Adjusted Mean Between-group Difference Research Articles

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.

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.

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.

Effect of Extracurricular After-School Physical Activities on Academic Performance of Schoolchildren

The beneficial effects of increasing outdoor physical activity time on children's myopia onset and physical well-being are widely acknowledged. However, in countries with competitive educational systems, such as China, parents and school administrators may be relatively reluctant to increase the extracurricular physical activity time for children due to concerns that this action will compromise children's academic performance. To investigate whether additional extracurricular physical activity time after school compromises the academic performance of schoolchildren. This cluster randomized clinical trial was conducted from October 2020 to June 2021 in Yudu, Jiangxi, China. Eligible children in grades 3 and 4 from 24 elementary schools were randomized to the intervention or control group. Primary analysis was conducted in the full sample using the intention-to-treat principle. The intervention group received 2 hours of after-school physical activity time outdoors on school days. The control group was free to arrange their after-school activity. The primary outcome was the between-group mean difference in mathematics test scores at the end of 1 academic year, with a noninferiority margin of -3.3 points. Standardized mathematics tests, physical fitness assessments (in reference to the 2018 National Physical Fitness Survey Monitoring Programme in China), and cycloplegic autorefraction were performed at baseline and the end of 1 academic year. Myopia was defined as a cycloplegic spherical equivalent refraction of -0.5 diopters or less in either eye. A total of 2032 children (mean [SD] age, 9.22 [0.62] years; 1040 girls [51.2%]) from 24 schools were randomized to the intervention group (12 schools; 1012 children) or control group (12 schools; 1020 children). The mean (SD) mathematics score at the end of 1 academic year was 78.01 (17.56) points in the intervention group and 77.70 (17.29) points in the control group. The adjusted between-group mean difference was 0.65 points (95% CI, -2.85 to 4.15). The adjusted between-group mean difference in physical fitness score was 4.95 points (95% CI, 3.56-6.34; P < .001) and -1.90% (95% CI, -18.72% to 14.91%; P > .99) in myopia incidence. Results of this trial indicate that, compared with the control practice of free play after school, adding 2 hours of extracurricular physical activity outdoors after school was noninferior in academic performance and had superior efficacy in improving physical fitness. ClinicalTrials.gov Identifier: NCT04587765.

Effect of a Remotely Delivered Self-directed Behavioral Intervention on Body Weight and Physical Health Status Among Adults With Obesity

The effectiveness of remotely delivered, self-directed, weight loss programs in routine clinical practice is largely unknown. To test whether a self-directed, remotely administered behavioral lifestyle intervention improves weight and self-reported general health status compared with usual care. In this randomized clinical trial, 511 adults with a body mass index (BMI) of 30 or more and less than 45 (based on electronic health record [EHR] weight and height), were enrolled from 30 Veterans Health Administration (VHA) sites between February 15, 2018, and December 18, 2018 (final follow-up February 18, 2021). Participants were randomly assigned to the intervention group (n = 254) or the control group (n = 257). Both received usual care. Participants randomized to the intervention received Diabetes Prevention Program-based self-directed videos, handouts, and coaching messages via an online platform or US mail for 12 months. Coprimary outcomes were weight measured in primary care and recorded in the EHR and self-reported general health status using the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) physical component score (PCS; higher scores are better [range, 0-100]) at the 12-month follow-up. The between-group minimal clinically important differences are 3 kg for weight and 5 points for the SF-12 PCS. Linear mixed models used weights and SF-12 PCS measured at either time point, with participants analyzed according to randomization assignment. Statistical significance for each coprimary outcome was based on a 2-sided α level of .025. Among 511 participants randomized (mean age, 57.4 [SD, 13.9] years; 231 female [45%]), 429 (84.0%) had EHR-based weights and 410 (80.2%) had SF-12 PCS data at 12 months. The unadjusted mean weight at 12 months declined from 102.7 kg to 99.8 kg in the intervention group compared with 101.9 kg to 101.0 kg in the control group (adjusted between-group mean difference, -1.93 [97.5% CI, -3.24 to -0.61]; P = .001). At 12 months, the unadjusted mean SF-12 PCS scores declined from 44.8 to 44.3 among intervention participants compared with 44.5 to 43.2 among control participants (adjusted between-group mean difference, intervention minus control, 0.69 [97.5% CI, -1.11 to 2.49]; P = .39). Cardiovascular events represented the highest percentage of serious adverse events, accounting for 25% of events in the intervention group and 35% in the control group. Among adults with obesity, a remotely delivered self-directed, behavioral lifestyle intervention, compared with usual care, resulted in statistically significantly greater weight loss at 12 months, although the difference was not clinically important. There was no significant difference in self-reported general physical health status at 12 months. ClinicalTrials.gov Identifier: NCT03260140.

