Intervention-related Adverse Events Research Articles

Efficacy and safety of adrenomedullin for acute ischemic stroke (AMFIS): a phase 2, randomized, double-blinded, placebo-controlled, clinical trial

Objective: Pulsed radiofrequency treatment of the dorsal root ganglion has been increasingly used to treat lumbosacral radicular pain in recent decades. However, there is no consensus in the literature regarding issues such as pulsed radiofrequency application duration. This study aimed to determine the efficacy and incidence of adverse events between 2-minute and 4-minute pulsed radiofrequency for lumbosacral radicular pain. Material and Method: This retrospective study included 160 patients who underwent 2-minute or 4-minute dorsal root ganglion pulsed radiofrequency treatment (Group-2 minutes 82 patients and Group-4 minutes 78 patients). The Numeric Rating Scale and Oswestry Disability Index scores before, 1 and 6 months after the interventions were evaluated to assess the effectiveness of the procedures. The rate of intervention-related adverse events was determined for both durations. Results: Both the 2-minute and 4-minute procedures provided effective analgesia at 1 and 6 months compared with baseline. There was no difference in the pain scores between the two groups at the measurement times. At the 1-month follow-up, 50% or greater pain relief was achieved in 39% of patients in the 2-minute group compared to 50% in the 4-minute group, with no difference between the groups. There was no significant difference in the rate of procedure-related adverse events between the groups. Conclusion: Although a higher success rate was achieved with 4-minute pulsed radiofrequency, there was no significant difference, and both 2 and 4-minute pulsed radiofrequency procedures provided safe and effective analgesia compared with baseline. Prospective studies with larger sample sizes are needed.

Current clinical guidelines for the management of type 2 diabetes mellitus (T2DM) in older adults recommend the use of antihyperglycemic medications, monitoring of blood glucose levels, regular exercise, and a healthy diet to improve glycemic control and reduce associated comorbidities. However, adherence to traditional exercise programs is poor (<35%). Common barriers to adherence include fear of hypoglycemia and the need for blood glucose level monitoring before exercise. Digital health strategies offer great promise for managing T2DM as they facilitate patient-practitioner communication, support self-management, and improve access to health care services for underserved populations. We have developed a novel web-based software program allowing practitioners to create tailored interventions and deliver them to patients via digital voice assistants (DVAs) in their own homes. We aim to evaluate the feasibility of a 12-week, home-based, personalized lifestyle intervention delivered and monitored by DVAs for older adults with obesity and T2DM. In total, 50 older adults with obesity aged 50-75 years with oral hypoglycemic agent-treated T2DM were randomized to the intervention (DVA, n=25) or a control group (n=25). Participants allocated to the DVA group were prescribed a home-based muscle strengthening exercise program (~20- to 30-min sessions) and healthy eating intervention, delivered via DVAs (Alexa Echo Show 8; Amazon) using newly developed software ("Buddy Link"; Great Australian Pty Ltd). Control group participants received generalized physical activity information via email. Outcomes were feasibility, DVA usability (System Usability Scale), and objectively assessed physical activity and sedentary time (wrist-worn accelerometers). In total, 45 (90%) out of 50 participants completed this study. Mean adherence to prescribed exercise was 85% (SD 43%) with no intervention-related adverse events. System usability was rated above average (70.4, SD 16.9 out of 100). Compared with controls, the DVA group significantly decreased sedentary time (mean difference -67, SD 23; 95% CI -113 to -21 min/d), which was represented by a medium to large effect size (d=-0.6). A home-based lifestyle intervention delivered and monitored by health professionals using DVAs was feasible for reducing sedentary behavior and increasing moderate-intensity activity in older adults with obesity and T2DM. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000307808; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381364&isReview=true.

