Restore and Rebuild (R&R): a protocol for a phase 2, randomised control trial to compare R&R as a treatment for moral injury-related mental health difficulties in UK military veterans to treatment as usual.

BACKGROUND: Exposure to potentially morally injurious events is increasingly recognised as a concern across a range of occupational groups, including UK military veterans. Moral injury-related mental health difficulties can be challenging for clinicians to treat and there is currently no validated treatment available for UK veterans. We developed Restore and Rebuild (R&R) as a treatment for UK veterans struggling with moral injury-related mental health difficulties. This trial aims to examine whether it is feasible to conduct a pilot randomised controlled trial (RCT) of R&R treatment compared with a treatment-as-usual (TAU) control group. METHODS: We will use a feasibility single-blind, single-site RCT design. The target population will be UK military veterans with moral injury-related mental health difficulties. We will recruit N=46 veteran patients who will be randomly allocated to R&R (n=23) or TAU (n=23). Patients randomised to R&R will receive the 20-session one-to-one treatment, delivered online. Veterans allocated to TAU, as there are currently no manualised treatments for moral injury-related mental health problems available, will receive the one-to-one treatment (online) typically provided to veterans who enter the mental health service for moral injury-related mental health difficulties. We will collect outcome measures of moral injury, post-traumatic stress disorder (PTSD), alcohol misuse, common mental disorders and trauma memory at pretreatment baseline (before randomisation), end of treatment, 12 weeks and 24 weeks post-treatment. The primary outcome will be the proportion of patients who screen positive for PTSD and moral injury-related distress post-treatment. ETHICS AND DISSEMINATION: This trial will establish whether R&R is feasible, well-tolerated and beneficial treatment for veterans with moral injury-related mental health difficulties. If so, the results of the trial will be widely disseminated and R&R may improve access to effective care for those who struggle following moral injury and reduce the associated negative consequences for veterans, their families and wider society. TRIAL REGISTRATION NUMBER: ISRCTN99573523.

The impact of addition of pearl millet starch-germ complex in white bread on nutritional, textural, structural, and glycaemic response: Single blinded randomized controlled trial in healthy and pre-diabetic participants.

The rise of pre-diabetes at the global level has created a significant interest in developing low glycaemic index food products. The pearl millet is a cheaper source of starch and its germ contains significant amount of protein and fat. The complexing of pearl millet starch and germ by dry heat treatment (PMSGH) resulted an increase in the resistant starch content upto 45.09 % due to formation of amylose-glutelin-linoleic acid complex. The resulting pearl millet starch germ complex was incorporated into wheat bread at 20, 25, and 30 %. The PMSGH incorporated into bread at 30 % reduced the glycaemic index to 52.31. The PMSGH incorporated bread had significantly (p < 0.05)increased in the hardness with a reduction in springiness and cohesiveness. The structural attributes of the 30 % PMSGH incorporated bread revealed a significant (p < 0.05)increase in 1040/1020 cm-1 ratio and relative crystallinity. The consumption of functional bread incorporated with pearl millet starch germ complex reduced blood glucose levels and in vivo glycaemic index in healthy and pre-diabetic participants when compared to white bread. Hence, the study showed that the incorporation of pearl millet starch-germ complex into food products could be a potential new and healthier approach for improving dietary options in pre-diabetes care.

Bleaching efficacy of in-office dental bleaching with different application protocols: a single-blind randomized controlled trial.

OBJECTIVE: This randomized controlled trial aimed to evaluate the equivalence in the color change, adverse effects, self-perception (AS) and the impact on oral condition (IO) of participants submitted to different application protocols of in-office dental bleaching. MATERIALS AND METHODS: 165 participants were bleached with a 35% hydrogen peroxide gel (Total Blanc Office One-Step, DFL), according to the following protocols: (1) 2 applications of 20-min each (2 × 20 min); (2) 1 × 40-min and; (3) 1 × 30-min. The color change was evaluated with the Vita Easyshade spectrophotometer, Vita Classical and Vita Bleachedguide scales. The intensity and risk of tooth sensitivity (TS) and gingival irritation (GI) were recorded using a 0-10 visual analogue scale (VAS). AS and IO was assessed before and after the bleaching procedure using the Orofacial Aesthetic Scale and Oral Health Impact Profile-14, respectively. RESULTS: Equivalent color change were observed (p < 0.001), with no significant difference between groups. The group 2 × 20 min presented the highest risk of TS (76%, 95% CI 63 to 85), compared to the 1 × 30 min (p < 0.04). The intensity of TS and GI and the risk of GI was similar between groups (p > 0.31). Irrespectively of the group (p = 0.32), significant improvements were observed for all items of AS and IO after bleaching (p < 0.02). CONCLUSIONS: The 1 × 30 min protocol produced equivalent color change to the other bleaching protocols with reduced risk of TS and shorter application time. CLINICAL RELEVANCE: A more simplified application regimen of a single application of 30 min yields effective bleaching and patient satisfaction while minimizing undesirable side effects and improving patient satisfaction.

