Non-inferiority Test Research Articles

Use of rubber dam versus cotton roll isolation on composite resin restorations’ survival in primary molars: 2-year results from a non-inferiority clinical trial

BackgroundThis non-inferiority randomised clinical trial aimed to evaluate the survival of direct bulk fill composite resin restorations in primary molars using different methods of moisture control: rubber dam isolation (RDI—local anaesthesia and rubber dam) and cotton roll isolation (CRI—cotton roll and saliva ejector). Secondary outcomes included baseline and 2-year incremental cost, self-reported child’s pain scores and patient behaviour during the restorative procedure.MethodsA total of 174 molars (93 children) with dentine caries lesions were randomly allocated to study groups (RDI or CRI) and restored with bulk fill composite resin by trained operators. Two blinded examiners assessed the restorations for up to 24 months. Wong-baker faces and Frankl's behaviour rating scales were used for accessing the child's pain and behaviour, respectively. The primary outcome (restoration survival) was analysed using the two-sample non-inferiority test for survival data using Cox Regression (non-inferiority/alternative hypothesis HR > 0.85; CI = 90%). Bootstrap Linear regression was used for cost analysis and logistic regression for pain and behaviour analysis (α = 5%).ResultsAfter 2-years, 157 restorations were evaluated (drop-out = 9.7%). The survival rate was RDI = 60.4% and CRI = 54.3%. The non-inferiority hypothesis was accepted by the Cox Regression analysis (HR = 1.33; 90% CI 0.88–1.99; p = 0.036). RDI was 53% more expensive when compared to the CRI group. No differences were found between the groups regarding pain (p = 0.073) and behaviour (p = 0.788).ConclusionCotton roll isolation proved to be non-inferior when compared to rubber dam for composite restorations longevity in primary molars. Furthermore, the latest presented the disadvantage of higher cost and longer procedure time.Clinical Significance The moisture control method does not influence the longevity of composite restorations in primary molars. Cotton roll isolation proved to be non-inferior to rubber dam isolation and is a viable option for restoring primary molars.Clinical trial registration registered NCT03733522 on 07/11/2018. The present trial was nested within another clinical trial, the CARies DEtection in Children (CARDEC-03-NCT03520309).

