Non-inferiority Test Research Articles

Efficacy and safety of aspirin in preventing venous thromboembolism after hip arthroplasty for femoral neck fracture: a noninferiority prospective cohort study

BackgroundVenous thromboembolism (VTE) is a common complication after hip arthroplasty. Here, we investigated the clinical efficacy and safety of prophylactic aspirin vs. conventional therapy in hip arthroplasty for femoral neck fracture.MethodsPatients who underwent total hip arthroplasty and hemiarthroplasty for femoral neck fractures between April 2021 and April 2024 were prospectively enrolled. Group A received oral aspirin (100 mg, once daily) as VTE prophylaxis; Group LR received low-molecular-weight heparin (4,250 U, once daily) sequentially followed by rivaroxaban (10 mg, once daily). The patients were followed up for 90 days postoperatively. Safety and efficacy were comprehensively evaluated based on postoperative VTE incidence, laboratory blood tests, bleeding events, and other complications.ResultsGroup A was noninferior to Group LR in preventing VTE (incidence rates of 11.6% and 10.1%, respectively, with a rate difference of 1.5%, 95% CI: 0.7–2.3%, P for non-inferiority test = 0.017). There was no significant difference between the groups in the incidence of bleeding events (3.3 vs. 8.4%; P = 0.092). Furthermore, the rates of other complications did not differ significantly between groups.ConclusionIn patients undergoing hip arthroplasty for femoral neck fractures, the efficacy and safety of oral aspirin for preventing VTE was similar to that of low-molecular-weight heparin followed by rivaroxaban.

A Randomized Non-Inferiority Clinical Trial of 14Fr Thal versus 28Fr Tube Thoracostomy for Traumatic Hemothorax.

The traditional treatment of traumatic hemothorax (HTX) is large bore chest tubes (CT) ≥28Fr. Recent evidence shows 14Fr pigtail catheters are as effective in drainage of HTX as larger CT. However, this has not been shown in 14Fr Thal tubes, a straight chest tube placed utilizing Seldinger technique. A single center, prospective randomized controlled trial was performed at an ACS verified Level 1 trauma center comparing 14Fr Thal CT (14CT) to 28Fr CT (28CT) between May 2017 and September 2021. The primary outcome was failure of drainage of hemothorax requiring additional intervention. Secondary outcomes included duration of chest tube placement, length of stay, tube-specific complications, and 90-day hospital readmission. Farrington-Manning approach was used for non-inferiority tests. Wilcoxon 2-samples test or t test was used for continuous variables, and Pearson chi-square or Fisher exact test was used for categorical variables. 109 patients were included in the randomized trial. There were 54 patients in the 14CT cohort, and 55 patients in the 28CT cohort. The primary outcome of drainage failure was similar between groups (8.3% 14CT vs 3.9% 28CT). Using a 15% non-inferiority margin 14CT is non-inferior to 28CT. No differences were identified in secondary outcomes. 14Fr Thal tubes have similar efficacy in drainage of traumatic hemothorax when compared with 28Fr chest tubes with similar complication rates (NCT03167723).

Early Childhood Exposures to Fluorides and Cognitive Neurodevelopment: A Population-Based Longitudinal Study.