The effect of oral motor intervention with different initiation times to improve feeding outcomes in preterm infants: protocol for a single-blind, randomized controlled trial.

BACKGROUND: Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants' quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants' oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants' oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. METHODS: This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. DISCUSSION: OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. TRIAL REGISTRATION: chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy.

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.

Effect of erbium, chromium-doped: yttrium, scandium, gallium, and garnet laser-assisted periodontal therapy using radial firing tip during early healing period: a randomized controlled split-mouth clinical trial.

BACKGROUND: This study aimed to demonstrate the efficacy of erbium, chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser-assisted nonsurgical periodontal therapy in periodontitis patients during 8 weeks of healing. METHODS: A split-mouth, single-blinded, randomized controlled clinical trial was conducted on 12 patients diagnosed with stage III/IV periodontitis and had a minimum of two teeth with probing pocket depth (PPD) > 5 mm in at least two quadrants. Upon randomization, each quadrant was assigned for conventional scaling and root planing (SRP) procedure or laser-assisted therapy (SRP + laser) using radial firing tip (RFPT 5, Biolase). Clinical measurements and gingival crevicular fluid collection were performed for statistical analysis. RESULTS: In the initial statistical analysis on the whole subject teeth, modified gingival index (MGI) reduction was greater in test group at 1(P = 0.0153), 4 (P = 0.0318), and 8 weeks (P = 0.0047) compared to the control in the same period. PPD reduction at 4 weeks in test group was -1.67 ± 0.59 showing significant difference compared to the control (-1.37 ± 0.63, P = 0.0253). When teeth with mean PPD ≥5 mm were sorted, MGI decrease was significantly greater in test group at 1 (P=0.003) and 8 week (P=0.0102) follow-ups. PPD reduction was also significantly greater in test group at 4 week period (-1.98 ± 0.55 vs -1.58 ± 0.56, test vs control, P=0.0224). CONCLUSIONS: Er,Cr:YSGG-assisted periodontal therapy is beneficial in MGI and PPD reductions during early healing period.

Bent ab interno needle goniotomy versus gonioscopy-assisted transluminal trabeculotomy in primary open-angle glaucoma: study protocol of a randomized clinical trial.

BACKGROUND: Minimally invasive glaucoma surgery (MIGS) is a new class of surgeries, which combines moderate to high success rates and a high safety profile. Bent Ab interno Needle Goniotomy (BANG) and Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) are two low-cost MIGS procedures that communicate the anterior chamber to Schlemm's canal. Most of the available publications on MIGS are either case series or retrospective studies, with different study protocols. The aim of this manuscript is to describe a randomized clinical trial (RCT) protocol to compare the long-term intraocular pressure (IOP) control and the safety of both procedures in eyes with primary open-angle glaucoma. METHODS: This is a parallel, double-arm, single-masked RCT that includes pseudophakic primary open-angle glaucoma (POAG) eyes. After inclusion criteria, medications will be washed out to verify baseline IOP before surgery. Patients will be randomized to BANG or GATT using a sealed envelope. Follow-up visits will be 1, 7, 15, 30, 60, 90, 180, 330 and 360 days after surgery. On PO330, a new medication washout will be done. The main outcome is the IOP reduction following the procedures. Complimentary evaluation of functional and structural parameters, safety, and quality of life will be done after 30, 90, 180, and 360 days. DISCUSSION: Our study was designed to compare the long-term efficacy and safety of two low-cost MIGS. Most of the published studies on this subject are case series or retrospective cohorts, with different study protocols, which included different types and severities of glaucomas, combined with cataract extraction. Our study only included mild to moderate POAG eyes, with previous successful cataract extraction. Moreover, it provides a standardized protocol that could be replicated in future studies investigating various types of MIGS. This would allow comparison between different techniques in terms of efficacy, safety, and patients' quality of life. TRIAL REGISTRATION: Retrospectively registered at the Registro Brasileiro de Ensaios Clínicos (ReBEC) platform RBR-268ms5y . Registered on July 29, 2023. The study was approved by the Ethics Committee of the University of Campinas, Brazil.

