Future Randomized Clinical Trials Research Articles

P0892 Real-life vs clinical trial access to biological therapy: findings from an Italian-American study on inflammatory bowel disease

Abstract Background Treatment goals in IBD have shifted from symptom control to mucosal healing and prevention of complications, as well as enhancing quality of life and reducing disability as proposed by the STRIDE II initiative1. Despite pharmacological advances, up to 50% of IBD patients present non-response to currently available advanced therapies (ADT), highlighting the need for alternative therapeutic options offered in randomized clinical trials (RCTs). However, strict eligibility criteria may reduce the access of real-life IBD populations to RCTs. This study aims to evaluate the percentage of eligibility and the representativeness of real-life IBD population in RCTs, deeply investigating the most under respected criteria responsible for patients’ exclusion from RCTs as well as clinical characteristics which distinguish eligible and ineligible patients, thereby suggesting new population clusters for future RCTs development. Methods This prospective, observational, multicentric study was conducted at Policlinico Gemelli in Rome and Crohn's&Colitis Center at University of Miami. Consecutive IBD patients indicated for a new ADT between October 2023 and April 2024 were included. Each patient was screened for eligibility in actively recruiting RCTs at both centres, respectively 6 in Rome (4 for UC, 2 for CD) and 5 in Miami (3 for UC, 2 for CD). Results A total of 140 IBD patients (61 UC and 79 CD) were enrolled, 103 from the Italian cohort and 37 from the American cohort. Among UC patients, 14 (23.0%) were eligible for at least 1 clinical trial, while 45 (77.0%) were ineligible [p<0.001]. Among CD patients, 5 (6.3%) were eligible for at least one clinical trial, while 74 (93.7%) were ineligible [p<0.001]. For UC patients the most frequently failed criteria were MMS between 5-9 (45%), bowel urgency (45%), Mayo Endoscopic Score ≥ 2 (40%), the required washout period from the previous ADT (40%), the lack of response to 1 or more ADTs (39%) and absence of topical 5-ASA or steroid in the past 4 weeks (46%). For CD patients, the CDAI score of 220–450 was the most unmet criterion (85%), followed by "very soft or liquid SF≥ 4" (50%), washout periods (22%), SES-CD≥6 (21%) and CD-related complications (13%). Conclusion Most real-life IBD patients, especially CD, are ineligible for RCTs, primarily due to mild clinical disease activity or the need for ongoing treatments. Notably, real-life CD patients often initiate a new ADT due to radiological evidence of disease activity, complications or to prevent post-operative recurrence, while UC patients initiate ADT also when corticodipendent even with no or mild disease activity. Future RCTs should aim to include a broader range of patients’ subgroups to make their findings directly applicable to clinical practice.

A multidisciplinary pain management program for patients with chronic low back pain: a randomized, single-blind, controlled, feasibility study

BackgroundMultidisciplinary programs are the first recommendation for non-specific chronic low-back pain, but implementing this type of program is complicated to get up and running. The primary aim of this study was to assess the feasibility and appropriateness of the PAINDOC multidisciplinary program for subjects with chronic low-back pain. The secondary objectives were to evaluate the decrease in pain intensity, pain-related disability and pain catastrophizing, as well as the improvement in quality of life with this program. Furthermore, another of the secondary objectives was to calculate the sample size for a future randomized clinical trial.MethodsThis study was conducted in a hospital pain unit using two successive recruitment waves. First, the feasibility outcomes (recruitment, completion, and drop-out rates) of a 5-month non-random prospective cohort (n = 227) were recorded. Then, the clinical outcomes (pain intensity, quality of life, disability, and pain catastrophizing) were recorded from a prospective, controlled, two-armed and single-blind feasibility study (ClinicalTrials.gov, NCT05974072). It included 41 participants that were randomly allocated to either the pharmacological treatment (n = 21) arm or PAINDOC program (n = 20) arm.ResultsThe recruitment rate was 66%, with the completion rate standing at 80.7% and the drop-out rate at 19.3%. Significant differences and a medium size effect were observed between groups in terms of pain intensity (p = .017, r = .408) at the 4-month follow-up. The intragroup analysis of the PAINDOC group revealed significant lessening in pain intensity (p = < 0.001) and improvements in quality of life (p = .030).ConclusionsThis study showed that the PAINDOC multidisciplinary program is a feasible treatment for patients with non-specific chronic low-back pain. Furthermore, the exploratory results of this study suggest that it could be an effective treatment to reduce pain intensity and improve on self-reported quality of life in these patients, although a future randomized clinical trial is needed to determine its effectiveness.Trial registrationNCT05974072 (registration date July 11, 2023; retrospectively registered; ClinicalTrials.gov).

