Recent Randomized Controlled Trials Research Articles

Substance Use Within Trials of Psychological Interventions for Psychosis: Sample Inclusion, Secondary Measures, and Intervention Effectiveness.

Current clinical guidelines recommend that patients with co-occurring psychosis and alcohol or substance use disorders (A/SUD) receive evidenced-based treatment for both disorders, including psychological intervention for psychosis. However, the efficacy of such treatments for individuals with co-occurring psychosis and A/SUD is unclear. Randomized controlled trials (RCTs) of psychological interventions for psychosis were systematically reviewed, to investigate how alcohol and substance use has been accounted for across sample inclusion and secondary measures. Findings from trials including individuals with co-occurring alcohol or substance use issues were then narratively summarized using the Synthesis Without Meta-Analysis guidelines, to indicate the overall efficacy of psychological interventions for psychosis, for this comorbid population. Across the 131 trials identified, 60.3% of trials excluded individuals with alcohol or substance use issues. Additionally, only 6.1% measured alcohol or substance use at baseline, while only 2.3% measured alcohol or substance use as a secondary outcome. Across trials explicitly including individuals with alcohol or substance use issues, insufficient evidence was available to conclude the efficacy of any individual psychological intervention. However, preliminary findings suggest that psychoeducation (PE) and metacognitive therapy (MCT) may be proposed for further investigation. Overall, co-occurring alcohol and substance use issues have been largely neglected across the recent RCTs of psychological interventions for psychosis; highlighting the challenges of making treatment decisions for these individuals using the current evidence base.

Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's disease: a meta-analysis of randomized controlled trials.

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12weeks. Brexpiprazole at any dose and 2mg also showed benefit in the Clinical Global Impression - Severity of illness (CGI-S) score as related to agitation over 12weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.Prospero registry: CRD42023486694.

Vitamin C for all?

Vitamin C can be a potential adjunctive treatment option for critically ill individuals due to its pleiotropic effects as electron donor in many enzymatic reactions throughout the body. Recently, several important randomized controlled trials (RCTs) investigating vitamin C in critically ill patients have been published. Two recent large RCTs administering high-dose vitamin C to patients with sepsis and COVID-19 showed signs of harm. Though performed at high standard, these trials had several limitations. Recent studies in cardiac surgery and burns showed decreased cardiac enzymes and improved clinical outcomes after cardiac surgery, and decreased fluid requirements, reduced wound healing time and in-hospital mortality after burns. Vitamin C may hold benefit in the management of other ischemia/reperfusion injury populations, including postcardiac arrest patients and after solid organ transplantation. Currently, covering basal vitamin C requirements during critical illness is recommended, though the exact dose remains to be determined. Future work should address optimal vitamin C timing, since early versus late drug administration are likely distinct, and duration of therapy, where withdrawal-induced injury is possible. Additionally accurate assessment of body stores with determination of individual vitamin requirements is crucial to ascertain patient and subgroups most likely to benefit from vitamin C.

A Real-World Study of the Effectiveness and Safety of Semaglutide for Weight Loss.

Introduction Recent randomized controlled trials (RCTs) have shown the great efficacy of semaglutide in achieving significant weight loss in overweight and obese adults. However, real-world data about its effectiveness are still limited. This study evaluated the effectiveness and adverse events of semaglutide for weight management in a real-life setting, excluding patients with diabetes mellitus (DM). Methods This is a retrospective chart review of 40 overweight or obese individuals with a median age of 47 years, weight of 111.7 kg, and body mass index (BMI) of 39.7 kg/m2 who were prescribed semaglutide for weight management. Results After three months of semaglutide administration, the median weight reduction was 7.4 kg (6.6% of the baseline weight), with 28 (70%) and eight patients (20%)achieving greater than 5% (5.6 kg) and 10% (11.2 kg) weight loss, respectively. Among25 patients with six-month data, 22 (88%), 17 (68%), and eight (32%) patients exceeded 5% (5.6 kg), 10% (11.2 kg), and 15% (16.8 kg) weight loss, respectively. The maintenance semaglutide dose was 1 mg in 16 cases and 2 mg in nine cases, leading to a similar weight loss of 13.6% (14.9 kg) and 12.8% (14 kg), respectively. Relatively low response rates were observed in males, with seven responders out of 12 (58.4%) compared to 24 out of 28 (85.8%) in females (P value = 0.057), and in five out of nine (55.6%) amongthose with a history of psychiatric disease. The rate of adverse events was 26 out of 40 patients (65%), mostly mild to moderate and of short duration, leading to discontinuation in only a single case (2.5%). Conclusion This retrospective study demonstrated the significant effectiveness of semaglutide for weight loss, even at lower than approved maintenance doses, combined with a good safety profile. Therefore, semaglutide may dramatically change the landscape of obesity treatment.

