Main Trial Research Articles

Cannabidiol (CBD): A Systematic Review of Clinical and Preclinical Evidence in the Treatment of Pain

Background/Objectives: Cannabis sativa L. is a plant that has been used for thousands of years for its industrial and medicinal properties. In recent years, there has been a rise in the study of this plant due to its bioactive compounds for pharmaceutical applications. Particularly, cannabidiol has demonstrated analgesic and non-psychoactive properties. The objective of this systematic review is to update and to gather the clinical and preclinical evidence on CBD in pain treatment. Methods: This study was performed following the PRISMA guidelines and using the following search terms “((cannabidiol) NOT (THC)) NOT (tetrahydrocannabinol)) AND (pain treatment)” in PubMed and Web of Science, with the following inclusion criteria: CBD pain treatment without THC in monotherapy, including both clinical and preclinical trials. From the initial sample of more than 500 articles, a total of 40 studies were selected, eliminating duplicate studies from the databases and considering the inclusion and exclusion criteria. On one hand, clinical trials were analyzed using CBD products without THC used in monotherapy, assigning a Jadad score to evaluate the quality/bias of the trials; on the other hand, the main preclinical trials were analyzed, grouping the results into in vivo and in vitro trials. Results: Based on the review conducted, there is sufficient clinical and preclinical evidence of CBD in pain treatment, so CBD could be an effective and safe treatment in reducing pain due to its analgesic and anti-inflammatory properties. These effects appear to be primarily mediated by the activation of TRPV-1, 5HT-1A, and CB1, with emerging therapeutic relevance in the management of osteoarthritis and chronic pain. Conclusions: Although clinical and preclinical research show promising results, clinical evidence is limited, and more studies should be performed in the future with isolated CBD.

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] <30mL/kg/1.73m2, QTc using the Fridericia’s formula >500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF <55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR <30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP <300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF <55%.

Facilitators and barriers to improving beverage consumption among primary school children in Belgium

Abstract Background School is seen as a relevant setting to intervene in children’s health behaviour, including their beverage consumption. A randomized controlled trial (DRINK) has been implemented to compare nutrition and sustainability-based interventions to reduce sugary beverages and to increase tap water consumptions among primary school children in French-speaking Belgium. The aim of this qualitative study was to describe the context before the intervention implementation and to identify the facilitators and barriers to implementing the project. Methods In 2021, the 48 schools included in the trial responded to a semi-structured interview prior to the intervention, and 30 were interviewed one year later. School characteristics (including socioeconomic index, SEI) and contextual components were summarised. The qualitative corpus was analysed using thematic content methods to identify emerging themes, then classified into obstacles and facilitators. Results Of the 48 schools, 70.8% were Walloon, 76.6% had a medium or high SEI, and 41.7% included less than 90 pupils. The majority had already implemented nutrition and sustainable development initiatives before the trial. While taps were available in classrooms and reusable bottles were used, the initiatives could be extended, e.g. to increasing the number of water points. The main facilitators were the interest to receive additional support by the schools already involved in other projects, and the flexibility of the intervention. The main barriers were related to lack of access to tap water; insufficient support for the implementation of the intervention; and poor availability of school staff to get involved in such a project. Conclusions Alongside the main trial findings, understanding the facilitators and barriers will enable the intervention to be further adapted and extended. Considering the school context and perceptions is essential to ensure effective and durable school health initiatives. Key messages • Largely involved in promoting nutrition and sustainability, the schools were keen to receive support to continue. • Strengthening access to water, communication and support for schools are essential.

Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway. In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria (defined as a 24-hour urinary protein-to-creatinine ratio of ≥1 [with protein and creatinine both measured in grams]) despite optimized supportive therapy. Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily for 24 months while continuing to receive supportive therapy. The primary objective of this prespecified interim analysis was to assess the efficacy of iptacopan as compared with that of placebo in reducing proteinuria at month 9; the primary end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at month 9. The proportion of patients who had a 24-hour urinary protein-to-creatinine ratio of less than 1 at month 9 without receiving rescue or alternative medication or undergoing kidney-replacement therapy (dialysis or transplantation) was a secondary end point. Safety was also assessed. The effect of iptacopan on kidney function will be assessed at the end of the 2-year double-blind treatment period. The main trial population included 222 patients in the iptacopan group and 221 in the placebo group. The interim efficacy analysis included the first 250 patients who underwent randomization in the main trial population (125 patients in each group) and who remained in the trial until month 9 or discontinued the trial by month 9. Safety was assessed in all the patients in the main trial population. At month 9, the adjusted geometric mean 24-hour urinary protein-to-creatinine ratio was 38.3% (95% confidence interval, 26.0 to 48.6; two-sided P<0.001) lower with iptacopan than with placebo. The reduction in proteinuria was supported by consistent results in secondary end point analyses. There were no unexpected safety findings with iptacopan. The incidence of adverse events that occurred during the treatment period was similar in the two groups; most events were mild to moderate in severity and reversible. No increased risk of infection was observed. Among patients with IgA nephropathy, treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo. (Funded by Novartis; APPLAUSE-IgAN ClinicalTrials.gov number, NCT04578834.).