Timing of Resistance Exercise and Cardiometabolic Outcomes in Adults with Prediabetes: A Secondary Analysis.

Objective: The objective of this study was to explore if the time of day (AM vs PM) resistance exercise is performed influences glucose and insulin concentrations, body composition, and muscular strength in adults with prediabetes. Methods: A secondary data analysis was conducted using data from the "Resist Diabetes" study, a phase II exercise intervention. Participants (Age:59.9±5.4 yrs; BMI:33±3.7 kg/m2) with prediabetes and overweight or obesity were categorized into AM (N=73) or PM (N=80) exercisers based on when they completed all of their supervised exercise sessions during a 12-week, 2x/week resistance exercise intervention. Blood glucose and insulin derived from oral glucose tolerance tests, body composition, and muscular strength were assessed pre and post resistance exercise training. Inverse propensity score weighting approach was used to estimate the efficacy of AM/PM exercise on the change of clinical responses. Paired samples t-test was used to compare pre-/post outcomes within AM/PM group. Results: No differences between AM and PM exercisers were detected in the change in glucose or insulin areas under the curve (AUC), body composition, or muscular strength. When exploring within-group changes, PM exercisers reduced glucose AUC (change: -800.6 mg/dl*120 min; p=0.01), whereas no significant change was detected for AM exercisers (change: -426.9 mg/dl*120 min; p=0.26). Only AM exercisers increased fat-free mass (change: 0.6 kg; p=0.001). Conclusions: The time of day of resistance exercise is performed may have some impact on glucose concentrations and body composition response. Future randomized clinical trials are needed to understand how exercise timing influences cardiometabolic outcomes in at-risk adults.

A protocol for lumbar spine surgery under spinal anesthesia in resource limited countries: illustrative case series

Introduction: Lumbar spine surgery can be performed under either general or spinal anesthesia. Numerous studies highlight the benefits of spinal anesthesia (SA), including cost-effectiveness, reduced anesthesia-related complications, and suitability for patients who do not favor general anesthesia (GA). Those informal case series emphasizes the advantages of SA and introduces a working protocol tailored for resource-limited countries (RLCs). Presentation of case: Two patients, aged 35 and 58, underwent spinal surgery using SA combined with local infiltration for the skin and facet joints. We implemented a new protocol believed to be beneficial in RLCs. In both cases, intraoperative vital signs remained stable, and there was effective pain control postoperatively. Clinical discussion: Spine surgery under SA has gained acceptance due to evidence indicating reduced perioperative risks and lower opioid consumption, alongside decreased healthcare costs. Although there are suggested protocols for SA in spine surgery, many are not applicable in RLCs. Our case series demonstrate similar advantages, suggesting that the protocol used in this study may be helpful. Despite its benefits, SA for spine surgery still faces resistance and has not been widely adopted in many neurosurgery centers. Conclusion: The study aim to outline essential steps for initiating SA for spine surgery in RLCs. The guidelines utilized in this study have proven effective. SA can lead to reduced healthcare costs, lower opioid usage, and increased patient turnover. The two cases series demonstrate improved anesthesia outcomes. Future randomized clinical trials with sufficiently large sample sizes are necessary to establish high-quality evidence regarding the safety, efficacy, and cost-effectiveness of SA.

Bone Regeneration Following Implantoplasty: A Retrospective Cohort Study with Long-Term Radiographic Assessment.

