Controlled Noninferiority Trial Research Articles

Electroacupuncture versus solifenacin succinate for female overactive bladder: study protocol for a multicentre, randomised, controlled, double-dummy, non-inferiority trial

IntroductionOveractive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for...

Safety and feasibility of triage and rapid discharge of patients with chest pain from emergency room: a pragmatic, randomised non-inferiority control trial of the European Society of Cardiology (ESC) 0–1 hour pathway vs. conventional 0-3 hour accelerated diagnostic protocol.

Patients presenting with chest pain represent a significant proportion of Emergency Department (ED) attendances but only a minority, typically 10%, have a final diagnosis of myocardial infarction (MI). Prompt discharge of patients without MI will alleviate ED overcrowding as well as improve patient satisfaction and reduce exposure to risk of hospital acquired infections such as Covid 19.The measurement of cardiac troponin (cTn) by a high sensitivity method is recommended by the National Institute for health and Care Excellence (NICE) for rapid categorisation of patients presenting with chest pain. Strategies proposed include measurement on admission and one hour from admission (ESC 0–1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and three hours from admission (0–3-hour pathway, which is conventional and widely adopted).The primary objective of this study is twofold: firstly, to assess the safety, feasibility, and impact of implementing the ESC (European Society of Cardiology) 0–1-hour pathway in clinical practice by reference to the more established ESC 0–3-hour protocol. The principal outcome measure will be the safety of the ESC 0–1-hour protocol. However, there are concerns that the time from sample draw to result availability (typically around 60 minutes) will impact on the feasibility of the ESC 0–1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyser (point of care testing, POCT), which will produce results in 15 minutes is a feasible alternative to laboratory testing. We will compare the results produced by POCT with the laboratory results in the context of the ESC 0-1 hour and 0–3-hour pathway, as a nested controlled study in the context of a randomised controlled trial. (clinicaltrials.gov: NCT05322395)

In-Person Versus Online Training in Simulations of Helping Babies Breathe: A Randomized Controlled Trial.

Birth asphyxia is a leading cause of neonatal deaths, but simple interventions may prevent it. The Helping Babies Breathe (HBB) course has significantly reduced neonatal mortality ratesin lower and middle-income countries (LMICs) by training healthcare providers (i.e. midwives and nurses) on the essential skills of bag-and-mask ventilation and postnatal care. Although several studies have supported the efficacy of virtual learning in other medical education programs, there is still a lack of knowledge regarding a virtual approach to HBB. This study aims to compare the effectiveness of online versus in-person learning of the HBB course among medical and nursing students. The study is a two-arm parallel randomized non-inferiority controlled trial, that includes medical and nursing students. Participants were randomly assigned to either online or in-person debriefing during the hands-on simulations of HBB. They attended a pre-recorded lecture before being assigned to one of three instructors for the simulation lab. Participants completed a seven-point anonymous Likert-based questionnaire and a standardized Debriefing Assessment for Simulation in Healthcare Student Version (DASH-SV) Short Form. The primary outcome was the Objective Structured Clinical Exam (OSCE) grade. The trial is listed on ClinicalTrials.gov with the registration number NCT05257499. 47 participants completed the study, with similar baseline characteristics in each arm (gender, age, and class). The participants in both arms reported high levels of satisfaction and confidence, with no significant difference between the two arms. The DASH score over 7 was also similar in the online arm(6.27±0.26) compared to the in-person arm (6.55±0.13) (p=0.07). The mean OSCE scorein the online arm (45.8±5.2) was comparable to the mean OSCE score in the in-person arm (41.3±5.0) (p=0.22). Both online and in-person participants failed the OSCE. The survey responses conveyed that online simulation training is comparable to in-person simulation for the HBB course. Both online and in-person participants failed the OSCE most likely because they needed more training on HBB. This could be due to the fact that the material is too new to the students who needed more practice to pass the OSCE. Further research is needed to confirm these results and explore the long-term impact of online neonatal resuscitation training.

