. Providing children free access to existing community summer programming can have a meaningful effect on children's zBMI gain during the summer. Future studies should replicate these findings across different regions and identify the optimal dose of programming to mitigate unhealthy zBMI gains. ClinicalTrials.gov Identifier: NCT04072549.

Short-Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia.

Hospitalization exacerbates sarcopenia and physical dysfunction in older adults. Whether tailored inpatient exercise prevents acute sarcopenia is unknown. This study aimed to examine the effect of a multicomponent exercise programme on muscle and physical function in hospitalized older adults. We hypothesized that participation in a brief tailored exercise regimen (i.e., 3-5 days) would attenuate muscle function and structure changes compared with usual hospital care alone. This randomized clinical trial with blinded outcome assessment was conducted from May 2018 to April 2021 at Hospital Universitario de Navarra, Spain. Participants were 130 patients aged 75 years and older admitted to an acute care geriatric unit. Patients were randomized to a tailored 3- to 5-day exercise programme (n = 64) or usual hospital care (control, n = 66) consisting of physical therapy if needed. The coprimary endpoints were between-group differences in changes in short physical performance battery (SPPB) score and usual gait velocity from hospital admission to discharge. Secondary endpoints included changes in rectus femoris echo intensity, cross-sectional area, thickness and subcutaneous and intramuscular fat by ultrasound. Among 130 randomized patients (mean [SD] age, 87.7 [4.6] years; 57 [44%] women), the exercise group increased their mean SPPB score by 0.98 points (95% CI, 0.28-1.69 points) and gait velocity by 0.09 m/s (95% CI, 0.03-0.15 m/s) more than controls (both p < 0.01). No between-group differences were observed in any ultrasound muscle outcomes. There were no study-related adverse events. Three to 5 days of tailored multicomponent exercise provided functional benefits but did not alter muscle or fat architecture compared with usual hospital care alone among vulnerable older patients. Brief exercise may help prevent acute sarcopenia during hospitalization. ClinicalTrials.gov identifier: NCT04600453.

Conceptualizing meaningful between-group difference in change over time: a demonstration of possible viewpoints.

Determining if group-level differences in health outcomes are meaningful has recently been neglected in favour of determining if individuals have experienced a meaningful change. We explore interpretation of a meaningful between-group difference (MBGD) in clinical outcome assessment scores, primarily in the context of randomized clinical trials. We constructed a series of possible 'viewpoints' on how to conceptualize MBGD thresholds. Each viewpoint is discussed critically in terms of potential advantages and disadvantages, with simulated data to facilitate their consideration. Five viewpoints are presented and discussed. The first considers whether thresholds for meaningful within-individual change over time can be equally applied at the group-level, which is shown to be untenable. Viewpoints 2-4 consider what would have to be observed in treatment groups to conclude a meaningful between-group difference has occurred, framed in terms of the proportion of patients perceiving that they had meaningfully improved. The final viewpoint considers an alternative framework where stakeholders are directly questioned on the meaningfulness of varying magnitudes of between-group differences. The choice of a single threshold versus general interpretative guidelines is discussed. There does not appear to be a single method with clear face validity for determining MBGD thresholds. Additionally, the notion that such thresholds can be purely data-driven is challenged, where a degree of subjective stakeholder judgement is likely required. Areas for future research are proposed, to move towards robust method development.

Rehabilitation Transition Program to Improve Community Participation Among Stroke Survivors

Interventions are needed to support the long-term needs of stroke survivors when they transition from inpatient rehabilitation to home, where they face new home and community environmental barriers. To compare the efficacy of a novel, enhanced rehabilitation transition program with attentional control to improve community participation and activity of daily living (ADL) performance and to reduce environmental barriers in the home and community after stroke. This phase 2b, parallel randomized clinical trial assessed patients 50 years or older who had experienced an acute ischemic stroke or intracerebral hemorrhage, were independent in ADLs before stroke, and planned to be discharged home. Patients were assessed at an inpatient rehabilitation facility in St Louis, Missouri, and their homes from January 9, 2018, to December 20, 2023. Community Participation Transition after Stroke (COMPASS), including home modifications and strategy training. The primary outcome was community participation (Reintegration to Normal Living Index). Secondary outcomes were daily activity performance (Stroke Impact Scale ADL domain and the In-Home Occupational Performance Evaluation [I-HOPE] activity, performance, and satisfaction scores) and environmental barriers in the home (I-HOPE environmental barriers score). A total of 185 participants (mean [SD] age, 66.3 [9.0] years; 105 [56.8%] male) were randomized (85 to the COMPASS group and 100 to the control group). The COMPASS and control participants experienced similar improvements in community participation by 12 months, with no significant group (mean difference, 0.3; 95% CI, -4.6 to 5.2; P = .91) or group × time interaction (between-group differences in changes over time, 1.3; 95% CI, -7.1 to 9.6; P = .76) effects. Improvements in I-HOPE performance and satisfaction scores were greater for COMPASS participants than control participants at 12 months (between-group differences in changes for performance: 0.39; 95% CI, 0.01-0.77; P = .046; satisfaction: 0.52; 95% CI, 0.08-0.96; P = .02). The COMPASS participants had greater improvements for I-HOPE environmental barriers than the control participants (P = .003 for interaction), with the largest differences at 6 months (between-group differences in changes: -15.3; 95% CI -24.4 to -6.2). In this randomized clinical trial of stroke survivors, participants in both groups experienced improvements in community participation. COMPASS participants had greater improvements in self-rated performance and satisfaction with performing daily activities as well as a greater reduction in environmental barriers than control participants. COMPASS reduced environmental barriers and improved performance of daily activities for stroke survivors as they transitioned from inpatient rehabilitation to home. ClinicalTrials.gov Identifier: NCT03485820.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