S139 Low Volume Preparation Regimen for Colon Capsule Endoscopy – Clinical Study

Introduction: Colon Capsule Endoscopy (CCE) procedure requires a preparation regimen (PR) to provide a clean visualization of the colon and promote capsule propulsion throughout the colon. Unfortunately, PR remains a significant barrier for patients, who must consume high volume preparation materials. The aim of this study was to demonstrate non-inferiority of a low-volume PR compared to a high-volume PR. Methods: Two new PRs were selected for this study (Table). Healthy participants (age 50+) were assigned to receive either Plenvu/SuPrep/prucalopride (Group A, n=101) or SuPrep/Pico-Salax/prucalopride (Group B, n=99), prior to CCE. The endpoints for this study were overall adequate cleansing, capsule excretion rate in 10 hours, completion and adverse events (AEs). For the historical control (HC) group, a subset of 142 subjects (age 50+) from a previously published diagnostic study which included high volume PR was utilized (1). The new PR groups and HC group were reviewed by the same experienced CCE reader. Sample size estimation and analysis assumed 15% margin for P< 0.025 one-sided non-inferiority Farrington-Manning test. Results: Group A demonstrated superior results as compared to the HC with regards to colon cleansing and completion (P< 0.0001) and was non-inferior with regards to capsule excretion in 10 hours (P< 0.0001) (Figure). Non-inferiority was not established for AEs (P=0.045) as Group A demonstrated a higher rate of AEs, which were mostly mild vomiting. Group B demonstrated non-inferior results as compared to the HC with regards to capsule excretion in 10 hours (P=0.0002), cleansing (P=0.028) and AE (P=0.027). Non-inferiority for completion was not established (P=0.07). Conclusion: A new low volume PR (Group A) achieved superior completion when compared to HC; however, the AE results were not inferior. AEs were mostly mild vomiting and the increase may be due to regulation changes in the past decade which led to more events being classified as AEs. Plenvu/SuPrep/prucalopride may be an alternative low volume PR for CCE procedure.Figure 1.: Study endpoints rate by regimens Table 1. - Description of the preparation regimens Low Volume Preparation Regimen High Volume Preparation Regimen Time Group A Group B Time Historical Control (HC) Group Day -2 All day Water At least 10 glasses At least 10 glasses Day -2 All day Water At least 10 glasses Evening Senna Tablets 40 mg (2 × 20 mg) 40 mg (2 × 20 mg) Bedtime Senna Tablets 4 Tablets (12 mg) Day -1 All day Clear liquid diet Day -1 All day Clear liquid diet 20:30 - 22:00 Evening prep 0.5 L Plenvu 0.5 L SuPrep 19:00 - 21:00 Evening prep 2 liters of PEG (SF-ELS) solution Water 1 L water 1 L water Day 0 07:00 - 07:30 Morning prep 0.5 L Plenvu 0.5 L SuPrep Day 0 07:00 - 08:30 Morning prep 2 liters of PEG (SF-ELS) solution 07:30 - 08:30 Water 1 L water 1 L water 08:30 Tablet Resolor**, 2 mg Resolor**, 2 mg 09:15 (up to 09:45) PillCam PillCam PillCam 09:15 PillCam PillCam 10:00 - 10:30 * Boost 1 (G2SB) 0.5 L SuPrep 0.15 L Pico-Salax 10:00 - 10:30* Boost 1 (G2SB) 0.5 L SuPrep 10:30 - 11:30 Water 1 L water 1 L water 10:30 - 11:30 Water 1 L Water 12:00 - 12:15 Boost 2 (2 hours after Boost 1) 0.25 L SuPrep 0.075 L Pico-Salax 13:00 - 13:15 Boost 2 (3 hours after Boost 1) 0.25 L SuPrep 12:15 - 12:45 Water 0.5 L water 0.5 L water 13:15 - 13:45 Water 1 L Water 14:00 - 14:15 Boost 3 (2 hours after Boost 2) 0.25 L SuPrep 0.075 L Pico-Salax 15:00 - 15:15 Suppository (2 hours after Boost 2) 10 mg bisacodyl 14:15 - 14:45 Water 0.5 L water 0.5 L water 15:00 Light meal (1 hour after Boost 3) 17:00 Light meal (2 hours after Suppository) 16:00 Suppository (1 hour after the meal) 10 mg bisacodyl 10 mg bisacodyl Maximum Solution Volume 2L 1.3L Maximum Solution Volume 4.75L *Time of capsule passage into small bowel (G2SB( is estimated. 10mg Reglan is administrated in case the capsule fails to enter SB within 1h from ingestion (alert 0).**Resolor is the specific brand of prucalopride that was used.

Image quality of abdominal ultrasonography after esophagogastroduodenoscopy is preserved by using carbon dioxide insufflation: A non-inferiority test in the same subject.

Because bowel gas deteriorates the image quality of abdominal ultrasonography (AUS), it is common to perform AUS prior to esophagogastroduodenoscopy (EGD). This one-way order limits the availability of examination appointments. To evaluate whether EGD using insufflation of carbon dioxide (CO2), which is rapidly absorbed by the gastrointestinal mucosa, preserves the image quality of AUS performed subsequently, we designed a non-inferiority test in which each subject underwent AUS, EGD with CO2 insufflation, and a second AUS, in that order. All saved AUS moving images were randomized and imaging quality was evaluated at 16 organs using a four-point Likert-like scale that divides the depiction rate by 25%. Sample size was calculated to be 26 using the following: non-inferiority margin of -0.40 corresponding to depiction rate of -10%, difference of means of 0.40, common standard deviation of 1.25, power of 90%, and 1-sided α-level of 0.025. We enrolled 30 subjects. The mean and 95% confidence interval (CI) of the image quality score of all 16 organs at pre- and post-EGD AUS in the 30 subjects were 3.54 [3.48-3.60] and 3.46 [3.39-3.52], respectively. The difference in the means was 0.08 of the scores, corresponding to a 2% depiction rate. The effect size was 0.172. The image quality of post-EGD AUS was not inferior, as demonstrated by the 97.5% CI of the difference, which did not cross the non-inferiority margin of -0.40. In conclusion, the use of CO2 for insufflation in EGD does not cause much deterioration in the image quality of AUS performed subsequently. Therefore, it is permissible to perform EGD prior to AUS, which is expected to improve the efficiency of examination setup.