Transcutaneous neuromodulation versus oxybutynin for neurogenic detrusor overactivity in persons with spinal cord injury: A randomized, investigator blinded, parallel group, non-inferiority controlled trial

Study design This study is a randomized, investigator-blinded, controlled trial with a non-inferiority design. Objective To investigate the effectiveness of neuromodulation by transcutaneous electrical stimulation of the somatic afferent nerves of the foot in neurogenic detrusor overactivity (NDO) in persons with spinal cord injury (SCI) and compare its effectiveness with oral oxybutynin. Setting The study was conducted in a rehabilitation in-patient ward of a tertiary care hospital. Methods Twenty-nine persons with SCI with NDO, either sex, aged 18 years and above were randomized into two groups, one group receiving oral oxybutynin (5 mg thrice a day for two weeks) and the other transcutaneous electrical stimulation (5 Hz, 200 µs pulse, biphasic, amplitude up to 60 mA, 30 min/day for two weeks). Bladder capacity was evaluated by clinical bladder evaluation (i.e. bladder capacity measured by adding leak volume, voiding volume if any, and post-void residue using a catheter) and cystometric bladder capacity by one-channel cystometry. Maximum cystometric pressure was evaluated by one-channel water cystometry. Data were analyzed with Fisher's Exact, t-test, and Wilcoxon rank sum tests. Results Bladder capacity improved significantly in the oxybutynin and neuromodulation groups as measured by one-channel water cystometry (136 ml vs. 120.57 ml) and clinical evaluation (138.93 ml vs. 112 ml). The increase in the neuromodulation group achieved the pre-decided non-inferiority margin of 30 ml over the oxybutynin group when measured by one-channel water cystometry but not by clinical evaluation. Maximum cystometric pressure did not significantly improve in either group when compared with the baseline. Conclusion Transcutaneous neuromodulation and oxybutynin effectively increased bladder capacity in persons with SCI with NDO. Neuromodulation by once-a-day transcutaneous electrical stimulation was non-inferior to thrice-a-day oxybutynin when evaluated by one-channel water cystometry. Trial registration: Clinical Trials Registry India identifier: CTRI/2018/05/013735.

State of the Science: Evidence‐based treatments for posttraumatic stress disorder delivered via telehealth

AbstractPsychotherapy delivered via telehealth technology is not an artifact of the COVID‐19 pandemic. Indeed, widespread, telehealth‐delivered, evidence‐based psychotherapy preceded the pandemic, as did randomized controlled noninferiority trials supporting this modality. It is, thus, not difficult to predict that telehealth will be an integral part of daily clinical life moving forward. With respect to posttraumatic stress disorder (PTSD) specifically, there is a substantial number of studies on the feasibility, acceptability, and effectiveness of evidence‐based treatments provided via videoconferencing. In this review, we delineate the literature establishing strong support for remote delivery of prolonged exposure (PE) and cognitive processing therapy (CPT); there is also promising support for written exposure therapy (WET) and trauma‐focused cognitive behavioral therapy (TF‐CBT). We also mention adjunctive and integrative modifications to better serve patients with PTSD. One such intervention, behavioral activation and therapeutic exposure (BATE), has several studies supporting telehealth delivery, whereas concurrent treatment of PTSD and substance use disorders using the PE protocol (COPE) and cognitive behavioral therapy for insomnia (CBT‐I) would benefit from further research. Integrating instrumental peer support into telehealth‐delivered PE shows promise in retaining patients in treatment. Finally, we provide ideas to maximize telehealth delivery effectiveness, explore future research directions, and discuss ways to advocate for the expansion of telehealth services from an equity perspective.

MP20-19 Bipolar Enucleation of the Prostate (BipolEP) versus Transurethral Resection of the Prostate: A Prospective Randomized Controlled Non-Inferiority Trial

MP20-19 Bipolar Enucleation of the Prostate (BipolEP) versus Transurethral Resection of the Prostate: A Prospective Randomized Controlled Non-Inferiority Trial

Feeds Alone versus Intravenous Fluids and Feeds for Treatment of Mild Hypernatremia in Otherwise Healthy Neonates – An Open-labeled Randomized Controlled Noninferiority Trial

Background: The treatment of hypernatremia in newborns is usually done by giving intravenous (IV) fluids. Methodology: This study aimed to determine whether treating neonates with hypernatremia using oral feeds was not inferior by a margin of 10% to treatment with IV fluids and feeds in achieving a safe decline in serum sodium. A decrease in serum sodium ≤0.5 mEq/L/h over 24 h of treatment was considered a safe decline. Neonates with serum sodium 150–155 mEq/L were randomized to receive oral feeds ad libitum (Group A) or 5% dextrose +0.45% normal saline (D5 ½ NS) and oral feeds (group B). Results: There were 43 neonates in Group A and 42 neonates in Group B. It was found that a safe decline in serum sodium was seen in 60.5% of Group A neonates and 47.6% of Group B neonates (P = 0.246). There was no significant difference in the duration of treatment or duration of hospital stay. Group B babies had more weight gain compared to Group A. No complications were observed in the groups. Conclusion: Treating mildly hypernatremic neonates with serum sodium 150–155 mEq/L using oral feeds alone may not be inferior to IV fluids with oral feeds in achieving a safe decline in serum sodium.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial

BackgroundKnee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA.Materials and methodsIn the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial.ConclusionThe results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future.Trial registration: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Online-Mediated HIV Pre-exposure Prophylaxis Care and Reduced Monitoring Frequency for Men Who Have Sex With Men: Protocol for a Randomized Controlled Noninferiority Trial (EZI-PrEP Study).

Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, "unprotected act") as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8. The results of the main analysis are expected in 2024. This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers. ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj. DERR1-10.2196/51023.

Wearable Integrated Volitional Control Electrical Stimulation Device as Treatment for Paresis of the Upper Extremity in Early Subacute Stroke Patients: A Randomized Controlled Non-inferiority Trial

ObjectiveTo investigate the effect of a wearable integrated volitional control electrical stimulation (WIVES) device that has been developed as more compact and simpler to use in daily life compared with conventional integrated volitional control electrical stimulation (IVES) devices. DesignRandomized controlled non-inferiority trial. SettingConvalescent rehabilitation ward. ParticipantsPatients with paresis of the upper extremity (UE) after early subacute stroke (N=20). InterventionsEligible patients were randomized to receive IVES treatment or WIVES treatment for 8 hours per day for 28 days in daily living, in addition to standard rehabilitation treatment. In both groups, the extensor digitorum communis on the affected side was the target muscle for stimulation. Main Outcome MeasurePrimary outcomes were assessed with Fugl–Meyer Assessment of the UE (FMA-UE) before and after treatment. Non-inferiority was determined with a specified margin of non-inferiority. ResultsTwenty patients completed the trial (IVES group: n=10, WIVES group: n=10). FMA-UE improved in both groups. The mean change in FMA-UE was 4.7 for the IVES group and 6.0 for the WIVES group (P>.05, 95% confidence interval: −6.73 to 4.13). The mean difference between the groups was 1.3, and the upper 95% confidence interval did not exceed the non-inferiority margin. ConclusionThe effectiveness of WIVES treatment is non-inferior to that of IVES treatment. As a portable device, IVES may facilitate the use of affected upper extremities in daily living and may help improve paresis of the UE.

Robot-assisted Simple Enucleation Versus Standard Robot-assisted Partial Nephrectomy for Low- or Intermediate-complexity, Clinical T1 Renal Tumors: A Randomized Controlled Noninferiority Trial

BackgroundAlthough partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. ObjectiveTo compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. Design, setting, and participantsThis is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18–80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). Outcome measurements and statistical analysisWe defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. Results and limitationsA cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference −0.7%, 95% CI −4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). ConclusionsRASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. Patient summaryWe carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.

Selective Removal to Soft Dentine versus Full Pulpotomy for Management of Proximal Deep Carious Lesions: A Randomized Controlled Non-Inferiority Trial

The management of the deep carious lesion with reversible pulpitis is a dilemma for the dentist. The current study compared selective removal to soft dentine (SRSD) and full pulpotomy (FP) for treating proximal deep carious lesions in teeth with reversible pulpitis. Visual-tactile examination and bitewing radiographs were used to determine the depth of carious lesion, and American Association of Endodontists recommendations were used to formulate pulp diagnosis. Sixty mandibular molar teeth from healthy patients between the ages of 16–35 years and a diagnosis of proximal deep carious lesion with reversible pulpitis were included. Teeth were randomly allocated to two study groups. SRSD group (n = 30): soft dentine was preserved over the pulpal aspect. A hard-setting calcium hydroxide cement liner and resin-modified glass ionomer cement base were applied over the remaining soft carious dentine. FP group (n = 30): complete caries removal followed by mineral trioxide aggregate FP was performed. The teeth in both groups were restored with composite resin restoration. The established criteria for outcome assessment of SRSD and pulpotomy were used. Accordingly, only asymptomatic teeth with no radiological evidence of periapical rarefaction were considered successful at the 12-month follow-up. Two-sample t test, Pearson χ² test/Fisher’s exact test, and percentage agreement were used for statistical evaluation. According to the per-protocol analysis, the success rate of both SRSD and FP treatment was 95.45% and 95.65%, respectively, and the actual difference between the two treatments was 1% (95% CI: [−10, 9]). The data suggests that both treatments (SRSD and FP) appear to have a good success rate (>95%) when used to manage permanent mandibular molar teeth with proximal deep carious lesion and reversible pulpitis. As SRSD is a noninvasive procedure, it should be favored over FP in these instances.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial

BackgroundGlobal guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. ObjectivesWe investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. MethodsA double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18–45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our ‘a priori’ noninferiority margin of 20 μg/L. ResultsBaseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) μg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] μg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] μg/L) and placebo groups (78 [95% CI: 74, 82] μg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. ConclusionsFerrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women.This trial was registered at clinicaltrials.gov registry as NCT04017598.

Robot-assisted Partial Nephrectomy with the Newly Developed KangDuo Surgical Robot Versus the da Vinci Si Surgical System: A Double-center Prospective Randomized Controlled Noninferiority Trial

BackgroundThe KangDuo surgical robot (KD-SR) was recently developed in China. ObjectiveTo compare the safety and efficacy of the KD-SR versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted partial nephrectomy (RAPN). Design, setting, and participantsA double-center prospective randomized controlled noninferiority trial of patients aged 18–75 yr with a suspicion of T1a N0M0 renal cancer (RENAL nephrometry score ≤9) was conducted. InterventionRAPN with the KD-SR versus the DV-SS-Si. Outcome measurements and statistical analysisThe primary endpoint was the success rate of operation. The operation was successful if (1) there was no open or laparoscopic conversion, (2) the warm ischemia time was <30 min for RENAL nephrometry scores of 4–6 or 40 min for RENAL nephrometry scores of 7–9, and (3) the pathological margin was negative. The secondary endpoint was the estimated glomerular filtration rate (eGFR). A threshold of 10% was set to demonstrate noninferiority. Results and limitationsFrom September 2020 to March 2021, 100 participants were enrolled, of whom 99 (49 in the KD-SR group and 50 in the DV-SS-Si group) were finally included in the full analysis set and 98 (49 in the KD-SR group and -49 in the DV-SS-Si group) in the per-protocol set. Baseline demographic and clinical characteristics were similar between the two groups. All surgeries were completed successfully. The eGFR at postoperative weeks 4–12 and adverse events were similar between the two groups. The docking time and suture time per stitch were longer in the KD-SR group. The main limitation was that a negative margin was considered as the primary outcome rather than survival. ConclusionsThe KD-SR achieved noninferior outcomes as compared with the DV-SS-Si regarding safety and efficacy for T1a tumors. Patient summaryThe first trial comparing the KangDuo surgical robot (KD-SR) versus the da Vinci Si Surgical System for robot-assisted partial nephrectomy showed that the KD-SR is a viable option for minimally invasive treatment of T1a renal tumors.

Biportal endoscopic versus microscopic discectomy for lumbar herniated disc: a randomized controlled trial

BACKGROUND CONTEXTBiportal endoscopic discectomy has been frequently performed in recent years and has shown acceptable clinical outcomes. However, evidence regarding its efficacy and safety remains limited. PURPOSEThis study aimed to compare the clinical efficacy and safety of biportal endoscopic with that of open microscopic discectomy in patients with single-level herniated lumbar discs. STUDY DESIGNProspective, randomized, multicenter, open-label, assessor-blind, non-inferiority controlled trial. PATIENT SAMPLESixty-four participants suffering from low back and leg pain with a single-level herniated lumbar disc and required discectomy. OUTCOME MEASURESOutcomes were assessed with the use of patient-reported outcome measures (PROMs), visual analog scale (VAS) pain score for surgical site, low back and lower extremity, Oswestry Disability Index (ODI) for lumbar disabilities, European Quality of Life-5 Dimensions value for quality of life, and painDETECT for neuropathic pain. Surgery-related outcomes such as hospital stay, operation time, and opioid usage were collected. Adverse events occurring during the follow-up period were also noted. METHODSAll participants were randomly assigned in a 1:1 ratio to undergo biportal endoscopic (biportal group) or microscopic discectomy (microscopy group). The primary outcome was the difference in ODI scores at 12-months post surgically based on a modified intention-to-treat strategy, with a non-inferiority margin of 12.8 points. The secondary outcomes included PROMs, surgery-related outcomes, and adverse events. RESULTSThe ODI score at the 12-month follow-up was 11.97 in the microscopy group and 13.89 in the biportal group (mean difference, 1.92; 95% confidence interval [CI], -3.50 to 7.34), showing the non-inferiority of biportal group. The results for the secondary outcomes were similar to those for the primary outcome. Creatinine phosphokinase ratios were low in the biportal group. Early surgical site pain was slightly lower in the biportal group (mean difference of VAS pain score at 48-hr, -0.98; 95% CI, -1.77 to -0.19). Adverse events including reoperation showed no significant difference between the groups. CONCLUSIONBiportal endoscopic discectomy was non-inferior to microscopic discectomy over a 12 month period. Biportal endoscopic discectomy is suggested to be a relatively safe and effective surgical technique with the slight advantage of reduced muscle damage. However, the clinical implications of surgical site pain should be carefully considered.