Inhibition of bone erosion, determined by high-resolution peripheral quantitative computed tomography (HR-pQCT), in rheumatoid arthritis patients receiving a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab vs csDMARD therapy alone: an open-label, randomized, parallel-group study

BackgroundThis exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsIn this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety.ResultsIn total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%).ConclusionsAlthough the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes

BackgroundIn persons with type 1 diabetes and high glycated hemoglobin levels, the benefits of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels are uncertain.MethodsIn a parallel-group, multicenter, randomized, controlled trial involving participants with type 1 diabetes and glycated hemoglobin levels between 7.5% and 11.0%, we investigated the efficacy of intermittently scanned continuous glucose monitoring as compared with participant monitoring of blood glucose levels with fingerstick testing. The primary outcome was the glycated hemoglobin level at 24 weeks, analyzed according to the intention-to-treat principle. Key secondary outcomes included sensor data, participant-reported outcome measures, and safety.ResultsA total of 156 participants were randomly assigned, in a 1:1 ratio, to undergo intermittently scanned continuous glucose monitoring (the intervention group, 78 participants) or to monitor their own blood glucose levels with fingerstick testing (the usual-care group, 78 participants). At baseline, the mean (±SD) age of the participants was 44±15 years, and the mean duration of diabetes was 21±13 years; 44% of the participants were women. The mean baseline glycated hemoglobin level was 8.7±0.9% in the intervention group and 8.5±0.8% in the usual-care group; these levels decreased to 7.9±0.8% and 8.3±0.9%, respectively, at 24 weeks (adjusted mean between-group difference, −0.5 percentage points; 95% confidence interval [CI], −0.7 to −0.3; P<0.001). The time per day that the glucose level was in the target range was 9.0 percentage points (95% CI, 4.7 to 13.3) higher or 130 minutes (95% CI, 68 to 192) longer in the intervention group than in the usual-care group, and the time spent in a hypoglycemic state (blood glucose level, <70 mg per deciliter [<3.9 mmol per liter]) was 3.0 percentage points (95% CI, 1.4 to 4.5) lower or 43 minutes (95% CI, 20 to 65) shorter in the intervention group. Two participants in the usual-care group had an episode of severe hypoglycemia, and 1 participant in the intervention group had a skin reaction to the sensor.ConclusionsAmong participants with type 1 diabetes and high glycated hemoglobin levels, the use of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels resulted in significantly lower glycated hemoglobin levels than levels monitored by fingerstick testing. (Funded by Diabetes UK and others; FLASH-UK ClinicalTrials.gov number, NCT03815006.)

Additional Fruit and Vegetable Vouchers for Pregnant WIC Clients: An Equity-Focused Strategy to Improve Food Security and Diet Quality.

Women with low household income and from racial/ethnic minority groups are at elevated risk of food insecurity. Food insecurity during pregnancy is associated with overall less healthy diets, lower intake of the pregnancy-supportive nutrients iron and folate, and significant variations in diet across the course of a month. The goal of this study was to explore the impact of an ongoing $40/month supplement for fruits and vegetables (F&Vs) provided to pregnant people enrolled in the Special Supplemental Nutrition Program for Women and Children (WIC). Our primary outcome was food insecurity using the USDA 6-item survey, and our secondary outcome was dietary intake of F&Vs based on the 10-item Dietary Screener Questionnaire. Participants in intervention and comparison counties completed surveys at enrollment and approximately three months later (n = 609). Mean ± SD food insecurity at baseline was 3.67 ± 2.79 and 3.47 ± 2.73 in the intervention and comparison groups, respectively, and the adjusted between-group change from baseline to follow-up in food insecurity was 0.05 [95% CI: −0.35, 0.44] (p > 0.05). F&V intake (in cup equivalents) was 2.56 ± 0.95 and 2.51 ± 0.89 at baseline in the two groups, and the adjusted mean between-group difference in changes from baseline was −0.06 [−0.23, 0.11] (p > 0.05). Recruitment and data collection for this study coincided with the most intensive of America’s COVID relief efforts. Our results may indicate that small increases in highly targeted food resources make less of a difference in the context of larger, more general resources being provided to individuals and households in need.

