Multicenter Randomized Control Research Articles

Efficacy and Tolerance of the Tampsec Vaginal Tampon for Treating Stress Urinary Incontinence. A Randomized Controlled Trial.

Stress urinary incontinence (SUI) is a highly prevalent condition in women. We hypothesized that the Tampsec™ vaginal tampon will be efficacious and well tolerated in its treatment. This was a multicenter open-label parallel-group randomized control trial. All participants were recommended to make lifestyle modifications and perform pelvic floor muscle training for SUI treatment. Additionally, women in the tampon group were instructed to use a Tampsec™ throughout the day. The primary outcome measure was a ≥50% reduction in pad weight by the end of treatment. Secondary outcome measures were women's perception of improvement evaluated using the Patient Global Impression of Improvement (PGI-I) questionnaire, decrease in the mean number of SUI episodes/day, and improvement in the impact of urinary incontinence (UI) on everyday life. Tampon tolerance and usability were also evaluated. Forty-six women with a positive urinary stress test were randomized 1:1 to tampon or control treatments. Regarding the primary outcome, a ≥50% reduction was achieved in 69.9% of patients in the tampon group and 26.1% in controls (RR 2.7; 95%CI 1.3-5.4). On the basis of PGI-I responses, the treatment was successful in 60.9% of women in the tampon group and 17.4% of controls (p = 0.003). The tampon group also reported greater decreases in SUI episodes/day (mean 2.0±2.2 vs 0.5±1.1; p = 0.007) and more improvement in the impact of UI on everyday life. Tolerance and usability were good in most women. The Tampsec™ tampon is efficacious and well tolerated in women with SUI. This treatment decreases the number of SUI episodes/day and improves UI-related quality of life.

First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study.

Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC. This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs). From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4-54.9), 32.4% (95%CI:17.4-50.5) and 43.3% (95%CI:25.5-62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED. Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/ ).

A comprehensive RCT in screening, surveillance, and diagnostic AI-assisted colonoscopies (ACCENDO-Colo study).

Adenoma detection rate (ADR) serves as a primary quality metric in colonoscopy. Various computer-aided detection (CADe) tools have emerged, yielding diverse impacts on ADR across different demographic cohorts. This study aims to evaluate a new CADe system in patients undergoing colonoscopy. This is an Italian multicenter randomized control trial (RCT) that included patients aged 40-85 scheduled for screening, surveillance or diagnostic colonoscopy randomly assigned to CADe or standard colonoscopy (SC). Patients with a Boston Bowel Preparation Scale < 2 in any segment were excluded. The primary outcome was ADR in both groups. Secondary outcomes included adenoma per colonoscopy (APC), polyp per colonoscopy (PPC) and sessile serrated lesion detection rate (SSLDR). 1228 patients were enrolled of whom 70 were excluded for inadequate bowel cleansing or missed cecal intubation. Therefore, 1158 subjects (578 CADe vs 580 SC) were included in the final analysis. ADR was significantly higher in CADe than in the control group (50.2 % vs 40.5 %, p = 0.001). CADe also significantly increased PPC and APC (1.64 ± 2.03 vs 1.23 ± 1.72, p < 0.001; 1.16 ± 1.82 vs 0.80 ± 1.46 p < 0.001; respectively). No significant differences were found in SSLDR between CADe and SC (12.1 % vs 11.0 %, p = 0.631). The results of this RCT indicate that AI-assisted colonoscopy significantly improved ADR in a non-selected population undergoing colonoscopy without causing any significant delay in procedure time or increasing the detection of nonneoplastic lesions. (Ethical committee approval: NCT05862948).

Association of postpartum oxytocin dose and postpartum bleeding outcomes in nulliparous patients at term.