This study aimed to compare the outcomes of two different postoperative management approaches following surgical fixation of ankle fractures: traditional cast immobilization versus the Early Motion and Directed Exercise (EMADE) programme. A total of 157 patients aged 18 years or older who underwent successful open reduction and internal fixation (ORIF) of Weber B (AO44B) ankle fractures were recruited to this randomized controlled trial. At two weeks post-surgical fixation, participants were randomized to either light-weight cast-immobilization or the EMADE programme, consisting of progressive home exercises and weekly advice and education. Both groups were restricted to non-weightbearing until six weeks post-surgery. The primary outcome was assessed using the Olerud-Molander Ankle Score (OMAS) questionnaire at 12 weeks post-surgery, with secondary measures at two, six, 24, and 52 weeks. Exploratory cost-effectiveness analyses were also performed. Overall, 130 participants returned their 12-week OMAS questionnaires. The mean OMAS was significantly higher in the EMADE group compared with the immobilized group (62.0 (SD 20.9) vs 48.8 (SD 22.5)), with a clinically meaningful mean difference of 13.2 (95% CI 5.66 to 20.73; p < 0.001). These differences were maintained at week 24, with convergence by week 52. No intervention-related adverse events, including instability, were reported. The EMADE programme demonstrated an accelerated recovery compared to traditional six-week cast immobilization for those who have undergone ORIF surgery to stabilize Weber B (AO44B) ankle fractures. The study found the EMADE intervention to be safe.

SummaryBackgroundOlder people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients’ care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study. We have previously described the benefits of PICLP reported by patients and clinicians. In this Article, we report the effectiveness and cost-effectiveness of PICLP-enhanced care, compared with usual care alone, in reducing time in hospital.MethodsWe did a parallel-group, multicentre, randomised controlled trial in 24 medical wards of three English acute general hospitals. Patients were eligible to take part if they were 65 years or older, had been admitted in an emergency, and were expected to remain in hospital for at least 2 days from the time of enrolment. Participants were randomly allocated to PICLP or usual care in a 1:1 ratio by a database software algorithm that used stratification by hospital, sex, and age, and randomly selected block sizes to ensure allocation concealment. PICLP clinicians (consultation-liaison psychiatrists supported by assisting clinicians) made proactive biopsychosocial assessments of patients’ problems, then delivered discharge-focused care as integrated members of ward teams. The primary outcome was time spent as an inpatient (during the index admission and any emergency readmissions) in the 30 days post-randomisation. Secondary outcomes were the rate of discharge from hospital for the total length of the index admission; discharge destination; the length of the index admission after random allocation truncated at 30 days; the number of emergency readmissions to hospital, the number of days spent as an inpatient in an acute general hospital, and the rate of death in the year after random allocation; the patient's experience of the hospital stay; their view on the length of the hospital stay; anxiety (Generalized Anxiety Disorder-2); depression (Patient Health Questionnaire-2); cognitive function (Montreal Cognitive Assessment-Telephone version); independent functioning (Barthel Index of Activities of Daily Living); health-related quality of life (five-level EuroQol five-dimension questionnaire); and overall quality of life. Statisticians and data collectors were masked to treatment allocation; participants and ward staff could not be. Analyses were intention-to-treat. The trial had a patient and public involvement panel and was registered with ISRTCN (ISRCTN86120296).Findings2744 participants (1399 [51·0%] male and 1345 [49·0%] female) were enrolled between May 2, 2018, and March 5, 2020; 1373 were allocated to PICLP and 1371 to usual care. Participants’ mean age was 82·3 years (SD 8·2) and 2565 (93·5%) participants were White. The mean time spent in hospital in the 30 days post-randomisation (analysed for 2710 [98·8%] participants) was 11·37 days (SD 8·74) with PICLP and 11·85 days (SD 9·00) with usual care; adjusted mean difference –0·45 (95% CI –1·11 to 0·21; p=0·18). The only statistically and clinically significant difference in secondary outcomes was the rate of discharge, which was 8.5% higher (rate ratio 1·09 [95% CI 1·00 to 1·17]; p=0·042) with PICLP—a difference most apparent in patients who stayed for more than 2 weeks. Compared with usual care, PICLP was estimated to be modestly cost-saving and cost-effective over 1 and 3, but not 12, months. No intervention-related serious adverse events occurred.InterpretationThis is the first randomised controlled trial of PICLP. PICLP is experienced by older medical inpatients and ward staff as enhancing medical care. It is also likely to be cost-saving in the short-term. Although the trial does not provide strong evidence that PICLP reduces time in hospital, it does support and inform its future development and evaluation.FundingUK National Institute for Health and Care Research.