It is important to maintain confidence in the risk and benefit balance of major caries-preventive programs using fluoride. The ongoing debate about potential effects of early-life exposures to fluoride on cognitive neurodevelopment requires high-quality scientific evidence. This study aimed to investigate the potential effects of fluoride exposure on cognitive neurodevelopment assessed with the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV) in an Australian population-based sample. The sample was selected from the National Child Oral Health Study (NCOHS) 2012-2014. NCOHS collected data on socioeconomic factors, oral health behaviors, and residential history to estimate percentage lifetime exposure to fluoridated water during the first 5 y of life (%LEFW). NCOHS children were also examined by trained and calibrated examiners to assess dental fluorosis (a reliable and valid individual biomarker of total fluoride intake during early childhood). The sample was followed up in 2022-2023 to collect data on cognitive neurodevelopment (intelligence quotient [IQ]) using the WAIS-IV, which was administered by trained and calibrated qualified psychologists. Multivariable regression models were generated to investigate associations between the 2 exposure measurements (%LEFW and dental fluorosis) with full-scale IQ (FSIQ) scores, controlling for important confounding effects. Hypotheses of noninferiority were also tested, contrasting different levels of exposure to fluoride. Some 357 participants aged 16 to 26 y completed the WAIS-IV, with a mean FSIQ score of 109.2 (95% confidence interval [CI]: 107.8-110.5). The estimates of the multivariable regression models demonstrated slightly higher FSIQ scores among the exposed than the nonexposed. The adjusted β of 100%LEFW versus 0%LEFW was 1.07 (95% CI: -2.86, 5.01) and of having dental fluorosis versus no fluorosis was 0.28 (95% CI: -3.00, 3.57). The hypothesis of noninferiority tests found that FSIQ scores of those exposed and nonexposed to fluoride were equivalent. The study provided consistent evidence that early childhood exposure to fluoride does not have effects on cognitive neurodevelopment.

Comparing Outcomes Between Standard Mepilex and Mepilex Silver for Tracheotomy Dressings.

The purpose of the study is to compare the incidence of early postoperative tracheotomy stoma wound complications in pediatric patients using a silver-impregnated barrier dressing (Mepilex Ag) versus a standard absorbent foam dressing (standard Mepilex). This is a prospective, non-blinded, randomized trial of pediatric patients undergoing tracheotomy at a tertiary care children's hospital. Patients were randomized to receive Mepilex Ag versus standard Mepilex tracheostoma dressings following tracheotomy. All patients received standard postoperative wound care and daily stomal examination. Wound related complications, breakdown, granulation, and infection were recorded for the first 7 days after surgery. A non-inferiority study design was used to test the hypothesis that the Mepilex group had a non-inferior wound complication rate (within 10% margin) compared to the Mepilex Ag group. Eighty-two patients were enrolled; 52 received Mepilex Ag, and 30 received standard Mepilex. There was no difference between the groups with respect to age, sex, race, surgical indication, or postoperative length of stay. Non-inferiority testing demonstrated that the Mepilex standard cohort had no more than 10% greater stomal wound complication rate than that of Mepilex Ag dressing group (p = 0.0108). Standard Mepilex was found to be non-inferior to Mepilex Ag in the prevention of tracheotomy stomal wound complications. Standard Mepilex may be used effectively in the postoperative period, potentially reducing costs to caregivers and the institution. Further work is needed to analyze additional factors that could contribute to poor postoperative stoma healing such as bacterial colonization. Randomized Controlled Trial, 2 Laryngoscope, 134:5160-5163, 2024.

Overnight Monitoring Criteria for Children with Obstructive Sleep-Disordered Breathing After Tonsillectomy: Revisited.

Previous studies indicate children who pass an Asleep Room Air Challenge (AsRAC) do not have significant postoperative adverse respiratory events after adenotonsillectomy (T&A). Subsequently, we revised our overnight monitoring (OM) criteria, allowing patients with an obstructive apnea/hypopnea index (OAHI) ≤20 or nonsevere obesity (Class I) to be considered for same-day surgery (SDS) if they passed an AsRAC. Our hypothesis is that our modified OM criteria would not increase the return visits or readmission rates for patients undergoing SDS within 48 h or 15 days of T&A. A retrospective review of all children aged ≥3 and <21 years who underwent T&A at a tertiary children's hospital and its satellite locations was performed from January 2017 to September 2022. Descriptive statistics and outcome measures were compared using a 3% margin noninferiority test before and after the new criteria implementation. Before intervention, 3,266 (58%) T&As were performed as SDS. Afterward, 74% of T&As were performed as SDS (p-value <0.05). There was no difference in the ED revisit rate for SDS within the 3% noninferiority margin. Following intervention, 29% more children with Class I obesity (62% vs. 33%) underwent SDS (p-value <0.001). Afterward, 19% more children with polysomnography underwent SDS (39% vs. 20%), p-value <0.001. After intervention, within 48 h of SDS, six (0.9%) children had revisits for bleeding and seven (1.2%) for vomiting. There were no perioperative respiratory events. Our revised monitoring criteria did not demonstrate an increase in ED visit or readmissions rates within 48 h or 15 days of T&A. Additionally, we found a 29% increase in Class I obese children undergoing SDS T&A. 3 Laryngoscope, 134:5223-5230, 2024.