Implantoplasty involves mechanically modifying the exposed implant surface by removing macro- and micro-structures and is typically considered a resective approach. The potential for bone regeneration with implantoplasty alone has not yet been studied. This research aimed to evaluate long-term changes in peri-implant bone levels without using regenerative materials. 56 patients (70 implants) were included in the study and were followed for up to 10 years, with a mean observation time of 59 months (~5 years). The implants were evaluated retrospectively through a radiographic, as well as clinical (bleeding on probing and suppuration) analysis. Out of the 70 implants, 11 (15.7%) were lost due to disease recurrence and additional bone loss. One implant (1.4%) experienced up to 1.0 mm of bone loss, 15 implants (21.4%) showed no change in marginal bone levels (MBL), and 43 implants (61.5%) gained bone up to 4.8 mm, all without the use of any graft material or membrane. The overall mean MBL change for the remaining 59 implants at the end of the follow-up period (84.3%) was a gain of 1.27 mm. Implantoplasty alone without osseous surgery, flap repositioning, or using graft material or membrane; may be a viable option for managing peri-implantitis defects. However, future randomized clinical trials with larger sample sizes are necessary to validate current findings.

Substitution of liposomal bupivacaine for lidocaine reduces incidence of injection-emergent adverse events after intraarticular therapies for knee osteoarthritis: a prospective cohort study.

Local anesthetics as a part of intraarticular therapies (IATs) are widely used for treating knee osteoarthritis (KOA). Whether substitution of liposomal bupivacaine (LB) for lidocaine is safe and effective in reducing incidence of injection-emergent adverse events after IATs remains unclear. We recruited outpatients who had a clinical diagnosis of KOA and decided to receive IATs from November 2023 to April 2024. The type of IAT (glucocorticoids, platelet-rich plasma and hyaluronic acid) for each participant was decided by the preference of patients after consulting with his or her treating physicians. Using lidocaine or LB as local anesthetics was determined by enrollment timing due to considerations on safety. The primary outcome was injection-emergent adverse events after IATs. Secondary outcome measures included Visual Analogue Scale (VAS) pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. In this study, 123 and 103 patients respectively received lidocaine and LB according to their enrollment date. Compared with lidocaine, using LB yielded reduced incidence of AE in the overall two weeks (LB versus lidocaine, 30.1% versus 45.5%, P=0.018) and Week1 (LB versus lidocaine, 23.3% versus 39.8%, P=0.008). After adjusting for sex, baseline BMI, age, baseline WOMAC pain subscale score and K-L grade, substitution of LB for lidocaine was significantly associated with the reduced incidence of AE in two weeks (OR [95%CI], 0.484 [0.274-0.853], P=0.012). In the initial three days, the LB groups reported better outcomes in terms of VAS pain score (change from baseline of VAS pain, LB versus lidocaine, Day 1-8.3±8.9 versus-1.9±9.3, P<0.001; Day 2-20.6±16.1 versus-13.7±19.4, P=0.005; Day 3-22.3±18.5 versus-16.3±19.3, P=0.020). The changes from baseline of WOMAC pain subscale at Day 14 were similar between the two groups (LB versus lidocaine,-32.2±11.7 versus-29.4±11.3, P=0.073). With substitution of LB for lidocaine, patient might reported reduced incidence of AEs, mainly derived from the superiority in Week 1. The substitution of LB for lidocaine was safe in different scenarios of IATs and future randomized clinical trials were warranted by the current study.

Is Platelet-rich Plasma Effective in Treating Achilles Tendinopathy? A Meta-analysis of Randomized Clinical Trials.

