Behavior Change Techniques Within Digital Interventions for the Treatment of Eating Disorders: Systematic Review and Meta-Analysis.

BACKGROUND: Previous systematic reviews of digital eating disorder interventions have demonstrated effectiveness at improving symptoms of eating disorders; however, our understanding of how these interventions work and what contributes to their effectiveness is limited. Understanding the behavior change techniques (BCTs) that are most commonly included within effective interventions may provide valuable information for researchers and developers. Establishing whether these techniques have been informed by theory will identify whether they target those mechanisms of action that have been identified as core to changing eating disorder behaviors. It will also evaluate the importance of a theoretical approach to digital intervention design. OBJECTIVE: This study aims to define the BCTs within digital self-management interventions or minimally guided self-help interventions for adults with eating disorders that have been evaluated within randomized controlled trials. It also assessed which of the digital interventions were grounded in theory and the range of modes of delivery included. METHODS: A literature search identified randomized controlled trials of digital intervention for the treatment of adults with eating disorders with minimal therapist support. Each digital intervention was coded for BCTs using the established BCT Taxonomy v1; for the application of theory using an adapted version of the theory coding scheme (TCS); and for modes of delivery using the Mode of Delivery Ontology. A meta-analysis evaluated the evidence that any individual BCT moderated effect size or that other potential factors such as the application of theory or number of modes of delivery had an effect on eating disorder outcomes. RESULTS: Digital interventions included an average of 14 (SD 2.6; range 9-18) BCTs. Self-monitoring of behavior was included in all effective interventions, with Problem-solving, Information about antecedents, Feedback on behavior, Self-monitoring of outcomes of behavior, and Action planning identified in >75% (13/17) of effective interventions. Social support and Information about health consequences were more evident in effective interventions at follow-up compared with postintervention measurement. The mean number of modes of delivery was 4 (SD 1.6; range 2-7) out of 12 possible modes, with most interventions (15/17, 88%) being web based. Digital interventions that had a higher score on the TCS had a greater effect size than those with a lower TCS score (subgroup differences: χ21=9.7; P=.002; I²=89.7%) within the meta-analysis. No other subgroup analyses had statistically significant results. CONCLUSIONS: There was a high level of consistency in terms of the most common BCTs within effective interventions; however, there was no evidence that any specific BCT contributed to intervention efficacy. The interventions that were more strongly informed by theory demonstrated greater improvements in eating disorder outcomes compared to waitlist or treatment-as-usual controls. These results can be used to inform the development of future digital eating disorder interventions. TRIAL REGISTRATION: PROSPERO CRD42023410060; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=410060.

Protocol for a randomised controlled unblinded feasibility trial of HD-DRUM: a rhythmic movement training application for cognitive and motor symptoms in people with Huntington's disease.

INTRODUCTION: Huntington's disease (HD) is an inherited neurodegenerative disease causing progressive cognitive and motor decline, largely due to basal ganglia (BG) atrophy. Rhythmic training offers promise as therapy to counteract BG-regulated deficits. We have developed HD-DRUM, a tablet-based app to enhance movement synchronisation skills and improve cognitive and motor abilities in people with HD. This paper outlines a randomised controlled unblinded trial protocol to determine the feasibility of a larger effectiveness trial for HD-DRUM. Additionally, the trial investigates cognitive and motor function measures, along with brain microstructure, aiming to advance our understanding of the neural mechanisms underlying training effects. METHODS, DESIGN AND ANALYSIS: 50 individuals with HD, confirmed by genetic testing, and a Total Functional Capacity (TFC) score of 9-13, will be recruited into a two-arm randomised controlled feasibility trial. Consenting individuals with HD will be randomised to the intervention group, which entails 8 weeks of at-home usage of HD-DRUM or a usual-activity control group. All participants will undergo cognitive and motor assessments, alongside ultra-strong gradient (300 mT/m) brain microstructural MRI before and after the 8-week period. The feasibility assessment will encompass recruitment, retention, adherence and acceptability of HD-DRUM following prespecified criteria. The study will also evaluate variations in cognitive and motor performance and brain microstructure changes resulting from the intervention to determine effect size estimates for future sample size calculations. ETHICS AND DISSEMINATION: The study has received favourable ethical opinion from the Wales Research Ethics Committee 2 (REC reference: 22/WA/0147) and is sponsored by Cardiff University (SPON1895-22) (Research Integrity, Governance and Ethics Team, Research & Innovation Services, Cardiff University, second Floor, Lakeside Building, University Hospital of Wales, Cardiff, CF14 4XW). Findings will be disseminated to researchers and clinicians in peer-reviewed publications and conference presentations, and to participants, carers and the general public via newsletters and public engagement activities. Data will be shared with the research community via the Enroll-HD platform. TRIAL REGISTRATION NUMBER: ISRCTN11906973.