Background/Objectives: The rising prevalence of musculoskeletal (MSK) conditions has not been balanced by a sufficient increase in healthcare providers. Scalability challenges are being addressed through the use of artificial intelligence (AI) in some healthcare sectors, with this showing potential to also improve MSK care. Digital care programs (DCP) generate automatically collected data, thus making them ideal candidates for AI implementation into workflows, with the potential to unlock care scalability. In this study, we aimed to assess the impact of scaling care through AI in patient outcomes, engagement, satisfaction, and adverse events. Methods: Post hoc analysis of a prospective, pre-post cohort study assessing the impact on outcomes after a 2.3-fold increase in PT-to-patient ratio, supported by the implementation of a machine learning-based tool to assist physical therapists (PTs) in patient care management. The intervention group (IG) consisted of a DCP supported by an AI tool, while the comparison group (CG) consisted of the DCP alone. The primary outcome concerned the pain response rate (reaching a minimal clinically important change of 30%). Other outcomes included mental health, program engagement, satisfaction, and the adverse event rate. Results: Similar improvements in pain response were observed, regardless of the group (response rate: 64% vs. 63%; p = 0.399). Equivalent recoveries were also reported in mental health outcomes, specifically in anxiety (p = 0.928) and depression (p = 0.187). Higher completion rates were observed in the IG (79.9% (N = 19,252) vs. CG 70.1% (N = 8489); p < 0.001). Patient engagement remained consistent in both groups, as well as high satisfaction (IG: 8.76/10, SD 1.75 vs. CG: 8.60/10, SD 1.76; p = 0.021). Intervention-related adverse events were rare and even across groups (IG: 0.58% and CG 0.69%; p = 0.231). Conclusions: The study underscores the potential of scaling MSK care that is supported by AI without compromising patient outcomes, despite the increase in PT-to-patient ratios.

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.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear.ObjectiveThe aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD.MethodsThis 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects.ResultsAmong the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants’ average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (β=–12.203, 95% CI –17.882 to –6.523; P<.001), owing to lower scores on the subscales Inattention (β=–3.966, 95% CI –6.285 to –1.647; P<.001), Hyperactivity/Impulsivity (β=–5.735, 95% CI –8.334 to –3.137; P<.001), and Oppositional Defiant Disorder (β=–2.995, 95% CI –4.857 to –1.132; P=.002). The intervention was associated with significant reduction in the Metacognition Index (β=–6.312, 95% CI –10.973 to –1.650; P=.006) and Global Executive Composite (β=–5.952, 95% CI –10.214 to –1.690; P=.003) on the BRIEF. No severe intervention-related adverse events were reported.ConclusionsThis novel digital cognitive-physical intervention was efficacious in school-age children with ADHD. A larger multicenter effectiveness trial with longer follow-up is warranted to confirm these findings and to assess the durability of treatment effects.Trial RegistrationChinese Clinical Trial Register ChiCTR2300070521; https://www.chictr.org.cn/showproj.html?proj=177806

Large variability exists in people’s responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020–2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41–70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = −0.13 mmol l−1; log-transformed 95% confidence interval = −0.07 to −0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268.

Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway.