Effect of a Home-Based, Walking Exercise Behavior Change Intervention vs Usual Care on Walking in Adults With Peripheral Artery Disease

Home-based walking exercise interventions are recommended for people with peripheral artery disease (PAD), but evidence of their efficacy has been mixed. To investigate the effect of a home-based, walking exercise behavior change intervention delivered by physical therapists in adults with PAD and intermittent claudication compared with usual care. Multicenter randomized clinical trial including 190 adults with PAD and intermittent claudication in 6 hospitals in the United Kingdom between January 2018 and March 2020; final follow-up was September 8, 2020. Participants were randomized to receive a walking exercise behavior change intervention delivered by physical therapists trained to use a motivational approach (n = 95) or usual care (n = 95). The primary outcome was 6-minute walking distance at 3-month follow-up (minimal clinically important difference, 8-20 m). There were 8 secondary outcomes, 3 of which were the Walking Estimated Limitation Calculated by History (WELCH) questionnaire (score range, 0 [best performance] to 100), the Brief Illness Perceptions Questionnaire (score range, 0 to 80 [80 indicates negative perception of illness]), and the Theory of Planned Behavior Questionnaire (score range, 3 to 21 [21 indicates best attitude, subjective norms, perceived behavioral control, or intentions]); a minimal clinically important difference was not defined for these instruments. Among 190 randomized participants (mean age 68 years, 30% women, 79% White race, mean baseline 6-minute walking distance, 361.0 m), 148 (78%) completed 3-month follow-up. The 6-minute walking distance changed from 352.9 m at baseline to 380.6 m at 3 months in the intervention group and from 369.8 m to 372.1 m in the usual care group (adjusted mean between-group difference, 16.7 m [95% CI, 4.2 m to 29.2 m]; P = .009). Of the 8 secondary outcomes, 5 were not statistically significant. At 6-month follow-up, baseline WELCH scores changed from 18.0 to 27.8 in the intervention group and from 20.7 to 20.7 in the usual care group (adjusted mean between-group difference, 7.4 [95% CI, 2.5 to 12.3]; P = .003), scores on the Brief Illness Perceptions Questionnaire changed from 45.7 to 38.9 in the intervention group and from 44.0 to 45.8 in the usual care group (adjusted mean between-group difference, -6.6 [95% CI, -9.9 to -3.4]; P < .001), and scores on the attitude component of the Theory of Planned Behavior Questionnaire changed from 14.7 to 15.4 in the intervention group and from 14.6 to 13.9 in the usual care group (adjusted mean between-group difference, 1.4 [95% CI, 0.3 to 2.5]; P = .02). Thirteen serious adverse events occurred in the intervention group, compared with 3 in the usual care group. All were determined to be unrelated or unlikely to be related to the study. Among adults with PAD and intermittent claudication, a home-based, walking exercise behavior change intervention, compared with usual care, resulted in improved walking distance at 3 months. Further research is needed to determine the durability of these findings. ISRCTN Identifier: 14501418; ClinicalTrials.gov Identifier: NCT03238222.

A Randomized Trial of the Effects of Exercise on Anxiety, Fear of Cancer Progression and Quality of Life in Prostate Cancer Patients on Active Surveillance.