Hypercholesterolemia and Alzheimer's Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies.

This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.

The CO-produced Psychosocial INtervention delivered by GPs to young people after self-harm (COPING): protocol for a feasibility study.

Self-harm in young people is a growing concern and reducing rates a global priority. Rates of self-harm documented in general practice have been increasing for young people in the UK in the last two decades, especially in 13-16-year-olds. General practitioners (GPs) can intervene early after self-harm but there are no effective treatments presently available. We developed the GP-led COPING intervention, in partnership with young people with lived experience and GPs, to be delivered to young people 16-25 years across two consultations. This study aims to examine the feasibility and acceptability of conducting a fully powered effectiveness trial of the COPING intervention in NHS general practice. This will be a mixed-methods external non-randomised before-after single arm feasibility study in NHS general practices in the West Midlands, England. Patients aged 16-25 years who have self-harmed in the last 12 months will be eligible to receive COPING. Feasibility outcomes will be recruitment rates, intervention delivery, retention rates, and completion of follow-up outcome measures. All participants will receive COPING with a target sample of 31 with final follow-up data collection at six months from baseline. Clinical data such as self-harm repetition will be collected. A nested qualitative study and national survey of GPs will explore COPING acceptability, deliverability, implementation, and likelihood of contamination. Brief GP-led interventions for young people after self-harm are needed to address national guideline and policy recommendations. This study of the COPING intervention will assess whether a main trial is feasible. ISRCTN (ISRCTN16572400; 28.11.2023).

Influence of Dietary Manipulation on the Blood Biochemical Profile and Growth Performance of Crossbred Dairy Heifer

This study aimed to assess the influence of dietary manipulation with commonly available concentrate sources on the nutritional status and growth performance of crossbred dairy heifer. Concentrates that were used alternatively in three feed preparation were (Wheat bran, rice polish and maize powder). Twelve crossbred dairy heifers (50% Holstein Friesian blood (HF) (age around 12-13 months; body weight (173-196) kg were chosen from the existing dairy herd of Bangladesh Agricultural University (BAU) Dairy Farm, Department of Dairy Science, BAU. Latin square design was used to conduct the study. The feeding experiment was lasted for a duration of 100 days (10 days for adjustment period and rest 90 days for main trial that was divided into 3 periods). Blood analysis, growth performance measurement, feed efficiency calculation and feed cost analysis were performed at 15 days interval. Among the twelve blood biochemical parameters no significant (p&lt;0.05) variation was found except the result of total cholesterol which was found highest in rice polish fed group (170.1 mg/dL). Body weight gain per 15 days was significantly higher (9.08 kg/15d) and dry matter intake per kg of body weight gain (9.56kg DMI/kg BWG) was significantly lower when heifers were supplied feed preparation containing wheat bran. Rest other body growth parameters didn’t show any significant difference when feed with three feed preparations.

Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment

BackgroundUse of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis.MethodsA descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection.ResultsAn ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The ‘ALABAMA unit’ within SystmOne was also created and provided a secure efficient environment to access participants’ EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis.ConclusionsALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs.Trial registrationClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Quality and completeness of, and spin in reporting of, pilot and feasibility studies in hip and knee arthroplasty: a protocol for a methodological survey

IntroductionPilot or feasibility trials examine the feasibility, viability and recruitment potential of larger, main trials. Specifically, a pilot trial can be instrumental in identifying methodological issues essential to the development...