Photodynamic Skincare: A Prospective Single-Center Study.

BACKGROUND: Peer-reviewed, clinical studies measuring the efficacy and usability of skin care products enhance their integrity and may guide experts in the field in providing recommendations. A single-blind, prospective clinical study was designed to assess the subject satisfaction, clinical benefit, and safety of three photodynamic topical formulations referred to as MMSRepose (MMSRep), MMSRevive (MMSRev), and MMSBalance (MMSB).  Methods: Thirteen male and female patients (mean age 49 +/- 17.8 years) applied one of the three topical serums twice daily over a period of 12 weeks. Subjects returned for photography, and blinded investigator evaluation of rhytides (fine lines) and dyspigmentation were measured on a 6- and 4-point scale, respectively. Patient-perceived efficacy of multiple clinical outcomes was measured on a 5-point scale.  Results: 100% of subjects reported at least a 1-grade improvement in global aesthetic at the conclusion of the study. Investigator assessment revealed an overall 53.3% decrease in rhytides, correlating to a mean point reduction from 1.65 +/- 0.77 to 0.77 +/- 0.53 (P<0.001) from baseline to week 12. Investigator assessment of dyspigmentation revealed a 62.7% decrease, correlating to a mean point reduction of 1.85 +/- 0.68 from week 1 to 0.69 +/- 0.48 at week 12 (P<0.001). CONCLUSION: Photodynamic serums demonstrate clinical efficacy in skin rejuvenation and high user satisfaction. There were no serious adverse events. This study is limited by the inability to randomize to placebo due to the small sample size, as subject retention was heavily impacted by the SARS-CoV-2 pandemic. Future studies may be indicated to undergo comparison with a larger cohort.  J Drugs Dermatol. 2024;23(5):332-337. doi:10.36849/JDD.7167.

The efficacy and safety of MARS-PD: Meridian activation remedy system for Parkinson's disease-A single-center, assessor and statistician-blinded, parallel-group randomized, controlled trial protocol.

BACKGROUND: Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. METHODS: In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. DISCUSSION: Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. TRIAL REGISTRATION: cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.

Laparoscopic sleeve gastrectomy vs one-anastomosis gastric bypass 5-year follow-up: a single-blinded randomized controlled trial.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most performed bariatric procedure worldwide, whereas one-anastomosis gastric bypass (OAGB) is the third most performed procedure. Both procedures have reported good weight loss (WL) and low complications. However, should both have differences in the durability of WL and malnutrition? METHODS: A single-blinded, randomized controlled trial of 300 patients was conducted to compare the outcomes of LSG and OAGB over a 5-year follow-up. The primary endpoint was WL in percentages of total WL (%TWL) and excess WL (%EWL). The secondary endpoints were complications, gastroesophageal reflux disease (GERD), associated medical problems, bariatric analysis and reporting outcome system (BAROS) assessment, and weight recurrence (WR). RESULTS: Overall, 201 patients (96 in the LSG group and 105 in the OAGB group) completed 5 years of follow-up. OAGB had significantly higher %TWL and %EWL than those of LSG throughout the follow-up. LSG had significantly higher WR and GERD. Both procedures had significant improvement in associated medical problems and BAROS scores compared with baseline, with no significant difference. WR was associated with higher relapse of associated medical conditions after initial remission and with lower BAROS scores regarding WL scores. CONCLUSION: OAGB had significantly higher WL, less WR, and less GERD. However, it had a higher incidence of bile reflux. Both procedures had comparable complication rates, excellent remissions in associated medical problems, and improved quality of life. WR was associated with significantly more relapse of associated medical problems and significantly lower BAROS scores.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial.

BACKGROUND: Ketamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain. METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia. RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026). CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness. TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).

