Double-blind Trial Research Articles

The therapeutic effect of omega-3 polyunsaturated fatty acids on symptom severity of psychosis: A systematic review and meta-analysis.

While omega-3 polyunsaturated fatty acids (PUFAs) have shown promise as an adjunctive treatment for schizophrenia and other psychotic disorders, the overall consensus about their efficacy across studies is still lacking and findings to date are inconclusive. No clinical trials or systematic reviews have yet examined if omega-3 PUFAs are associated with differential levels of efficacy at various stages of psychosis. A systematic bibliographic search of randomized double-blind placebo-controlled trials (RCTs) examining the effect of omega-3 PUFAs as a monotherapy or adjunctive therapy versus a control group in adults and children at ultra-high risk (UHR) for psychosis, experiencing a first-episode psychosis (FEP), or diagnosed with an established psychotic disorder was conducted. Participants' clinical symptoms were evaluated using total and subscale scores on validated psychometric scales. No beneficial effect of omega-3 PUFAs treatment was found in comparison with that of placebo (G = -0.26, 95% CI -0.55 to 0.03, p = 0.08). Treatment of omega-3 PUFAs did not prove any significant improvement in psychopathology in UHR (G = -0.09, 95% CI -0.45 to 0.27, p = 0.63), FEP (G = -1.20, 95% CI -5.63 to 3.22, p = 0.59), or schizophrenia patients (G = -0.17, 95% CI -0.38 to -0.03, p = 0.10). These findings confirm previous evidence that disputes the original reported findings of the beneficial effect of omega-3 PUFAs in schizophrenia. Furthermore, accumulative evidence of the use of omega-3 as a preventive treatment option in UHR is not supported, suggesting that the need for future studies in this line of research should not be promoted.

Randomized Clinical Trial of Intraocular Pressure-Lowering Medications on Preventing Spikes in Intraocular Pressure Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections. This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group. The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30min were within 21mmHg and returned to their baseline at 1h. Mean IOP measurements between baseline and 30min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30min and 1h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52mmHg, respectively, p < 0.001. Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion. TCTR20241005001, retrospectively registered.

Potassium Nitrate in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Nitric oxide deficiency may contribute to exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Prior pilot studies have shown improvements in exercise tolerance with single-dose and short-term inorganic nitrate administration. To assess the impact of chronic inorganic nitrate administration on exercise tolerance in a larger trial of participants with HFpEF. This multicenter randomized double-blinded crossover trial was conducted at the University of Pennsylvania, the Philadelphia Veterans Affairs Medical Center, and Northwestern University between October 2016 and July 2022. Participants included patients with symptomatic (New York Heart Association class II/III) HFpEF who had objective signs of elevated left ventricular filling pressures. Image quantification, physiological data modeling and biochemical measurements, unblinding, and statistical analyses were completed in 2024. Potassium nitrate (KNO3) (6 mmol 3 times daily) vs equimolar doses of potassium chloride (KCl) for 6 weeks, each with a 1-week washout in between. The coprimary end points included peak oxygen uptake and total work performed during a maximal effort incremental cardiopulmonary exercise test. Secondary end points included the exercise systemic vasodilatory reserve (ie, reduction in systemic vascular resistance with exercise) and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire. Eighty-four participants were enrolled. Median age was 68 years and 58 participants were women (69.0%). Most participants had NYHA class II disease (69%) with a mean 6-minute walk distance of 335.5 (SD, 97.3) m. Seventy-seven participants received the KNO3 intervention and 74 received the KCl intervention. KNO3 increased trough levels of serum nitric oxide metabolites after 6 weeks (KNO3, 418.4 [SD, 26.9] uM vs KCl, 40.1 [SD, 28.3] uM; P < .001). KNO3 did not improve peak oxygen uptake (KNO3, 10.23 [SD, 0.43] mL/min/kg vs KCl, 10.17 [SD, 0.43] mL/min/kg; P = .73) or total work performed (KNO3, 25.9 [SD, 3.65] kilojoules vs KCl, 23.63 [SD, 3.63] kilojoules; P = .29). KNO3 nitrate did not improve the vasodilatory reserve or quality of life, though it was well-tolerated. In this study, potassium nitrate did not improve aerobic capacity, total work, or quality of life in participants with HFpEF. ClinicalTrials.gov Identifier: NCT02840799.