We examined the effects of exercise on prostate cancer-specific anxiety, fear of cancer progression, quality of life and psychosocial outcomes in patients with prostate cancer on active surveillance. The ERASE (Exercise during Active Surveillance for Prostate Cancer) Trial randomized 52 patients with prostate cancer undergoing active surveillance to high-intensity interval training (HIIT, 26 patients) or usual care (UC, 26 patients). The HIIT group performed a 12-week, thrice weekly, supervised, aerobic HIIT program. The UC group did not exercise. Patient-reported outcomes were assessed at baseline and after intervention, including prostate cancer-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), fear of cancer progression (Fear of Cancer Recurrence Inventory), prostate cancer symptoms (Expanded Prostate Cancer Index Composite), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core) and psychological health outcomes (eg fatigue, stress and self-esteem). Analysis of covariance was used to compare between-group differences. Fifty of 52 participants (96%) completed patient-reported outcome assessments at 12 weeks. Adherence to HIIT was 96%. Compared to UC, HIIT significantly improved total prostate cancer-specific anxiety (adjusted between-group mean difference -2.7, 95% confidence interval, range -5.0 to -0.4, p=0.024), as well as the fear of progression subscale (p=0.013), hormonal symptoms (p=0.005), perceived stress (p=0.037), fatigue (p=0.029) and self-esteem (p=0.007). A 12-week supervised HIIT program may improve prostate cancer-specific anxiety, fear of cancer progression, hormone symptoms, stress, fatigue and self-esteem in men with prostate cancer on active surveillance. Larger trials are needed to confirm the effects of HIIT on patient-reported outcomes in the active surveillance setting.

Behavioural activation to prevent depression and loneliness among socially isolated older people with long-term conditions: The BASIL COVID-19 pilot randomised controlled trial.

Older adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to "shield" to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed. We undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of -0.50 PHQ-9 points (95% CI -2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI -1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI -0.51 to 1.06) and at 3 months -0.87 (95% CI -1.56 to -0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (-1.33, 1.73) and at 3 months 0.31 (-1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (-4.17, 4.85) and at 3 months 0.11 (-4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (-2.64, 5.15) and at 3 months 1.26 (-2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness. In this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT). ISRCTN94091479.

Changes In Anxiety, Fear Of Cancer Progression, And Quality Of Life In Prostate Cancer Patients On Active Surveillance After A 12-week Exercise Program: A Randomized Controlled Trial

PURPOSE: Prostate cancer (PCa) patients undergoing active surveillance often experience psychological distress such as anxiety or fear or cancer progression. This study was to investigate the impacts of a 12-week exercise program on patient-reported outcomes in PCa patients undergoing active surveillance. METHODS: 52 PCa patients on active surveillance were randomized to high-intensity interval training (HIIT; n = 26) or usual care (UC; n = 26). The HIIT group performed a 12-week, thrice-weekly, supervised, aerobic HIIT intervention. Patient-reported outcomes were assessed at baseline and postintervention (12-weeks), including PCa-specific anxiety (Memorial Anxiety Scale for Prostate Cancer; MAX-PC), fear of cancer progression (Fear of Cancer Recurrence Inventory; FCRI), PCa-related symptoms (Expanded Prostate Cancer Index Composite-26; EPIC-26), cancer-related quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item; EORTC QLQ-C30), and generic psychosocial outcomes (e.g., fatigue, stress, and self-esteem). Analysis of covariance was used to compare between-group differences. RESULTS: 50/52 (96%) participants completed patient-reported outcome assessments at 12-weeks and adherence to the HIIT program was 96%. Compared to UC, HIIT significantly reduced total PCa-specific anxiety (adjusted between-group mean difference, -2.7; 95% confidence interval[CI], -5.0 to -0.4; p = 0.024; d = 0.28) and fear of recurrence (adjusted between-group mean difference, -2.0; 95% CI, -3.5 to -0.4; p = 0.013; d = 0.67) in MAX-PC; hormonal dysfunction (p = 0.005) in EPIC-26; and perceived stress (p = 0.037), fatigue (p = 0.029), and self-esteem (p = 0.007). CONCLUSIONS: A 12-week supervised HIIT program reduced PCa-specific anxiety, fear of cancer progression, hormone symptoms, stress, and fatigue, and increased self-esteem in men with PCa on active surveillance. Larger trials are warranted to determine the longer-term effects of exercise on patient-reported outcomes and whether such effects influence willingness to continue on active surveillance.

A phase II randomized controlled trial of exercise on biochemical progression in men with prostate cancer on active surveillance.