Abstract Background/Aims Systemic sclerosis (SSc) is a multi-system autoimmune disease with significant morbidity and mortality, and an unmet therapeutic need. The pathogenesis of SSc involves dysfunctional immune signalling, fibroblast behaviour and vascular development. Factor XIII (FXIII) is an enzyme involved in coagulation, and in wound healing where it promotes angiogenesis via inhibition of thrombospondin-1 (TSP-1). Therapeutic administration of FXIII in SSc is proposed to increase angiogenesis via suppression of TSP-1, which is known to be dysregulated in SSc. Previous preclinical and clinical studies suggest that therapeutic administration of factor XIII could improve vascular function in SSc. Methods Two interlinked clinical trials were conducted at a single centre. First, a single-dose open-label study was performed to assess the safety and pharmacokinetics of FXIII treatment in SSc. Eight adult patients with limited or diffuse SSc received a single dose of intravenous purified human FXIII, followed by a 6-week monitoring period. Second, a phase II, double-blind, randomised, placebo-controlled study was performed to investigate the safety and efficacy of factor XIII treatment in SSc. 18 adult patients with limited or diffuse SSc were randomised 2:1 to receive study intervention (intravenous purified human FXIII) or placebo (intravenous 0.9% sodium chloride solution). Safety endpoints were assessment of the safety and tolerability of FXIII treatment via review of adverse events, physical examination and monitoring of physiological function. Efficacy was explored as change in skin severity by modified Rodnan skin score (mRSS) at week 24 compared to baseline, and change in severity of Raynaud’s phenomenon, assessed by review of the Raynaud’s Condition Score (RCS) at week 24, compared to baseline. The study is registered with ClinicalTrials.gov (number NCT02551042). Results The main objective of the clinical trial was met by demonstrating that FXIII is safe and well tolerated in SSc. Pharmacokinetic analysis showed a predictable rise and fall in FXIII level following therapeutic administration, with the mean time taken for the FXIII level to return to within 10 IU/dL of the endogenous level being 16.6 days (SD 8.7). Adverse event and safety monitoring did not reveal any concerning pattern. Study intervention-related adverse events were self-resolving and tolerable. There was no statistically significant change in mRSS or RCS during the trial, but there was a trend towards improvement in RCS in the FXIII group (mean change in RCS of -1.2 (95% CI -2.26 to -0.14) in the FXIII group versus -0.83 (95% CI -3.44 to 1.77) in the placebo group). Conclusion Our results suggest that therapeutic strategies to modulate links between coagulation and tissue repair using FXIII are safe and feasible. Further studies with different patient populations and FXIII doses could investigate the role of FXIII in SSc further. Disclosure A. Leslie: Other; A.L. is an employee of GSK. S. Vigneswaran: None. K. Khan: None. V. Ong: None. C.P. Denton: Consultancies; C. D. has received consulting fees from Roche, Janssen, GlaxoSmithKline, Sanofi, Galapagos, Boehringer Ingelheim, and CSL Behring, and Acceleron. Grants/research support; C. D. has received research funding from CSL Behring, Horizon, Abbvie, and GlaxoSmithKline.

Abstract Introduction Poor sleep quality is highly prevalent among individuals with mild cognitive impairment (MCI). Further, poor sleep quality is associated with reduced quality of life, increased stress response, memory impairments, and progression to dementia among individuals with MCI. Pharmacological treatments for sleep have mixed efficacy and can lead to dependency. Therefore, alternatives to pharmacological treatments for improving sleep among individuals with MCI are needed. The present study reports on the feasibility of a non-pharmacological. It was hypothesized that the hypnosis intervention program would be feasible and have acceptable levels of adherence to daily hypnosis practice. Methods A two-armed randomized controlled pilot trial was conducted using a sample of 21 adults with MCI. Eligible participants were randomly assigned to listen to either hypnosis audio recordings or sham hypnosis recordings for five weeks. Program feasibility, program adherence, pain intensity, stress, and sleep quality were measured using a daily home practice log, questionnaires, and wrist actigraphy. Results The results found mid or higher levels of treatment satisfaction, ease of use, and perceived effectiveness at one-week follow-up, with participants in the hypnosis arm reporting greater perceived benefit. Adherence to assigned audio recordings and meetings were likewise within acceptable margins in both groups. No intervention-related adverse events were reported in either treatment condition. Significant improvements in sleep quality, sleep duration, and daytime sleepiness were found for the hypnosis intervention. Conclusion The results of this study can be used to inform future research on the effects of hypnosis on sleep quality in adults with MCI. Support (if any)

BackgroundIn the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission.AimsTo develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data.MethodsPatients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction.ResultsWe included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval.ConclusionThe final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice.Clinical Trial Registration NumberClinicalTrials.gov, number NCT03172377.