Postpartum hemorrhage is a leading cause of morbidity and mortality. The use of prophylactic oxytocin in the third stage of labor is globally accepted as standard of care for the prevention of postpartum hemorrhage, however the most effective dose of oxytocin is unknown. While studies suggest a possible benefit of higher doses of postpartum prophylactic oxytocin, results are inconclusive, and data are limited. Our objective was to compare rates of postpartum hemorrhage and the need for additional postpartum hemorrhage interventions between high-dose (80 IU) and low-dose (10-30 IU) postpartum oxytocin regimens. Secondary analysis of a multicenter randomized control trial of 2,404 nulliparous women with term singleton pregnancies that investigated immediate versus delayed pushing in women in the second stage of labor (5/2014-12/2017). Postpartum oxytocin regimens were ascertained from each of the 6 participating centers and categorized as high-dose (80 IU/500 mL over 1-4 hours after placental delivery) and low-dose (10-30 IU/500-1000 mL over 1-4 hours). The primary outcome was a composite of uterotonic use after initial postpartum oxytocin, any blood transfusion, and postpartum hemorrhage. Postpartum hemorrhage was defined as estimated blood loss >500 mL after vaginal delivery and >1000 mL after cesarean delivery. Secondary outcomes included individual composite components and select bleeding outcomes. Logistic regression using covariates identified as significant in parsimonious modeling were used to estimate adjusted odds ratios and 95% confidence intervals using the low-dose group as the reference. Dose effect analysis by total dose and effect modification by mode of delivery were also performed. All 2,404 patients from the primary trial were included: 455 (19%) in the high-dose group and 1,949 (81%) in the low-dose group. Women in the high-dose group were more likely to be younger, African American, obese, have magnesium sulfate exposure, and achieve vaginal delivery. Compared to low-dose oxytocin, patients receiving high-dose oxytocin had lower odds of the primary composite outcome (aOR 0.53, 95% CI 0.34-0.82), primarily driven by decreased odds of postpartum hemorrhage (aOR 0.44, 95% CI 0.27-0.72). While frequencies of other secondary outcomes were lower in the high-dose group, there was no significant difference in odds of these outcomes after adjustment. Analysis of dose effect by total dose between low- (10-20 IU), moderate- (30 IU), and high- (80 IU) dose oxytocin revealed a decreased odds of the primary composite outcome with moderate- and high-dose (moderate-dose - OR 0.57, 95% CI 0.41-0.80; high-dose - OR 0.39, 95% CI 0.25-0.61; interaction p<0.01).The effect of oxytocin dose on the primary outcome did not differ by delivery mode (interaction p=0.35). High-dose postpartum oxytocin was associated with lower rates of postpartum hemorrhage than lower oxytocin doses. Results appeared consistent for both vaginal and cesarean deliveries (at second stage given primary trial). Given the widespread use of oxytocin globally and its relatively low cost, future multicenter trials of postpartum oxytocin dose are warranted.

A randomized controlled trial evaluated the efficacy and safety of apixaban for prevention of recurrent thrombosis after thrombectomy of hemodialysis vascular access.

Dialysis vascular access thrombosis poses a substantial challenge for individuals undergoing hemodialysis. The efficacy and safety of apixaban, a direct oral coagulation factor Xa inhibitor, in preventing recurrent access thrombosis have yet to be explored. Here, a multicenter randomized control study (NCT04489849) enrolled hemodialysis patients to evaluate this who underwent successful endovascular thrombectomy within 48 hours. Participants were assigned to standard care or standard care plus apixaban, 2.5 mg twice daily for three months. The trial design involved open-label administration, with independent adjudication of endpoints. The primary efficacy endpoint was recurrent access thrombosis within three months after thrombectomy. A total of 186 patients with well-balanced baseline characteristics were enrolled, 93 randomized to the apixaban group and 93 to the control group. The apixaban group demonstrated a significantly lower rate of access thrombosis at three months than the control group (24.0% vs. 40.8%; hazard ratio, 0.52 [95% confidence interval 0.31-0.88]), along with a significantly better primary patency failure rate (32.2% vs. 49.5%, 0.57 [0.36-0.91]). Safety outcomes showed comparable death rates and major bleeding incidents but significantly higher incidence of minor bleeding in the apixaban group (22.6% vs. 7.5%). The effect of apixaban did not show interaction in subgroups of different access types, antiplatelet usage, severity of comorbidities, or history of thrombosis. Thus, apixaban effectively reduced the risk of recurrent thrombosis in hemodialysis vascular access post-thrombectomy. Despite a minor increase in bleeding adverse effects, the net clinical benefit favors the use of apixaban in this context.

A multicenter randomized control trial: Point-of-care syndromic assessment versus standard testing in urgent care center patients with acute respiratory illness.