Endovascular Therapy in Large Core Ischemic Strokes: Real-World Indian Experience.

Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer functional outcomes. However, recent randomized controlled trials (RCTs) indicate that EVT for large vessel occlusion (LVO) strokes improves functional outcomes compared to medical management alone, despite higher hemorrhagic transformation rates, with no corresponding increase in symptomatic intracerebral hemorrhage (sICH) rates. The real-world outcomes of this intervention in Indian patients remain underexplored. To evaluate the real-world outcomes of EVT for large core acute ischemic strokes with LVO in an Indian population. We conducted a single-center, retrospective observational study using a 7 years prospective database of EVT in anterior circulation stroke patients. Patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3-5 were included. Clinical and radiologic data were analyzed, with the primary endpoint being 90-day modified Rankin scale (mRS) scores. Safety outcomes included rates of sICH and mortality. Descriptive statistical analysis was done using Microsoft Excel. The study included 25 patients who met the inclusion criteria. Mean age of patients was 52.9 ± 14.3 years, and there were 13 (52%) males. Median ASPECTS was 5 (interquartile range 4-5). Successful recanalization, classified by modified Thrombolysis in Cerebral Infarction score, was 92%. Good functional recovery, that is, 90-day mRS 0-3, was achieved in nine (36%) patients. Safety outcomes: sICH was seen in four (16%) and mortality was reported in nine (36%) patients. Our results reaffirm findings from RCTs, provide updated real-world evidence, and suggest that EVT is a viable option to be considered in selected patients with large core ischemic infarcts.

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Colchicine for the Prevention of Cardiovascular Disease: Potential Global Implementation.

Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD). Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD.

Current views on treatment of halitosis: foreign practice

Traditional halitosis treatment involves reducing microbial contamination through chemical and/or mechanical action; however, these methods are ineffective in the long-term.&#x0D; According to recent systematic reviews, there is no scientific evidence of the effectiveness of halitosis treatments, and even when reports indicate a positive effect, it is temporary. To increase the number of studies being compared, analysis of the results of randomized controlled trials (RCTs) should be performed considering already published data. Therefore, a review of recent RCTs is required for conducting and planning further scientific research on halitosis treatment.&#x0D; Purpose of the investigation — to study the effectiveness of oral halitosis treatment based on materials from foreign publications from 2019 to 2023.&#x0D; This article provides a descriptive review of foreign scientific publications on modern methods of treating oral halitosis. A search for full-text articles was conducted in the electronic databases PubMed and Google Scholar for 2019–2023. The most relevant articles that met the selection criteria were selected and included in this review: 31 publications on oral halitosis treatment: 3 Cochrane reviews of RCTs; 14 literature reviews, including meta-analyses; 12 RCTs and clinical studies; and 2 experimental studies.&#x0D; In foreign studies, the use of probiotics and photodynamic therapy and their combination with standard treatment methods are most widely presented; RCTs have established their effectiveness, especially when used together with traditional methods of mechanical tongue cleaning. To prevent halitosis, it appears relevant to use materials with antibacterial properties in prosthetics, particularly the modification of polymethyl methacrylate with silver and graphene nanoparticles.&#x0D; However, against the backdrop of positive results obtained in individual reviews, the conclusions of systematic reviews are contradictory. There is no evidence of the long-term effectiveness of the proposed treatment methods, and there is a weak evidence base for studies, which makes it challenging to use them in the practical work of dentists. In this regard, new RCTs with a longer observation period and considering published data are required.