Telehealth overcomes common geographical barriers to community/clinic-based healthcare and lifestyle interventions, (1,2) but whether it is a feasible and safe mode of healthcare service delivery for lifestyle-based interventions in those with non-alcoholic fatty liver disease (NAFLD) remains unknown. This study evaluated the feasibility and safety of a home exercise program with dietary advice to increase plant-based protein delivered and monitored by healthcare professionals via telehealth in adults with NAFLD. Secondary aims were to assess changes in macronutrient intake including protein from plant and animal sources, body weight, physical activity and physical function. This was a 12-week pilot feasibility randomised controlled trial conducted in 28 inactive adults (&gt;45 years) with NAFLD. Participants were randomly allocated to receive: 1) a home-based, muscle strengthening exercise program (3 days/week) delivered and monitored remotely by an exercise physiologist using the TeleHab exercise platform/app (VALD Health) plus support from a nutritionist to increase daily protein intake to ~1.2-1.5 g/kg/day from predominately plant-based sources and behavioural change support delivered via 3-4 weekly text messages (Pro-Ex, n = 14) or 2) usual care (UC, n = 14). Feasibility was assessed via retention (defined as ≤10% attrition), adherence [≥66% to the muscle strengthening program and ≥80% to the recommended daily protein serves [total (≥3-3½), plant (≥2) and animal (≤1-1½) per day (via protein checklist)] and safety (intervention-related adverse events). Secondary outcomes included macronutrient intake (3x24-hour records), weight (self-reported), habitual physical activity (PA) [moderate-to-vigorous (MVPA), minutes/week via the Short International Physical Activity Questionnaire], and physical function [30-second sit-to-stand (STS) performance]. Since this was a pilot feasibility study, mean group differences (6 and 12-weeks) were estimated, with 95% confidence intervals, and standardised effects [Cohen D, effect size (ES)] reported for secondary outcomes. Overall, 25 participants (89%) completed the intervention. In Pro-Ex, mean adherence to the exercise program was 52%, while adherence to the recommended plant, animal and total protein serves/day was 32%, 42% and 14% of participants, respectively. One minor exercise-related adverse event occurred from 241 completed sessions over 12 weeks. Relative to UC, Pro-Ex experienced a mean 2.7 (95%CI: 0.9, 4.4; large ES d = 1.29) increase in 30-sec STS number, 46 minute (95%CI: −153, 245; small ES d = 0.19) increase in MVPA, 1.7kg (95%CI: −3.5, 0.2; moderate ES d = 0.54) decrease in body weight, 35.2g (95%CI: 11.0, 59.3; large ES d = 1.23) increase in protein and 8.3g (95%CI:-20.5, 4.0; moderate ES d=-0.57) reduction in saturated fat. In middle-aged and older adults with NAFLD, a home exercise and plant-based dietary protein intervention delivered via telehealth was safe, but not feasible in terms of achieving the desired level of adherence. Despite this, exploratory analysis indicates this mode of healthcare service delivery could play a role to support weight management and improve physical activity and physical function in adults with NAFLD.

This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48h) in critical care units. We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.

Study designThis was a sub-group analysis of a multicentre, randomised, placebo-controlled, double-blind trial (ECLISP trial)ObjectivesTo assess the efficacy of a probiotic containing at least 6.5 × 109 live Lactobacillus casei Shirota (LcS) in preventing antibiotic associated diarrhoea (AAD) in patients with spinal cord injury (SCI) who consumed proton pump inhibitor (PPI) regularly. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. The trial was registered with ISRCTN:13119162.SettingThree SCI centres (National Spinal Injuries Centre, Midland Centre for Spinal Injuries and Princess Royal Spinal Cord Injuries Centre) in the United KingdomMethodsBetween November 2014, and November 2019, 95 eligible consenting SCI patients (median age: 57; IQ range: 43-69) were randomly allocated to receive LcS (n = 50) or placebo (n = 45). The primary outcome is the occurrence of AAD up to 30 days after finishing LcS/placebo.ResultsThe LcS group had a significantly lower incidence of AAD at 30 days after finishing the antibiotic course (28.0 v 53.3%, RR: 95% CI: 0.53, 0.31–0.89; z = 2.5, p = 0.01). Multivariate logistic regression analysis identified that LcS can reduce the risk of AAD at 30 days (OR: 0.36, 95% CI 0.13, 0.99, p < 0.05). No intervention-related adverse events were reported during the study.ConclusionsLcS has the potential to prevent AAD in what could be considered a defined vulnerable group of SCI patients on regular PPI. A confirmatory, randomised, placebo-controlled study is needed to confirm this apparent therapeutic success to translate it into appropriate clinical outcomes.SponsorshipYakult Honsha Co., Ltd.

Efficacy and safety of herbal medicine Gongjin-Dan and Ssanghwa-Tang in patients with chronic fatigue: A randomized, double-blind, placebo-controlled, clinical trial

IntroductionPrevious systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to...

BackgroundThe effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear.Trial designThe RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes.MethodsParticipants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates.ResultsGlobal QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. ConclusionsRBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research.Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32–5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644.