5080 Background: Men with prostate cancer (PCa) undergoing active surveillance (AS) are at increased risks of cardiovascular death and disease progression. Any intervention that can address these issues during AS would be highly beneficial. Clinical and preclinical studies have demonstrated the benefits of exercise to improve cardiovascular health in cancer patients and suggested the potential role of exercise in suppressing PCa progression in men with PCa undergoing AS. Therefore, the purpose of this study was to investigate the effects of exercise on cardiorespiratory fitness and biochemical progress of PCa in men with PCa on AS. Methods: The Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial was a single-centre, two-armed, randomized controlled trial in Edmonton, Canada. 52 men with localized PCa who were undergoing AS were randomized to high-intensity interval training (HIIT; n = 26) or usual care (UC; n = 26). The HIIT group performed thrice-weekly, supervised, aerobic HIIT on a treadmill at 85-95% of peak cardiorespiratory fitness (VO2peak) for 12 weeks. The primary outcome was VO2peak, and the secondary and exploratory outcomes included biochemical progression of PCa (prostate-specific antigen [PSA]), PSA kinetics, and growth of prostate cancer cell line LNCaP. Results: 46/52 participants (88%) completed the postintervention VO2peak assessment and adherence to HIIT was 96%. Compared to UC, HIIT significantly improved VO2peak (adjusted between-group mean difference, 1.6 ml·kg-1·min-1; 95% confidence interval [CI], 0.3 to 2.9; p= 0.014). HIIT also significantly reduced PSA level (adjusted between-group mean difference, -1.1 ug/L; 95% CI, -2.1 to 0.0; p= 0.043) and PSA velocity ( p= 0.040), and suppressed LNCaP cell growth ( p =0.024). No significant differences were found in PSA doubling time ( p= 0.10) and testosterone ( p= 0.24). Conclusions: The ERASE Trial is the first randomized controlled trial to demonstrate the impact of HIIT exercise for improving physical fitness and inhibiting biochemical progression of PCa in men with localized PCa on AS. Our findings suggest that supervised aerobic HIIT may be a promising intervention in this clinical setting. Larger-scale randomized controlled trials are warranted to determine if improvements in physical fitness and PCa-related markers translate into improved long-term clinical outcomes in these men such as disease progression, receipt of radical treatments, posttreatment complications, and survival. Clinical trial information: NCT03203460.

Effect of Telephone Cognitive Behavioral Therapy for Insomnia in Older Adults With Osteoarthritis Pain

Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment. To evaluate the effectiveness of telephone CBT-I vs education-only control (EOC) in older adults with moderate to severe osteoarthritis pain. This is a randomized clinical trial of 327 participants 60 years and older who were recruited statewide through Kaiser Permanente Washington from September 2016 to December 2018. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis (OA) pain symptoms. Blinded assessments were conducted at baseline, after 2 months posttreatment, and at 12-month follow-up. Six 20- to 30-minute telephone sessions provided over 8 weeks. Participants submitted daily diaries and received group-specific educational materials. The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and OA. The primary outcome was score on the Insomnia Severity Index (ISI) at 2 months posttreatment and 12-month follow-up. Secondary outcomes included pain (score on the Brief Pain Inventory-short form), depression (score on the 8-item Patient Health Questionnaire), and fatigue (score on the Flinders Fatigue Scale). Of the 327 participants, the mean (SD) age was 70.2 (6.8) years, and 244 (74.6%) were women. In the 282 participants with follow-up ISI data, the total 2-month posttreatment ISI scores decreased 8.1 points in the CBT-I group and 4.8 points in the EOC group, an adjusted mean between-group difference of -3.5 points (95% CI, -4.4 to -2.6 points; P < .001). Results were sustained at 12-month follow-up (adjusted mean difference, -3.0 points; 95% CI, -4.1 to -2.0 points; P < .001). At 12-month follow-up, 67 of 119 (56.3%) participants receiving CBT-I remained in remission (ISI score, ≤7) compared with 33 of 128 (25.8%) participants receiving EOC. Fatigue was also significantly reduced in the CBT-I group compared with the EOC group at 2 months posttreatment (mean between-group difference, -2.0 points; 95% CI, -3.1 to -0.9 points; P = <.001) and 12-month follow-up (mean between-group difference, -1.8 points; 95% CI, -3.1 to -0.6 points; P = .003). Posttreatment significant differences were observed for pain, but these differences were not sustained at 12-month follow-up. In this randomized clinical trial, telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and OA pain in a large statewide health plan. Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment. Clinical Trials.gov Identifier: NCT02946957.

