International Clinical Trials Research Articles

Natural Language Processing to Adjudicate Heart Failure Hospitalizations in Global Clinical Trials.

Background: Medical record review by a physician clinical events committee is the gold standard for identifying cardiovascular outcomes in clinical trials, but is labor-intensive and poorly reproducible. Automated outcome adjudication by artificial intelligence (AI) could enable larger and less expensive clinical trials, but has not been validated in global studies. Methods: We developed a novel model for automated AI-based heart failure adjudication ("HF-NLP") using hospitalizations from three international clinical outcomes trials. This model was tested on potential heart failure hospitalizations from the DELIVER trial, a cardiovascular outcomes trial comparing dapagliflozin with placebo in 6063 patients with heart failure with mildly reduced or preserved ejection fraction. AI-based adjudications were compared with adjudications from a clinical events committee that followed FDA-based criteria. Results: AI-based adjudication agreed with the clinical events committee in 83% of events. A strategy of human review for events that the AI model deemed uncertain (16%) would have achieved 91% agreement with the clinical events committee while reducing adjudication workload by 84%. The estimated effect of dapagliflozin on heart failure hospitalization was nearly identical with AI-based adjudication (hazard ratio 0.76 [95% CI 0.66-0.88]) compared to clinical events committee adjudication (hazard ratio 0.77 [95% CI 0.67-0.89]). The AI model extracted symptoms, signs, and treatments of heart failure from each medical record in tabular format and quoted sentences documenting them. Conclusions: AI-based adjudication of clinical outcomes has the potential to improve the efficiency of global clinical trials while preserving accuracy and interpretability.

Hyaluronidase for reducing perineal trauma.

Perineal trauma after vaginal birth is common and can be associated with short- and long-term health problems. Perineal hyaluronidase (HAase) injection has been widely used to reduce perineal trauma, perineal pain and the need for episiotomy since the 1950s. The administration of HAase is considered to be a simple, low risk, low cost and effective way to decrease perineal trauma without causing adverse effects. To assess the effectiveness and safety of perineal HAase injection for reducing perineal trauma, episiotomy and perineal pain during vaginal delivery. To identify studies for inclusion in this review, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, CINAHL (EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) in November 2023. Randomised and quasi-randomised controlled trials comparing women giving birth to their first baby receiving perineal HAase injection compared to placebo injection or no intervention during vaginal delivery of a single foetus with vertex foetal presentation (foetus with head engaging the maternal pelvis). We used standard methodological procedures expected by Cochrane. Two review authors independently assessed trials for inclusion, extracted and checked data, and evaluated the risk of bias in the studies. Our primary outcomes were perineal trauma (tears or episiotomy, or both), episiotomy and perineal pain. Our secondary outcomes were first and second degree perineal lacerations, third and fourth degree perineal lacerations, perineal oedema 1 hour after vaginal delivery, perineal oedema 24 hours after vaginal delivery and neonatal Apgar scores of less than 7 at five minutes after birth (Apgar score is a measure of the health status of a newborn). We assessed the certainty of the evidence using the GRADE approach. We included five randomised controlled trials involving a total of 747 women (data were available for 743 women). The dosage of HAase used in the perineal injection varied from 750 turbidity-reducing units to 5000 international units. The certainty of the evidence was largely low (ranging from very low to moderate). Perineal HAase injection versus placebo injection Data from three trials involving 426 women provided low-certainty evidence that there may be no difference between the HAase and placebo groups in the incidence of perineal trauma (tears or episiotomy, or both) (RR 0.94, 95% CI 0.87 to 1.03; 426 participants, 3 studies), episiotomy (RR 0.91, 95% CI 0.71 to 1.15; 427 participants, 3 studies), first and second degree perineal lacerations (RR 1.02, 95% CI 0.87 to 1.18; 341 participants, 3 studies), third and fourth degree perineal lacerations (RR 0.46, 95% CI 0.11 to 2.05; 426 participants, 3 studies), and perineal oedema one hour after vaginal delivery (RR 0.99, 95% CI 0.78 to 1.25; 303 participants, 2 studies). Moreover, perineal HAase injection during the second stage of labour likely resulted in a reduction in incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection (RR 0.42, 95% CI 0.26 to 0.70; 303 participants, 2 studies; moderate-certainty evidence). There may be no difference between groups in Apgar scores less than 7 at five minutes (RR 5.00, 95% CI 0.24 to 105.95; 148 participants, 1 study; low-certainty evidence). Perineal HAase injection versus no intervention Data from three trials involving 373 women suggested that perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) (RR 0.61, 95% CI 0.42 to 0.88; 373 participants, 3 studies; low-certainty evidence) compared with no intervention. The evidence is very uncertain for episiotomy (RR 0.79, 95% CI 0.44 to 1.42; 373 participants, 3 studies), first and second degree perineal lacerations (RR 0.59, 95% CI 0.30 to 1.18; 373 participants, 3 studies) and perineal oedema one hour after vaginal delivery (RR 0.32, 95% CI 0.01 to 7.71; 139 participants, 1 study), all very low certainty evidence. No third and fourth degree perineal lacerations, perineal oedema 24 hours after vaginal delivery or Apgar scores less than 7 at five minutes were reported in these three trials. No side effects were reported in the included trials. Perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) compared with no intervention, but not compared with placebo injection, in women having a vaginal delivery. Meanwhile, perineal HAase injection likely reduces the incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection. The potential use of perineal HAase injection as a method to reduce perineal trauma and perineal oedema remains to be determined as the number of high-quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries, including evaluating whether there is any differential effect based on the dose, frequency and positioning of HAase injection.

Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes. We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and The International Clinical Trials Registry Platform for randomized controlled trials of drug therapy in comatose survivors of cardiac arrest (last searched 20th October 2024). The primary outcome was mortality at 30 days / hospital discharge. Other outcomes reflected those of the Core Outcome Set for Cardiac Arrest. Risk of bias was assessed using Cochrane Risk-Of-Bias Version 1. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed. From 2,562 records, 207 full texts were screened and 45 studies (5,800 patients) investigating 30 therapies were included. Studies were grouped thematically as supportive drug therapies (n = 10), neuroprotective agents (n = 19), and anti-inflammatory / antioxidants (n = 16). Four studies reported reduced mortality at 30 days / hospital discharge: one of the anticholinergic penehyclidine hydrochloride, two of intra-arrest vasopressin and methylprednisolone plus hydrocortisone for post resuscitation shock, and one of the traditional Chinese medicine, shenfu. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed. We could not detect an effect on mortality with steroids (n = 739, risk ratio (RR), 0.93; 95 % CI 0.83-1.04, p = 0.21; I2 = 60 %, low certainty), coenzyme Q10 (n = 107, RR, 0.91; 95 % CI 0.61-1.37, p = 0.65; I2 = 0 %, low certainty), or thiamine (n = 149, RR, 1.11; 95 % CI 0.88-1.40, p = 0.39; I2 = 0 %, very low certainty). In comatose survivors of cardiac arrest, the majority of trials of drug therapy reported no effect on mortality. Meta-analyses of steroids, coenzyme Q10 and thiamine demonstrated no evidence of an effect on mortality. However, the low certainty of evidence warrants further research.

Efficacy of Interventions Intended to Increase Lung Cancer Screening Rates: A Systematic Review and Meta-analysis.