Syndromic assessment with multiplex polymerase chain reaction (mPCR) testing in patients with acute respiratory illness (ARI) allows for simultaneous identification of multiple possible infectious etiologies. Point-of-care (POC) syndromic assessment can be conducted in a clinical setting, such as an urgent care center (UCC), without requiring certified laboratories. The primary objective of this study was to determine whether POC syndromic assessment improved patient satisfaction for patients seen at an UCC with ARI; secondary objectives included whether syndromic assessment reduced self-isolation time, increased diagnostic confidence, and reduced overall antibiotic utilization. We conducted an unblinded multicenter randomized controlled trial on UCC patients with an ARI. Patients were randomized to either SC (defined as standard UCC testing for ARI) or syndromic assessment with POC mPCR. Patients were surveyed for patient satisfaction, self-isolation plans, diagnostic confidence, and overall antibiotic utilization. Among the 360 patients enrolled, those in the syndromic assessment group were more satisfied with the time required to communicate the results (98.4%vs. 42.4%, p<0.001) on day of treatment, more likely to resume normal activities sooner (83.3%vs. 69.4%, p=0.039), and more confident in their illness cause (60.7%vs. 29.6%, p<0.001); however, the rate of antibiotic utilization did not differ (33.5%vs. 26%, p=1.0). In conclusion, our study provides evidence supporting the use of syndromic assessment in UCCs for ARI diagnosis, including patient-centered outcomes such as greater confidence in diagnosis and more efficient isolation strategies. This study did not show a difference in more clinically oriented outcomes, such as a change in antibiotic utilization. Future studies should identify clinical care pathways to improve antibiotic stewardship for likely viral syndromes and whether the increased initial cost of syndromic assessment is offset by the clinical benefits and subsequent cost savings.

Equal Treatment, Unequal Outcomes? Debunking the Racial Disparity in Renin Angiotensin Aldosterone System Inhibitor Associated Reduction in Heart Failure Hospitalizations

BackgroundRenin angiotensin aldosterone system inhibitors (RAASi) are a mainstay treatment in patients with heart failure with reduced ejection fraction (HFrEF) in part to prevent hospitalizations. However, whether RAAS inhibitors reduce the risk of hospitalization in Black patients is not entirely clear because enrollment of Black patients in previous clinical trials was low, and a previous meta-analysis showed a significant racial disparity: reduction in hospitalizations with an RAAS inhibitor in White patients but not Black patients. Previous studies relied on the use of self-identified race instead of genomic ancestry. Therefore, this study aimed to investigate the role of self-identified race and genomic ancestry in the racial disparity in RAAS inhibitor associated reductions in HFrEF hospitalizations. MethodsThe primary outcome was time to first heart failure hospitalization. A (de-identified) heart failure patient registry and data from the GUIDE-IT multi-center randomized control trial were analyzed with Cox proportional hazards models un/adjusted for clinical risk factors, death as a competing risk, and time-varying RAAS inhibitor exposure. The proportion of Yoruba African ancestry was quantified.. Analysis of self – identified race were performed in both the registry and GUIDE-IT. Analysis of genomic ancestry was only performed in the registry since this information was not available in GUIDE-IT. A fixed effect meta-analysis combined results of both the registry and GUIDE-IT for race. ResultsThe registry had 1010 total HFrEF patients (Black = 509 and White = 501) with 852 having ancestry quantification (>80% Yoruba African Ancestry = 381 and <5% Yoruba African Ancestry = 471). GUIDE-IT had 810 HFrEF patients (Black = 322 and White = 488). There was no significant difference in the association of RAAS inhibitor exposure with heart failure hospitalization by race (meta-analysis p-value for race*RAAS inhibitor exposure interaction = 0.49; Black patients HR [95% CI] for RAAS inhibitor exposure = 0.89 [0.64-1.23)] P = 0.47; White patients = 1.20 (0.83-1.75) P = 0.34). Results were similar when analyzed by ancestry (p-value for ancestry*RAAS inhibitor exposure interaction = 0.57; >80% Yoruba African Ancestry = 0.93 [0.51-1.69] P = 0.80; <5% Yoruba African Ancestry = 1.29 [0.57-2.92] P = 0.54). ConclusionsIn contrast to a previous meta-analysis, this more contemporary analysis of 2 HFrEF patient datasets demonstrates the absence of a racial disparity in RAAS inhibitor associated reductions in heart failure hospitalizations. The difference in this racial disparity over time may be due to improvements in background heart failure therapies, racial differences in healthcare usage, and the use of more advanced statistical approaches.

