Randomized Control Trial Design Research Articles

The impact of leucine supplementation on body composition and glucose tolerance following energy restriction: an 8-week RCT in adults at risk of the metabolic syndrome

BackgroundL-Leucine (Leu) supplementation may benefit fat-free mass (FFM) per se and glucose metabolism.ObjectivesTo determine whether Leu supplementation during energy restriction blunted the loss of FFM, enhanced the loss of fat mass (FM) and improved glucose tolerance.DesignThirty-seven adults, aged 20–65 years, with increased waist circumference and at least one other metabolic syndrome (MetS) component, were selected. We employed a two-arm parallel, double blind, randomized control trial (RCT) design. Participants were randomly assigned to an intervention group (leucine – 3 g/d) or placebo (lactose - 2.67 g/d), while following an individualised energy restricted diet for an 8-week period. Detailed body composition (DEXA), oral glucose tolerance test (OGTT), insulin and components of MetS were measured before and after the trial. Analysis of covariance (ANCOVA) assessed the effect of Leu on an intention-to-treat (ITT) principle. Bootstrapping method with 1000 bootstrap samples was used to derive parameter estimates, standard errors, p-values, and 95% confidence intervals for all outcomes.ResultsAdjusted for baseline values and other covariates, FFM (p = 0.045) and lean tissue mass (LTM) (p = 0.050) were significantly higher following Leu. These outcomes were modified by a significant treatment x sex interaction that indicated Leu had the greater effect in men. However, on adjustment for body composition changes, there was no difference in insulin sensitivity, oral glucose tolerance, or change in MetS components following Leu.ConclusionShort-term leucine supplementation during energy restriction resulted in a greater preservation of FFM and LTM particularly in men, but did not impact glucose metabolism.

CommunityRx, a social care assistance intervention for family and friend caregivers delivered at the point of care: two concurrent blinded randomized controlled trials

BackgroundCommunityRx is an evidence-based social care intervention delivered to family and friend caregivers (“caregivers”) at the point of healthcare to address health-related social risks (HRSRs). Two CommunityRx randomized controlled trials (RCTs) are being fielded concurrently on Chicago’s South Side, a predominantly African American/Black community. CommunityRx-Hunger is a double-blind RCT enrolling caregivers of hospitalized children. CommunityRx-Dementia is a single-blind RCT enrolling caregivers of community-residing people with dementia. RCTs with caregivers face recruitment barriers, including caregiver burden and lack of systematic strategies to identify caregivers in clinical settings. COVID-19 pandemic-related visitor restrictions exacerbated these barriers and prompted the need for iteration of the protocols from in-person to remote operations. This study describes these protocols and methods used for successful iteration to overcome barriers.Methods and findingsCommunityRx uses individual-level data to generate personalized, local community resource referrals for basic, health and caregiving needs. In early 2020, two in-person RCT protocols were pre-tested. In March 2020, when pandemic conditions prohibited face-to-face clinical enrollment, both protocols were iterated to efficient, caregiver-centered remote operations. Iterations were enabled in part by the Automated Randomized Controlled Trial Information-Communication System (ARCTICS), a trial management system innovation engineered to integrate the data collection database (REDCap) with community resource referral (NowPow) and SMS texting (Mosio) platforms. Enabled by engaged Community Advisory Boards and ARCTICS, both RCTs quickly adapted to remote operations. To accommodate these adaptations, launch was delayed until November (CommunityRx-Hunger) and December (CommunityRx-Dementia) 2020. Despite the delay, 65% of all planned participants (CommunityRx-Hunger n = 417/640; CommunityRx-Dementia n = 222/344) were enrolled by December 2021, halfway through our projected enrollment timeline. Both trials enrolled 13% more participants in the first 12 months than originally projected for in-person enrollment.DiscussionOur asset-based, community-engaged approach combined with widely accessible institutional and commercial information technologies facilitated rapid migration of in-person trials to remote operations. Remote or hybrid RCT designs for social care interventions may be a viable, scalable alternative to in-person recruitment and intervention delivery protocols, particularly for caregivers and other groups that are under-represented in traditional health services research.Trial registrationClinicalTrials.gov: CommunityRx-Hunger (NCT04171999, 11/21/2019); CommunityRx for Caregivers (NCT04146545, 10/31/2019).