A Blended Learning Course on the Diagnostics of Mental Disorders: Multicenter Cluster Randomized Noninferiority Trial.

Clinical diagnoses determine if and how therapists treat their patients. As misdiagnoses can have severe adverse effects, disseminating evidence-based diagnostic skills into clinical practice is highly important. This study aimed to develop and evaluate a blended learning course in a multicenter cluster randomized controlled trial. Undergraduate psychology students (N=350) enrolled in 18 university courses at 3 universities. The courses were randomly assigned to blended learning or traditional synchronous teaching. The primary outcome was the participants' performances in a clinical diagnostic interview after the courses. The secondary outcomes were diagnostic knowledge and participants' reactions to the courses. All outcomes were analyzed on the individual participant level using noninferiority testing. Compared with the synchronous course (74.6% pass rate), participation in the blended learning course (89% pass rate) increased the likelihood of successfully passing the behavioral test (odds ratio 2.77, 95% CI 1.55-5.13), indicating not only noninferiority but superiority of the blended learning course. Furthermore, superiority of the blended learning over the synchronous course could be found regarding diagnostic knowledge (β=.13, 95% CI 0.01-0.26), course clarity (β=.40, 95% CI 0.27-0.53), course structure (β=.18, 95% CI 0.04-0.32), and informativeness (β=.19, 95% CI 0.06-0.32). Blended learning can help to improve the diagnostic skills and knowledge of (future) clinicians and thus make an important contribution to improving mental health care. ClinicalTrials.gov NCT05294094; https://clinicaltrials.gov/study/NCT05294094.

Open-Door Cervical Laminoplasty Using Instrumentation of Every Level Versus Alternate Levels: A Multicenter, Randomized Controlled Trial.

In the setting of cervical open-door laminoplasty, the question of whether or not every opened laminar level should be instrumented has not been sufficiently investigated. We postulated that the surgical outcomes of open-door laminoplasty with instrumentation of every second opened level (skip-fixation) might not be inferior to those of laminoplasty with instrumentation of every opened level (all-fixation). The purpose of the present study was to test the noninferiority of laminoplasty with skip-fixation in improving myelopathy at 2 years postoperatively compared with all-fixation. Additionally, we compared radiographic and surgical outcomes between the 2 types of procedures. This prospective, multicenter, unblinded randomized controlled trial included patients ≥60 years of age who underwent C3 to C6 open-door cervical laminoplasty for the treatment of degenerative cervical myelopathy. Patients were allocated to the skip-fixation group (n = 80) or the all-fixation group (n = 75) using a permuted block method. The primary outcome was the between-group difference in the Japanese Orthopaedic Association (JOA) score at 2 years postoperatively. Secondary outcomes included surgical data, complications, 2-year change in the JOA score, Neck Disability Index (NDI), EQ-5D-5L (EuroQol 5-dimension 5-level instrument) score, visual analog scale (VAS) score for neck pain, and radiographic outcomes. One hundred and thirty patients (including 66 in the skip-fixation group and 64 in the all-fixation group) completed the trial at 2 years (follow-up rate, 83.9%). The difference in the JOA score at 2 years was 0.0298 (95% confidence interval [CI], -0.706 to 0.766), which was within the noninferiority margin (p < 0.0001; noninferiority test). In the secondary analyses, laminoplasty with skip-fixation demonstrated a significantly shorter surgical time (p = 0.010; Mann-Whitney U test) and greater improvement in the VAS score for neck pain, NDI, and EQ-5D-5L score (p = 0.006, p = 0.047, p = 0.037, respectively; mixed-effect model) compared with all-fixation. There were no significant between-group differences in radiographic outcomes, including the hinge union rate. Skip-fixation may be sufficient to achieve noninferior 2-year postoperative improvement in myelopathy. Additionally, laminoplasty with skip-fixation potentially can lead to improvements in terms of neck pain, neck disability, and quality of life compared with all-fixation. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Comparing standard- and low-dose CBCT in diagnosis and treatment decisions for impacted mandibular third molars: a non-inferiority randomised clinical study