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap. METHODS: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979). RESULTS: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77). CONCLUSION: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Effect of game-based teaching on the oral health of children: a systematic review of randomised control trials.

Poor oral health during childhood can lead to various oral diseases and have long-term implications for dental health. Innovative and engaging oral health educational approaches such as game-based teaching have emerged as a promising modality for health education. This systematic review examined the effectiveness of game-based teaching methods on the oral health of children (4-12 yrs). Scopus, Medline and Web of Science databases were searched according to specific inclusion and exclusion criteria. Inclusion criteria included randomised trials that compared traditional methods of oral health education with game-based interventions in preschoolers and school-age children. The quality of the data was determined using Cochrane risk-of-bias tool for randomized trials (ROB-2). A total of seven studies that examined 1097 children (4-12 yrs) were included in this systematic review with the association of game-based teaching of oral health. The findings indicated that the utilization of game-based methods significantly improved children's oral health outcomes when compared to traditional teaching approaches. Specifically, the game-based interventions demonstrated positive effects on various aspects of oral health, including enhanced oral health knowledge, improved oral hygiene scores, and reductions in debris and plaque scores. The game-based interventions were found to be more effective in promoting oral health when compared to conventional methods of teaching, such as verbal instructions or educational posters. Based on the limited evidence available, game-based teaching appears to be an effective approach for promoting oral health among children, consistently demonstrating positive outcomes, including improved oral health knowledge, enhanced oral hygiene scores, and reductions in debris and plaque scores. Further well-designed trials adhering to reporting guidelines and using objective measures are necessary before outlining universal guidelines for best practice.

Efficacy of Antibiotic Regimens for Pneumonia in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Pneumonia is a leading cause of death in young infants. OBJECTIVES: To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. LIMITATIONS: Trials were heterogeneous, which precluded data pooling. RESULTS: Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. CONCLUSIONS: We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.

Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. OBJECTIVES: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. DATA EXTRACTION: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. RESULTS: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes. CONCLUSIONS: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.

Efficacy of Antibiotic Regimens for Sepsis or Possible Serious Bacterial Infection in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Sepsis is a leading cause of young infant mortality. OBJECTIVE: To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We performed random-effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. RESULTS: Of 2390 publications, we included 41 RCTs (n = 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin + gentamicin (RR 1.03, 95% CI 0.93-1.13]; n = 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin + intramuscular gentamicin versus intramuscular penicillin + gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72-1.02]; n = 5054; low certainty of evidence). Other studies were heterogeneous. LIMITATIONS: RCTs evaluated heterogeneous regimens, limiting our ability to pool data. CONCLUSIONS: We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI.

Continuous adductor canal block versus continuous femoral nerve block for postoperative pain in patients undergoing knee arthroplasty: An updated meta-analysis of randomized controlled trials.

Continuous adductor canal block (CACB) is almost a pure sensory nerve block and can provide effective analgesia without blocking the motor branch of the femoral nerve. Thus, the objective of this study was to systematically evaluate the efficacy of CACB versus continuous femoral nerve block (CFNB) on analgesia and functional activities in patients undergoing knee arthroplasty. PubMed, Embase and the Cochrane Central Register of Controlled Trials (from inception to 3 October 2023) were searched for randomized controlled trials (RCTs) that compared CACB with CFNB in patients undergoing knee arthroplasty. Registration in the PROSPERO International prospective register of the meta-analysis was completed, prior to initiation of the study (registration number: CRD42022363756). Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. Revman 5.4 software was used for meta-analysis and the summary effect measure were calculated by mean differences and 95% confidence intervals. Eleven studies with a total of 748 patients were finally included. Pooled analysis suggested that both CACB and CFNB showed the same degree of pain relief at rest and at motion at 12 h, 24 h and 48 h in patients undergoing knee arthroplasty. Compared with CFNB, CACB preserved the quadriceps muscle strength better (P<0.05) and significantly shortened the discharge readiness time (P<0.05). In addition, there was no significant difference in opioid consumption, knee extension and flexion, timed up and go (TUG) test, or risk of falls between the two groups. Thus, Compared with CFNB, CACB has similar effects on pain relief both at rest and at motion and opioid consumption for patients undergoing knee arthroplasty, while CACB is better than CFNB in preserving quadriceps muscle strength and shortening the discharge readiness time.

Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma subtype with a significant relapse rate and poor prognosis in relapsed/refractory (R/R) patients. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) has demonstrated promising efficacy and safety as salvage therapy for R/R DLBCL. This systematic review protocol aims to comprehensively evaluate the efficacy of Pola-BR for the treatment of R/R DLBCL by synthesizing data from relevant randomized controlled trials. METHODS: This protocol details the eligibility criteria, search strategy, study selection, data extraction, and analysis methods for the systematic review. Randomized controlled trials comparing Pola-BR with other interventions for R/R DLBCL will be included. The primary endpoint is overall survival, with secondary endpoints being progression-free survival and incidence of adverse events. A comprehensive search will be conducted across databases such as Medline/PubMed, Cochrane Library, Web of Science, Scopus, EMBASE, ProQuest, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov from the January 2000 to April 2024. To assess the potential risk of bias, the Cochrane Risk of Bias 1 tool will be used. Data synthesis will utilize fixed-effect or random-effects models, and subgroup and meta-regression analyses will examine heterogeneity. Additionally, publication bias and sensitivity analyses will be performed, and the GRADE approach will be applied to assess the certainty of the evidence. CONCLUSION: This systematic review and meta-analysis protocol provides a rigorous framework for evaluating the efficacy of Pola-BR in the treatment of R/R DLBCL. The results will inform clinical decision-making and guideline development, addressing the unmet need for effective and tolerable treatments for this challenging patient population. Potential limitations and biases will be acknowledged, and future research directions will be discussed.

Nordic inflammatory bowel disease treatment strategy trial: protocol for the NORDTREAT randomised controlled biomarker-strategy trial.

INTRODUCTION: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. METHODS AND ANALYSIS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. ETHICS AND DISSEMINATION: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.

Aerobic Exercise: Randomized Controlled Trial Data Suggest Qualified Benefits for Erectile Dysfunction.

Erectile dysfunction (ED) refers to the difficulty in achieving and maintaining a degree of penile erection that suffices for satisfactory sexual activity. ED is multifactorial in origin; its prevalence therefore varies with the population studied. In the general population, ED is present in 18-52% of men in younger to older age groups and in 43-76% of men with different medical conditions. Phosphodiesterase-5 inhibitor drugs are gold standard treatments for ED. However, because many lifestyle disorders predispose to ED and because aerobic exercise is beneficial for these lifestyle disorders, aerobic exercise may be a possible intervention for ED. In this context, a recent systematic review and meta-analysis identified 11 randomized controlled trials (RCTs; pooled N = 1,147) of aerobic exercise vs nonexercising control conditions for the treatment of ED. These RCTs had been conducted in men with different medical and surgical conditions, commonly obesity, metabolic syndrome, diabetes mellitus, and cardiovascular disease. The exercise interventions were varied but mostly involved 30-60 minutes sessions of activity, 3-5 times a week, for a median duration of 6 months. Advice for diet and weight loss was also commonly provided. The meta analysis found that aerobic exercise was significantly superior to nonexercising control conditions, with greater improvement in erectile functioning observed in subjects with greater baseline impairment. Limitations of the findings were that subjects could not be blinded to the nature of the intervention and that the magnitude of benefit with exercise, although statistically significant, fell below thresholds suggested for clinical significance. Aerobic exercise might therefore be more useful for the primary prevention of ED, for which preliminary evidence already exists. Exercise can also be recommended, along with other lifestyle guidance, to improve sexual functioning in both men and women and to improve health across a range of domains.

Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis.

QUESTION: Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder. STUDY SELECTION AND ANALYSIS: We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or 'active placebo' for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17. FINDINGS: We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference -3.77 HDRS-17 points; 95% CI -5.91 to -1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference. CONCLUSIONS: The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence. PROSPERO REGISTRATION NUMBER: CRD42021226161.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Hypothermia for Hypoxic-ischemic Encephalopathy: Second-generation Trials to Address Gaps in Knowledge.