The Clinical Effectiveness of Blended Cognitive Behavioral Therapy Compared With Face-to-Face Cognitive Behavioral Therapy for Adult Depression: Randomized Controlled Noninferiority Trial

BackgroundInternet-based cognitive behavioral therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (FtF) consultations in a blended format may produce a new treatment format (B-CBT) with multiple benefits from both traditional CBT and iCBT, such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation.ObjectiveThe primary aim of this study is to compare directly the clinical effectiveness of B-CBT with FtF-CBT for adult major depressive disorder.MethodsA 2-arm randomized controlled noninferiority trial compared B-CBT for adult depression with treatment as usual (TAU). The trial was researcher blinded (unblinded for participants and clinicians). B-CBT comprised 6 sessions of FtF-CBT alternated with 6-8 web-based CBT self-help modules. TAU comprised 12 sessions of FtF-CBT. All participants were aged 18 or older and met the diagnostic criteria for major depressive disorder and were recruited via a national iCBT clinic. The primary outcome was change in depression severity on the 9-item Patient Health Questionnaire (PHQ-9). Secondary analyses included client satisfaction (8-item Client Satisfaction Questionnaire [CSQ-8]), patient expectancy (Credibility and Expectancy Questionnaire [CEQ]), and working (Working Alliance Inventory [WAI] and Technical Alliance Inventory [TAI]). The primary outcome was analyzed by a mixed effects model including all available data from baseline, weekly measures, 3-, 6, and 12-month follow-up.ResultsA total of 76 individuals were randomized, with 38 allocated to each treatment group. Age ranged from 18 to 71 years (SD 13.96) with 56 (74%) females. Attrition rate was 20% (n=15), which was less in the FtF-CBT group (n=6, 16%) than in the B-CBT group (n=9, 24%). As many as 53 (70%) completed 9 or more sessions almost equally distributed between the groups (nFtF-CBT=27, 71%; nB-CBT=26, 68%). PHQ-9 reduced 11.38 points in the FtF-CBT group and 8.10 in the B-CBT group. At 6 months, the mean difference was a mere 0.17 points. The primary analyses confirmed large and significant within-group reductions in both groups (FtF-CBT: β=–.03; standard error [SE] 0.00; P<.001 and B-CBT: β=–.02; SE 0.00; P<.001). A small but significant interaction effect was observed between groups (β=.01; SE 0.00; P=.03). Employment status influenced the outcome differently between groups, where the B-CBT group was seen to profit more from not being full-time employed than the FtF group.ConclusionsWith large within-group effects in both treatment arms, the study demonstrated feasibility of B-CBT in Denmark. At 6 months’ follow-up, there appeared to be no difference between the 2 treatment formats, with a small but nonsignificant difference at 12 months. The study seems to demonstrate that B-CBT is capable of producing treatment effects that are close to FtF-CBT and that completion rates and satisfaction rates were comparable between groups. However, the study was limited by small sample size and should be interpreted with caution.Trial RegistrationClinicalTrials.gov NCT02796573; https://clinicaltrials.gov/ct2/show/NCT02796573International Registered Report Identifier (IRRID)RR2-10.1186/s12888-016-1140-y

Online Learning versus Hands-On Learning of Basic Ocular Ultrasound Skills: A Randomized Controlled Non-Inferiority Trial.