Starting position during colonoscopy: a systematic review and meta-analysis of randomized controlled trials.

Traditional teaching has been to place patients in the left lateral decubitus starting position for colonoscopies. Recent randomized controlled trials (RCTs) have compared left lateral decubitus starting position to other approaches. The aim of this systematic review and meta-analysis was to compare different starting positions for colonoscopies and their effect on cecal intubation. MEDLINE, Embase, and CENTRAL were searched from inception to July 2023. Articles were eligible for inclusion if they were RCTs comparing at least two different starting positions for adults undergoing colonoscopy. The main outcome was cecal intubation time. Meta-analysis used an inverse variance random effects model. Risk of bias was assessed with the Cochrane Tool for RCTs 2.0. After screening 1523 citations, 14 RCTs were included. Four studies compared left lateral decubitus to right lateral decubitus, four studies compared left lateral decubitus to left lateral tilt-down, three studies compared left lateral decubitus to prone, and three studies compared left lateral decubitus to supine. There were no statistically significant differences in cecal intubation time in seconds across all comparisons: left lateral decubitus vs. right lateral decubitus (MD 14.9, 95%CI - 111.8 to 141.6, p = 0.82, I2 = 85%); left lateral decubitus vs. left lateral tilt-down (MD - 31.3, 95%CI - 70.8 to 8.3, p = 0.12, I2 = 82%); left lateral decubitus vs. prone (MD 17.2, 95%CI - 174.9 to 209.4, p = 0.86, I2 = 94%); left lateral decubitus vs. supine (MD - 149.9, 95%CI - 443.6 to 143.9, p = 0.32, I2 = 89%). The starting position for colonoscopies likely does not influence cecal intubation time. This study was limited by heterogeneity.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis

BackgroundThe majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. MethodsWe searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. ResultsWe included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20–0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45–1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76–0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94–4.22, I2 = 85%). There was no increase in the incidence of adverse events. ConclusionsMolnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Effects of Goal Management Training on self-efficacy, self-esteem, and quality of life for persons with schizophrenia spectrum disorders.

Persons with schizophrenia often show executive dysfunction assessed with both subjective (self-report) and objective (neuropsychological tests) measures. In a recent randomized controlled trial (RCT), subjective executive functioning in everyday life was improved following Goal Management Training (GMT). The aim of the current study is to investigate the potential of GMT to improve secondary well-being outcomes from that RCT, including self-esteem, self-efficacy, and quality of life in persons with schizophrenia spectrum disorders. Since well-being is frequently lower in persons with schizophrenia compared to healthy individuals, further knowledge about well-being as an outcome after cognitive remediation may have implications for clinical treatment. Sixty-five participants were randomly assigned to GMT (n = 31) or a waiting list control condition (n = 34). Assessments were conducted at baseline (T1), immediately after the intervention (T2-5 weeks), and at six-month follow-up (T3). Measures included the Rosenberg Self-Esteem Scale, the Perceived Quality of Life Scale, and the General Self-Efficacy Scale. Results were analyzed using a linear mixed model analysis for repeated measures. There were no significant effects of GMT on self-esteem or quality of life. Only the GMT group showed a significant increase in self-efficacy that was most evident at six months follow-up, F(1, 34) = 10.71, p = 0.002, d = 0.71. Improved self-efficacy was found to correlate significantly with a reduction in perceived executive dysfunction in an exploratory post hoc analysis. Our findings demonstrate the potential of GMT in improving self-efficacy in schizophrenia Clinical trial registration:https://clinicaltrials.gov, NCT03048695.

Identifying who benefits most from supportive versus expressive techniques in psychotherapy for depression: Moderators of within- versus between-individual effects.