ObjectiveThis randomised clinical study aimed to assess the influence of low-dose cone-beam computed tomography (CBCT) on the visibility of the mandibular canal (MC) and its proximity to mandibular third molars (M3Ms) as assessed by general dental practitioners (GPs) and oral-maxillofacial surgeons (OMFSs), as well as its impact on their clinical decisions, when compared to standard-dose CBCT.Methods154 impacted M3Ms from 90 patients were randomly assigned to three groups for two CBCT exposures using one standard-dose (333 mGy×cm2) and one of the three investigated low-dose (78–131 mGy×cm2) protocols. Blinded assessments of the MC visibility, M3M-MC proximity, surgical approach, crown/root sectioning, and referral decisions, were made by GPs and OMFSs on the images separately. Pairwise comparisons for MC visibility between paired scans were evaluated using Wilcoxon signed rank test, followed by a non-inferiority test with non-inferiority margin of 0.5 on a four-point scale. Differences in other variables between paired scans were evaluated using Wilcoxon signed-rank or McNemar tests.ResultsThe majority (78.5–99.3%) of MCs were clearly identified on standard-dose CBCT by all observers. Pairwise comparisons showed significant differences between paired scans only in MC visibility but not in the M3M-MC proximity or treatment decisions. The mean differences in MC visibility between paired scans ranged 0-0.22 with the upper bounds of the 95% confidence intervals (0.09–0.36) falling within the non-inferiority region.ConclusionsThe investigated low-dose CBCT protocols could provide acceptable image quality for the evaluation of impacted M3Ms in most cases. When compared to standard-dose CBCT, these low-dose CBCT images did not significantly affect the assessments of the M3M-MC proximity, treatment strategies, and patient management decisions made by GPs and OMFSs.Clinical relevanceThe low-dose protocols might be clinically acceptable for M3M management while greatly reducing radiation exposure.

Efficacy of indirect intense pulsed light irradiation on meibomian gland dysfunction: a randomized controlled study.

To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. After three IPL treatments, both groups had significant improvement in MGYSS (both P<0.05). The non-inferiority test showed that improvement in 10-mm group was not inferior to that in 3-mm group (P<0.001). In both groups, temporal regions of both upper and lower eyelids showed significant improvement in MGYSS. Scores of SPEED questionnaire in both groups declined significantly (both P<0.001) and changes of SPEED had no difference between two groups (P=0.57). Density of central corneal subepithelial nerves and TBUTs showed no statistically significant changes. The 3-mm group had improvement on corneal fluorescein staining (P=0.048) and meibomian gland morphology (acini wall thickness P=0.003, hyperreflective points P=0.024) while the 10-mm group had not. The efficacy of IPL indirect irradiation in improving meibomian gland secretion and alleviating dry eye symptoms remains unchanged with increase in treatment distance. IPL may primarily act on the functional improvement of the meibomian glands and corneal nerves.

