Multicenter Randomized Trial Research Articles

Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation – Clinical and safety results

IntroductionWe investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. Material and methodsPatients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. ResultsTwenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (−5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01).Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DiscussionOur results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

Reverse shoulder arthroplasty or nothing for patients with displaced proximal humeral fractures: a randomized controlled trial

The benefits of reverse shoulder arthroplasty compared to nonoperative treatment for patients presenting with complex proximal fractures have been rarely explored. The aim of this prospective study was to compare the functional results of reverse shoulder arthroplasty with those of nonsurgical treatment in patients with displaced proximal humeral fractures. A multicentric prospective randomized control trial of patients older than 70years who sustained an acute proximal humeral fracture (3 or 4 parts), with less than 3weeks of evolution, and had no previous condition or surgery on the affected shoulder was conducted. Patients were randomly assigned to the intervention group (implantation of a reverse shoulder arthroplasty and tuberosities reattachment) or the control group (nonoperative treatment). Functional outcome was assessed using the Constant-Murley score (CMS) at the 1-year follow-up. Complications and reinterventions were considered secondary outcomes. The power of the study relied on the inclusion of 81 patients to recognize a statistically significant difference of 10 points between CMS scores in the groups. Analysis was performed based on the intention to treat principle. Eighty-one patients were randomized to surgical treatment or nonoperative treatment, while 66 patients completed the 1-year follow-up evaluation. There was no significant difference between the groups in terms of age (76.1 yo vs. 77.43 yo, P=.43), sex (81.08% women in the surgical group vs. 84.09% in the nonoperative group, P=.72), or type of fracture according to Neer's classification system (P=.06). At the 1-year follow-up, the group assigned to undergo the intervention had better functional outcomes than the nonoperative treatment group (mean CMS; 61.24, SD: 13.33 vs. mean CMS: 52.44, SD: 16.22, P: .02), with a mean difference of 8.84 points, 95% CI (1.57, 16.11). Two patients in the intervention group (6.5%) suffered major complications (periprosthetic joint infection and axillary nerve palsy). No major complications were observed in the nonoperative group. One patient in the intervention group underwent secondary surgery for a periprosthetic joint infection. Treatment with reverse shoulder arthroplasty provides superior functional outcomes compared with conservative treatment for patients presenting with an acute proximal humeral fracture. The difference in CMS is close to the clinically significant thresholds, and some harms are associated with the operative treatment.

Effectiveness of a pharmacist-led, community group-based education programme in enhancing diabetes management: A multicentre randomised control trial

AimsThis study presents a protocol for the Pharmacy Integrated Community Care (PICC) program, meticulously designed to enhance Hemoglobin A1c (HbA1c) levels and augment knowledge about diabetes mellitus (DM) among individuals diagnosed with Type 2 Diabetes Mellitus (T2DM) in the Sarawak State of Malaysia. MethodsFrom 1 May to December 31, 2023, a prospective, multicenter, parallel-design randomised controlled trial will be conducted with two groups, each consisting of 47 participants. The intervention group will receive a structured, four-session group-based program guided by experienced pharmacists, focusing on medication adherence and diabetes management. The control group will follow the standard Diabetes Mellitus Adherence Clinic program. The primary outcomes of this study encompass enhancements in knowledge regarding diabetes medication management and adherence, followed by subsequent changes in HbA1c levels. ConclusionsThe successful implementation of the PICC program holds promise for enhancing health outcomes in the T2DM population, potentially leading to more effective diabetes management initiatives and better health practices in the community. Trial registration clinicaltrials.gov identifierNCT05106231.

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

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

Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study

Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

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

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

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

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

Randomized Multicenter Trial for the Validation of an Easy-to-Administer Algorithm to Define Penicillin Allergy Status in Sexually Transmitted Infection Clinic Outpatients.

Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs. Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted. Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics. An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746).

Randomized Trial of Augmented Pelvic Fixation in Patients Undergoing Thoracolumbar Fusion for Adult Spine Deformity: Initial Results from a Multicenter Randomized Trial