Targeting inflammation to reduce recurrent stroke.

Approximately one in four stroke patients suffer from recurrent vascular events, underlying the necessity to improve secondary stroke prevention strategies. Immune mechanisms are causally associated with coronary atherosclerosis. However, stroke is a heterogeneous disease and the relative contribution of inflammation across stroke mechanisms is not well understood. The optimal design of future randomized control trials (RCTs) of anti-inflammatory therapies to prevent recurrence after stroke must be informed by a clear understanding of the prognostic role of inflammation according to stroke subtype and individual patient factors. In this narrative review, we discuss (1) inflammatory pathways in the etiology of ischemic stroke subtypes; (2) the evidence on inflammatory markers and vascular recurrence after stroke; and (3) review RCT evidence of anti-inflammatory agents for vascular prevention. Experimental work, genetic epidemiological data, and plaque-imaging studies all implicate inflammation in atherosclerotic stroke. However, emerging evidence also suggests that inflammatory mechanisms are also important in other stroke mechanisms. Advanced neuroimaging techniques support the role of neuroinflammation in blood-brain barrier dysfunction in cerebral small vessel disease (cSVD). Systemic inflammatory processes also promote atrial cardiopathy, incident and recurrent atrial fibrillation (AF). Although several inflammatory markers have been associated with recurrence after stroke, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are presently the most promising markers to identify patients at increased vascular risk. Several RCTs have shown that anti-inflammatory therapies reduce vascular risk, including stroke, in coronary artery disease (CAD). Some, but not all of these trials, selected patients on the basis of elevated hsCRP. Although unproven after stroke, targeting inflammation to reduce recurrence is a compelling strategy and several RCTs are ongoing. Evidence points toward the importance of inflammation across multiple stroke etiologies and potential benefit of anti-inflammatory targets in secondary stroke prevention. Taking the heterogeneous stroke etiologies into account, the use of serum biomarkers could be useful to identify patients with residual inflammatory risk and perform biomarker-led patient selection for future RCTs.

Comparing the effectiveness of extracorporeal shockwave therapy and myofascial release therapy in chronic pelvic pain syndrome: study protocol for a randomized controlled trial

BackgroundChronic prostatitis/chronic pelvic pain syndrome is a highly prevalent syndrome. Previous studies showed that extracorporeal shockwave therapy and myofascial release therapy could improve the quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Theoretically, combined therapy with extracorporeal shockwave therapy and myofascial release therapy will likely have significant advantages in treating CP/CPPS. We, therefore, present a protocol for conducting a well-designed randomized controlled trial to compare the efficacy and safety of each therapy.MethodsThe proposed study will be a three-group randomized control trial (RCT) design that includes 150 participants from Zhongda Hospital Affiliated to Southeast University, with equal allocation of participants to the three intervention groups. The study duration will be 8 weeks, which includes a 4-week treatment period and a 4-week follow-up period. The primary outcome will be the changes in surface electromyography (sEMG) assessment and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). The secondary outcomes will include the changes in three-dimensional quantification, shear wave elastography (SWE), and sympathetic skin response (SSR) testing. Assessments will be conducted before the intervention (T0), before the 5th intervention (T1), immediately after the 8th intervention (T2), and the 4th week after the end of the 8th intervention (T3).DiscussionThis trial will compare the differences in efficacy between single extracorporeal shockwave therapy, single myofascial release therapy, and combined therapy to select the most appropriate treatment option for patients with CP/CPPS. The possible pathogenesis of CP/CPPS would also be analyzed by comparing the intercorrelation between each objective and subjective measurement (NIH-CPSI score, sEMG, SWE, SSR).Trial registrationThe name of the registry: Extracorporeal Shockwave and Myofascial Release Therapy in Chronic Pelvic Pain Syndrome.Registration number: NCT05659199. Date of registration: December 2022.

Oral analgesic for musculoskeletal injuries in children: A systematic review and network meta-analysis.