Effects of trehalose on bone healing, physical function, and pain in patients with pertrochanteric fractures: a randomized controlled trial protocol

BackgroundAppropriate management of fractures is crucial for restoring natural bone function and preventing long-term complications. Previous research on animal models indicates that trehalose can improve bone fracture healing by inhibiting the inflammatory cascade. We hope that trehalose can accelerate bone fracture healing in humans, alleviate pain, and ultimately enhance the individual’s quality of life.MethodsThis randomized, double-blind clinical trial will be conducted at Taleghani Hospital in Tehran, Iran. Sixty-four patients admitted to the orthopedic ward will be enrolled based on eligibility criteria. The participants will be randomly allocated based on the permuted block randomization into two groups: those receiving trehalose (32 patients) or placebo (32 patients). The patients in the trehalose and placebo groups will receive 3.3 g of trehalose or placebo for 12 weeks, respectively. A consent form, general questionnaire, as well as the Visual Analog Scale (VAS), Harris Hip Score (HHS), and radiological analyses will be used to assess fracture healing quality. The intention-to-treat principle will form the basis of the statistical analysis.DiscussionThe trial results may provide a convenient and safe adjuvant treatment option for the Pertrochanteric Fractures population.Trial registrationIranian Registry of Clinical Trials. IRCT20240605062013N1. URL of the trial registry record: https://irct.behdasht.gov.ir/trial/77212. Registration date: 16 June 2024.

Efficacy of Perineural Dexmedetomidine in Ultrasound-guided Interscalene Block on Rebound Pain after Shoulder Arthroscopy.

This prospective, randomized, double-blind trial was performed to investigate the effect on rebound pain incidence of mixing dexmedetomidine (DEX) with local anesthetics in a combined injection interscalene block (ISB) during shoulder arthroscopy. 47 patients were enrolled in this study. Patients were randomly assigned to 2 groups: Group DEX and Group Control received ultrasound-guided ISB using 12mL of 0.5% ropivacaine with 50ug of dexmedetomidine or without dexmedetomidine. Pain scores at 6, 12, 24, 48 h after surgery were assessed with Numeric Pain Rating Scale (NRS). Additional analgesic requirements and side effects in the first 48h postoperatively, as well as sleep disturbance on the night and other complications of surgery were examined. The incidence of rebound pain was lower in the group DEX than in the Control group. Perineural DEX decreased pain scores at 12 h and 24 h postoperatively. Group DEX had a prolonged time to first analgesic request, PCA sufentanil consumption in group DEX was less than group Control during the first 48 hours postoperatively. The number of patients with sleep disturbance and nausea and vomiting in the DEX group was lower on the first night postoperative. Perineural dexmedetomidine added to ISB exerts beneficial effect on the incidence of rebound pain after ISB in patients with pain catastrophizing undergoing shoulder arthroscopy. Perineural dexmedetomidine facilitated the implementation of multimodal analgesia in the early stage after operation.

Human cold pain: a randomized crossover trial.

The mechanism causing cold pain in humans is unresolved. Animal data suggest a nonredundant contribution to cold pain for transient receptor potential channels TRPM8 and TRPA1 for detection and voltage-gated sodium channels NaV1.7 and NaV1.8 for conduction at these temperatures. We established an intradermal injection-based cold pain model, which allows pharmacologically addressing molecular targets at the site of cooling. Lidocaine, added to the injection solution as positive control, largely reduced cold-induced pain in 36 volunteers. The 4 mentioned molecular targets were blocked by antagonists in a double-blinded crossover trial. Pain induced by 3°C intradermal fluid was not reduced to a relevant extent by any of the 4 antagonists alone or by the quadruple combination. However, the temperature threshold for cold pain appeared shifted by the inhibition of TRPA1, TRPM8, and NaV1.7 and to a lesser extent by NaV1.8 inhibition, 4-fold inhibition decreased the threshold by 5.8°C. Further mechanisms contributing to human cold pain need to be considered.

Efficacy of a Dietary Supplement Extracted from Persimmon (Diospyros kaki L.f.) in Overweight Healthy Adults: A Randomized, Double-Blind, Controlled Clinical Trial

A single-center, randomized, double-blind, and placebo-controlled clinical trial assessed the efficacy in improving body composition and in weight management of a dietary supplement consisting of 400 mg of a standardized extract of the persimmon fruit (Diospyros kaki L.f.) in adult subjects with a BMI between 25 and 34.99 kg/m2 administered for 120 consecutive days. In total, 36 participants were assigned to the placebo group and 35 to the experimental group (registered at ClinicalTrials.gov (NCT05750342)). Primary analysis focused on overweight subjects (placebo, n = 26; experimental, n = 23). In this group, fat mass expressed in kg and percentage evaluated by both dual-energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA) decreased significantly (between-group differences p &lt; 0.001) in those receiving the persimmon extract as compared with the placebo. No significant reduction in lean mass was observed, suggesting that the muscle mass was maintained during fat loss. The use of the investigational product improved classic anthropometric parameters to a statistically significantly greater extent than the placebo, including body weight, BMI, and waist and abdominal circumference (p &lt; 0.001), in the overweight group. In the overall population, similar improvements were observed, with significant between-group differences (p &lt; 0.001) in fat mass reduction and improvements in body composition. Changes in the biochemical lipidic, glycemic, and anti-inflammatory profile were not found, except for between-group significant differences (p &lt; 0.001) in decreases in tumor necrosis factor-alpha (TNFα) and increases in total antioxidant capacity (TAC) in favor of the experimental condition. There was a significant increase in fecal fat excretion in the experimental group at the end of the study in subjects with low fecal fat (9%) at baseline. Consumption of the investigational product vs. placebo improved the quality of life, with significantly greater scores in the total score and the mental health component of the SF-12 questionnaire. The persimmon extract was safe and well tolerated.