Few eligible patients in the United States participate in lung cancer screening (LCS) with low-dose computed tomography (LDCT). What is the efficacy of interventions to increase LCS participation? We performed a systematic review following a prespecified protocol registered in PROSPERO (CRD42021283984). In June/July of 2021, we searched Ovid MEDLINE, Embase, Cochrane, CENTRAL, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Epistemonikos from 1946 to October 2021 to identify studies evaluating interventions to increase LCS participation. Thirteen of 2761 studies met inclusion criteria for data extraction. Of these, six had results available (five RCTs and one prospective observational study). The studies had predominantly White and non-Hispanic participants. An intention-to-treat analysis was used to calculate each study's relative risk (RR) to increase LCS. Effect sizes were pooled using a random-effects model with a subgroup analysis for multi- versus single-step interventions. Risk of bias was evaluated with the revised Cochrane risk-of-bias tool (RoB 2) and risk of bias in non-randomized studies of interventions (ROBINS-I). Overall, the proportion of screening LDCTs performed did not improve in the intervention group relative to the comparator group (RR [95% CI] of 1.30 [0.74, 2.29]), and meta-analysis indicated high heterogeneity of studies (I2 = 91%). Subgroup analysis suggests that interventions targeting multiple barriers may increase LCS participation (RR [95% CI] for multistep vs single-step; 2.68 [1.77, 4.05] vs 0.99 [0.89, 1.10], P < 0.01). Quality assessment revealed that three of five RCTs showed some concerns or high risk of bias. Evidence on efficacy of interventions to increase LCS participation is limited due to a small number of prospective studies performed in non-diverse populations with critical risk of bias. Further, overall, studied interventions did not improve lung cancer screening participation, though interventions targeting multiple barriers may have some benefit.

Clinical Trials in Nail Psoriasis: Cross-Sectional Analysis of the Current State of Research

Introduction: Nail involvement occurs in approximately 90% of patients with cutaneous psoriasis and in isolation in 5%-10% of patients. There is an unmet need for diagnostic and therapeutic algorithms for nail psoriasis (NP), partially due to limited number of clinical trials. Methods: The ClinicalTrials.gov, the EU, the Australian New Zealand, and the World Health Organization International Clinical Trials Registries were queried for the term “nail psoriasis”. Trial data characteristics were collected and analyzed. Results: One-hundred-twelve clinical trials were included, with mean trial length 46.7 weeks, and mean number of participants 272.7. Medications were most often studied in 97 (86.6%) trials, followed by lasers in 7 (6.3%) trials. NP Severity Index score was the most often studied outcome measure in 91 (84.3%) trials, and only 56 (52.8%) trials assessed adverse events. Only 3 (2.83%) trials included children, and many clinical trials excluded patients ages 65+ and 85+. Results were posted for 46 (41.4%) trials with mean participant age 45.1 years, mean percentage of females of 38.3%, and 87.8% of participants being White. Conclusion: Our findings highlight a need for clinical trials assessing efficacy and long-term therapeutic safety with a broad range of age groups and increased representation of minorities and female patients.

Interventions for Aboriginal and Torres Strait Islander people with type 2 diabetes that modify its management and cardiometabolic risk factors: asystematic review.

To review studies of interventions for reducing the impact of type 2 diabetes in Aboriginal and Torres Strait Islander people. The primary aim was to review and summarise the characteristics and findings of the interventions. The secondary aims were to assess their effects on diabetes and cardiometabolic risk factors, and the proportions of people with type 2 diabetes who achieved therapeutic targets with each intervention. We searched eight electronic databases for publications of studies including Aboriginal or Torres Strait Islander people aged 15 years or older with diagnoses of type 2 diabetes, describing one or more diabetes interventions, and published in English during 1 January 2000 - 31 December 2020. Reference lists in the assessed articles were checked for further relevant publications. MEDLINE (Ovid), Web of Science (Clarivate), the Cochrane Library, Global Health (EBSCO), Indigenous Collection and Indigenous Australia (Informit), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP). The database searches yielded 1424 unique records; after screening by title and abstract, the full text of 55 potentially relevant articles were screened, of which seventeen met our eligibility criteria: eleven cohort studies (seven retrospective audits and four prospective studies), three randomised controlled trials, and three observational, non-randomised follow-up studies. Twelve publications reported site-based (Aboriginal or Torres Strait Islander health service or diabetes clinic) rather than individual-based diabetes interventions. Interventions with statistically significant effects on mean glycated haemoglobin (HbA1c) levels were laparoscopic adjustable gastric banding, a 5-day diabetes self-management camp, treatment of Strongyloides stercoralis infections, community-based health worker-led management, point-of-care testing, and self-management approaches. Few interventions for Aboriginal and Torres Strait Islander people with type 2 diabetes have been reported in peer-reviewed publications. Improving diabetes care services resulted in larger proportions of people achieving therapeutic HbA1c targets. Outcomes were better when Aboriginal and Torres Strait Islander communities were involved at all levels of an intervention. High quality studies of holistic, culturally safe and accessible interventions should be the focus of research.