P318. SYGEN (GM1 Ganglioside) promotes faster recovery after traumatic spinal cord injury compared to placebo; a contemporary analysis of the SYGEN multicenter randomized control study

P318. SYGEN (GM1 Ganglioside) promotes faster recovery after traumatic spinal cord injury compared to placebo; a contemporary analysis of the SYGEN multicenter randomized control study

P319. Time to 50% recovery after traumatic spinal cord injury may be a more meaningful outcome measure than absolute total motor score recovery; a novel analysis of the SYGEN multicenter randomized control study

P319. Time to 50% recovery after traumatic spinal cord injury may be a more meaningful outcome measure than absolute total motor score recovery; a novel analysis of the SYGEN multicenter randomized control study

Effect of in-line filtration in newborns: study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial

BackgroundParticulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines.MethodsA multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a “full analysis set.” The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm.DiscussionThis is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30–35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs.Trial registrationClinicalTrials.gov, NCT05537389, registered on 12 September 2022 (https://classic.clinicaltrials.gov/ct2/show/results/NCT05537389?view=results).

O-218 Prospective validation of an artificial intelligence platform for automated follicle counting

Abstract Study question How often are fully automated follicle counts and measurements modified in expert review? Summary answer Automatic follicle annotations provided by an artificial intelligence platform in regular operation of a clinic were edited 3.27% of the time. What is known already Ovarian follicle counting is frequently performed, time-consuming, and subject to noticeable inter-observer variability; as such, it is well-suited to automatizing with artificial intelligence. FOLLISCAN (MIM Fertility) is a software platform that automatically annotates follicles on 2D or 3D ultrasound cine videos, with exact outlines and measurements, without any manual pre-processing. It has undergone several retrospective tests of its precision and recall in detecting ovarian follicles, accuracy of measurements, and time-savings compared to manual counting Study design, size, duration The platform was integrated with a clinic’s existing picture archiving and medical record systems. Ultrasound scans of ovaries were performed as part of regular infertility treatment in two IVF centers. Scans were made by 3 experts in a period from November to December 2023, automatically sent to the platform, analyzed, and then immediately visualized for review by the person performing the ultrasound, in place of manual annotation. Participants/materials, setting, methods The study included 294 cine videos from 147 examinations of 101 patients, with 4347 follicles in total (14.7 per ovary on average, from 2mm). The platform allows users to modify proposed measurements and introduce new follicle annotations. After confirming the review, results were automatically sent back to the clinic’s system to be used in medical decisions just as manual annotations would be. Main results and the role of chance Among all videos the average number of editions (follicle additions, modifications, or deletions) was 0.48 (CI: 0.37-0.61). In total, 142 follicles out of 4347 (3.27%, CI: 2.74-3.80) were edited: 66 follicles were added (1.52%, CI: 1.15-1.88), 26 were modified, (0.60%, CI: 0.37-0.83 ), and 50 were deleted (1.15%, CI: 0.83–1.47). Out of the 151 edited follicles, 13 (9.2%) had 2–5 mm, 29 (20.4%) had 5-10 mm, 51 (35.9%) had 10-15 mm, 42 (29.6%) had 15-20 mm, and 7 (4.9%) had 20 mm or more in diameter. Among follicles of 15 mm or more in size, 49 were edited. Out of 294 videos, 87 (29.6%, 95% Confidence Interval: 24.4-34.6) were edited in review in any way. Limitations, reasons for caution The study was limited in scope and did not track patients until success rates in IVF treatments could be observed. A multi-center randomized control trial could compare pregnancy rates for treatments performed with and without the platform. Wider implications of the findings An integrated platform allows for easy review, while significantly reducing the time spent on follicle counting in a real-world setting. Automated annotations result in consistent, reliable, and quick measurements, with the number of expert modifications smaller than the inter-observer reliability reported in previous studies. Trial registration number Project support was provided by the Polish National Center for Research and Development no. POIR.01.01.01-00-1634/20-00 and ERC Consolidator Grant TUgbOAT no. 772346. This study was conducted following the approval of the research protocol by the review board of the Regional Medical Chamber in Gdańsk (approval no. KB – 51/22).

Improved Cardiac Rehabilitation Referral Rate Utilizing a Multidisciplinary Quality Improvement Team.