Non-Inferiority Testing on the Accuracy of Two Qualitative Microbiological Methods on Paired Binary Data

Before implementing a new microbiological test method in pharmaceutical industry, it is required to assess whether it matches or surpasses the detection of microorganisms of the current microbiological method. The United Stated Pharmacopoeia Chapter 1223 (USP < 1223>) proposes two statistical approaches for testing non-inferiority of two qualitative microbiological methods when they can both test the same samples (paired design). The first approach compares the positive rates of the two methods. The non-inferiority test is not influenced by the performance of the methods alone, it is also affected by the spiked bacterial density. The second approach compares most probable numbers (MPNs) between the two methods, but the MPN assumes that the microbiological methods are perfect. To address the two above mentioned flaws, a generalized MPN (gMPN) approach is being proposed. Estimators for the accuracy, detection proportion, and bacterial density parameter are being derived using the method of moments. It will be shown that estimation of the accuracy and detection proportion has limited to no bias, but the bias for the bacterial density can become substantial. A test statistic for non-inferiority of accuracy, along with a sample size formula, is presented, showing nominal Type I error and appropriate power. The proposed approach is demonstrated using real data.

HPB SO46 - Risk Stratification for Acute Pancreatitis: A Retrospective Comparative Analysis between Glasgow-Imrie and BISAP Scoring Systems within a District General Hospital

Abstract Background Risk stratification for acute pancreatitis (AP) is an important tool in clinical decision making. The BISAP score has been validated to be a comparable risk prognostication tool to current models[1, 2]. Current trust practice is the Glasgow-Imrie score, which involves more invasive and non-routine investigations, resulting in an increased cost and labour burden. Additionally, a previous local audit demonstrated poor compliance with only 55% of admissions having a documented score, limiting utility and prognostication. By demonstrating non-inferiority, we aim to implement BISAP as the standard of practice with earlier severity assessment, improved patient experience and minimising unnecessary investigations. Method A retrospective analysis of 153 admissions with acute pancreatitis admitted to a single-site district general hospital over a 12-month period was performed, reviewing electronic patient records for documentation, observations and investigations. Both Glasgow-Imrie and BISAP scores were calculated within 48 and 24 hours of admission retrospectively and respectively. Descriptive statistics was used to summarise data and compare trends between both scores and the severity of acute pancreatitis, ICU admissions and mortality. Logistic regression was utilised to model the relationship between both systems and binary outcomes with area under the curve (AUC) and non-inferiority tests derived to determine efficacy. Results The cohort had a mean age of 57 ± 18.53 (52:48 male:female) with an average LOS of 7.25 ± 10.12 days. 6.54% had severe AP, 3.92% required ICU admisison and 3.26% mortality rate. The AUC value for both models was 0.868 in predicting severity (p&amp;lt;0.001) with Glasgow-Imrie performing better in predicting ICU admission (AUC 0.954 &amp;gt; 0.855, p&amp;lt;0.01) and BISAP outperforming Glasgow-Imrie in predicting mortality (AUC 0.903 &amp;gt; 0.867, p&amp;lt;0.01). Bootstrapping resampling demonstrated no significant difference between models in predicting severity (δAUC 0.0007, 95%CI -0.01181, 0.1167), ICU admission (δAUC 0.1010, 95%CI -0.0113, 0.2140) and mortality (δAUC -0.0366, 95%CI -0.0788, 0.0045). Conclusion Both the Glasgow-Imrie and BISAP scoring systems are accurate in predicting the severity of pancreatitis, ICU admission and mortality. The BISAP score is similar in prognostic accuracy to the Glasgow-Imrie score and is advantageous in being simpler to obtain in clinical practice with a higher rate of completeness. We recommend the BISAP score as a non-inferior, pragmatic risk stratification tool in acute pancreatitis.

Abstract 4128187: Does Health-related Quality of Life Differ by Race over time in Older Patients with Heart Failure from Before to After Heart Transplantation or Long-term Mechanical Circulatory Support?