BackgroundThe optimal configuration for spinopelvic fixation during multilevel spine fusion surgery for adult spine deformity remains unclear. Postoperative sacroiliac (SI) joint pain, S2AI screw loosening and implant breakage could be related to continued motion of the SI joint with use of only a single point of fixation across the SI joint. MethodsProspective, international, multicenter randomized controlled trial of 222 patients with adult spine deformity scheduled for multilevel (4 or more levels) spine fusion surgery with pelvic fixation. Subjects were randomized to S2AI screws alone for pelvic fixation or S2AI + triangular titanium implants placed cephalad to S2AI screws. Quad rod techniques were not allowed or used. Baseline spinal deformity measures were read by an independent radiologist. Site-reported perioperative adverse events were reviewed by a clinical events committee. Quality of life questionnaires and other clinical outcomes are in process with planned two-year follow-up. Results113 participants were assigned to S2AI and 109 to S2AI + TTI. 35/222 (16%) of all subjects had a history of SI joint pain or were diagnosed with SI joint pain during preoperative workup. 3-month follow-up was available in all but 4 subjects. TTI placement was successful in 106 of 109 (98%) subjects assigned to TTI. In 2 cases, TTI could not be placed due to anatomical considerations. Three TTI ventral iliac breaches were observed, all of which were managed non-surgically. One TTI subject had a transverse sacral fracture and one TTI subject had malposition of the implant requiring removal. ConclusionsSI joint pain is common in patients with adult spinal deformity who are candidates for multilevel spine fusion surgery. Concurrent placement of TTI parallel to S2AI screws during multilevel spine fusion surgery is feasible and safe. Further follow-up will help to determine the clinical value of this approach to augment pelvic fixation.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study

IntroductionThe prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and...

Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: Arandomized placebo-controlled trial.

Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Role of decompressive craniectomy in the management of acute ischemic stroke (Review).

The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent.

CPR Quality Officer role to improve CPR quality: A multi-centred international simulation randomised control trial

BackgroundAn out-of-hospital cardiac arrest requires early recognition, prompt and quality clinical interventions, and coordination between different clinicians to improve outcomes. Clinical team leaders and clinical teams have high levels of cognitive burden. We aimed to investigate the effect of a dedicated Cardio-Pulmonary Resuscitation (CPR) Quality Officer role on team performance. MethodsThis multi-centre randomised control trial used simulation in universities from the UK, Poland, and Norway. Student Paramedics participated in out-of-hospital cardiac arrest scenarios before randomisation to either traditional roles or assigning one member as the CPR Quality Officer. The quality of CPR was measured using QCPR® and Advanced Life Support (ALS) elements were evaluated. ResultsIn total, 36 teams (108 individuals) participated. CPR quality from the first attempt (72.45%, 95% confidence interval [CI] 64.94 to 79.97) significantly increased after addition of the CPR Quality role (81.14%, 95% CI 74.20 to 88.07, p = 0.045). Improvement was not seen in the control group. The time to first defibrillation had no significant difference in the intervention group between the first attempt (53.77, 95% CI 36.57–70.98) and the second attempt (48.68, 95% CI 31.31–66.05, p = 0.84). The time to manage an obstructive airway in the intervention group showed significant difference (p = 0.006) in the first attempt (168.95, 95% CI 110.54–227.37) compared with the second attempt (136.95, 95% CI 87.03–186.88, p = 0.1). ConclusionA dedicated CPR Quality Officer in simulated scenarios improved the quality of CPR compressions without a negative impact on time to first defibrillation, managing the airway, or adherence to local ALS protocols.

Long-term outcome of early surgery versus endoscopy-first approach in painful chronic pancreatitis (ESCAPE): multicentre randomised trial

Long-term outcome of early surgery versus endoscopy-first approach in painful chronic pancreatitis (ESCAPE): multicentre randomised trial

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

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

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

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

*SMARTSIM* A multicenter prospective randomized trial of 3D virtual reality versus traditional patient simulation.

Simulations are an integral part of paramedic education. Technological advancements have introduced three-dimensional virtual reality patient simulations (3DVRS), offering a low-cost, accessible alternative. This study compares the impact of 3DVRS and traditional simulation on paramedic students. Students selected from a convenience sample of 11 cohorts in 10 accredited programs distributed across the United States were allocated to 2 groups using a stratified random sampling. One group received simulations via 3DVRS, the second used traditional in-person simulation. Students were exposed to 6 scenarios over 2h from the National Association of Emergency Medical Technicians (NAEMT) Advanced Medical Life Support (AMLS) program. Altered mental status scenarios were selected a priori by the research team containing approximately 30 potential differential diagnoses. A 50-item posttest was administered using validated cognitive items provided by Fisdap. A multicenter prospective randomized trial of 174 paramedic students was undertaken from April until August of 2022. The traditional simulation group was comprised of 88 students and the 3DVRS group had 86 students. A Mann-Whitney U test (U=4064.5, n 1=88, n 2=86, p=0.396) detected no statistical difference between two distributions or median exam score (70%), the range of values and interquartile range (IQR) for both groups: TS IQR=64-75 (range, 32-82); 3DVRS IQR=64-76 (range, 34-86). No difference in exam scores using 3DVRS versus traditional simulation was detected. Paramedic programs may have an effective new option when incorporating simulation with 3DVRS, potentially reducing financial and real-estate resources required with in-person simulations. Larger studies are needed to truly evaluate the impact and usability of virtual reality on paramedic education.