Immediate effects of Kinesio taping on pain, proprioception, and posture in round shoulder individuals with subacromial impingement syndrome: A randomized, double-blinded controlled trial.

Round shoulder posture (RSP), characterized by forward shoulder positioning from weakened and tense muscles, disrupts normal biomechanics and can cause Subacromial impingement syndrome (SIS), resulting in pain during specific movements or positions. This study examines the immediate effects of Kinesio taping (KT) on pain, proprioception, and posture in individuals in round shoulder individuals with SIS. The study involved 114 patients diagnosed with RSP and SIS. Pain intensity was assessed using a Visual Analog Scale (VAS), proprioception was measured with an inclinometer, and posture was evaluated using The New York Posture Rating Chart (NYPRC). Participants were randomly assigned to experimental group (EG) (n = 57), which received KT application, or to sham group (SG) (n = 57), which underwent a sham procedure. KT was applied to the affected shoulder and scapular regions. Assessments were conducted both before and after the application of Kinesio tape. According to the study results, the differences in VAS scores (P = .002), proprioception abduction (P = .023) and NYPRC scores (P = .04), were statistically significant in the EG compared to the SG (P < .05). However, there was no significant difference in proprioception flexion between the groups (P > .05). KT demonstrates immediate benefits in reducing pain and improving scapular alignment in individuals with RSP and chronic shoulder pain. These findings underscore its potential effectiveness as a therapeutic intervention for managing symptoms associated with RSP and impingement syndrome, particularly in terms of pain relief and posture enhancement.

Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial

BackgroundAlarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.MethodsWild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17’s pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.ResultsAnimal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.ConclusionIn the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05332834.

Comparison of Hemodynamic Responses to Ketofol versus Etomidate During Anesthesia Induction in Elderly Patients

Background: Nausea While elderly patients are at an increased risk of perioperative morbidity and mortality; old age alone is not a contraindication for surgery. General factors that should be considered in preoperative risk assessments include age, functional status, cognition, nutritional status, and comorbidities, such as cardiac, pulmonary, renal, and endocrine disorders. Induction of anesthesia is a critical step in surgery, particularly for elderly patients and those with a high physical status. Commonly used drugs for this purpose include etomidate and propofol. Therefore, this study aimed to compare the impact of Ketofol versus etomidate alone on the hemodynamic status of patients who fall under the ASA class II or higher. Methods: The study was a prospective randomized double-blind clinical trial, with a study population of age of ≥65 years, ASA physical status class II or higher, that were randomized into two groups. Ketofol (n=45) and, Etomidate (n=45) groups. Patients followed for clinical outcomes including their hemodynamic status during the induction period. Results: The present study showed that, the examination of hemodynamic parameters up to 10 minute after laryngoscopy showed that none of these parameters were significantly different between the two groups, while immediately after anesthesia induction, heart rate and blood pressure were found to be significantly different. However, there was no significant difference in terms of SPO2 among the two groups in any given interval. Conclusion: The results of the present study revealed that Ketofol resulted in better regulation and stability of blood pressure and heart rate in patients undergoing endotracheal intubation, compared to etomidate alone.

Antifungal Efficacy of Ganoderma lucidum and Clotrimazole for Treatment of Denture Stomatitis: A Randomized Clinical Trial

Objectives: This study aimed to compare the antifungal efficacy of Ganoderma lucidum (G. lucidum) and clotrimazole for treatment of denture stomatitis (DS). Materials and Methods: This double-blind randomized clinical trial was conducted on 50 patients with DS types I and II assigned to two groups (N=25). In the first group, G. lucidum extract was administered in the form of 5% gel while 1% clotrimazole gel was prescribed for the second group. Pain intensity according to the visual analog scale (VAS), and the percentage of DS recovery based on the Budtz-Jorgenson index were evaluated and recorded after 7 and 14 days. Data were analyzed using the Chi-square test, independent samples t-test, repeated measures ANOVA, and logistic regression (alpha=0.05). Results: The percentage of complete recovery on day 7 in the G. lucidum group (28%) was higher than that in the clotrimazole group (16%) but not significantly (P=0.592). Not wearing dentures overnight significantly increased the odds of recovery by 6.56 times, while the odds of recovery decreased by 0.03 times in DS type II, as compared to DS type I (P= 0.009). Conclusion: No significant difference existed between the antifungal efficacy of G. lucidum and clotrimazole for clinical treatment of DS. Thus, Ganoderma may be regarded as an alternative treatment, especially in patients’ resistant to azoles. Nonetheless, further clinical studies are required to shed more light on this topic.