Non-inferiority testing for qualitative microbiological methods:Assessing and improving the approach in USP

ABSTRACT The United States Pharmacopoeia (USP) presents two approaches for showing non-inferiority of an alternate qualitative microbiological method versus a compendial method. One approach compares the positive rates for the alternate and compendial methods at one spike level, while the other one compares multiple most probable number (MPN) estimates from a multi-spike design using a t-test. In this paper, we discuss these approaches under certain assumptions and propose a third approach that can be used for both single and multiple dilutions, which we call the generalized MPN (gMPN) approach. Simulations, using Poisson distributed numbers of microorganisms in test samples, confirm that the USP approach based on rates is not suitable, that the USP approach based on MPNs is appropriate for non-inferiority, but the gMPN approach outperforms the MPN-based approach and is therefore recommended.

Cerclage in surgically shortened uterine cervix and pregnancy outcome: A retrospective comparison between the abdominal and vaginal procedures.

Cerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy. The aim of this study was to compare TAC and TVC in post-cervical conization pregnancies. A retrospective, two-group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n=14; TVC, n=18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups. The preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p=0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p=0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter. Women who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial

The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Feasibility of dance therapy using telerehabilitation on trunk control and balance training in patients with stroke: A pilot study.

Background:This randomized controlled trial aimed to investigate the effects of dance therapy using telerehabilitation on trunk control and balance training in patients with stroke and compare them with the effects of conventional treatment.Methods:We enrolled 17 patients with subacute or chronic stroke who were randomly assigned to either an experimental or a control group. In addition to conventional physical therapy, the experimental group (n = 9) participated in 40-minute, non-face-to-face, dance-therapy sessions and the control group (n = 8) received conventional physical therapy. The primary outcome measures were the Trunk Impairment Scale (TIS) scores to assess trunk control and balance function between the 2 groups as a measure of change from baseline to after the intervention.Results:We found that the TIS scores of the patients in the experimental group significantly improved (P = .017). The TIS results indicated non-inferiority within a predefined margin for dance therapy using telerehabilitation (difference = -0.86, 95% confidence interval [CI] = -2.21 to 0.50).Conclusion:Dance therapy using telerehabilitation significantly improved the TIS scores in the experimental group and was not inferior to conventional rehabilitation treatment when compared in a non-inferiority test. The remote dance program may therefore have similar effects to those of conventional treatment regarding trunk-control improvement in patients with stroke.

Survival outcomes in a prospective randomized multicenter Phase III trial comparing patients undergoing anatomical segmentectomy versus standard lobectomy for non-small cell lung cancer up to 2 cm