A recent randomized controlled trial (RCT) indicated that individuals with higher levels of attachment anxiety exhibited better treatment outcomes in supportive-expressive therapy (SET) relative to supportive therapy (ST). But to gain insight into within-patient therapeutic changes, a within-individual design is required. The present study contrasts previous findings based on theory-driven between-patient moderators with data-driven moderators of within-patient processes to investigate whether findings converge or diverge across these two approaches. We used data of 118 patients from the pilot and active phases of a recent RCT for patients with major depressive disorder, comparing ST with SET, a time-limited psychodynamic therapy. The predefined primary outcome measure was the Hamilton Rating Scale for Depression. Supportive versus expressive techniques were rated based on patients' end-of-session perspective. We compared previous findings based on moderators of between-patient effects with a data-driven approach for identifying moderators of within-patient effects of techniques on subsequent outcome. After false discovery rate corrections, of 10 preselected moderators, patients' attachment anxiety and domineering style remained significant. Of these, bootstrap resampling revealed significant differences between ST and SET techniques for the attachment anxiety moderator: Those with higher attachment anxiety benefited more from greater use of ST than SET techniques in a particular session, as evidenced by lower levels of symptoms at the subsequent session. Our within-individual findings diverge from previously published between-individual analyses. This proof-of-concept study demonstrates the importance of complementing between-individuals with within-individual analyses to achieve better understanding of who benefits most from specific treatment techniques. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Requirements for essential micronutrients during caloric restriction and fasting.

Caloric restriction (CR) or energy restriction, when carefully designed, monitored, and implemented in self-motivated and compliant individuals, proves to be a viable non-pharmacologic strategy for human weight control and obesity management. Beyond its role in weight management, CR has the potential to impede responses involved not only in the pathogenesis of various diseases but also in the aging process in adults, thereby being proposed to promote a healthier and longer life. The core objective of implementing caloric restriction is to establish a balance between energy intake and expenditure, typically involving a reduction in intake and an increase in expenditure-a negative balance at least initially. It may transition toward and maintain a more desired equilibrium over time. However, it is essential to note that CR may lead to a proportional reduction in micronutrient intake unless corresponding supplementation is provided. Historical human case reports on CR have consistently maintained adequate intakes (AI) or recommended dietary allowances (RDA) for essential micronutrients, including vitamins and minerals. Similarly, longevity studies involving non-human primates have upheld micronutrient consumption levels comparable to control groups or baseline measures. Recent randomized controlled trials (RCTs) have also endorsed daily supplementation of multivitamins and minerals to meet micronutrient needs. However, aside from these human case reports, limited human trials, and primate experiments, there remains a notable gap in human research specifically addressing precise micronutrient requirements during CR. While adhering to AI or RDA for minerals and vitamins appears sensible in the current practice, it's important to recognize that these guidelines are formulated for generally healthy populations under standard circumstances. The adequacy of these guidelines in the setting of prolonged and profound negative energy balance remains unclear. From perspectives of evidence-based medicine and precision nutrition, this field necessitates comprehensive exploration to uncover the intricacies of absorption, utilization, and metabolism and the requirement of each hydrophilic and lipophilic vitamin and mineral during these special periods. Such investigations are crucial to determine whether existing daily dietary recommendations for micronutrients are quantitatively inadequate, excessive, or appropriate when energy balance remains negative over extended durations.

The Statistical Fragility of Marrow Stimulation for Cartilage Defects of the Knee: A Systematic Review of Randomized Controlled Trials.

Marrow stimulation is used to address knee cartilage defects. In this study, we used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate statistical fragility of outcomes reported in randomized controlled trials (RCTs) evaluating marrow stimulation. PubMed, Embase, and MEDLINE were queried for recent RCTs (January 1, 2010-September 5, 2023) assessing marrow stimulation for cartilage defects of the knee. The FI and rFI were calculated as the number of outcome event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI by the study sample size. Across 155 total outcomes from 21 RCTs, the median FI was 3 (interquartile range [IQR], 2-5), with an associated median FQ of 0.067 (IQR, 0.033-0.010). Thirty-two outcomes were statistically significant, with a median FI of 2 (IQR, 1-3.25) and FQ of 0.050 (IQR, 0.025-0.069). Ten of the 32 (31.3%) outcomes reported as statistically significant had an FI of 1. In total, 123 outcomes were nonsignificant, with a median rFI of 3 (IQR, 2-5). Studies assessing stem cell augments were the most fragile, with a median FI of 2. In 55.5% of outcomes, the number of patients lost to follow-up was greater than or equal to the FI. Statistical findings in RCTs evaluating marrow stimulation for cartilage defects of the knee are statistically fragile. We recommend combined reporting of P-values with FI and FQ metrics to aid in the interpretation of clinical findings in comparative trials assessing cartilage restoration.

Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines

The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77–94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.

Healing of diabetic foot ulcer with topical and oral administrations of herbal products: A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed to qualitatively synthesize recent randomized controlled trials (RCTs) regarding the effect of topical application and oral intake of herbal products on the healing of diabetic foot ulcer (DFU). Also, we sought to pool the obtained findings in a meta-analysis using a random-effects model, if RCTs were relatively comparable and homogenous. A comprehensive search was performed on five electronic data sources from their inception through 23 January 2024. The RCTs, without restriction on the country of origin, were included if they compared the effect of administering standard treatments and/or placebo (i.e. control condition) to applying standard treatments and/or herbal products in topical or oral routes (i.e. experimental condition). Out of 1166 retrieved records, 28 RCTs were included. Studies used different poly and single herbal formulations. Based on the meta-analysis, administration of standard care plus daily dressing of the ulcer site with olive oil for 28 days significantly increased the total ulcer healing score (3 RCTs; weighted mean difference [WMD] = 89.30; p < 0.001), raised frequency of complete ulcer healing (2 RCTs; risk ratio [RR] = 12.44; p = 0.039) and declined ulcer degree (3 RCTs; WMD = -22.28; p = 0.002). Also, daily use of the bitter melon leaf extract in oral form for 28 days significantly increased the total ulcer healing score (2 RCTs; WMD = 0.40; p = 0.001). Additionally, based on qualitative synthesis, the adjuvant use of herbal agents seems an intriguing choice to manage DFU. Nonetheless, considering the undesirable methodological quality of most studies and the high heterogeneity in administered herbal formulations, more robust trials are required to build a solid conclusion regarding the use of herbal products for healing DFU.

Interpreting the Current Literature on Outcomes of Robotic-Assisted Versus Conventional Total Knee Arthroplasty Using Fragility Analysis: A Systematic Review and Cross-Sectional Study of Randomized Controlled Trials

BackgroundFragility analysis is a method of further characterizing outcomes in terms of the stability of statistical findings. This study assesses the statistical fragility of recent randomized controlled trials (RCTs) evaluating robotic-assisted versus conventional total knee arthroplasty (RA-TKA versus C-TKA). MethodsWe queried PubMed for RCTs comparing alignment, function, and outcomes between RA-TKA and C-TKA. Fragility index (FI) and reverse fragility index (RFI) (collectively, “FI”) were calculated for dichotomous outcomes as the number of outcome reversals needed to change statistical significance. Fragility quotient (FQ) was calculated by dividing the FI by the sample size for that outcome event. Median FI and FQ were calculated for all outcomes collectively as well as for each individual outcome. Subanalyses were performed to assess FI and FQ based on outcome event type and statistical significance, as well as study loss to follow-up and year of publication. ResultsThe overall median FI was 3.0 (interquartile range, [IQR] 1.0 to 6.3) and the median reverse fragility index was 3.0 (IQR 2.0 to 4.0). The overall median FQ was 0.027 (IQR 0.012 to 0.050). Loss to follow-up was greater than FI for 23 of the 38 outcomes assessed. ConclusionsA small number of alternative outcomes is often enough to reverse the statistical significance of findings in RCTs evaluating dichotomous outcomes in RA-TKA versus C-TKA. We recommend reporting FI and FQ alongside P values to improve the interpretability of RCT results.

Summary of the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) Statement: Recommendations on Screening for Syphilis in Non-Pregnant Adults and Adolescents.