Exploring How the Kidney BEAM Physical Activity Digital Health Intervention Improved Mental Health-Related Quality of Life for People Living With Kidney Disease: a Mixed Methods Approach

IntroductionThe Kidney BEAM randomised controlled trial reported clinically meaningful and statistically significant improvements in mental health-related quality of life (HRQoL), physical function (sit-to-stand-60, but not the physical component of HRQoL) and patient activation following a 12-week physical activity digital health intervention (DHI). This study explores factors that contributed to the effectiveness of Kidney BEAM through mixed methods analyses. MethodsQuantitative data analysis was taken from the recently published primary manuscript. Participants from the Kidney BEAM trial intervention group (n=30) completed individualized semi-structured interviews after the 12-week DHI. Interviews were analysed using the framework method with inductive and deductive coding. Quantitative and qualitative data collection and analyses occurred concurrently, and independently, before combining using a mixed methods analysis with joint displays to triangulate datasets and further explore the primary findings. ResultsThe integrated mixed methods analyses facilitated explanation of the primary findings. The Kidney BEAM intervention was shown to have mental and physical wellbeing benefits and enhanced self-management in this cohort of people living with CKD. Elements that contributed to the effectiveness of the intervention were reported, including the different functional levels and gradual progression of the program, shared lived experiences with other participants, self-monitoring, the sense of achievement, taking back control of their health, moving beyond medications and feeling safe and confident to exercise. ConclusionElements of the Kidney BEAM intervention that contributed to the main quantitative trial findings were identified. This will allow researchers and practitioners to maximize the effectiveness of DHI’s to enhance healthy behaviours in people living with CKD.

Development of Project Based Learning E-Module on Salt Hydrolysis Material to Improve Student Learning Outcomes

The conventional printed modules used in schools have not been able to make students active and understand chemical concepts. Therefore, it is necessary to develop an interactive multimedia-based e-module grounded in Project Based Learning (PjBL), equipped with videos, images, and interactions to engage students and facilitate easier comprehension of chemical materials. The iam of this study is to improve the learning outcomes of class XI Science Muhammadiyah 1 High School Pontianak. The method used in this research is development (research and development) employing the ADDIE model, which includes the stages of (analysis, design, development, implementation, and evaluation). The research findings indicate very high criteria with an average validity coefficient of 0.93 for each aspect of media, materials, and language. The practicality analysis, based on the response questionnaires from the small group trial and the main field trial, showed practicality values of 71% and 74%, respectively, both with practical criteria. It can be concluded that the project based learning e-module developed is feasible to be used as an effective and practical learning tool for XI Science students and chemistry teachers in high schools.

Effects of a single oral dose of azithromycin in laboring women on antimicrobial resistance (AMR) and the microbiome: a protocol for the Antimicrobial Resistance Sub-Study of the A-PLUS trial

Background The Azithromycin Prevention in Labor Use Study (A-PLUS), a large, multi-national randomized trial, was performed to evaluate the improvement of maternal and newborn outcomes following a single dose of azithromycin (AZ) given during labor. However, the immediate and long-term impact of this single dose on the microbiome and the development or prevalence of antimicrobial resistance are unknown. We designed a sub-study to assess AZ resistance of bacterial isolates from clinical infections and of three target bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli) from the serial surveillance of the nasopharynx and rectum. Additionally, the serially surveilled samples will be evaluated for changes to the microbiome and the resistome of the nasopharynx and rectum. Methods and Analysis As part of the large, randomized APLUS trial, maternal and neonatal clinical infections were monitored for up to 42 days postpartum, and samples collected for culture using site-specific routine methods. For this sub-study, cultured bacterial isolates will be assessed for AZ resistance using an antibiotic susceptibility method. Additionally, a random subset of maternal-neonatal dyads from the main trial will be selected for serial surveillance with aseptic swab collections of the nasopharynx and the rectum at baseline, and subsequently at 1-week, 6-weeks, 3-months, 6-months, and 12-months postpartum. The serial samples will undergo selective culturing of sentinel bacterial species and screened for AZ resistance. An additional set of serial samples will be stored for future microbiome and resistome analyses. Ethics and Dissemination The study protocol was reviewed, and ethics approval obtained from all the relevant ethical review boards at each research site. All participants will provide informed written consent prior to their enrollment. Results of the trial will be disseminated through peer-reviewed publications, presentations at relevant conferences, and at dissemination meetings with the ministries of health and local stakeholders at each research site. Trial Registration NCT03871491.