ObjectivesThe oncological equivalence of anatomical segmentectomy for early stage non-small cell lung cancer (NSCLC) is still controversial. Primary aim of this study was survival outcomes in combination with improved quality of life after segmentectomy compared with lobectomy in patients with pathological stage Ia NSCLC (up to 2 cm, 7th edition) Materials and MethodsWe conducted a prospective, randomized, multicenter phase III trial to confirm the non-inferiority of segmentectomy to lobectomy in regard to prognosis (trial No. DRKS00004897). Patients were randomized to undergo either segmentectomy or lobectomy and followed up for 5-years survival and tumor recurrence. The 5-year hazard ratio comparing lobectomy with segmentectomy was required to remain above 0.5. ResultsBetween October 2013 and June 2016, 108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled; 54 were assigned to lobectomy and 54 (1 drop-out) to segmentectomy. In-hospital and 90 days mortality was 0% in both groups. Overall survival at 5 years was 86.52% in the lobectomy compared to 78.21% in the segmentectomy group (HR = 0.61, (95% CI 0.23–1.66), p-value of non-inferiority test, p-ni = 0.687). Disease free survival was 77.29% for the lobectomy and 77.96% for the segmentectomy patients (HR = 1.50, (95% CI 0.60–3.76), p-ni = 0.019). At a median follow-up of 5 years, no differences were noted in either the locoregional or distant recurrent disease in both groups (9.4% vs 7.4%, p-ni = 0.506). ConclusionOverall survival, locoregional and distant recurrences was not significantly difference for patients undergoing either segmentectomy or lobectomy for stage Ia NSCLC. The targeted non-inferiority of segmentectomy to lobectomy could not be proven for primary endpoint overall survival, but was significant for the secondary endpoint of disease free survival.

Noninferiority testing with censoring when the event rate is low.

The PREDICT TB trial tests noninferiority of an abbreviated treatment regimen (arm A) vs a conventional treatment regimen (arm C). Treatment trials of drug-susceptible tuberculosis are expected to have low event rates (ie, relapse probabilities around 3-5%). We examine the question of what is the "best" way to test for noninferiority in a setting with low event rates. In a series of simulations supported by theoretical arguments, we examine operating characteristics of five tests, including normal approximation, exact, and simulation-based tests. Two of these tests are constructed from Kaplan-Meier based-estimators, which account for variable follow-up time (and those lost to follow-up). We evaluate the effect of loss to follow-up via simulations. We also examine the results of the five tests on a data set similar to PREDICT TB, the REMoxTB trial. We find that the normal approximation tests perform well, albeit with small type I error rate inflation. We also find that the Kaplan-Meier methods generally have larger power than the other tests, especially when there is between 10-30% loss to follow-up.

Safety and Effectiveness of a Catheter With Contact Force and 6-Hole Irrigation for Ablation of Persistent Atrial Fibrillation in Routine Clinical Practice

The ThermoCool SmartTouch catheter (ablation catheter with contact force and 6-hole irrigation [CF-I6]) is approved by the US Food and Drug Administration (FDA) for paroxysmal atrial fibrillation (AF) ablation and used in routine clinical practice for persistent AF ablation, although clinical outcomes for this indication are unknown. There is a need to understand whether data from routine clinical practice can be used to conduct regulatory-grade evaluations and support label expansions. To use health system data to compare the safety and effectiveness of the CF-I6 catheter for persistent AF ablation with the ThermoCool SmartTouch SurroundFlow catheter (ablation catheter with contact force and 56-hole irrigation [CF-I56]), which is approved by the FDA for this indication. This retrospective, comparative-effectiveness cohort study included patients undergoing catheter ablation for persistent AF at Mercy Health or Mayo Clinic from January 1, 2014, to April 30, 2021, with up to a 1-year follow-up using electronic health record data. Use of the CF-I6 or CF-I56 catheter. The primary safety outcome was a composite of death, thromboembolic events, and procedural complications within 7 to 90 days. The exploratory effectiveness outcome was a composite of AF-related hospitalization events after a 90-day blanking period. Propensity score weighting was used to balance baseline covariates. Risk differences were estimated between catheter groups and averaged across the 2 health care systems, testing for noninferiority of the CF-I6 vs the CF-I56 catheter with respect to the safety outcome using 2-sided 90% CIs. Overall, 1450 patients (1034 [71.3%] male; 1397 [96.3%] White) underwent catheter ablation for persistent AF, including 949 at Mercy Health (186 CF-I6 and 763 CF-I56; mean [SD] age, 64.9 [9.2] years) and 501 at Mayo Clinic (337 CF-I6 and 164 CF-I56; mean [SD] age, 63.7 [9.5] years). A total of 798 (55.0%) had been treated with class I or III antiarrhythmic drugs before ablation. The safety outcome (CF-I6 - CF-I56) was similar at both Mercy Health (1.3%; 90% CI, -2.1% to 4.6%) and Mayo Clinic (-3.8%; 90% CI, -11.4% to 3.7%); the mean difference was noninferior, with a mean of 0.5% (90% CI, -2.6% to 3.5%; P < .001). The effectiveness was similar at 12 months between the 2 catheter groups (mean risk difference, -1.8%; 90% CI, -7.3% to 3.7%). In this cohort study, the CF-I6 catheter met the prespecified noninferiority safety criterion for persistent AF ablation compared with the CF-I56 catheter, and effectiveness was similar. This study demonstrates the ability of electronic health care system data to enable safety and effectiveness evaluations of medical devices.