Acupuncture for uremic pruritus: A systematic review and meta-analysis protocol.

Uremic pruritus (UP) or chronic kidney disease-associated pruritus (CKD-aP) is one of the most intractable dermatologic symptom in patients with chronic kidney disease. Several randomized controlled trials (RCTs) have been conducted to investigate the antipruritic effects of acupuncture on UP/CKD-aP and suggested a significant therapeutic effect, while the evidence supporting the application of acupuncture is limited. This study will assess the efficacy and safety of acupuncture for patients with UP/CKD-aP. Data Sources: RCTs will be searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Database, VIP Database, the WHO International Clinical Trials Registry Platform portal and www.ClinicalTrials.gov from inception to 31st August 2024. Study eligibility criteria: RCTs in English and Chinese conducted on UP/CKD-aP patients will be included. Participants: Adult patients diagnosed with UP/CKD-aP will be included. Interventions: All acupuncture interventions in the management of UP/CKD-aP will be included, compared with no treatment, placebo or sham acupuncture, or other treatment agents. Outcome measures: The primary outcome will be the change in the severity of itching evaluated by validated scales. Study appraisal and svnthesis methods: If necessary, a meta-analysis will be performed for the pooled therapeutic effect by Review Manager 5.3, or a qualitative descriptive analysis will be presented. The data will be transformed into the risk ratio (RR) for binary data and the mean difference (MD) or standardized MD for continuous data for analysis. This review will update evidence of RCTs evaluating acupuncture for UP/CKD-aP. Anticipated challenges contain the methodological and clinical heterogeneity in terms of evaluation tools and acupuncture interventions within included studies. It will benefit patients and impact health-care decision-making regarding the models of care that are feasible for patients. PROSPERO CRD42021257001.

Pigtail Catheter Compared to Formal Intercostal Catheter for the Management of Isolated Traumatic Pneumothorax: A Systematic Review and Meta-Analysis

(1) Background: The optimal management approach for adults with traumatic pneumothorax without haemothorax remains an area of debate. Specifically, there is lack of consensus as to whether insertion of a pigtail catheter is superior to a formal intercostal catheter in improving complication rates. (2) Methods: Medline, EMBASE, Cochrane Central, and the World Health Organisation International Clinical Trials Registry Platform databases were systematically searched for studies evaluating pigtail catheters compared to formal intercostal catheters for the management of traumatic pneumothorax. Investigative outcomes of interest included pain, duration management, failure, need for formal thoracoscopic surgery, need for supplemental oxygen, length of stay, infection and overall total complications. (3) Results: Three studies evaluating 280 patients were included in this analysis. There was no significant difference in total complications, rates of failure, length of stay or duration of management between pigtail catheters and formal intercostal catheters. This evidence was based on studies of low to moderate risk of bias with poor control for confounding factors. (4) Conclusions: This systematic review and meta-analysis demonstrates lack of evidence to suggest pigtail catheters are superior to formal intercostal catheter for traumatic pneumothorax. These findings may reflect a true absence of effect between either approach for this patient cohort or non-committal findings in light of limitations of the underlying evidence. Further prospective trials with larger sample sizes and control for confounders are required to validate the outcomes between these two modalities of treatment.

Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial.

The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited. This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors. We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR). We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120-188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%-8.9%) for ciprofloxacin, 0.3% (IQR 0.0%-1.3%) for piperacillin, 0.2% (IQR 0.0%-1.3%) for tazobactam, 12.2% (IQR 6.3%-16.1%) for trimethoprim, 0.4% (IQR 0.2%-3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%-2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01). Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose. NTR8499The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.

Patient and public involvement in the design of an international clinical trial: real world experience

BackgroundThe value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.MethodsA 12-month “accelerator” award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research.ResultsSixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement.ConclusionsIn general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.

Safe and well-tolerated long-term parenteral nutrition regimen: omega-3-fatty-acid-enriched Medium Chained/ Long Chained Triglycerides emulsion.