Utilization of Real-World Data in the Intervention to Reduce Early Peanut Allergy in Children (iREACH) Trial

ObjectiveTo demonstrate the use of linked, real-world data in the context of a pediatric practice-based clinical trial. ApproachThe Intervention to Reduce Early Peanut Allergy in Children (iREACH) is a two-arm, cluster randomized, controlled trial. The intervention included clinician education and clinical decision support to increase pediatric clinician adherence to the NIAID’s 2017 Prevention of Peanut Allergy guidelines during infants’ 4- and 6-month well child care visits. Electronic health record (EHR) data were shared with the data coordinating center under a Health Insurance Portability and Accountability Act (HIPAA) waiver. All caregivers of eligible infants were invited to complete two surveys via REDCap, an online survey platform. The consents included an optional HIPAA authorization to link EHR data with survey responses and authorization to collect and link administrative data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program, if applicable. ResultsOverall, 30 Illinois pediatric practices participated. EHR data was collected for 18,480 infants of whom 4,331 had any caregiver survey data (23.4% response rate). Permission to link survey responses to EHR data was obtained for 3,950 infants among those with any survey data (91.2%). Consent for linking WIC data with study data was obtained for 229 infants and 194 mothers. ConclusionsAuthorization for data linkage in the consent forms allowed investigators to amass data to compare caregiver and clinician responses, generate hypotheses, and propose future research outside the scope of the main trial. ImplicationsMultiple real-world data sources can be effectively combined to extend the findings of clinical trials.

Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial

BackgroundHighly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up. MethodsWe electronically surveyed SIMPLIFY participants every 4 weeks for 24 weeks after trial completion but before the main trial results were publicly disclosed. We asked them how often they used medications during the previous week. We estimated covariate-adjusted odds ratios (ORs) of DA or HS non-use by logistic regression with generalized estimating equations. ResultsAfter exclusions mostly due to lack of any surveys, 472 participants were included in the analysis population, 181 from the HS trial and 291 from the DA trial. Approximately half of the analysis population completed all six surveys. At every month of follow-up in both trials, the percentage of individuals reporting non-use of DA or HS during the previous week was greater among those randomized to discontinue therapy. Among participants with responses at 24 weeks, 30/122 (24.6 %) in the HS trial and 79/222 (35.6 %) in the DA trial reported non-use of the respective study medication. After adjusting for covariates, participants randomized to discontinue DA were 8.7-times (95 % CI: 4.3–17.7) more likely to not use DA during follow-up than those randomized to continue DA, and participants randomized to discontinue HS were 5.2-times (95 % CI: 2.1–12.8) more likely to not use HS during follow-up compared to those randomized to continue. ConclusionsIn healthy pwCF on ETI, randomization to discontinue DA or HS during SIMPLIFY was associated with greater odds of not using each medication after the trial compared to randomization to continue. These findings suggest that participation in a treatment discontinuation trial can influence participants’ post-trial treatment decisions. This possibility may be relevant during discussions about research participation and clinical care.

Development of a digital app-based sambo sports book for students at high school level extracurricular activities

The survey in North Sumatra was conducted by researchers in the areas of Medan, Tanah Karo, Tebing Tinggi, Asahan, Serdang Bedagai, Deli Serdang, Labuhan Batu, Tanjung Balai, Humbahas, and Binjai, many coaches and athletes still do not have adequate guidance in Indonesian. Most of the information is still in foreign languages, making it difficult to understand Sambo's techniques and rules. This study aims to develop a digital application-based sambo sports book. Method, in this research, uses the research and development (R&amp;D) method. The research subjects consisted of 10 athletes, coaches, and sambo sports enthusiasts for the main field trial and 20 athletes, coaches, and sambo sports enthusiasts for the operational field trial. Data were collected through observation, interviews, and questionnaires, with instruments in the form of feasibility assessment sheets from sambo sports experts, linguists, media experts, and user subjects. Data analysis was carried out using a percentage quantitative descriptive technique. The results showed that this digital application-based sambo sports book was very good and feasible. This book has great potential to improve the understanding of sambo techniques and rules among athletes, coaches, and sambo enthusiasts by providing easy-to-understand guidelines in Indonesian and emphasizing the importance of technology-based approaches in Sambo.

Cross-border access to early phase clinical trials for children with cancer in the Nordic region

IntroductionAs 15 % of childhood cancers are still incurable, early phase clinical trials are essential in developing better therapies for children with cancer. Accessing relevant trials can be challenging, exacerbated by increasingly specialized therapies which are not available in every country. Copenhagen houses the main early phase trial center for children with cancer in the Nordic region, with about half of trial participants coming from abroad. We explored factors facilitating cross-border access to early phase pediatric cancer trials in Copenhagen. Methods and materialsInterviews were conducted with 11 family members from five families and nineteen healthcare providers on socio-cultural aspects of traveling for the trial. A thematic analysis was conducted. ResultsThree major themes were identified: proximity to a trial center, facilitation of referral and logistics, and families’ and providers’ perceptions. Both geographic proximity and socio-cultural proximity facilitated access. Provider networks facilitated referrals and sponsors paid for travel, improving feasibility for families. Finally, families’ feelings of hope and providers’ positive perceptions of experimental therapy also promoted access to early phase trials. ConclusionsOur findings highlight the importance of fully supporting families through logistics, expenses, and challenges associated with traveling to a clinical trial, the value of robust provider networks in facilitating referrals, and the need for awareness of potential socio-cultural bias in referring patients. While factors like geography and attitude also mitigate access, many barriers can be overcome by comprehensive support for families, improving access to early phase trials for children with cancer.