Assessment of Plasma Amyloid-β42/40 and Cognitive Decline Among Community-Dwelling Older Adults

Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Plasma Aβ42 and Aβ40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aβ assessment was defined as the baseline for this study. Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aβ42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aβ42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aβ42/40 ratio greater than 0.107. In this study, low plasma Aβ42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aβ42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.

Effectiveness of progressive tendon-loading exercise therapy in patients with patellar tendinopathy: a randomised clinical trial

ObjectiveTo compare the effectiveness of progressive tendon-loading exercises (PTLE) with eccentric exercise therapy (EET) in patients with patellar tendinopathy (PT).MethodsIn a stratified, investigator-blinded, block-randomised trial, 76 patients with clinically diagnosed...

Adductor Canal Block Combined With iPACK (Interspace Between the Popliteal Artery and the Capsule of the Posterior Knee) Block vs Periarticular Injection for Analgesia After Total Knee Arthroplasty: A Randomized Noninferiority Trial

BackgroundThe combination of adductor canal block (ACB) and infiltration between the popliteal artery and the posterior capsule of the knee (iPACK) block may provide sufficient motor-sparing anterior and posterior knee analgesia after total knee arthroplasty. This study aimed to determine if ACB with iPACK block was noninferior to ACB with periarticular injection (PAI) when combined with postoperative multimodal analgesia regimen. MethodsSeventy-six patients were randomized to receive either ACB + iPACK block and continuous ACB (CACB) (ACB + iPACK group) or PAI and CACB (ACB + PAI group). Noninferiority was concluded for the primary outcome if the adjusted mean between-group difference in pain on movement at 12 postoperative hours was within 1.3 points on a visual analog pain scale. Pain scores, morphine consumption, functional performance, and adverse events were the secondary outcome measures assessed for superiority. ResultsAdjusted mean differences, (ACB + iPACK) − (ACB + PAI), in anterior and posterior knee pain scores on movement at 12 postoperative hours were −0.66 (−1.86, 0.54) and −0.19 (−1.36, 0.99), respectively. The upper limit of 95% confident interval was lower than the prespecified noninferiority limit. The mean visual analog scale pain scores were low and no clinically significant differences between groups. However, morphine requirement at 48 postoperative hours was significantly higher (P < .05) and showed greater reduced quadriceps strength at 0 and 45 degrees on postoperative day 0 (P = .006 and .04, respectively) in the ACB + iPACK group. ConclusionsACB with iPACK block provides a noninferior analgesia compared with PAI when combined with CACB. However, patients who received ACB + iPACK block may require higher amounts of opioids and have worse immediate functional performance. Level of evidenceTherapeutic level I.

Feasibility And Preliminary Efficacy Of High-intensity Interval Training During Neaodjuvant Chemoradiotherapy For Rectal Cancer

PURPOSE: To assess the feasibility, safety, and preliminary efficacy of a supervised high-intensity interval training (HIIT) program in rectal cancer patients undergoing 5-6 weeks of neoadjuvant chemoradiotherapy (NACRT). METHODS: Thirty-six rectal cancer patients scheduled to receive NACRT followed by surgery were randomized to either exercise training (n=18) or usual care (n=18) in the Exercise During and After Rectal Cancer Treatment (EXERT) Trial in Edmonton, Alberta. Patients in the exercise group were asked to complete 3 supervised HIIT sessions/week for the duration of NACRT. Feasibility was determined by eligibility rate, recruitment rate, follow-up rate and exercise adherence. Safety was assessed by tracking serious adverse events related to exercise. The primary efficacy outcome was cardiorespiratory fitness (VO2 peak) assessed immediately post-NACRT by a graded exercise test. Secondary efficacy outcomes included functional fitness assessed by the Senior’s Fitness Test. RESULTS: From June 2017 to August 2019, 205 rectal cancer patients were screened, 131 (64%) were eligible, and 36 (27%) were recruited. Follow-up fitness testing post-NACRT was completed in 75% (exercise n=14; control n=13). Reasons for missed fitness testing were medical issues. Median attendance for the supervised HIIT sessions during NACRT was 82%. No serious adverse events were observed, however, 2 patients in the exercise group experienced musculoskeletal events which resulted in 4 missed exercise sessions. Analyses of covariance showed no statistically significant or clinically meaningful difference between groups for the primary outcome of VO2 peak (adjusted between-group mean difference, 0.9 ml/kg/min; 95% CI, -1.6, 3.3; p = 0.47). The 8-foot up-and-go was significantly better in the exercise group post-NACRT (adjusted between group mean difference, -0.4 seconds; 95% CI, -0.7, 0.0, p = 0.031). No other significant group differences in functional fitness were observed. CONCLUSIONS: Supervised HIIT during NACRT for rectal cancer was feasible and safe. Further research is needed, however, to better understand the feasibility of completing fitness testing immediately following NACRT and whether HIIT can produce meaningful improvements in fitness in this challenging clinical setting.