Background and AimsA limited number of randomized controlled trials (RCTs) have examined the use of lipid emulsions (LEs) of different compositions in home parenteral nutrition (HPN), and there are very few data on the long-term use of omega-3 (n-3) polyunsaturated fatty acids (PUFAs). The study´s objective was to assess safety and tolerability of an n-3 PUFA-enriched LE in adult patients suffering from chronic intestinal failure (CIF) requiring long-term HPN. MethodsIn this prospective, randomized, controlled, double-blind, multicentre, international clinical trial, which was conducted at eleven sites, adult patients in need of HPN including lipids received either the investigational product, an n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) LE, or the reference product, a standard MCT/LCT LE, for an average duration of eight weeks. The primary outcome was the sum of changes of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives included fatty acid pattern in plasma and red blood cells (RBCs) and triene:tetraene ratio in plasma. Results74 patients were enrolled up to premature study termination. Liver function parameters showed no clinically relevant differences between study groups and remained within normal ranges. The n-3 PUFAs EPA and DHA increased in plasma and RBCs in the Lipidem group and were higher in the Lipidem group than the reference group at the end of the study resulting in an increased n-3-index in RBCs with Lipidem. Average n-3-index was >8. The plasma triene:tetraene ratio decreased in both groups. ConclusionThis study is one of the largest comparing two LEs in the complex setting of HPN treatment of adult patients. Although it has been early terminated its results considerably contribute to the evidence on safety and efficacy of longer-term use of LEs in HPN treatment. The n-3 PUFA-enriched LE Lipidem was safe and well-tolerated, particularly in terms of liver function. Lipidem provided an additional supply of n-3 PUFAs and led to positive changes in fatty acid profiles of plasma and RBCs. The n-3-index was in the desirable range at the end of the study in patients receiving Lipidem. There was no evidence of essential fatty acid deficiency with Lipidem. ClinicalTrials.gov IdentifierNCT03282955 Trial RegistrationEudraCT Number: 2015-000849-23

Traditional, complementary and integrative medicine therapies for the treatment of mild/moderate acute COVID-19: protocol for a systematic review and network meta-analysis

BackgroundIncreasing evidence has emerged for traditional, complementary and integrative medicine (TCIM) to treat COVID-19 which requires systematic summaries of the net benefits of interventions against standard care and one another....

Non-surgical treatment for tandem spinal stenosis: a systematic review protocol

BackgroundTandem Spinal Stenosis (TSS) is a disease characterised by the narrowing of the spinal canal in two or more non-adjacent areas of the spine, often affecting both the cervical and lumbar vertebrae. Doctors and patients increasingly favour non-surgical treatments that have the function of relieving symptoms and improving outcomes. This systematic review aims to evaluate the effectiveness and safety of non-surgical therapies for TSS and comprehensively summarise existing evidence.Methods and analysisWe will conduct comprehensive searches, both manual and electronic, of literature published up to 30 September 2024; database searches will commence after the publication of this agreement, with an estimated commencement date of 1 December 2024, and the end date is 31 May 2025, without language restrictions. Key databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, WHO International Clinical Trial Registration Platform, China National Knowledge Infrastructure, China Biomedical Literature Database, China Scientific Journal Database and Wan-Fang Database will be explored. In addition, we will include resources such as library journals and conference abstracts. Following the identification and screening of all randomised controlled trials focusing on non-surgical treatments for TSS, two investigators will perform a meta-analysis of the included studies. The findings will be summarised as the risk ratio for binary data and the standardised or weighted mean difference for continuous data.Ethics and disseminationEthical approval is not required, as the review does not involve individual patient data. The review’s findings will provide clinicians with evidence on using non-surgical treatments for TSS, disseminated through peer-reviewed publications or conferences.PROSPERO registration numberCRD42024496634.

Pain control post total knee replacement in patients given local infiltrative analgesia combined with adductor canal block compared to either modality alone: a systematic review and meta-analysis

ObjectivesOptimising postoperative pain following knee replacement is important for patients, healthcare professionals and healthcare funders. Adductor canal blocks (ACB) are widely used but there is uncertainty about their efficacy when...