Comparison between propofol and total inhalational anaesthesia on cardiovascular outcomes following on-pump cardiac surgery in higher-risk patients: a randomised controlled pilot and feasibility study.

OBJECTIVES: Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS: In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS: All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS: It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER: NCT04039854.

Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial.

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. METHODS: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. RESULTS: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). CONCLUSION: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. TRIAL REGISTRATION: (NCT03873298, MOH_2018-04-24_002331).

ØCD: protocol for the development and evaluation of a cognitive-behavioral prevention program for obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) imposes significant burdens on individuals, families, and healthcare systems and the COVID-19 pandemic appears to have exacerbated OCD symptoms. Currently, there are no validated prevention programs for OCD, highlighting a critical gap in mental health services. This study aims to develop and validate the first ØCD prevention program, for at-risk adults, utilizing cognitive-behavioral therapy (CBT) and exposure response prevention (ERP) techniques. METHODS: A single-blind, randomized controlled trial comparing the ØCD prevention program to a waitlist control group will be conducted. Participants, at-risk adults (18-65 years) with subclinical OCD symptoms (OCI-R score ≥ 12), will be recruited for the study. The ØCD prevention program compresise of six online group sessions incorporating CBT and ERP techniques over three modules. The primary outcomes are OCD symptom severity (measured by the Obsessive-Compulsive Inventory- revised form; OCI-R), depression symptoms (measured by the Patient Health Questionnaire; PHQ-9), and anxiety symptoms (measured by the Generalised Anxiety Disorder 7-item; GAD-7). Secondary outcomes include OCD-related beliefs, experiential avoidance, resilience, quality of life, uncertainty intolerance, automatic thoughts, and distress. Outcome measures will be collected at baseline, at completion of the intervention, and one year later (follow-up). At follow-up, we will also analyze the OCD diagnostic incidence, using the Structured Clinical Interview for DSM-5. We will employ a multivariate analysis of variance (MANOVA) to explore whether significant differences exist between groups across dependent variables. To compare the OCD incidence levels from the pre-test to the follow-up we will use the chi-squared test. DISCUSION: The present study may contribute novel data on the efficacy of OCD prevention approaches, leading to the development of an evidence-based OCD prevention program that could alleviate individual and societal burdens associated with OCD. TRIAL REGISTRATION: This trial was approved by the University Ethical Review Authority (937/ 28.11.2023) at Babeș-Bolyai University and is registered on clinicaltrials.gov (ID: NCT06262464).

A randomised controlled trial to compare blind intubation success through LMA Blockbuster® and I-Gel® LMA.

INTRODUCTION: Laryngeal mask airway-blockbuster (LMA-BT) is a relatively new supraglottic airway device (SGAD). In this study, we compared LMA-BT with I-Gel LMA for efficacy of blind tracheal intubation. MATERIAL AND METHODS: We conducted a single-blind prospective study after ethical approval. One hundred American Society of Anesthesiology (ASA) Grade I-III (age 18-60 years) patients scheduled for elective surgery under general anaesthesia with endotracheal intubation were included and randomly divided into 2 groups. Blind tracheal intubation was performed through LMA-BT ( n = 50) and I-Gel ( n = 50) in groups 1 and 2, respectively. The primary aim was to evaluate the first pass success rate of blind tracheal intubation through the LMAs. The secondary objectives noted were attempts and ease of LMA insertion, total time taken for LMA insertion, airway seal pressure of LMA, ease of NGT insertion through LMA, fibre-optic grading of laryngeal view through LMA, overall success rate and time of intubation through LMA, time for LMA removal, and complications, if any. RESULTS: In the LMA-BT group, the first pass success rate ( P < 0.019) and the overall success rate of intubation ( P < 0.005) were significantly higher than in the I-Gel group. Using LMA-BT also resulted in statistically significant shorter intubation time ( P < 0.0001) with higher airway seal pressure as compared to I-Gel ( P < 0.001). The difference in the first attempt insertion, number of insertion attempts, ease and time of LMA insertion and removal after intubation, and postoperative complications were comparable among the groups. CONCLUSIONS: LMA-BT is a superior device as compared to I-Gel LMA as a conduit for blind tracheal intubation.

Quantitative analysis of the effects of brushing, flossing, and mouthrinsing on supragingival and subgingival plaque microbiota: 12-week clinical trial.