Development, feasibility, and preliminary effects of a culturally adapted, evidence-based, and theory-driven diabetes self-management programme for Chinese adults with type 2 diabetes receiving insulin injection therapy

AimsTo describe the development of a culturally adapted, evidence-based, and theory-driven diabetes self-management programme for Chinese adults with type 2 diabetes receiving insulin injection therapy and to assess the feasibility, acceptability, and preliminary effects of the newly developed intervention. MethodsThe Medical Research Council framework was adopted to guide the intervention development and a feasibility study. A prospective, two-arm, parallel-group, assessor-blinded randomised controlled trial was conducted. Participants were randomly allocated to receive either the newly developed intervention or parallel attention control contact from community nurses. Between-group differences in changes in outcome variables were analysed using the Mann-Whitney U test. ResultsThe newly developed intervention consists of one individual interview session, three group-based education sessions, and two telephone-based maintenance sessions. A total of 24 participants were recruited with the recruitment rate and overall retention rate of 77.4 % and 95.8 %, respectively. The results indicated that the intervention participants reported significantly greater improvements in self-efficacy (Hedge’s g = 1.69) and self-management behaviours (Hedge’s g = 3.24), and reductions in diabetes-related distress (Hedge’s g = 1.49) compared with those in the control group (all p< 0.05). ConclusionThe diabetes self-management programme was feasible and acceptable. The intervention showed promising patient-centred benefits. A future large-scale randomised controlled trial is warranted.

Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial.

An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis. Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed in patients with reduced and preserved LVEF. Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%; P<0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61-1.22]; P=0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42-0.73]; P<0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29-2.19]; P=0.0001; Pinteraction<0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF. Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03499236.

Fusion versus decompression alone for lumbar degenerative spondylolisthesis and spinal stenosis: a target trial emulation with index trial benchmarking

PurposeThe value of adding fusion to decompression surgery for lumbar degenerative spondylolisthesis and spinal canal stenosis remains debated. Therefore, the comparative effectiveness and selected healthcare resource utilization of patients undergoing decompression with or without fusion surgery at 3 years follow-up was assessed.MethodsUsing observational data from the Lumbar Stenosis Outcome Study and a target trial emulation with index trial benchmarking approach, our study assessed the comparative effectiveness of the two main surgical interventions for lumbar degenerative spondylolisthesis—fusion and decompression alone in patients with lumbar degenerative spondylolisthesis and spinal canal stenosis. The primary outcome-measure was change in health-related quality of life (EuroQol Health Related Quality of Life 5-Dimension 3-Level questionnaire [EQ-5D-3L]); secondary outcome measures were change in back/leg pain intensity (Numeric Rating Scale), change in satisfaction (Spinal Stenosis Measure satisfaction subscale), physical therapy and oral analgesic use (healthcare utilization).Results153 patients underwent decompression alone and 62 had decompression plus fusion. After inverse probability weighting, 137 patients were included in the decompression alone group (mean age, 73.9 [7.5] years; 77 female [56%]) and 36 in the decompression plus fusion group (mean age, 70.1 [6.7] years; 18 female [50%]). Our findings were compatible with no standardized mean differences in EQ-5D-3L summary index change score at 3 years (EQ-5D-3L German: 0.07 [95% confidence interval (CI), − 0.25 to 0.39]; EQ-5D-3L French: 0.18 [95% CI, − 0.14 to 0.50]). No between-group differences in change in back/leg pain intensity or satisfaction were found. Decompression plus fusion was associated with greater physical therapy utilization at 3 years follow-up.ConclusionDecompression alone should be considered the primary option for patients with lumbar degenerative spondylolisthesis and spinal stenosis.

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.

Hamstring Muscle-Tendon Geometric Adaptations to Resistance Training Using the Hip Extension and Nordic Hamstring Exercises.

Targeted resistance training stimulates hamstring muscle hypertrophy, but its effect on tendon-aponeurosis geometry is unknown. This study examined changes in hamstring muscle, free tendon, and aponeurosis geometry following a 10 week Nordic or hip extension exercise intervention. Thirty recreationally active males were randomly allocated (n = 10 per group) to a Nordic, hip extension, or control group. Magnetic resonance imaging of both thighs was acquired pre- and post-intervention. Changes in free tendon and aponeurosis volume for each hamstring muscle, biceps femoris long head (BFlh) aponeurosis interface area and muscle volume-to-interface area ratio were compared between groups. Regional changes in muscle CSA were examined via statistical parametric mapping. The change in semimembranosus free tendon volume was greater for the Nordic than control group (mean difference = 0.06 cm3, 95% CI = 0.02-0.11 cm3). No significant between-group differences existed for other hamstring free tendons or aponeuroses. There were no between-group differences in change in BFlh interface area. Change in BFlh muscle volume-to-interface area ratio was greater in the hip extension than Nordic (mean difference = 0.10, 95% CI = 0.007-0.19, p = 0.03) and control (mean difference = 0.12, 95% CI = 0.03-0.22, p = 0.009) groups. Change in muscle CSA following training was greatest in the mid-portion of semitendinosus for both intervention groups, and the mid-portion of BFlh for the hip extension group. There was limited evidence for tendon-aponeurosis hypertrophy after 10 weeks of training with the Nordic or hip extension exercises. For the BFlh, neither intervention altered the interface area although hip extension training stimulated an increase in the muscle volume-to-interface area ratio, which may have implications for localized tissue strains. Alternative muscle-tendon loading strategies appear necessary to stimulate hamstring tendon adaptations.

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

AimsTo 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.MethodsIn 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) (70–180 mg/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).ResultsThirty-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.ConclusionsApplying 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.