Effect of Sodium Hypochlorite Concentration on the Outcome of Full Pulpotomy in Mature Permanent Teeth with Irreversible Pulpitis - A Systematic Review.

To determine the outcome of full pulpotomy in management of mature permanent teeth with irreversible pulpitis when 2.5% versus other concentrations of sodium hypochlorite (NaOCl) were used to achieve haemostasis. Electronic searches were performed in PubMed, Embase, Web of Science, International Clinical Trials Registry Platform, and ClinicalTrials.gov for English language articles until July 2021. Randomised clinical trials and cohort, cross-sectional, and case-control studies where full pulpotomy was performed to manage mature permanent molar teeth with irreversible pulpitis and no periapical radiolucency were included. Newcastle Ottawa Scale and the Cochrane risk of bias tool were used for quality assessment. The success rate for full pulpotomy was documented. The protocol was registered in PROSPERO database (CRD42020177214). Out of 861 studies, four were considered for data analysis. Three studies were single-arm prospective trials on pulpotomy, while one was a randomised control trial comparing pulpotomy and root canal treatment. A combined success rate of 93% from 117 teeth was reported from three studies using 2.5% NaOCl as a haemostatic agent. One study used 5% NaOCl and reported a success rate of 100% (n = 6 teeth). The certainty of evidence substantiated by the GRADE approach was of low quality. Overall quality assessment revealed a considerable risk of bias in three studies. Irrespective of the NaOCl concentration, the success rate of pulpotomy in mature permanent teeth with irreversible pulpitis was high. No study compared the different concentrations of NaOCl as a haemostatic agent. Further, randomised controlled trials are required to investigate the effect of NaOCl concentration for haemostasis on the outcome of pulpotomy.

Median nerve electrical stimulation for restoring consciousness in patients with traumatic brain injury: study protocol for a systematic review and meta-analysis

IntroductionTraumatic brain injury (TBI) is one of the prevalent critical illnesses encountered in clinical practice, often resulting in a spectrum of consciousness disorders among survivors. Prolonged states of impaired consciousness...

Comparison of Implant Placement Accuracy Between Manual, Robot-Assisted, Computer-Navigated, Augmented Reality Navigated, Patient-Specific Instrumentation, and Accelerometer Navigated Total Hip Arthroplasty: A Systematic Review and Network Meta-Analysis.

Malpositioning of the acetabular cup during total hip arthroplasty (THA) can lead to complications. Robotic surgery and navigation techniques aim to address this issue, but there is limited evidence regarding which method can achieve better clinical outcomes. Therefore, this network meta-analysis (NMA) aimed to compare the efficacy of various navigation methods. This NMA of prospective randomized controlled trials compared robot-assisted systems (RAS), computer-assisted navigation systems (CAS), augmented reality-based portable navigation (AR), patient-specific instrumentation (PSI), portable accelerometer-based navigation (PN), and conventional methods (C) for THA procedures. We searched MEDLINE, EMBASE, Cochrane, Central Register of Controlled Trials, International Clinical Trials Platform Search Portal, and ClinicalTrials.gov. databases. The primary outcomes included revision surgery and postoperative clinical scores, and the secondary outcomes encompassed cup placement accuracy, acetabular cup placement outliers from the Lewinnek safe zone, surgical time, and complications. We used a Bayesian random-effects NMA, and confidence of evidence was assessed using confidence in NMA. We identified 45 studies including 2,122 patients. We did not find large differences in revision surgery, clinical outcome scores, cup inclination, or anteversion angle accuracy among the modalities. AR, CAS, and PSI exhibited a lower risk of outliers from safe zones than C. In addition, RAS and CAS had a longer surgical time than C. Robotic and navigation tools did not reduce the revision risk or enhance clinical outcomes. AR, CAS, PSI, and PN may decrease the risk of cup placement outliers in safe zones. However, the cup placement accuracy was equivalent, and the surgical time may be longer in RAS and CAS than in C. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Paraaortic lymph node metastasis in endometrial cancer patients: a comprehensive analysis of rates, survival outcomes, and risk factors through systematic review and meta-analysis.