Clinical validation of Wave-CAIPI susceptibility-weighted imaging for routine brain MRI at 1.5 T.

Wave-CAIPI (Controlled Aliasing in Parallel Imaging) enables dramatic reduction in acquisition time of 3D MRI sequences such as 3D susceptibility-weighted imaging (SWI) but has not been clinically evaluated at 1.5 T. We sought to compare highly accelerated Wave-CAIPI SWI (Wave-SWI) with two alternative standard sequences, conventional three-dimensional SWI and two-dimensional T2*-weighted Gradient-Echo (T2*w-GRE), in patients undergoing routine brain MRI at 1.5 T. In this study, 172 patients undergoing 1.5 T brain MRI were scanned with a more commonly used susceptibility sequence (standard SWI or T2*w-GRE) and a highly accelerated Wave-SWI sequence. Two radiologists blinded to the acquisition technique scored each sequence for visualization of pathology, motion and signal dropout artifacts, image noise, visualization of normal anatomy (vessels and basal ganglia mineralization), and overall diagnostic quality. Superiority testing was performed to compare Wave-SWI to T2*w-GRE, and non-inferiority testing with 15% margin was performed to compare Wave-SWI to standard SWI. Wave-SWI performed superior in terms of visualization of pathology, signal dropout artifacts, visualization of normal anatomy, and overall image quality when compared to T2*w-GRE (all p < 0.001). Wave-SWI was non-inferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall image quality (all p < 0.001). Wave-SWI was superior to standard SWI for motion artifact (p < 0.001), while both conventional susceptibility sequences were superior to Wave-SWI for image noise (p < 0.001). Wave-SWI can be performed in a 1.5 T clinical setting with robust performance and preservation of diagnostic quality. • Wave-SWI accelerated the acquisition of 3D high-resolution susceptibility images in 70% of the acquisition time of the conventional T2*GRE. • Wave-SWI performed superior to T2*w-GRE for visualization of pathology, signal dropout artifacts, and overall diagnostic image quality. • Wave-SWI was noninferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall diagnostic image quality.

Clinical application of absorbable collagen thread and cosmetic suture technique in emergency treatment of children's facial trauma.

To explore the effect of absorbable collagen thread and cosmetic suture technique on scar inhibition after emergency facial trauma in children, and to explore the application value of absorbable collagen thread in emergency facial trauma. Children who received emergency treatment of facial trauma in plastic surgery department from January 2021 to January 2022 were analysed retrospectively, and were divided into absorbable collagen thread group and non-absorbable nylon thread group. The general data, scar appearance and local symptoms of the two groups were analysed, and the scar appearance was scored by scar beauty rating scale and non-inferiority test was analysed statistically. A total of 632 children with facial trauma were included in this study, including 458 patients with absorbable collagen thread and 174 patients with non-absorbable nylon thread. The SCAR score of the absorbable collagen thread group (3.03 ± 1.57) was similar to that of the non-absorbable nylon thread group (2.98 ± 2.39) (95% confidence interval), and the final scar outcome score was not statistically different (P > 0.05). All families of the patients were satisfied with the results of the procedure, 95% very satisfied. The use ofabsorbable collagen thread and cosmetic suture technique to treat the wounds of children with facial emergency trauma, resulted in good wound healing, little scar expansion, low incidence of erythema and pigment abnormality, no obvious surgical trace, and no scar hypertrophy or atrophy.The overall impression was good, the pain of stitch removal was avoided for children's patients, and the satisfaction of family members was high. Cosmetic suture technique with absorbable sutures is worthy of clinical application.