Social Cognitive Effects and Mediators of a Pilot Telephone Counseling Intervention to Increase Aerobic Exercise in Hematologic Cancer Survivors.

Theory-based telephone counseling exercise (TCE) interventions can increase aerobic exercise behavior in cancer survivors. Few studies, however, assess intervention effects on social cognitive variables. Here, the authors examined changes in social cognitive variables from a TCE intervention based on the multi-process action control framework in hematologic cancer survivors. A total of 51 hematologic cancer survivors were randomized to weekly TCE (n = 26) or self-directed exercise (n = 25) for 12 weeks. Participants self-reported on demographic and cancer variables, as well as motivational, regulatory, and reflexive ratings pertaining to aerobic exercise at baseline and post-intervention. Small-to-large between-group differences in all variables favored the TCE group. The most prominent effects were noted for differences in coping planning (adjusted mean between-group difference [MBGDadj] = 1.4, 95% confidence interval [CI], 0.7 to 2.2, d = 1.04), instrumental attitude (MBGDadj = 0.5, 95% CI, 0.1 to 1.0, d = 1.11), affective attitude (MBGDadj = 0.6, 95% CI, 0.1 to 1.2, d = 0.71), and perceived opportunity (MBGDadj = 0.4, 95% CI, -0.3 to 1.2, d = 0.50). Changes in coping planning (b = 24.98, β = 0.18, 95% CI, -0.03 to 0.56), perceived opportunity (b = 17.95, β = 0.13, 95% CI, 0.01 to 0.36), exercise identity (b = 17.43, β = 0.12, 95% CI, -0.05 to 0.41), and habit (b = 14.64, β = 0.10, 95% CI, -0.01 to 0.42) accounted for the largest mediating effects on aerobic exercise behavior. Multi-process action control framework-based TCE interventions may strengthen motivational, regulatory, and reflexive profiles that translate into increased aerobic exercise behavior in hematologic cancer survivors.

Intensive exercise program after spinal cord injury (SCIPA full-on): A randomized controlled trial

While upper body training is effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies (ABT) intended to activate the paralysed extremities have been reported to promote neurological improvement. We investigated the effectiveness of intensive ABT compared with upper body training for people with SCI. One hundred and sixteen participants (C2-T12, AIS A-D) were recruited from six SCI units in Australia and New Zealand, and randomised to experimental or control groups. Experimental participants received a 12-week ABT program including locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while control group participants undertook upper body strength and aerobic fitness training. The primary outcome measure was the ASIA motor scores for upper and lower extremities. One hundred and three participants completed the interventions and were included in the primary analysis. Mean (SD) upper extremity motor scores for experimental ( n = 49) and control ( n = 54) groups were 41.45 (12.11) and 39.39 (11.94), respectively, with an adjusted mean between-group difference of −0.039 (95% CI: −1.12 to 1.04). Mean (SD) lower extremity motor scores were 12.51 (17) and 10.24 (17.19) for experimental and control groups, with an adjusted mean between-group difference of 0.895 (95% CI: −0.48 to 2.27). There were 15 serious adverse events within each group, but only one of these was related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). Activity-based therapy did not lead to greater improvements in ASIA motor scores compared to upper body training.