Pain in pediatric musculoskeletal (MSK) injuries can lead to increased anxiety, fear, and avoidance of medical care, making analgesic management critical. Therefore, we evaluated analgesic efficacy and adverse effects to select the optimal analgesic agent in pediatric patients with MSK injuries. Four databases were searched from inception to March 2023 for peer-reviewed, open randomized controlled trials (RCTs). Inclusion criteria were: (1) trials with RCT design, (2) children aged 1 month-18 years with MSK injury, (3) outpatient setting, (4) interventions and control, (5) primary outcome of pain score at 60 and 120 min and secondary outcome of adverse effects, and (6) full-text and peer-reviewed articles. Two reviewers screened, extracted data, and assessed the risk of bias. A frequentist random-effects network meta-analysis (NMA) was performed. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach. We included eight trials comprising 1645 children. Ibuprofen was significantly associated with pain reduction at 120 min, compared with acetaminophen (SMD 0.31 [95% CI 0.11-0.51]; moderate certainty) and opioids (SMD 0.34 [95% CI 0.20-0.48]; moderate certainty). Compared with opioids alone, ibuprofen-opioid combination was significantly associated with pain reduction at 120 min (SMD 0.19 [95% CI 0.03-0.35]). No significant differences were found in pain interventions at 60 min. Ibuprofen had statistically fewer adverse events than opioids (RR, 0.54 [95% CI 0.33-0.90]; moderate certainty) and ibuprofen with opioids (RR 0.47 [95% CI 0.25-0.89]; moderate certainty). In terms of limitations, the eight RCTs included had relatively small sample sizes; only two were high-quality RCTs. Our NMA found ibuprofen to be the most effective and least adverse analgesic in pediatric patients with MSK injuries.

The effect of bed exercises following major abdominal surgery on early ambulation, mobilization, pain and anxiety: A randomized-controlled trial.

This randomized-controlled trial aimed to investigate the effect of bed exercises on postoperative anxiety, pain, early ambulation and mobilization. This study was conducted with a randomized-controlled trial design and in the general surgical clinic of a research and training hospital. A total of 120 patients (60 in the experimental group and 60 in the control group) scheduled for major abdominal surgery took part in the study. The data were collected using a patient information form, the Anxiety Specific to Surgery Questionnaire and the Visual Analog Scale through face-to-face interviews. The patients in the experimental group performed 15-min bed exercises on the day of their operation, as well as on the postoperative first and second days, and the control group underwent only the routinely performed procedures in the clinic. The data were analysed using descriptive statistics, analysis of variance and t-tests. The sample of our study included major abdominal surgery patients. Ambulation was achieved at a mean time of 4 h earlier in the experimental group. On the postoperative first and second days, the patients in the experimental group had mean mobilization durations that were approximately 2 h longer compared with the patients in the control group. Moreover, the postoperative pain and anxiety levels of the patients in the experimental group were significantly lower than those of the patients in the control group (p < 0.05). We recommend that bed exercises be performed to lower anxiety and pain severity, achieve early ambulation and increase the duration of mobilization among patients following major abdominal surgery.

A growth mindset intervention to improve mental health in adolescents during COVID‐19

AbstractCOVID‐19 poses a considerable threat to adolescent mental health. We investigated depression rates in teens from pre to post‐COVID. We also explored if leveraging a growth mindset intervention (“Healthy Minds”) could improve adolescent mental health outcomes during the pandemic, especially for adolescents experiencing the most distress. In Study 1, we recruited youth from schools in a rural southern community (N = 239) and used a pre‐post design. In Study 2, we recruited an online sample (N = 833) and used a longitudinal randomized control trial design to test the effectiveness of Healthy Minds. Across both studies, there is evidence of higher rates of depression in youth during COVID‐19, relative to pre‐pandemic numbers. In Study 1, the intervention effectively changed psychological and behavioral processes related to mental health, especially for adolescents experiencing greater COVID‐19 stress. However, in Study 2, the intervention failed to impact depression rates or symptoms at follow‐up.

Chinese Neurosurgical Randomized Controlled Trials: Dynamics in Trial Implementation and Completion.

The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic. We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China. The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far. Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial.

Quality evaluation of the literature on randomized controlled clinical trials of traditional Chinese medicine for treatment of gastric precancerous lesions in last 20 years.