This study aims to explore the incidence of different metastatic patterns in paraaortic lymph nodes and their corresponding survival outcomes in patients with endometrial cancer, as well as to identify the associated risk factors of such metastasis. PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov were searched from inception to February 10, 2024.The analysis was conducted using R version 4.2.3. A total of 47 studies involving 33,425 endometrial cancer patients were analyzed. Meta-analysis results revealed that the rate of isolated paraaortic lymph node metastasis, where pelvic lymph nodes were negative but paraaortic lymph nodes were positive (PLN-PAN+), was found to be 2.58% (95% CI 0.0195-0.0329). The rates for PLN+PAN- and PLN+PAN+ were notably higher at 8.54% (95% CI 0.0642-0.1092) and 8.37% (95% CI 0.0613-0.1090), respectively. For clinical stage I EC, the occurrence rate was 5.92% for PLN+PAN- (95% CI 0.0258-0.1032), 1.00% for PLN-PAN+ (95% CI 0.0081-0.0120), and 2.99% for PLN+PAN+ (95% CI 0.0188-0.0431). The survival outcomes indicate a decreasing trend from the PLN-PAN+ and PLN+PAN- groups to the PLN+PAN+ group. Additionally, the survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. The analysis indicated that pelvic lymph node metastasis (OR 16.72, 95% CI 10.03-27.86), myometrial invasion ≥50% (OR 5.18, 95% CI 3.09-8.69), lymph-vascular space invasion (LVSI) (OR 3.46, 95% CI 2.49-4.81), cervical invasion (OR 4.00, 95% CI 2.09-7.66), and non-endometrioid cancer (OR 2.39, 95% CI 1.17-4.86) were risk factors for paraaortic lymph node metastasis. Isolated paraaortic lymph node metastasis, though relatively rare, can still occur even in clinical stage I endometrial cancer. The survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. Even in patients with negative pelvic lymph nodes, careful consideration should be given to the possibility of paraaortic lymph node metastasis, especially in those with high-risk factors. https://www.crd.york.ac.uk/prospero/, identifier CRD42024503959.

Impact of selective reporting bias on stroke trials: potential compromise in evidence synthesis - A cross-sectional study

BackgroundAccurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect.MethodsA search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting.ResultsAmong the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38).ConclusionsRegistered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

Efficacy of the ABC Pathway for Integrated Care Across Phenotypes of Patients with Atrial Fibrillation: A Latent-Class Analysis Report from the mAFA-II Clinical Trial

Abstract Background The mAFA-II cluster randomised trial demonstrated the efficacy of a mobile health-technology implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for integrated care management of patients with AF. Objective To evaluate the effect of mAFA intervention across phenotypes of patients with AF. Design We conducted a latent-class analysis (LCA) according to eight variables, including age and comorbidities. Participants The mAFA-II trial enrolled AF patients between June 2018 and August 2019 across 40 centres in China. Main Measures We evaluated the interaction between the groups identified through LCA, and the effect of mAFA intervention on the risk of the primary composite outcome of all-cause death, stroke/thromboembolism, and rehospitalisations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). Key Results Across the 3324 patients included in the trial (mean age 68.5 ± 13.9 years, 38.0% females), we identified three phenotypes: (i) low morbidity phenotype (n = 1234, 37.1%), (ii) hypertensive/coronary artery disease (CAD) phenotype (n = 1534, 46.2%), and (iii) mixed morbidity phenotype (n = 556, 16.7%). The effect of mAFA intervention on the primary outcome appeared greater in the low morbidity phenotype (aHR, 0.08; 95% CI 0.02–0.33) compared to the hypertensive/CAD (aHR, 0.30; 95% CI 0.16–0.58) and the mixed morbidity phenotype (aHR, 0.68; 95% CI 0.37–1.24), with a statistically significant interaction (pint = 0.004). Conclusions In patients with AF, the ABC pathway improved prognosis across different comorbidity phenotypes, although with some differences in the magnitude of risk reduction. Patients with more complex phenotypes require further efforts to improve their outcomes, considering their high baseline risk of adverse events. Trial Registration WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR-OOC-17014138.