Multiple randomized controlled trials of hypothermia for moderate or severe neonatal hypoxic-ischemic encephalopathy (HIE) have uniformly demonstrated a reduction in death or disability at early childhood evaluation. These initial trials along with other smaller studies established hypothermia as a standard of care in the neonatal community for moderate or severe HIE. The results of the initial trials have identified gaps in knowledge. This article describes 3 randomized controlled trials of hypothermia (second-generation trials) to address refinement of hypothermia therapy (longer and/or deeper cooling), late initiation of hypothermia (after 6 hours following birth), and use of hypothermia in preterm newborns.

A randomized controlled trial of acupuncture and receptive music therapy for sleep disorders in the elderly-ELAMUS: study protocol.

BACKGROUND: Globally, the demographic shift towards an aging population leads to significant challenges in healthcare systems, specifically due to an increasing incidence of multimorbidity resulting in polypharmacy among the elderly. Simultaneously, sleep disorders are a common complaint for elderly people. A treatment with pharmacological therapies often leads to side effects causing a high potential for dependency. Within this context, there is a high need to explore non-pharmacological therapeutic approaches. The purpose of this study is to evaluate the effectiveness of acupuncture and music therapy, both individually and combined as a multimodal therapy, in the treatment of sleep disorders in individuals aged 70 years and older. METHODS: We conduct a confirmatory randomized controlled trial using a two-factorial study design. A total of n = 100 elderly people receive evidence-based standard care information for age-related sleep disorders. Beyond that, patients are randomly assigned into four groups of n = 25 each to receive acupuncture, receptive music therapy with a monochord, multimodal therapy with both acupuncture and music therapy, or no further therapy. The study's primary outcome measurement is the improvement in sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) (global score), at the end of intervention. Additionally, depression scores (Geriatric Depression Scale), health-related quality of life (Short-Form-Health Survey-12), neurovegetative activity measured via heart rate variability, and safety data are collected as secondary outcomes. Using a mixed-methods approach, a qualitative process evaluation will be conducted to complement the quantitative data. DISCUSSION: The study is ongoing and the last patient in is expected to be enrolled in April 2024. The results can provide valuable insights into the effectiveness of non-pharmacological interventions for sleep disorders among the elderly, contributing to a more personalized and holistic approach in geriatric healthcare. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00031886).

Implementation of integrated care for type 2 diabetes Mellitus and Periodontitis in Germany: study protocol for a practice-based and cluster-randomized trial.

BACKGROUND: Type 2 Diabetes mellitus (T2DM) and periodontitis share common risk factors and influence one another. However, primary care and oral health care continue to operate separate from each other and fail to synchronize care for patients with T2DM and periodontitis. The purpose of this practice-based trial is to evaluate the implementation of a new integrated care pathway for patients with T2DM and periodontitis. The new approach integrates a screening for T2DM risk in dental care settings in patients with periodontitis, a screening for periodontitis risk in primary care settings in patients with T2DM, and mutual referrals between dentists and primary care physicians. METHODS: Two practice-based studies will be carried out in parallel: (i) In dental care settings: a practice-based, multi-centric, cluster-randomized, controlled trial with a control and an intervention group; (ii) in primary care settings: a practice-based, multi-centric, non-randomized, controlled trial with a synthetic control group calculated from claims data. Following a two-step recruitment approach, 166 dentists and 248 general practitioners will be recruited, who themselves will recruit a total of 3808 patients in their practices. Patient data will be collected at baseline, 12 months, and 24 months after study enrollment. The evaluation comprises: (i) impact evaluation, using a hierarchical linear mixed model; (ii) process evaluation, based on surveys alongside the trials; (iii) economic evaluation. In addition, a Discrete-Choice-Experiment will identify provider's payment preferences for the new care approach. DISCUSSION: Upon successful implementation, the intervention will enable health care providers to detect a risk for T2DM and periodontitis in patients at an early stage, thus providing patients an opportunity for timely diagnosis and therapy. Ultimately, this can lead to increased quality of life and reduced health care expenditures. On a methodologic level, the project provides novel insights into a complex intervention on the intersection of general practice and dental care. TRIAL REGISTRATION: The study was prospectively registered at the German Clinical Trials Register ( https://drks.de/search/de/trial/DRKS00030587 ) on 3. July 2023 under ID "DRKS00030587".

Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis.

BACKGROUND: Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. METHODS: We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. DISCUSSION: This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023402365.