Stepped Care Versus Standard Care for Children After Trauma: A Randomized Non-Inferiority Clinical Trial.

Trauma-focused cognitive-behavioral therapy (TF-CBT) is an evidence-based therapist-led treatment for children after trauma. Parents often experience barriers to treatment engagement, including cost. Stepped care TF-CBT (SC-TF-CBT) was developed as an alternative delivery system. Step One is a parent-led therapist-assisted treatment. Step Two provides therapist-led TF-CBT for children who did not benefit from Step One and require more intensive treatment. This study compared SC-TF-CBT to standard TF-CBT in a community-based non-inferiority trial. A total of 183 children (aged 4-12 years) experiencing posttraumatic stress symptoms (PTSS) and their caregivers were randomly assigned to SC-TF-CBT or standard TF-CBT within 6 community clinics. Assessments occurred at baseline, mid- and posttreatment, and 6 and 12 months. Primary outcomes included PTSS and impairment. Secondary outcomes included severity, diagnostic status, remission, and response. Treatment cost, acceptability, and satisfaction were measured. Difference and non-inferiority tests were applied. SC-TF-CBT participants changed at rates comparable to participants in TF-CBT for primary and secondary measures. SC-TF-CBT was non-inferior to TF-CBT for PTSS, impairment, and severity at all time points except for impairment at the 6-month assessment. Attrition did not differ between treatment arms (132 participants were completers). Baseline treatment acceptability was lower for SC-TF-CBT parents, although there was no difference in expected treatment improvements or treatment satisfaction at posttreatment. Based on regression estimates, total costs were 38.4% lower for SC-TF-CBT compared to TF-CBT, whereas recurring costs were 53.7% lower. Stepped Care TF-CBT provides an alternative way to deliver treatment for some children and parents, with reduced cost for providers and parents. Stepped Care for Children after Trauma: Optimizing Treatment; https://clinicaltrials.gov; NCT02537678.

Non-sterile gloves and dressing versus sterile gloves, dressings and drapes for suturing of traumatic wounds in the emergency department: a non-inferiority multicentre randomised controlled trial

BackgroundPatients with traumatic wounds frequently present to the ED. Literature on whether to treat these wounds sterile or non-sterile is sparse. Non-sterile treatment has the advantage of saving resources and...

Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Assessing the practicality of using a single knowledge-based planning model for multiple linac vendors.

PurposeKnowledge‐based planning (KBP) has been shown to be an effective tool in quality control for intensity‐modulated radiation therapy treatment planning and generating high‐quality plans. Previous studies have evaluated its ability to create consistent plans across institutions and between planners within the same institution as well as its use as teaching tool for inexperienced planners. This study evaluates whether planning quality is consistent when using a KBP model to plan across different treatment machines.Materials and methodsThis study used a RapidPlan model (Varian Medical Systems) provided by the vendor, to which we added additional planning objectives, maximum dose limits, and planning structures, such that a clinically acceptable plan is achieved in a single optimization. This model was used to generate and optimize volumetric‐modulated arc therapy plans for a cohort of 50 patients treated for head‐neck cancer. Plans were generated using the following treatment machines: Varian 2100, Elekta Versa HD, and Varian Halcyon. A noninferiority testing methodology was used to evaluate the hypothesis that normal and target metrics in our autoplans were no worse than a set of clinically‐acceptable baseline plans by a margin of 1.8 Gy or 3% dose‐volume. The quality of these plans were also compared through the use of common clinical dose‐volume histogram criteria.ResultsThe Versa HD met our noninferiority criteria for 23 of 34 normal and target metrics; while the Halcyon and Varian 2100 machines met our criteria for 24 of 34 and 26 of 34 metrics, respectively. The experimental plans tended to have less volume coverage for prescription dose planning target volume and larger hotspot volumes. However, comparable plans were generated across different treatment machines.ConclusionsThese results support the use of a head‐neck RapidPlan models in centralized planning workflows that support clinics with different linac models/vendors, although some fine‐tuning for targets may be necessary.