Several meta-analyses have evaluated the use of platelet-rich plasma (PRP) in the treatment of Achilles tendinopathy. Although they generally did not find PRP to be effective, an updated meta-analysis containing all the available, high-quality randomized trial evidence that addresses the methodological shortcomings identified in earlier meta-analyses needs to be performed. This systematic review and meta-analysis aimed to evaluate the efficacy of PRP in improving (1) pain and function as assessed using the Victorian Institute of Sports Assessment-Achilles (VISA-A) score 3 months, 6 months, and 1 year after treatment and (2) VAS pain scores 3 months after treatment in patients with chronic Achilles tendinopathy. We conducted a systematic search of PubMed, Scopus, Embase, and Cochrane CENTRAL from their inception until June 2024, focusing on randomized clinical trials (RCTs) comparing PRP with placebo or other treatments for Achilles tendinopathy. Our search identified 1289 studies, of which 1262 were excluded after removing duplicates and screening titles and abstracts, leaving 27 studies for detailed review. Six RCTs met the inclusion criteria, encompassing 422 patients, with a predominance of participants who were men. Publication bias was suggested by funnel plot asymmetry, which suggested that, if anything, the results may have overstated the apparent benefit of PRP treatment. Risk of bias was evaluated using the Cochrane Risk of Bias tool for randomized trials, revealing an overall low or unclear risk of bias. The primary outcomes were pain relief and functional improvement, assessed using the VAS, scored 0 to 10, with higher scores representing more severe pain, and VISA-A score, scored 0 to 100, with higher scores representing better pain and function. Heterogeneity was assessed using the Cochran Q test and I2 statistics, and a random-effects model was applied due to substantial heterogeneity. Statistical analyses were performed using Review Manager 5.4 and RStudio, version 764. We found no benefit in terms of VISA-A scores favoring PRP over placebo at 3 months (mean difference 1.7 [95% confidence interval (CI) -1.8 to 5.2]; p = 0.34), 6 months (mean difference 0.5 [95% CI [-8.5 to 9.3]; p = 0.92), or 1 year (mean difference -7.9 [95% CI -27.3 to 11.6]; p = 0.43). PRP did not improve VAS pain scores at 3 months (mean difference -0.22 [95% CI -0.56 to 0.12]; p = 0.21). Sensitivity analyses confirmed these findings. PRP showed no difference compared with stromal vascular fraction and was less effective in the short term compared with high-volume injection. Until future high-quality RCTs show a clear clinical benefit, PRP should not be used to treat Achilles tendinopathy. Our analysis found that PRP does not improve pain or function compared with placebo, and potential publication bias suggests that the apparent benefits may be inflated. Surgeons should be cautious when considering PRP for this condition, and future research should focus on larger trials with standardized protocols to provide more definitive guidance. Level II, therapeutic study.

Comparisons of Intravesical Treatments with Mitomycin C, Gemcitabine, and Docetaxel for Recurrence and Progression of Non-Muscle Invasive Bladder Cancer: Updated Systematic Review and Meta-Analysis.

Background: Non-muscle-invasive bladder cancer (NMIBC) comprises about 75% of all bladder cancers. Although NMIBC is treatable, it poses significant costs and burdens to patients due to high recurrence rates. We conducted an updated meta-analysis of studies that evaluated the efficacy of and outcomes after treatment with mitomycin C (MMC), gemcitabine (GEM), and docetaxel (DOCE) for NMIBC recurrence and progression. Methods: We searched the PubMed and Cochrane databases for observational cohort studies and randomized clinical trials (RCT) conducted between 2009 and 2022 that assessed the efficacy of GEM, DOCE, or MMC, alone or in combination, regarding NMIBC outcomes. A total of 49 studies that met the inclusion criteria were reviewed for their quality, sample size, outcomes, and potential for bias, and relevant data were extracted for the meta-analysis. Separate meta-analyses were performed to assess the risks of recurrence or progression when comparing GEM/DOCE or MMC vs. other treatments. Study heterogeneity was assessed by I2 statistics. Results: Among 31 studies comparing GEM or MMC to other treatments for NMIBC recurrence, there were statistically significant risk reductions of 24% for GEM (pooled relative risk (RR) of 0.76; 95% confidence interval (CI) 0.64-0.87) and 37% for MMC (pooled RR = 0.63; 95% CI 0.58-0.68). Recurrence-free survival (RFS) for GEM or MMC alone was 69.5% (95% CI 66.6-72.3%) and 67.2% (95% CI 66.2-68.2%), respectively. Studies assessing the combination of treatments had a pooled RFS of 44.6% (95% CI 40.4-48.7%). Fewer studies examined the risk of NMIBC progression, with large variability and inconclusive results across them. Conclusions: Our findings corroborate recent guidelines indicating that both GEM and MMC are effective treatments that reduce tumor recurrence and improve survival of NMIBC, although with large variability across the studies. Fewer studies evaluated DOCE treatment, with inconclusive results. Women and minorities were generally underrepresented, raising concerns about the generalizability of the findings and highlighting the importance of including a broader patient population in future RCTs.

Endpoint Selection in Randomized Clinical Trials for Hypertrophic Cardiomyopathy.