BACKGROUND: Translational microbiome research using next-generation DNA sequencing is challenging due to the semi-qualitative nature of relative abundance data. A novel method for quantitative analysis was applied in this 12-week clinical trial to understand the mechanical vs. chemotherapeutic actions of brushing, flossing, and mouthrinsing against the supragingival dental plaque microbiome. Enumeration of viable bacteria using vPCR was also applied on supragingival plaque for validation and on subgingival plaque to evaluate interventional effects below the gingival margin. METHODS: Subjects with gingivitis were enrolled in a single center, examiner-blind, virtually supervised, parallel group controlled clinical trial. Subjects with gingivitis were randomized into brushing only (B); brushing and flossing (BF); brushing and rinsing with Listerine® Cool Mint® Antiseptic (BA); brushing and rinsing with Listerine® Cool Mint® Zero (BZ); or brushing, flossing, and rinsing with Listerine® Cool Mint® Zero (BFZ). All subjects brushed twice daily for 1 min with a sodium monofluorophosphate toothpaste and a soft-bristled toothbrush. Subjects who flossed used unflavored waxed dental floss once daily. Subjects assigned to mouthrinses rinsed twice daily. Plaque specimens were collected at the baseline visit and after 4 and 12 weeks of intervention. Bacterial cell number quantification was achieved by adding reference amounts of DNA controls to plaque samples prior to DNA extraction, followed by shallow shotgun metagenome sequencing. RESULTS: 286 subjects completed the trial. The metagenomic data for supragingival plaque showed significant reductions in Shannon-Weaver diversity, species richness, and total and categorical bacterial abundances (commensal, gingivitis, and malodor) after 4 and 12 weeks for the BA, BZ, and BFZ groups compared to the B group, while no significant differences were observed between the B and BF groups. Supragingival plaque vPCR further validated these results, and subgingival plaque vPCR demonstrated significant efficacy for the BFZ intervention only. CONCLUSIONS: This publication reports on a successful application of a quantitative method of microbiome analysis in a clinical trial demonstrating the sustained and superior efficacy of essential oil mouthrinses at controlling dental plaque compared to mechanical methods. The quantitative microbiological data in this trial also reinforce the safety and mechanism of action of EO mouthrinses against plaque microbial ecology and highlights the importance of elevating EO mouthrinsing as an integral part of an oral hygiene regimen. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov on 31/10/2022. The registration number is NCT05600231.

Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.

INTRODUCTION: Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. METHODS AND ANALYSIS: This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. ETHICS AND DISSEMINATION: Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.

Effectiveness of Applying Green Heart, a Smartphone-Based Self-management Intervention to Control Smoking: A Randomized Clinical Trial.

BACKGROUND: Cardiovascular diseases (CVDs) pose a significant global health concern and are the most common cause of death and disability, necessitating preventive interventions targeting modifiable risk factors. Recently, mobile-health technology has been developed to improve the delivery of cardiovascular prevention by risk factor modification. The "Green Heart" mobile application (app) was designed to aid in risk factor control among coronary artery disease (CAD) patients. METHODS: This parallel-group, single-blinded randomized controlled trial enrolled 1590 CAD patients, including 668 current smokers, randomly assigned to control (paper-based education) and intervention (application-based) groups. The app encompassed three modules targeting smoking cessation, dyslipidemia control, and blood pressure management. This study evaluated the impact of the smoking cessation module on behavioral change among current smokers. Green Heart assesses nicotine dependence, offering personalized quit plans, educational content, motivational messages, and automated progress tracking. The odds of smoking behavior changes during the 24-week follow-up underwent assessment. RESULTS: The intention-to-treat analysis highlighted significantly elevated rates of smoking cessation and reductions in the intervention group versus the control group. Adherence to the app (per-treatment analysis) also demonstrated significantly more favorable smoking behavior changes among the application users. Logistic regression emphasized higher odds of quitting and reduction in smoking in the application group, showing an odds ratio of 2.14 (95% CI: 1.16-3.97) compared to those not using the app (P=0.015). CONCLUSION: Our results confirmed that complete adherence to the app for at least 24 weeks was linked to alterations in cigarette smoking behavior among CAD patients. Trial Registration Number: IRCT20221016056204N1.