To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years. The studies of RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the Chinese full-text journal database, Wanfang database, VIP database, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional indicators. A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the concealed risk of uncertainty in the allocation scheme was 98.93%; the low risk of bias for blinding of patients or testers was 1.30%; the risk of bias for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.44%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries of introduction, objectives and interventions; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature implemented a randomized program, 1.07% of the literature hid the randomized program and 1.31% of the literature was blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods; additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation, etc. The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence of clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.

Evaluation of the Strengthening a Palliative Approach in Long Term Care (SPA-LTC) programme: a protocol of a cluster randomised control trial

IntroductionDespite the high mortality rates in long-term care (LTC) homes, most do not have a formalised palliative programme. Hence, our research team has developed the Strengthening a Palliative Approach in...

A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study

BackgroundDelirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible.MethodsThe study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants’ own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals.DiscussionFindings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care.Trial registrationThe feasibility study was registered: ISRCTN15676570

The effect of Cocoa Fruits (Theobroma cacao L.) extracts on serum blood glucose levels in white rats (Rattusnovergicus)

Checking blood glucose levels supports healthy lifestyle and pattern changes to avoid foods that contain high glucose, which can increase blood glucose levels. This study aims to analyze the administration of cocoa pod extract (Theobroma cacao L.) to describe serum blood glucose levels in white rats (Rattusnovergicus). This study used an RCT (randomized controlled trial) design involving five groups of cocoa pod extract samples through an evaporation process using a rotary vacuum evaporator after going through the maceration process for 3 x 24 hours divided into three concentrations of 50 mg/Kg body wt, 100 mg/Kg body wt, 150 mg/Kg body wt. Furthermore, serum blood glucose levels will be measured on the 3rd, 7th, and 14th day after administration of metformin and waste extract of cocoa pod shell (Theobroma cacao L.). Analysis of the research data used a paired t-test. The results showed that the average fasting blood glucose levels of K1 rats (Mus musculus) to the average fasting glucose levels in K2, K3, K4, and K5, respectively, were as follows: 0.037 (p &lt;0.05); 0.000 (p &lt; 0.05); 0.028 (p &lt; 0.05); and 0.015 (p &lt;0.05). This shows that the average fasting blood glucose level is significantly different (p &lt;0.05). The average fasting blood glucose levels of K2 (metformin group) to the average glucose levels in K3 (extract group 50 mg/kg body wt), K4 (extract group 100 mg/kg body wt), and K5 (extract group 150 mg/kg body wt) respectively are as follows: 0.157 (p &gt; 0.05); 1.000 (p &gt; 0.05); and 0.995 (p &gt; 0.05). This shows that the average blood glucose levels between K2, K3, K4, and K5 did not differ significantly (p &lt;0.05) after measuring cocoa pod extract for two days. Based on the results of data analysis from this experimental study, it can be concluded that there is an effect of giving cocoa pod extract (Theobroma cacao L.) on fasting blood glucose levels of mice (Mus musculus) with type 2 diabetes mellitus hypercholesterolemia model. Keywords: Diabetes mellitus; Cacao; Blood Glucose; Rats

The effect of vibration-hinged ankle foot orthoses on gait and spasticity in children with cerebral palsy: A randomized clinical trial design.

Hinged ankle foot orthoses (HAFO) are commonly prescribed for children with cerebral palsy (CP) to improve their ambulatory function. The aim of this study was to compare the effect of vibration-HAFO with that of the same orthosis without vibration on gait, function, and spasticity in hemiplegic CP children. Randomized Control Trial Design (a pilot study). Twenty-three children with hemiplegic CP participated in this study. The control group (n = 12) used HAFO, and the intervention group (n = 11) used vibration-HAFO for four weeks. Pre-post three-dimensional gait analysis was done. Calf muscle spasticity and function were also measured. Results showed significant differences between the two groups in the one-minute walking test (p = 0.023) and spasticity (after intervention [p = 0.022], after follow-up [p = 0.020]). Also, significant differences were detected between the two groups in the step width (p = 0.042), maximum hip abduction (p = 0.008), stance maximum dorsiflexion (p = 0.036) and mean pelvic tilt (p = 0.004) in the barefoot condition. Gait cycle time (p = 0.005), maximum hip abduction (p = 0.042), and cadence (p = 0.001) were different between groups in the braced condition. We couldn't find any significant within and between groups differences in knee kinematic parameters. The mean time of using vibration was 16.83 minutes per day. The vibration-hinged AFO is feasible, safe, and acceptable for children with hemiplegic CP to be integrated into practice. Temporospatial and clinical parameters, especially spasticity, were improved. There were slight trends toward improvement in pelvic and knee kinematics. Vibration-HAFO is of benefit to ambulatory CP children with mild and moderate spasticity. It improved the walking capacity of the children.

Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study

There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.

Feasibility of conducting a cohort randomized controlled trial assessing the effectiveness of a nurse-led package of care for knee pain.

To evaluate the feasibility of conducting a cohort randomized controlled trial (RCT) of a nurse-led package of care for knee pain and determining a treatment sequence for use in a future trial. This study was an open-label, three-arm, single-centre, mixed-methods, feasibility cohort RCT. Adults aged ≥40 years with moderate-to-severe knee pain for ≥3 months were eligible. Participants were randomized into group A (non-pharmacological treatment first), group B (pharmacological treatment first), or group C (usual care). The intervention was delivered over 26 weeks. Outcomes were dropout rate, recruitment rate, intervention fidelity, ability to collect outcome data, and treatment acceptability. Seventeen participants were randomized and enrolled into each of groups A and B (5.2% recruitment rate), and 174 participants were randomized to group C. The participant characteristics at randomization were comparable across the three arms. Coronavirus disease (COVID-19) paused the study from March-November 2020. Participants enrolled in groups A and B before March 2020 were withdrawn at the restart. Of the 20 participants enrolled after the restart, 18 completed the study (10% dropout). The nurse reported delivering most aspects of the intervention with high fidelity. The participants viewed the package of care as structured, supportive and holistic, they learnt about self-managing knee pain, and they could engage with and follow the non-pharmacological treatment. Most found the non-pharmacological treatment more useful than the pharmacological treatment, preferring to receive it before or alongside analgesia. Many self-report questionnaires were not fully completed. The nurse-led package of care for knee pain was acceptable, with low dropout, although the cohort RCT design may not be feasible for a definitive trial. ClinicalTrials.gov, https://clinicaltrials.gov, NCT03670706.

Randomised controlled trials evaluating anticancer therapies in haematological cancers: an overview of global research activity.

Design, results, and interpretation of oncology randomised controlled trials (RCTs) have changed substantially over the past decade. In this study, we describe all RCTs evaluating anticancer therapies in haematological cancers published globally during 2014-2017 with comparisons with solid tumours RCTs. A PubMed literature search identified all phase 3 RCTs of anticancer therapy for haematological cancers and solid tumours published globally during 2014-2017. Descriptive statistics, chi-square tests and the Kruskal-Wallis test were used to compare RCT design results, and output between haematological cancers and solid tumours as well as for different haematological cancer subtypes. 694 RCTs were identified; 124 in haematological cancers and 570 in solid tumours. Overall survival (OS) was the primary endpoint in only 12% (15/124) of haematological cancer trials compared to 35% (200/570) in solid tumours (p < 0.001). Haematological cancer RCTs evaluated the systemic novel therapy more often than the solid tumour RCT (98% versus 84%, p = 0.002). Use of surrogate endpoints like progression-free survival (PFS) and time to treatment failure (TTF) were more common in haematological cancers than solid tumours (47% versus 31%, p < 0.001). Within haematological cancers, the use of PFS and TTF was more prevalent in chronic lymphocytic leukaemia and multiple myeloma as compared to others (80%-81% versus 0%-41%, p < 0.001). Seventy-eight percent of haematologic trials were funded by industry as compared to 70% of solid tumour trials. Only 4% (5/124) of haematologicalcancer trials were led by investigators in upper-middle and lower-middle-income countries as compared to the 9% of solid tumour trials. The fact that only 12% of haematological cancer RCTs are designed to show improvements in OS is of grave concern for the field and the care of future patients. This is further compounded by the highly prevalent use of alternative primary endpoints that are rarely valid surrogates for OS in haematological cancers.