Randomized clinical trials (RCTs) for hypertrophic cardiomyopathy (HCM) have long been challenging caused by the condition's rarity, low event rates, and diverse clinical presentations. However, recent advances in targeted therapies have sparked increased interest in HCM research. Despite this, designing effective RCTs remains complex, particularly in identifying clinically meaningful endpoints. HCM, often linked to sequence variation in sarcomeric protein genes like MYH7 and MYBPC3, exhibits varied phenotypic expressions that influence disease progression and treatment responses. This genetic variability underscores the need for personalized approaches in clinical trials. Emerging gene therapies, such as CRISPR/Cas9, show promise in addressing these genetic factors. A major challenge in HCM RCTs is ensuring that endpoints are both statistically and clinically significant, given issues like test-retest variability and missing data. Primary endpoints often focus on symptom relief and functional improvement, while secondary and exploratory endpoints provide broader insights into treatment effects. Regulatory authorities are increasingly open to a wider range of endpoints, including patient-reported outcomes and functional measures, although the cost-risk balance is crucial, especially for high-risk interventions. Future HCM RCTs may incorporate hard clinical endpoints such as heart failure hospitalization, atrial fibrillation recurrence, and all-cause mortality, offering a more comprehensive evaluation of treatment efficacy. Integrating genetic insights and advanced technologies will be essential to improving trial design and enhancing patient outcomes in HCM.

The goal-oriented collaborative approach with postural management strategies intervention via telehealth for children with non-ambulant cerebral palsy: Feasibility randomized clinical trial protocol

IntroductionChildren with non-ambulant Cerebral Palsy (CP), have limitations in terms of self-mobility and require the use of assistive technology with extensive adaptations. However, purchasing assistive technology equipment is expensive and difficult to access in low- and middle-income countries, like Brazil. Guidelines recommend a postural management program to children with CP and emphasize the need for high doses of practice to achieve functional goals. Furthermore, collaborative practices are recommended, with active parental participation in the intervention. AimsThis study describes a protocol for assessing the feasibility of a future randomized clinical trial using a goal-oriented collaborative approach with postural management strategies via telehealth for non-ambulant children with CP. MethodsEighteen children (1–5 years) with CP and their families will be randomized into two groups for 12 weeks: (A) goal-oriented collaborative approach with postural management strategies intervention via telehealth associated with conventional physical therapy or (B) conventional physical therapy. Feasibility measures will be verified, and outcomes will include parents' perceptions of performance and satisfaction, gross motor function, postural control, goal achievement and participation at home, preschool, and community. ImplicationsThe findings will inform the planning and preparation of a future randomized clinical trial of interventions for non-ambulant CP children via telehealth.

Non-invasive imaging to guide percutaneous coronary revascularization in chronic total occlusion: a systematic review and meta-analysis

Abstract Background and aims Whether recanalization of coronary chronic total occlusions (CTO) leads to improved patient outcomes is uncertain. We set out to investigate the use of noninvasive imaging modalities to guide patient selection for percutaneous recanalization of coronary chronic total occlusions (CTO-PCI) and its association with outcomes. Methods Systematic review and meta-analysis of studies involving patients undergoing CTO-PCI to detail use of preprocedural non-invasive imaging, change in clinical endpoints and the occurrence of clinical events in these patient cohorts. PubMed and Embase, the Cochrane Database of Systematic Reviews, the PROSPERO database and the Clinical Trials Registry were searched for relevant randomized and observational studies up to May 2023. This study is registered with PROSPERO. The study primary endpoint was a composite of all-cause death and nonfatal myocardial infarction (MI), with a secondary composite endpoint of cardiovascular death, nonfatal MI and target vessel revascularization (TVR). Additional endpoints were individual components of the composite endpoints along with changes in angina burden, LV ejection fraction, ischemic burden, and infarct extent after PCI. Results Of 1264 publications retrieved, 31 studies (26 observational and 5 randomized) were finally included for a total of 7260 patients. Guidance to CTO-PCI varied greatly among included studies, with only a minority implementing routine preprocedural inducible ischemia and myocardial viability assessment. At a median of 3.1 years (range 1-5 years), the primary endpoint occurred at a rate of 3.1 events per 100 patient-years (95%CI: 2.4-3.7). When non-invasive imaging was used to guide CTO-PCI, patients with myocardial ischemia and/or viability, a reduced risk for the primary endpoint was observed (OR 0.3 95%CI 0.2-0.5) compared to CTO-PCI without evidence of myocardial ischemia and/or viability. CTO-PCI was associated with improvements in SAQ summary score, LVEF, reduction of ischemic burden, improvement in myocardial perfusion (all P-values &amp;lt; 0.01), with no change in the burden of myocardial scarring. At meta-regression analysis, a greater improvement in LVEF was observed in studies enrolling patients with lower average baseline LVEF (≤ 45%) (R2 = 63%, p &amp;lt; 0.0001). Conclusions CTO-PCI led to a significant improvement in symptom status (reduction of chest pain) and LV ejection fraction. CTO-PCI guided by the presence of ischemia and/or viability was associated with improved patient outcomes compared with CTO-PCI in the absence of ischemia and/viability, or in patients where non-invasive imaging testing was not performed. Future randomized clinical trials testing whether ischemia and viability-guided CTO-PCI improves clinical outcomes are lacking and warranted.PRISMA Flow diagramGraphical abstract

Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients (PRoFLUID)-study protocol for an international multicenter observational cohort study.

The practice of intravenous fluid and vasopressor therapy in intensive care unit (ICU) patients, particularly in those who receive invasive ventilation, has been subject to change. Traditional approaches of 'early and liberal fluid administration' and 'late and restrictive vasopressor use' have been challenged, leading to recommendations for giving less fluids and earlier administration of vasopressors. Recommendations for fluid deresuscitation-active fluid removal-are absent. The global approach to fluid and vasopressor therapy in invasively ventilated patients is currently unclear. Our aim is to explore the practice of intravenous fluid and vasopressor therapy in invasively ventilated ICU patients in a study named 'Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients' (PRoFLUID). PRoFLUID is an international, multicenter, observational cohort study in critically ill adult patients that are invasively ventilated for more than 24 hours. The outcomes include various aspects of fluid and vasopressor therapy, urine output and cumulative fluid balances. We will also collect duration of ventilation, lengths of stay and mortality in ICU and hospital. We expect to collect granular data on fluid and vasopressor therapy in a sample of at least 2,500 patients. PRoFLUID will provide useful insights into the practice of fluid and vasopressor therapy in invasively ventilated critically ill patients. PRoFLUID also allows us to determine whether geo-economic differences in management of intravenous fluid and vasopressor therapy exist, and allows for analyses of associations of aspects of fluid and vasopressor therapy with outcomes. Last but not least, its findings could feed sample size calculations of future randomized clinical trials of fluid and vasopressor therapy. In conclusion, PRoFLUID will collect data on fluid and vasopressor therapy in invasively ventilated ICU patients worldwide, providing insights that will guide future clinical decisions and randomized trial designs. ClinicalTrials.gov NCT05968066. Registered on August 1, 2023. Intensive care; invasive ventilation; fluid therapy; fluid management; vasopressor.

Efetividade e segurança do uso do ar ambiente em comparação ao oxigênio a 100% em prematuros em parada cardiorrespiratória: protocolo de revisão sistemática

Introduction: Cardiorespiratory arrest is a clinical situation characterized by the interruption of blood circulation. It is estimated that 11.1% of all live births in the world are premature, generating short and long-term repercussions. One of the main challenges during cardiacarrest in premature infants is providing sufficient, but not excessive, oxygen during assisted ventilation. Objective: To compare the effectiveness and safety of using room air in relation to 100% oxygen in the resuscitation of premature infants in cardiorespiratory arrest. Methods: To this end, we will carry out a systematic review of randomized clinical trials (RCTs). The study protocol was registered on the Prospero Platform (CRD42024519724). We will include preterm infants with gestational age &lt;37 weeks with CA. The searches were carried out in the following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) via Pubmed, Excerpta Médica dataBASE (Embase) via Elsevier, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, Latin American Literature and the Caribbean Doctor in Health Sciences (LILACS) through the Virtual Health Library Portal, without restrictions on language or year of publication. The selection of studies, transmission of data, assessment of the bias of included studies and assessment of the certainty of the evidence will be carried out by two independent investigators. Expected results: Clarify the transit and safety of using room air compared to 100% oxygen, provide useful information for clinical decision-making, and support future high-quality randomized clinical trials on the topic. Conclusion: This study aims to compile existing research to analyze the effectiveness and safety of application of 100% oxygen in the resuscitation of premature infants. Keywords: Heart arrest; infant premature; systematic review.