Background: Minority patients are disproportionately affected by heart failure. Therefore, we aimed to determine the impact of race on health-related quality of life in three groups of older patients (60-80 years) with heart failure who underwent advanced surgical therapies (within race and by surgery group): (1) heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS]), (2) HT without pre-transplant MCS (HT Non-MCS), or (3) long-term MCS, if ineligible for HT. Methods: Secondary analyses were conducted using data from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support study. From 10/1/15 to 12/31/18, 396 patients with heart failure were recruited at 13 U.S. medical centers, of which 305 patients underwent HT (n=161 [68 HT MCS and 93 HT Non-MCS]) or long-term MCS (n=144) and had data through 1 year follow-up. Analysis included non-inferiority testing (Long-term MCS vs HT MCS; Long-term MCS vs HT Non-MCS). To demonstrate non-inferiority, the surgical strategies by race needed to show a difference of at least 5 percentage points, with a 95% lower confidence boundary and a two-tailed p-value&lt;0.05 in health-related quality of life, using the Kansas City Cardiomyopathy-12 Questionnaire Overall Summary Score at baseline and 3-, 6-, and 12 months. Results: The entire cohort was on average 66.2±4.7 years, 78% male, and 84% White. All three surgical groups experienced improved health-related quality of life from before to 1 year follow-up; with the largest gain through 3-months. Using non-inferiority testing, the long-term MCS minority group did not demonstrate non-inferiority when compared to both the HT MCS minority group and HT Non-MCS minority group confidence limits above the non-inferiority margin of -5 (Figure). Also, the White long-term MCS group did not demonstrate non-inferiority when compared to the White HT MCS and White HT Non-MCS groups. Conclusion: Differences in health-related quality of life among groups based on race were not statistically significant. Per non-inferiority testing, HT is superior to long-term MCS for health-related quality of life, regardless of race.

Personalized tourniquet pressure versus uniform tourniquet pressure in trauma orthopedic surgery of extremities: a prospective randomized controlled study

BackgroundTourniquets are widely used in limb fracture surgeries. Controversies still exist about the pressure inflated, including unified tourniquet inflation pressure (UTIP) and personalized tourniquet inflation pressure (PTIP). This study evaluated the hemostatic effect between UTIP and PTIP based on systolic blood pressure (SBP) in extremity fracture patients.Materials and methodsPatients with fresh extremity fractures requiring tourniquets during surgeries were prospectively enrolled and randomly assigned to the UTIP and PTIP groups. The inflation pressure was set to 250 mmHg for the upper extremities and 300 mmHg for the lower extremities in the UTIP group and SBP plus 50 mmHg for the upper extremities and SBP plus 100 mmHg for the lower extremities in the PTIP group. The primary outcome was a hemostatic effect evaluated by the surgeon (satisfied or dissatisfied). Other secondary outcomes included postoperative changes in limb swelling and tourniquet-related complications.ResultsA total of 144 patients were enrolled and randomly assigned to the UTIP group or the PTIP group, and each group has 72 patients (36 upper limb and 36 lower limb). Totally, the hemostasis effect of the PTIP group was worse than that of the UTIP group by non-inferiority test. The hemostatic effect of upper limb fractures with SBP plus 50 mmHg for tourniquet inflation pressure was also worse than that with 250mmHg; however, there was no statistically significant difference between 300mmHg and SBP plus 100 mmHg in the lower limb group hemostasis effect due to a lack of power. Also, no difference was observed in the incidence of complications (p = 1.000) and postoperative changes in limb swelling during 2 days after surgery (upper limb: P1 = 0.546, P2 = 0.545; lower limb: P1 = 0.408, P2 = 0.857) between the PTIP and UTIP group.ConclusionIn the surgery of limb fractures, setting SBP + 50mmHg as tourniquet pressure may not be sufficient for upper limbs. Also, we found no difference between the SBP + 100mmHg and the unified 300mmHg for lower limb surgeries.

Comparing the Efficacy of Empirical Anti-Infective Therapy and Follow-Up Observation for Newly Diagnosed Pulmonary Ground-Glass Nodules With Suspected Inflammatory Etiology: A Multicenter Prospective Observational Study Protocol.