Background and objectives: Ocular ultrasound is a core application of point-of-care ultrasound (POCUS) to assist physicians in promptly identifying various ocular diseases at the bedside; however, hands-on POCUS training is challenging during a pandemic. Materials and Methods: A randomized controlled non-inferiority trial was conducted in an academic emergency department from October 2020 to April 2021. Thirty-two participants were randomly assigned to one of two groups. Group H (hands-on learning group) participated individually in a hands-on session with a standardized patient for 30 min, whereas Group O (online learning group) learned training materials and video clips for 20 min. They scanned four eyeballs of two standardized patients sequentially following the ocular POCUS scan protocol. Repeated POCUS scans were performed 2 weeks later to assess skill maintenance. Both groups completed the pre- and post-surveys and knowledge tests. Two emergency medicine faculty members blindly evaluated the data and assigned a score of 0–25. The primary endpoint was the initial total score of scan quality evaluated using non-inferiority analysis (generalized estimating equation). The secondary endpoints were total scores for scan quality after 2 weeks, scan time, and knowledge test scores. Results: The least squares means of the total scores were 21.7 (0.35) for Group O and 21.3 (0.25) for Group H, and the lower bound of the 95% confidence interval (CI) was greater than the non-inferiority margin of minus 2 (95% CI: −0.48–1.17). The second scan scores were not significantly different from those of the first scan. The groups did not differ in scanning time or knowledge test results; however, Group H showed higher subjective satisfaction with the training method (p < 0.001). Conclusion: This study showed that basic online ocular ultrasound education was not inferior to hands-on education, suggesting that it could be a useful educational approach in the pandemic era.

Treat-to-target dose reduction and withdrawal strategy of TNF inhibitors in psoriatic arthritis and axial spondyloarthritis: a randomised controlled non-inferiority trial

ObjectivesTumour necrosis factor inhibitors (TNFi) are effective in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), but are associated with a small (0.6%) increase in serious infection risk, patient burden due...

Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial

To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in invitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence. Randomized, double-blinded, controlled noninferiority trial. Academic infertility practice. Women aged 18-41 undergoing IVF with antral follicle count ≥8, body mass index ≤30 kg/m2, and no history of ≥2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome. Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation. The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol. A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62-1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48-1.11). No participants had a failed retrieval. Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose. NCT02310919.

Safe birth in cultural safety in southern Mexico: a pragmatic non-inferiority cluster-randomised controlled trial

BackgroundAvailable research on the contribution of traditional midwifery to safe motherhood focuses on retraining and redefining traditional midwives, assuming cultural prominence of Western ways. Our objective was to test if supporting traditional midwives on their own terms increases cultural safety (respect of Indigenous traditions) without worsening maternal health outcomes.MethodsPragmatic parallel-group cluster-randomised controlled non-inferiority trial in four municipalities in Guerrero State, southern Mexico, with Nahua, Na savi, Me’phaa and Nancue ñomndaa Indigenous groups. The study included all pregnant women in 80 communities and 30 traditional midwives in 40 intervention communities. Between July 2015 and April 2017, traditional midwives and their apprentices received a monthly stipend and support from a trained intercultural broker, and local official health personnel attended a workshop for improving attitudes towards traditional midwifery. Forty communities in two control municipalities continued with usual health services. Trained Indigenous female interviewers administered a baseline and follow-up household survey, interviewing all women who reported pregnancy or childbirth in all involved municipalities since January 2016. Primary outcomes included childbirth and neonatal complications, perinatal deaths, and postnatal complications, and secondary outcomes were traditional childbirth (at home, in vertical position, with traditional midwife and family), access and experience in Western healthcare, food intake, reduction of heavy work, and cost of health care.ResultsAmong 872 completed pregnancies, women in intervention communities had lower rates of primary outcomes (perinatal deaths or childbirth or neonatal complications) (RD -0.06 95%CI − 0.09 to − 0.02) and reported more traditional childbirths (RD 0.10 95%CI 0.02 to 0.18). Among institutional childbirths, women from intervention communities reported more traditional management of placenta (RD 0.34 95%CI 0.21 to 0.48) but also more non-traditional cold-water baths (RD 0.10 95%CI 0.02 to 0.19). Among home-based childbirths, women from intervention communities had fewer postpartum complications (RD -0.12 95%CI − 0.27 to 0.01).ConclusionsSupporting traditional midwifery increased culturally safe childbirth without worsening health outcomes. The fixed population size restricted our confidence for inference of non-inferiority for mortality outcomes. Traditional midwifery could contribute to safer birth among Indigenous communities if, instead of attempting to replace traditional practices, health authorities promoted intercultural dialogue.Trial registrationRetrospectively registered ISRCTN12397283. Trial status: concluded.