Understanding and enhancing post-stroke recovery: Insights from a nested qualitative study within the MindFit Project randomized clinical trial

BackgroundStroke survivors experience a wide range of physical, cognitive, and emotional challenges. In the MindFit Project, a randomized clinical trial, 141 chronic stroke patients were divided into three groups: mindfulness-based stress reduction (MBSR) with computerized cognitive training (CCT), physical exercise (PE) with CCT, and CCT alone. The interventions were conducted remotely over 12 weeks, including online group and individual sessions. ObjectiveThis exploratory nested qualitative study aimed to investigate chronic stroke survivors’ experiences, opinions, and perceived changes due to the interventions within the MindFit Project. The secondary objective was to describe the broader experience of their recovery journey. MethodsTwenty-seven participants were recruited through purposive sampling and engaged in semi-structured one-on-one interviews. Twelve received MBSR+CCT, nine received PE+CCT, and six received CCT-only. The interviews were recorded, transcribed, and analyzed using thematic analysis. ResultsParticipants shared insights into their lives after stroke, including emotional and physical challenges, coping mechanisms, and the impact of societal perceptions. The interventions were generally positively valued, with MBSR aiding in emotional regulation, PE enhancing physical capabilities, and CCT improving cognition. The group setting provided valuable peer support and motivation, although some participants noted challenges owing to the heterogeneity. The telematic format was also appreciated for its accessibility, although it posed challenges to personal interaction and intervention supervision. ConclusionsOur study emphasizes the complexity of stroke recovery and the importance of holistic, patient-centered rehabilitation approaches. It also highlights the value of combining physical and non-physical interventions in a group setting, along with the potential of remote platforms to enhance the accessibility of rehabilitation programs. These findings generate hypotheses for future randomized clinical trials aimed at improving post-stroke recovery.

Metronomic chemotherapy for paediatric extracranial solid tumours: a systematic review and meta-analysis of randomised clinical trials

BackgroundMetronomic chemotherapy (‘less is more, regularly’) could be an alternative to the maximum tolerated dose (‘the more, the better’) in the chemotherapeutic cancer treatment of high-risk malignant solid extracranial tumours...

Effect of powered circular stapler in colorectal anastomosis after left-sided colic resection: systematic review and meta-analysis

PurposeAnastomotic leak (AL) remains the most important complication after left-sided colic anastomoses and technical complications during anastomotic construction are responsible of higher leakage incidence. Powered circular stapler (PCS) in colorectal surgery has been introduced in order to reduce technical errors and post-operative complications due to the manual circular stapler (MCS).MethodsA systematic review and meta-analysis were performed. An electronic systematic search was performed using Web of Science, PubMed, and Embase of studies comparing PCS and MCS. The incidence of AL, anastomotic bleeding (AB), conversion, and reoperation were assessed. PROSPERO Registration Number: CRD42024512644.ResultsFive observational studies were eligible for inclusion reporting on 2379 patients. The estimated pooled Risk Ratios for AL and AB rates following PCS were significantly lower than those observed with MCS (0.44 and 0.23, respectively; both with p < 0.01). Conversion and reoperation rate did not show any significant difference: 0.41 (95% CI 0.09–1.88; p = 0.25) and 0.78 (95% CI 0.33–1.84; p = 0.57); respectively.ConclusionThe use of PCS demonstrates a lower incidence of AL and AB compared to MCS but does not exhibit a discernible influence on reintervention or conversion rates. The call for future randomized clinical trials aims to definitively clarify these issues and contribute to further advancements in refining surgical strategies for left-sided colonic resection.

Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) in Urogynecological Surgery: A Systematic Review.

Background: Minimally invasive surgery could improve cosmetic outcomes and reduce the risks of surgical injury with less postoperative pain and a quicker patient's discharge. Recently, transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has been introduced in urogynecology with exciting results. Evidence Acquisition: After PROSPERO registration (n°CRD42023406815), we performed a comprehensive literature search on Pubmed, Embase, and Cochrane CENTRAL, including peer-reviewed studies evaluating transvaginal natural orifice transluminal endoscopic surgery. No limits on time or type of study were applied. Evidence synthesis: Overall, 12 manuscripts were included in the analysis. Seven studies evaluated uterosacral ligament suspension, four studies evaluated sacral colpopexy, three evaluated sacrospinous ligament suspension, and one study evaluated lateral suspension. Overall success rates were high (>90%); however, definitions of success were heterogeneous. In terms of complication, most of the studies reported low-grade complications (Clavien-Dindo I and II); only two patients needed mesh removal because of mesh exposure. The risk of bias of the trials was rated in the medium to high-risk category. Conclusions: The present review highlights important initial results for vNOTES. Future randomized clinical trials are needed to better define its role in the management of urogynecological procedures.