Sustained and significant increases in Canadian rates of infectious syphilis prompted the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) to update the existing screening recommendation for non-pregnant adults and adolescents. These guidelines were developed following the 2014 World Health Organization Handbook. The research question was: "What is the clinical utility of syphilis screening using risk-based versus population-wide approaches for adolescents and adults?" The evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The environmental scan included 11 guidelines on syphilis screening published between 2014 and January 2023. Two systematic reviews were identified and included. In the updated literature search from November 6, 2019, to January 17, 2023, there were no published systematic reviews on the effectiveness of risk-based screening or the comparison of risk-based and interval screening; however, one recent randomized control trial in Canada was published. Evidence for outcomes, patient values and preferences, resources, acceptability, equity, cost and cost effectiveness and feasibility were reviewed. This statement provides two screening recommendations for adults and adolescents. Recommendation 1: NAC-STBBI recommends syphilis screening in all sexually active persons with a new or multiple partners and/or upon request of the individual. They also recommend screening every three to six months in individuals with multiple partners. Recommendation 2: NAC-STBBI recommends that targeted "opt-out" screening programs should be considered as frequently as every three months when serving population groups and/or communities experiencing a high prevalence of syphilis (and other STBBI). Both are strong recommendations with moderate certainty of evidence.

Abstract WP205: Development and Validation of a Prediction Model for Outcome in Mechanical Thrombectomy for Large-Vessel Occlusion Anterior Circulation Stroke With Low ASPECTS

Introduction: Recent randomized control trials suggested that mechanical thrombectomy (MT) was associated with good functional outcomes after acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in patients presenting with low Alberta Stroke Program Early CT Score (ASPECTS) (defined as ASPECTS 2-5). The aim of this study is to develop and validate a stroke prediction tool for outcome in MT for AIS patients with low ASPECTS using data from an ongoing international multicenter registry, the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: 236 AIS patients with low ASPECTS caused by LVO who undertook MT between January 2010 and December 2022 were retrospectively investigated. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of 90-day modified Rankin Scale scores (mRS) 0-3. The performance of the model was detected by using receiver operating characteristic analysis. The bootstrap resampling method was considered internal validation of the model. Results: Age (&lt; 70 years), premorbid status (mRS 0), National Institutes of Health Stroke Scale (NIHSS) (&lt; 20), and recanalization status after the MT (modified Thrombolysis in Cerebral Ischemia [mTICU] ≥2b) were related to 90-day mRS 0-3. Predictive score was calculated by adding 1 point for age (&lt; 70 years), premorbid status (mRS 0), and NIHSS &lt; 20 and 3 points for a mTICI ≥2b (ranging 0-6). 90-day mRS 0-3 was observed in 0% of patients with a score of 0 or 1, 6.3% with a score of 2, 17.7% with a score of 3, 22.2% with a score of 4, 45.7% with a score of 5, and 73.7% with a score of 6. The score showed relatively high performance in predicting 90-day mRS0-3 (area under the curve: 0.79 [95% CI 0.73-0.79] and 0.78 [95% CI 0.78-0.78] for derivation and validation cohorts, respectively). Conclusions: This study indicates the STAR score can be calculated with baseline and periprocedural characteristics to predict the 90-day outcome after MT in AIS patients with low ASPECTS.

Automated Insulin Delivery for Pregnant Women With Type 1 Diabetes: Where do we stand?

Automated insulin delivery (AID) systems mimic an artificial pancreas via a predictive algorithm integrated with continuous glucose monitoring (CGM) and an insulin pump, thereby providing AID. Outside of pregnancy, AID has led to a paradigm shift in the management of people with type 1 diabetes (T1D), leading to improvements in glycemic control with lower risk for hypoglycemia and improved quality of life. As the use of AID in clinical practice is increasing, the number of women of reproductive age becoming pregnant while using AID is also expected to increase. The requirement for lower glucose targets than outside of pregnancy and for frequent adjustments of insulin doses during pregnancy may impact the effectiveness and safety of AID when using algorithms for non-pregnant populations with T1D. Currently, the CamAPS® FX is the only AID approved for use in pregnancy. A recent randomized controlled trial (RCT) with CamAPS® FX demonstrated a 10% increase in time in range in a pregnant population with T1D and a baseline glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (6.5%). Off-label use of AID not approved for pregnancy are currently also being evaluated in ongoing RCTs. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and provide an overview of the completed and ongoing RCTs evaluating AID in pregnancy. In addition, we discuss the advantages and challenges of the use of current AID in pregnancy and future directions for research.