The optimal management strategy for newly diagnosed pulmonary ground-glass nodules (GGNs) with suspected inflammatory etiology remains controversial in clinical practice. Empirical anti-inflammatory therapy is commonly used, but its efficacy compared with that of follow-up observation lacks high-quality evidence. Therefore, this study aims to compare the effectiveness of empirical anti-infective therapy and follow-up observation for pulmonary GGNs in real-world settings. This study intends to include 254 participants with newly discovered pulmonary ground-glass opacities (GGOs) suspected to be related to inflammation but without current radiographic features suggestive of malignancy. Antibiotics will be recommended when the doctor considers the GGOs may be infection-related. Upon enrollment, all participants will be assessed with the Self-Rating Anxiety Scale (SAS) and divided into either the intervention or observation group. A repeat CT scan and SAS assessment will be conducted with all participants after 1 month ( ± 2 weeks) following the initial discovery of the GGOs. The primary outcome is the participants' response rate at the first follow-up CT. The secondary outcome is the GGO response rate and total scores of SAS at 1 month after enrollment. A non-inferiority test will be conducted to compare the outcomes between the two groups. To date, the efficacy and necessity of using antibiotics for GGOs suspected to be inflammatory upon primary CT screening remain controversial. This protocol describes the rationale and methodology to address this unmet clinical need using real-world data, aiming to bridge the gap between clinical guidelines and real-world practice. Trial Registration: ChiCTR2200056975.

Deep Learning Algorithms for Breast Cancer Detection in a UK Screening Cohort: As Stand-alone Readers and Combined with Human Readers.

Background Deep learning (DL) algorithms have shown promising results in mammographic screening either compared to a single reader or, when deployed in conjunction with a human reader, compared with double reading. Purpose To externally validate the performance of three DL algorithms as mammographic screen readers in an independent UK data set. Materials and Methods Three commercial DL algorithms (DL-1, DL-2, and DL-3) were retrospectively investigated from January 2022 to June 2022 using consecutive full-field digital mammograms collected at two UK sites during 1 year (2017). Normal cases with 3-year follow-up and histopathologically proven cancer cases detected either at screening (that round or next) or within the 3-year interval were included. A preset specificity threshold equivalent to a single reader was applied. Performance was evaluated for stand-alone DL reading compared with single human reading, and for DL reading combined with human reading compared with double reading, using sensitivity and specificity as the primary metrics. P < .025 was considered to indicate statistical significance for noninferiority testing. Results A total of 26 722 cases (median patient age, 59.0 years [IQR, 54.0-63.0 years]) with mammograms acquired using machines from two vendors were included. Cases included 332 screen-detected, 174 interval, and 254 next-round cancers. Two of three stand-alone DL algorithms achieved noninferior sensitivity (DL-1: 64.8%, P < .001; DL-2: 56.7%, P = .03; DL-3: 58.9%, P < .001) compared with the single first reader (62.8%), and specificity was noninferior for DL-1 (92.8%; P < .001) and DL-2 (96.8%; P < .001) and superior for DL-3 (97.9%; P < .001) compared with the single first reader (96.5%). Combining the DL algorithms with human readers achieved noninferior sensitivity (67.0%, 65.6%, and 65.4% for DL-1, DL-2, and DL-3, respectively; P < .001 for all) compared with double reading (67.4%), and superior specificity (97.4%, 97.6%, and 97.6%; P < .001 for all) compared with double reading (97.1%). Conclusion Use of stand-alone DL algorithms in combination with a human reader could maintain screening accuracy while reducing workload. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial.