An Overview of Possible Beneficial Effects of Black Seeds (Nigella Sativa) on the Management of "Disease X".

A mystery pathogen that has not yet infected the entire world's population is predicted to be the cause of Disease X, which will be contagious. According to WHO scientists, 50 million people are expected to die from Disease X, which would be 20 times deadlier than coronavirus disease 2019 (COVID-19). Many international initiatives are currently in motion to get ready for future pandemics. These include updating the International Health Regulation and the European Legislation, establishing the Health Emergency Preparedness and Response Authority (HERA), establishing international hubs, taking on the international challenge of developing a vaccine for Disease X within 100 days of recognition of emerging Pathogen X, and updating the prepared-ness plan of National Institute of Allergy and Infectious Diseases. Our current review's main objective is to determine whether black seeds (Nigella sativa) can manage Disease X. It has been established by several studies that black seeds (N. sativa) have antiviral, antibacterial, antimicro-bial, immunomodulatory, anti-inflammatory, and antioxidant properties, which would be useful in the management of Disease X. Black seeds (N. sativa) may be utilized in conjunction with supportive care and symptomatic therapy to manage Disease X in early phases. Future random-ized controlled clinical trials would further evaluate the safety and effectiveness of black seeds (N. sativa) in patients with Disease X.

The effect of consuming nuts on cognitive function: a systematic review and meta-analysis of randomized clinical trials.

Results from clinical trials investigating the effect of nuts consumption on cognition are conflicting. We decided to conduct the current meta-analysis to summarize all available evidence on the effect of consuming nuts on cognition scores. We conducted a comprehensive search in the online databases using relevant keywords up to June 2024. We included all the published Randomized clinical trials (RCTs) investigating the effect of nuts, compared to control, on cognition scores. Overall, 5 trials were included with a total sample size of 928 adults. Based on 6 effect sizes from these 5 trials, we did not find a significant effect of nuts on cognition function [Standardized Mean Difference (SMD): 0.27, 95% CI: -0.65 to 1.19, p = 0.57]. Our review could not find a significant effect of nuts on cognition function. Future high-quality RCTs with larger sample sizes should be conducted to shed light on the impact of nuts on cognition.

Optimal Pair Matching Combined with Machine Learning Predicts a Significant Reduction in Myocardial Infarction Risk in African Americans Following Omega-3 Fatty Acid Supplementation.

Conflicting clinical trial results on omega-3 highly unsaturated fatty acids (n-3 HUFA) have prompted uncertainty about their cardioprotective effects. While the VITAL trial found no overall cardiovascular benefit from n-3 HUFA supplementation, its substantial African American (AfAm) enrollment provided a unique opportunity to explore racial differences in response to n-3 HUFA supplementation. The current observational study aimed to simulate randomized clinical trial (RCT) conditions by matching 3766 AfAm and 15,553 non-Hispanic White (NHW) individuals from the VITAL trial utilizing propensity score matching to address the limitations related to differences in confounding variables between the two groups. Within matched groups (3766 AfAm and 3766 NHW), n-3 HUFA supplementation's impact on myocardial infarction (MI), stroke, and cardiovascular disease (CVD) mortality was assessed. A weighted decision tree analysis revealed belonging to the n-3 supplementation group as the most significant predictor of MI among AfAm but not NHW. Further logistic regression using the LASSO method and bootstrap estimation of standard errors indicated n-3 supplementation significantly lowered MI risk in AfAm (OR 0.17, 95% CI [0.048, 0.60]), with no such effect in NHW. This study underscores the critical need for future RCT to explore racial disparities in MI risk associated with n-3 HUFA supplementation and highlights potential causal differences between supplementation health outcomes in AfAm versus NHW populations.