Introduction Cardiac rehabilitation (CR) is an underutilized resource in patients with ischemic heart disease, despite being a Class IA recommendation. In this study, a multidisciplinary quality improvement (QI) team aimed to improve CR referrals by standardizing the ordering process at our hospital system. Method By using a collaborative approach involving the electronic medical record (EMR), medical provider education, and hospital protocols, our two-hospital healthcare system was able to successfully identify barriers to CR referral rates and implement interventions for these barriers. All physicians and medical providers, including ancillary staff, were educated on the EMR order sets to improve compliance by using automated order sets in the EMR. The CR referral order in the EMR included a statement regarding the application of evidence-based medicine, and a computerized provider order entry was included as a reminder to the ordering provider. The use of EMR was monitored monthly by the QI committee. Chi-square test and odds ratios were obtained for statistical analysis. Results Through provider-EMR education and patient education on discharge, CR referral rates significantly improved from 51.2 to 87.1% (p = 0.0001) in a 12-month period. The study included 1,499 patients in total. The improvement was statistically significant regardless of patient gender, race, or insurance coverage. Additionally, subgroup analysis in this study found that prior to standardization of the ordering process, African American patients were significantly less likely to be referred to CR compared to Caucasian patients. (51.2% vs. 41.0%, p=0.01). There was no statistically significant difference in the likelihood of CR referral between Caucasian and African American patients following the intervention (84.0% vs. 78.0%, p = 0.166). Conclusion This study shows that CR is an underutilized resource and that effective QI initiatives may not only increase CR referral rates but also close the gap between racial inequities in referral rates. Future research with multi-center randomized control trials is needed to further enhance its external generalizability to other institutions.

Safety of remimazolam in comparison with midazolam for colonoscopy: A systematic review and meta-analysis

Background Remimazolam is an ester-based ultra-short-acting benzodiazepine that efficiently achieves sedation within a short period and is now being assessed as a suitable alternative to midazolam. This meta-analysis aims to pool the available data assessing and focusing on the safety aspect of remimazolam compared with midazolam. Methods A multi-center randomized control trial for patients undergoing endoscopic procedures like colonoscopy was conducted, comparing remimazolam to placebo for the midazolam group as the intervention group. The safety of remimazolam was the primary endpoint of this meta-analysis. Results A total of 3 studies were included. The total study population was 697, including the placebo, remimazolam, and midazolam groups. The types of studies included are i. randomized, double-blind, parallel-group, active-controlled clinical trial ii. prospective, randomized, parallel-group study comparing remimazolam to placebo (blindly), RCT, and iii. prospective, double-blind, randomized, parallel-group study RCT.; Treatment-emergent adverse effects included vascular disorders (P=0.42), cardiac disorders (p=0.06), respiratory, thoracic, and mediastinal disorders (p=0.26), infections and infestations (0.88), hematologic abnormalities such as anemia (p=0.63), and derangements in Blood pressure (systolic p=0.47 and diastolic p=0.68 and respiratory parameters (p=0.34). Analysis of the reported data suggests that the remimazolam group had a significantly higher incidence of treatment-emergent adverse effects compared to the midazolam group (RR: 0.84; 95% CI [0.78, 0.91]; P &lt;0.00001; I2 = 5%). Conclusions In conclusion, this meta-analysis of three randomized controlled trials showed outcomes favoring both remimazolam and midazolam as successful sedatives, yet the higher requirement of top-up dosage and rescue sedatives in the midazolam group indicates that remimazolam can be used as its replacement, especially in colonoscopy procedures.

The Role of Proton Pump Inhibitors in the Realm of Idiopathic Pulmonary Fibrosis and its Associated Comorbidities: A Systematic Review.

As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management ofpatients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITYand ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic reviewand meta-analysison antacid and antireflux surgery in IPFnegate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.

The application of artificial intelligence for Rapid On-Site Evaluation during flexible bronchoscopy.

Rapid On-Site Evaluation (ROSE) during flexible bronchoscopy (FB) can improve the adequacy of biopsy specimens and diagnostic yield of lung cancer. However, the lack of cytopathologists has restricted the wide use of ROSE. To develop a ROSE artificial intelligence (AI) system using deep learning techniques to differentiate malignant from benign lesions based on ROSE cytological images, and evaluate the clinical performance of the ROSE AI system. 6357 ROSE cytological images from 721 patients who underwent transbronchial biopsy were collected from January to July 2023 at the Tangdu Hospital, Air Force Medical University. A ROSE AI system, composed of a deep convolutional neural network (DCNN), was developed to identify whether there were malignant cells in the ROSE cytological images. Internal testing, external testing, and human-machine competition were used to evaluate the performance of the system. The ROSE AI system identified images containing lung malignant cells with the accuracy of 92.97% and 90.26% on the internal testing dataset and external testing dataset respectively, and its performance was comparable to that of the experienced cytopathologist. The ROSE AI system also showed promising performance in diagnosing lung cancer based on ROSE cytological images, with accuracy of 89.61% and 87.59%, and sensitivity of 90.57% and 94.90% on the internal testing dataset and external testing dataset respectively. More specifically, the agreement between the ROSE AI system and the experienced cytopathologist in diagnosing common types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, demonstrated almost perfect consistency in both the internal testing dataset (κ) and the external testing dataset (κ). The ROSE AI system demonstrated feasibility and robustness in identifying specimen adequacy, showing potential enhancement in the diagnostic yield of FB. Nevertheless, additional enhancements, incorporating a more diverse range of training data and leveraging advanced AI models with increased capabilities, along with rigorous validation through extensive multi-center randomized control assays, are crucial to guarantee the seamless and effective integration of this technology into clinical practice.

Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017-2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan-Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in (21.8 %) patients. Only 13 % () met ICM criteria definition no.1 for one-stage exchange; 12 % () met definition no.2. In both definitions, infection-free survivorship at 2years did not differ between patients who met and did not meet criteria (). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial)

BackgroundEndoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate.MethodsThis is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study.DiscussionThis is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors.Trial registrationJapan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Evaluation of cerebral autoregulation of oxygen by NIRS method during postnatal transition period in term and late preterm newborns without resuscitation requirement.

Pulse oximetry is commonly used to monitor arterial oxygen saturation and heart rate during the transition period and reference intervals have been determined. However, the effect of the change in arterial oxygen saturation on tissue oxygenation does not seem to be the same. So, a non-invasive method for monitoring cerebral or regional tissue oxygenation will be potentially useful for vulnerable infants. This study aims to evaluate the effectiveness of cerebral autoregulation in the first 10 min after delivery in term and late preterm newborns without resuscitation requirement. Cerebral tissue oxygen saturation was measured in the first 10 min after birth with near-infrared spectroscopy (NIRS) from the left forehead. Peripheral oxygen saturation was measured with pulse oximetry from the right hand and cerebral fractional tissue oxygen extraction was calculated. Nineteen late preterms and 20 term infants were included in the study. There was no statistically significant difference between median cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction values of late preterm and term infants (p < 0.001). There was a strong inverse relationship between cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction (p < 0.001). In late preterm infants similar to term infants, arterial oxygen saturation and cerebral tissue oxygen saturation increased with time, but inverse reduction of cerebral fractional tissue oxygen extraction showed the presence of an active autoregulation in the brain. This can be interpreted as the ability of the brain to protect itself from hypoxia by regulating oxygen uptake during normal fetal-neonatal transition process. A larger scale multi-center randomized control trial is now needed to further inform practice.

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline.

Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results. Multiple strategies were used to recruit community-dwelling 70-84-year-old participants with adult-onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in-person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility. Over a 24-month period, 3004 telephone screenings resulted in 2344 in-person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site. The ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well-established observational study. The ACHIEVE study tests the effect of hearing intervention on cognitive decline.The study is partially nested within an existing cohort study.Over 2 years, 977 participants recruited and enrolled.Eligibility assessed by telephone and in-person for hearing, vision, and cognitive screening.The ACHIEVE study findings will have significant public health implications.

The role of low-molecular-weight heparin on recurrent abortion: a review

Recurrent abortion (RA) remains a significant challenge in gynecological practice. It is not only emotionally devastating for pregnant women but is also medically challenging. RA is the spontaneous loss in the first trimester of three or more consecutive pregnancies. The current review was aimed at investigating the role of low-molecular-weight heparin (LMWH) in RA. The online databases MEDLINE and Google Scholar were used to perform a literature search for publications published between 2015 and 2013, without any date or language restrictions. We used a combination of relevant search terms &amp;quot;role, low, molecular, weight, heparin, recurrent, and abortion.&amp;quot; We independently identified publications and systematically screened titles, abstracts, and full texts of the collected publications. LMWH was found to be used to treat RA due to its anticoagulants and anti-inflammatory effect. Its use is associated with a substantial improvement in live birth rates in most studies reviewed, with a few inconclusive. There was no significant improvement in late pregnancy complications in women treated with LMWH in the control group. Women treated with LMWH experienced very few adverse medication responses, and those that did occur were often moderate and self-limiting, making LMWH therapy a safe option. To create a consensus recommendation on the treatment of RA, further research on the use of LMWH is required, ideally in the form of sizable multicenter randomized control trials.