Inversed probability case-control analysis of operative burr hole evacuation versus subdural evacuating port system for chronic subdural hematomas: Clinical and economic outcomes

IntroductionThere are multiple treatments for a chronic subdural hematoma, a significant cause of neurosurgical morbidity that cost the healthcare system $5B in 2007, but few generalizable prospective studies. The purpose of this study was to examine outcomes of bedside Subdural Evacuation Port System (SEPS) placement as compared to operating room burr hole evacuation (BHE) to acquire data to support a randomized trial. MethodsAll procedures were performed in a single institution between 2011 and 2019. Patients were included if > 18 years of age, had chronic subdural hematoma, and were treated by SEPS or BHE. Patients with prior neurosurgical history, mass lesions or bilateral hematomas were excluded. Patients who met inclusion for SEPS (n = 55) or BHE (n = 105). Samples were propensity matched to account for variability. Non-inferiority tests compared outcomes. Cost data was obtained through billable charges. ResultsPatients with multiple comorbidities were more likely to undergo SEPS drainage. Noninferiority tests reported no statistically significant evidence to suggest SEPS drains were worse in reoperation-rate (18% vs 9%), post-operative seizure, or functional outcome. SEPS drain placement trended towards a faster time to procedure (3 h faster; p = 0.07) but the overall hospital stay was longer (4.23 vs 5.81, p = 0.01). SEPS drain placement costs are less than BHE, but these patients had 25% higher overall hospital costs (p = 0.01) due to comorbidities and increased hospital stay.

Local Infiltration Analgesia Versus Interscalene Block for Pain Management Following Shoulder Arthroplasty: A Prospective Randomized Clinical Trial.

While providing effective analgesia following shoulder arthroplasty, an interscalene block has known complications. Local infiltration analgesia (LIA) using ropivacaine has been successfully employed in other joint arthroplasties, but its efficacy in shoulder arthroplasty has not been studied extensively. The purpose of this study was to compare pain and opioid consumption between LIA and an interscalene block following shoulder arthroplasty. Patients undergoing primary shoulder arthroplasty were prospectively randomized into 2 groups: the block group received an interscalene block using liposomal bupivacaine, and the injection group received an LIA injection intraoperatively. The LIA injection included ropivacaine, epinephrine, ketorolac, and normal saline solution. Postoperative visual analog scale pain scores, opioid consumption in morphine milligram equivalents, and complications were compared between the groups. The mean pain scores during the first 24 hours postoperatively were used to test noninferiority of LIA compared with an interscalene block. The study included 74 patients (52 men and 22 women with a mean age of 69 years; 37 were in the injection group and 37 in the block group). There was no significant difference between the groups with respect to pain scores at any postoperative time points (p > 0.05), except for the 8-hour time point, when the injection group had a significantly higher pain score than the block group (p = 0.01). There was no significant difference in opioid consumption between the groups at any time points postoperatively (p > 0.05). The amount of intraoperative opioid consumption was significantly higher in the injection group (p < 0.001). In noninferiority testing for the mean pain scores during the first 24 hours, the injection group was found to be noninferior to the block group. One patient in the block group developed transient phrenic nerve palsy. One patient in the injection group developed dislocation after reverse arthroplasty related to noncompliance. The mean procedure hospital charge was $1,718 for an interscalene block and $157 for LIA. LIA and an interscalene block provided similar analgesia during the first 24 hours after primary shoulder arthroplasty. LIA was associated with worse pain at 8 hours postoperatively and more intraoperative opioid consumption but was also substantially less costly. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Removal of the cervical collar from alpine rescue protocols? A biomechanical non-inferiority trial in real-life mountain conditions