Management of Fatigue in Post-Stroke Patients

Post-stroke patients often have sequelae that are difficult to avoid. One of the impacts that can occur after a stroke is the onset of cognitive impairment, physical disability, and even death due to the extent of brain damage that occurs. Another impact of stroke is Fatigue Post Stroke (FPS), where most stroke patients experience fatigue, and this condition can persist even though other symptoms caused by stroke have improved. This literature review aims to determine the appropriate management of fatigue after a stroke. The method in this study is a literature review by collecting published literature from databases such as ResearchGate, Google Scholar, and PLOS using Boolean stroke management and post-stroke fatigue. The literature search focused on articles related to fatigue in stroke patients. Both used RCT (Randomized Control Trial) design, Quasi Experiment, Qualitative study, and Survey study from the year (2015-2022). Based on the results of data extraction from the author, two themes can be taken by the author, post-stroke patients who experience fatigue and fatigue management in stroke. The update in this literature review is the manifestation of fatigue conditions that, on average, will be experienced by stroke patients. If not handled properly, it will have a worse impact physically and psychologically, which can certainly interfere with the recovery process. So, it is necessary to appropriately manage both physical exercise and psychological interventions following the fatigue conditions of post-stroke patients. We recommend that in health services, nurses pay more attention to patient responses related to fatigue to provide appropriate nursing interventions and increase patients' desire to undergo rehabilitation.

The effect of nature-based music intervention on adaptation and anxiety levels in patients with COVID-19 placed in the prone position: A randomized controlled trial

ObjectiveTo examine the effect of listening to nature-based music on anxiety, physiological parameters, and adjustment to the prone position in conscious and hypoxemic COVID-19 patients. DesignA single-blinded randomized control trial design. SettingThe study was conducted in the intensive care unit of a state hospital in Turkey. Sixty-four patients were randomized into an intervention group and a control group. MethodsA nature-based music intervention was applied in addition to routine care to the intervention group in the prone position, while the control group received routine care in the same position. The study outcomes included state-trait anxiety, physiological parameters, and prone time within 24 h. Measurements were performed in the supine position (Time: T0), in the 30th minute in the prone position (T1), and in the 30th minute of the supine position given following the prone position (T2). Data analysis included independent samples t-test in independent groups and repeated measures ANOVA in dependent groups. ResultsState anxiety fell statistically significantly in the intervention group compared to that of the control group (39.1 ± 6.6 vs. 43.4 ± 7.9, p = 0.025). At T2, the heart rate of the intervention group did not increase, but it increased significantly in the control group compared to T0 and T1 values (87.8 ± 9.8 vs. 91.1 ± 10.8; p = 0.000). The oxygen saturation of the intervention group increased significantly compared to that of the control group (94.5 ± 2.3 vs. 93.4 ± 1.9, p = 0.035). The prone position time of the intervention group was significantly greater than that of the control group (11.5 ± 1.5 vs. 10.8 ± 1.1, p = 0.04). ConclusionsIt was found that nature-based music intervention applied to conscious and hypoxemic COVID-19 patients in the prone position improved anxiety and oxygen saturation and increased the prone position time. Implications for clinical practiceListening to nature-based music in prone position may reduce anxiety in conscious patients with hypoxemic respiratory failure, it may increase adjustment to the prone position, and it may improve oxygenation and heart rate.

Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

The effect of aerobic exercise alone and in combination with cognitive behavioural therapy on obsessive compulsive disorder: A randomized control study

PurposeCognitive behavioural therapy (CBT) has been found to be an effective treatment for OCD, but there remains a significant proportion of individuals who fail to show a treatment response. Aerobic exercise has previously been associated with decreases in anxiety and depression, as well as improvements in OCD symptoms in small-scale studies. The purpose of the present research was to use a randomized control trial design to examine the effects of exercise alone and in combination with CBT, on OCD symptoms and secondary symptoms. Method125 participants were randomly assigned to one of four treatment groups: waitlist control, exercise, CBT, and CBT with exercise. OCD symptom severity was measured at four points over the course of treatment, secondary outcome measures were gathered at three points over treatment. ResultsCBT alone and combined with exercise was associated with significantly greater OCD symptom reduction than exercise alone or the control groups. Total exercise frequency predicted OCD symptom reduction in the groups in which exercise was measured. Group membership did not significantly predict reductions in secondary outcome measures. ConclusionExercise frequency, rather than the presence or absence of exercise, appears to predict OCD symptom reduction, as did participation in CBT.