To assess if off-label oral solution of misoprostol compared with licensed oral tablet of misoprostol approved for induction of labour (IOL) is as efficient in resulting in vaginal delivery within 24 h, using a non-inferiority design. Prospective, randomised, non-inferiority, open-label, blinded endpoint trial. Two tertiary level hospitals, Stockholm, Sweden, January 2022 to May 2023. In all, 874 women, without previous caesarean section, with an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks, with a normal cardiotocography, planned for IOL were included. Women were randomised 1:1 to intervention (25 μg oral solution of misoprostol) or control (25 μg oral tablet of misoprostol) two-hourly for a maximum of eight doses. Subsequent methods of induction followed clinical practice. The primary outcome was vaginal delivery within 24 h tested using non-inferiority testing procedures at a non-inferiority margin of 5 percentage points. Secondary efficacy outcomes were tested for superiority of either treatment. Analyses were by intention-to-treat. There were 207 (47.4%) vaginal deliveries within 24 h for women receiving oral solution and 192 (43.9%) vaginal deliveries within 24 h for women receiving oral tablet, establishing non-inferiority with an absolute risk difference of 3.4% (95% CI -3.2% to 10.0%). Women receiving oral solution required fewer doses to reach active labour than women receiving oral tablet (5.7 vs. 6.1, p = 0.007). There were no significant differences for other secondary or safety outcomes. Off-label oral solution of misoprostol was non-inferior to the licensed oral tablet regarding efficacy of IOL defined as vaginal delivery within 24 h. Clinicaltrials.gov identifier: NCT05424445.

A preliminary comparison of the clinical efficacy of repetitive transcranial magnetic stimulation with facial feature point localization and navigated localization in the treatment of depression

ObjectiveTo compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression. Methods42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05. ResultsThe absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. ConclusionThere was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

Using non-inferiority test of proportions in design of randomized non-inferiority trials with time-to-event endpoint with a focus on low-event-rate setting.

For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions. This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions. The sample size required by the two design methods are compared for a wide range of scenarios, varying the underlying Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. Our results showed that there are scenarios for which the non-inferiority test of proportions can have significantly reduced sample size. Specifically, the non-inferiority test of proportions can be considered for cancers with more than 80% long-term survival rate. We provide guidance in choice of this design approach based on parameters of the Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. For cancers with low incidence and low event rates, a non-inferiority trial based on the logrank test is not feasible due to its large required sample size and prolonged enrollment duration. The use of a non-inferiority test of proportions can make a randomized non-inferiority Phase III trial feasible.

Comparative effectiveness trial: Modular behavior approach for young autistic children compared to comprehensive behavioral intervention.

This 24-week single-blind trial tested a modular approach for young autistic children (MAYAC) that was delivered for fewer hours per week and modified based on child progress and parental input compared to comprehensive behavioral intervention treatment as usual (CBI, TAU). Participants were autistic children, ages 18-60 months of age. MAYAC was initially 5 h of intervention per week, one of which was parent training and the other four direct therapy focusing on social communication and engagement, but additional modules could be added for up to 10 h per week. Comprehensive behavior intervention was delivered for ≥15 h per week. Outcome measures included the Vineland Adaptive Behavior Scales; VABS, the Ohio Autism Clinical Improvement Scale - Autism Severity; OACIS - AS and the Pervasive Developmental Disorder Behavior Inventory - Parent; PDDBI-P. Implementation and parent satisfaction measures were also collected. Fifty-six children, mean age of 34 months, were randomized. Within-group analysis revealed significant improvements from baseline to week 24 for both MAYAC (p < 0.0001) and CBI, TAU (p < 0.0001) on the VABS. The noninferiority test was performed to test between group differences and MAYAC was not inferior to CBI, TAU on the VABS (p = 0.0144). On the OACIS - AS, 48.0% of MAYAC and 45.5% of CBI were treatment responders there were no significant changes on the PDDBI-P, for either group. Treatment fidelity was high for both groups (>95%) as was parent satisfaction. Findings from this small trial are promising and suggest MAYAC may be an alternative for some young autistic children and their families to CBI, TAU.

Prospective selective embedding of radical prostatectomy specimens is not inferior to full embedding regarding established and new prognostic parameters.

The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information.