BackgroundAlpine skiing rescues are challenging because of the mountainous environment and risks of cervical spine motion (CSM) induced during victims’ extrications (EXs) and downhill evacuations (DEs). The benefits of applying a cervical collar (CC) over manual in-line stabilization without CC (MILS) in terms of spinal motion restriction during simulated alpine rescues are undocumented. Our hypothesis was that CSM recorded using MILS alone is non-inferior to CSM recorded with a CC according to a 10 degrees margin.MethodsA total of 32 alpine extrications and 4 downhill evacuations on different slope conditions were performed using a high fidelity mannequin designed with a motion sensors instrumented cervical spine. The primary outcome was the peak extrication 3D excursion angle (Peak 3D θEX,) of the mannequin’s head. The secondary objectives were to describe the time to extrication completion (tEX) and to highlight which extrication manipulation is more likely to induce CSM.ResultsThe median Peak 3D θEX recorded during flat terrain extrications using CC was 10.77° (95% CI 7.31°–16.45°) compared to 13.06° (95% CI 10.20°–30.36°) using MILS, and 16.09° (95% CI 9.07°–37.43°) for CC versus 16.65° (95% CI 13.80°–23.40°) using MILS on a steep slope. Peak 3D θEX with CC or using MILS during extrications were equivalent according to a 10 degrees non-inferiority hypothesis testing (p < 0.05). Time to extrication completion (tEX) was significantly reduced using MILS without CC on a flat terrain with a median duration of 237,3 s (95% CI 197.8 s, 272.2 s) compared to 358.7 s (95% CI 324.1 s, 472.4 s). During downhill evacuations, CSM with and without CC across all terrain conditions were negligible (< 5°). When CC is used; its installation manipulation induces the highest CSM. When EXs are done using MILS without CC, the logroll initiation is the manipulation inducing the highest risk of CSM.ConclusionFor experienced ski patrollers, the biomechanical benefits of spinal motion restriction provided by CC over MILS during alpine skiing rescues appear to be marginal and CC use negatively affects rescue time.

Impact of Early Oral Antibiotic Therapy in Infants With Bacteremic Urinary Tract Infections.

To determine the effect of early conversion to oral antibiotics in infants ≤90 days with gram-negative bacteremia and concomitant urinary tract infection on hospital length of stay (LOS) and 30-day revisits for urinary tract infection. This retrospective cohort study included infants ≤ 90 days who had concomitant positive blood and urine cultures with gram-negative bacteremia at 22 hospitals from January 1, 2002 through January 31, 2020. Early oral conversion was defined as a maximum intravenous (IV) duration of 4 days. We conducted a noninferiority test to compare early oral conversion to long IV therapy. A propensity score framework was used to assess comparisons in survey-weighted regression models using matched weights. Among 174 infants, 73 infants received early oral conversion. The LOS was shorter in infants receiving early oral conversion compared to long IV therapy (median 2 days [interquartile range 2, 3] vs 4 days [3, 5]), descriptively (P < .001) and in noninferiority analysis (ratio = 0.43; 90% CI 0.35, 0.53, P < .001). Thirty-day revisits occurred in 5 of 174 (2.8%) of total patients. Early oral conversion did not meet our noninferiority criteria for the 30-day revisits (odds ratio: 4.22, 90%; confidence interval: 0.83, 21.34, P = .91). Early oral conversion was associated with shorter LOS. The rate of 30-day revisit rates overall was low.