HEARING INTERVENTION TO REDUCE COGNITIVE DECLINE: DESIGN AND FINDINGS OF THE ACHIEVE RANDOMIZED CONTROLLED TRIAL

Abstract Epidemiologic data consistently link age-related hearing loss with accelerated cognitive decline and incident dementia in large, population-based studies. Mechanistic pathways that could underlie this association include the effects of distorted peripheral encoding of sound on cognitive load, changes to brain structure/function, and/or reduced social engagement and increased loneliness. Importantly, these pathways may be amenable to comprehensive hearing rehabilitative treatment including hearing assistive technologies (e.g., hearing aids, other integrated hearing assistive devices) and rehabilitative training. To date, however, there has never been a randomized trial that has investigated whether hearing loss treatment could reduce cognitive and other functional decline in older adults without dementia. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial is a multicenter randomized control trial of 977 cognitively intact adults with untreated, mild-to-moderate hearing loss aged 70-84 years at baseline (2018-19) to determine efficacy of best-practices hearing intervention to reduce cognitive decline over 3 years (Clinicaltrials.gov Identifier: NCT03243422). This session, on behalf of the ACHIEVE Collaborative Research Group, will describe the overall design of the ACHIEVE trial including details about recruitment and implementation of both the hearing (amplification, auditory rehabilitation) and successful aging health education control interventions. We will also present the primary findings of the study – the effect of the hearing intervention vs. control on 3-year cognitive decline – as well as the effect of the hearing intervention on several pre-specified outcomes important for the health of older adults, including social engagement, mood disorders and quality of life.

Evaluation of a Cannabis Harm Reduction Intervention for People With First-Episode Psychosis: Protocol for a Pilot Multicentric Randomized Trial.

Cannabis use is highly prevalent in young people with first-episode psychosis (FEP). Most report cannabis use and are often diagnosed with a cannabis use disorder upon admission to specialized services for psychosis. Cannabis use in this population is associated with worse clinical and psychosocial outcomes, rendering it an important clinical target. Despite this, few cannabis-specific interventions have been developed for FEP and empirically evaluated through randomized controlled trials. Most evaluated interventions have targeted cannabis abstinence, with limited efficacy, but none have centered on harm reduction outcomes for people with FEP who use cannabis. Early intervention services (EIS), the standard of care for FEP, have not successfully addressed problematic cannabis use in people with FEP either. Clinical trials are needed to explore the potential of harm reduction strategies, although these should be preceded by robust pilot studies to establish optimal design and approaches. Recognizing the need for harm reduction strategies for individuals with FEP who use cannabis and based on research on patients' preferences supporting harm reduction interventions, we developed a mobile app-based cannabis harm reduction intervention for this population. This intervention is called Cannabis Harm-reducing Application to Manage Practices Safely (CHAMPS). Here, we describe the protocol for a multicenter, 2-arm, parallel group, randomized pilot trial evaluating the acceptability of CHAMPS for people with FEP who use cannabis and the feasibility of conducting a full-scale trial in this population using CHAMPS. The impact on key clinical outcomes will also be explored. This pilot trial aims to recruit 100 young people with FEP using cannabis from 6 Canadian EIS clinics. Participants will be randomized in a 1:1 ratio to CHAMPS+EIS or EIS-only. CHAMPS acceptability will be assessed using completion rates for the intervention arm. Trial feasibility will be assessed using a retention rate for randomized participants. Secondary outcomes will explore tendencies of change in the use of protective behavioral strategies and in motivation to change strategies. Exploratory outcomes include cannabis use-related problems, other substance use, the severity of dependence, psychotic symptoms, and health care service use. Recruitment began in December 2021. Data collection and analysis are expected to be completed in early 2024. Study results describing CHAMPS acceptability and trial feasibility will then be submitted for publication in a peer-reviewed journal. CHAMPS uniquely combines evidence-based approaches, patient perspectives, and mobile health technology to support harm reduction in people with FEP who use cannabis. Attaining adequate acceptability and feasibility through this trial may justify further exploration of harm reduction tools, particularly within the context of conducting a larger-scale randomized controlled trial. This pilot trial has the potential to advance knowledge for researchers and clinicians regarding a feasible and user-acceptable research design in the cannabis and early psychosis fields. ClinicalTrials.gov NCT04968275, https://clinicaltrials.gov/ct2/show/NCT04968275. DERR1-10.2196/53094.

Turpentine Ointment for the Treatment of Folliculitis: An Open, Prospective, Randomized, Placebo- and Comparator-Controlled Multicenter Trial

Introduction: Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis. Methods: Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient’s global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording. Results: A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events. Conclusion: The turpentine ointment is an effective and safe option for the treatment of folliculitis.