Effect of Animal-Assisted Activities on Symptoms and Emotions of Children with Neoplastic Disease: A Systematic Review with Meta-Analysis

BACKGROUND: Animal-assisted activities (AAAs) have long been present in pediatric oncology as a nonpharmacological intervention aimed at helping children cope with symptoms and negative emotions during hospitalization and antineoplastic treatment. Among the systematic reviews in the literature, there is a lack of one with meta-analysis that includes only RCTs centered on the effect of the intervention on symptoms and emotions in children with neoplastic disease. OBJECTIVE: To synthesize the effect of AAAs on symptoms and emotions of children with neoplastic disease. METHODS: Studies were searched from biomedical databases Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, Scopus, AMED, sciELO, LILACS, CNKI, J-GLOBAL, J-STAGE, main trial registries and major sources of grey literature. Searching for useful documents took place from the inception of each resource until April 18, 2024. The risk of bias of included studies was assessed with RoB 2, and the overall effect size of the intervention was calculated by creating random-effects meta-analyses graphically represented by forest plots. The summary of findings was illustrated with a table in accordance with the GRADE method. RESULTS: Three parallel-group randomized controlled trials with low risk of bias were included (N = 151, mean age: 8.5-11.2 years). AAAs are promising for anxiety reduction (N = 134; SMD = -0.07 [95% CI: -0.40, 0.27], p &gt; 0.05) and quality of life improvement (N = 84; SMD = -0.11 [95% CI: -0.53, 0.31], p &gt; 0.05) in children and for anxiety reduction (N = 154; SMD = -0.50 [95% CI: -1.52, 0.52], p &gt; 0.05) in parents/caregivers. The certainty/quality of evidence is low to very low. CONCLUSIONS: The effect of animal-assisted activities to reduce anxiety and improve the quality of life of children with neoplastic disease and to reduce parent/caregiver anxiety is small to moderate; however, the quality/certainty of evidence is very low to low. Therefore, further studies on the topic that overcome the current limitations need to be conducted in order to collect more robust data in favor of implementing the intervention in pediatric oncology.

Serum Chloride and the Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload: A Post Hoc Analysis From the ADVOR Trial.

Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure. This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment. Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide (P<0.001). Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03505788.

Introduction of a New Satellite Model for Participation in Clinical Trials in a Consortial Comprehensive Cancer Center with Four University Hospitals in Germany

Introduction: The trend toward personalized medicine leads to very small study cohorts for clinical trials, which makes it difficult to recruit patients in a single study center. On the other hand, the administrative effort required to initiate a clinical trial is very high. As a result, Germany runs the risk of falling behind other countries as a trial location. For this reason, the Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) has been working on the challenge of a new satellite model in which the main trial center is the only one to conclude a trial center contract with the sponsor and also handles all formalities with it. The remaining sites constitute the satellites. In contrast to former satellite models, the entire study-related interventions are carried out at each site in the present model. Methods: In order to evaluate the approvability of the model, contact was made with both higher federal authorities and the responsible inspectorate, and none of them declared themselves responsible for a possible basic approval. The four ethics committees contacted agreed to the model subject to certain framework conditions. In addition, the model was validated by the preparation of several legal opinions on various issues (medical, labor, antitrust law). Conclusion: Study participation close to home is a decisive advantage for multimorbid patients. As up to four locations form a trial site in the model, a large catchment area can be covered with reduced administrative costs. The satellite model developed is intended to give patients broader access to medical innovations in cancer therapy.

Protocol for the process evaluation of the GOAL trial: investigating how comprehensive geriatric assessment (CGA) improves patient-centred goal attainment in older adults with chronic kidney disease in the outpatient setting

IntroductionThe GOAL Cluster Randomised Controlled Trial (NCT04538157) is now underway, investigating the impact of comprehensive geriatric assessment (CGA) for frail older people with chronic kidney disease (CKD). The primary outcome...