Trained dogs can detect canine urothelial carcinoma of the bladder

Dog have been trained to detect a variety of human cancers. However, studies examining their ability to find canine cancer are sparse and show variable results. Whilst dogs were shown to be successful at detecting malignant tumors from saliva samples, they were previously unsuccessful at finding canine urothelial carcinoma (UC) from urine. We used advanced training methods to explore if dogs can accurately detect urothelial carcinoma (UC) from canine urine.Urine samples from healthy dogs without urinary tract abnormalities (control), with non-malignant urinary tract disease (control), and with UC (positive) were collected prospectively. Urothelial carcinoma was diagnosed using cytology and/or histopathology. All dogs were naïve of chemotherapy, underwent bladder ultrasound and urinalysis. Residual urine remaining after conventional diagnostic procedures was frozen in glass jars until analysis and used for dog training and testing.Three dogs previously trained to detect human cancer underwent up to 29 days of additional training. They were each presented with 20 control samples (from either 13 or 14 unique individuals), 10 UC positive samples (from between 5 and 7 individuals), in a double-blind trial and their behavioral responses recorded.When considering only unique donor dogs, a mean of 66.7% (range 40–85.7%) of UC were correctly indicated and a mean of 87.5% (range 78.6–92.3%) were correctly ignored. The overall sensitivity (considering all samples) was 80% (range 70–90%), and specificity was 91.7% (range 85–95%). This study suggests that, when using appropriate methods, dogs can be trained to detect canine UC from urine and could serve as an additional non-invasive diagnostic test for the disease.

The additional effect of 5% atorvastatin shampoo in the treatment of adult patients with mild to moderate seborrheic dermatitis of the scalp: A prospective, randomised, double-blind trial

Background Seborrheic dermatitis (SD) is a long-lasting inflammatory skin condition that predominantly impacts regions abundant in sebaceous glands, including the scalp. Objectives To assess the efficacy and anti-inflammatory effect of atorvastatin as an additive treatment among SD patients. Materials and Methods In a prospective, randomised, double-blind trial, 46 patients over 18 years old with mild to moderate scalp SD were randomly assigned to receive either 2% ketoconazole shampoo or 2% ketoconazole shampoo plus 5% atorvastatin. The severity of dermatitis was assessed based on the symptom scale of seborrheic dermatitis (SSSD), and the variables of erythema, scaling, and itching, at baseline and 4 weeks after the intervention. Results Based on our analyses, both treatment methods significantly reduced the SSSD scores. However, the average SSSD score in patients using ketoconazole shampoo plus atorvastatin decreased by an average of five points after 1 month. This reduction was comparable to the average decline of 3.5 points observed in the group using ketoconazole shampoo alone. Specifically, the severity of dermatitis, as assessed by the SSSD score, significantly decreased by 1.92 points more, in individuals using the atorvastatin-containing shampoo compared to the comparison group (P = 0.02). Limitation This research was conducted at a single centre which limits the validity of the findings. Conclusion The results of this study suggest that shampoo containing atorvastatin provides a statistically significant effect compared to ketoconazole shampoo alone, indicating its potential as an alternative treatment for SD. The treatment notably alleviates symptoms associated with scaling and itching which are the common manifestations of the condition.

A randomized double-blind noninferiority clinical multicenter trial on oral moxifloxacin versus placebo in the outpatient treatment of uncomplicated acute appendicitis: APPAC IV study protocol.

Antibiotic therapy is currently considered a safe and effective treatment alternative for computed tomography (CT)-confirmed uncomplicated acute appendicitis with recent studies reporting good results on both oral antibiotics only and outpatient management. Furthermore, there are promising pilot results on uncomplicated acute appendicitis management with symptomatic treatment (placebo). This trial aims to assess whether both antibiotics and hospitalization can be safely omitted from the treatment of uncomplicated acute appendicitis. The APPAC IV (APPendicitis Acuta IV) trial is a randomized, double-blind, multicenter noninferiority clinical trial comparing oral moxifloxacin with oral placebo in an outpatient setting with a discharge directly from the emergency room (ER). Adult patients (18-60 years) with CT-confirmed uncomplicated acute appendicitis (absence of appendicolith, abscess, perforation, tumor, appendiceal diameter ⩾15 mm on CT, or body temperature >38 °C) will be enrolled in nine Finnish hospitals. Primary outcome is treatment success at 30 days, that is, the resolution of acute appendicitis resulting in discharge from the hospital without appendectomy during the 30-day follow-up evaluated using a noninferiority design with a noninferiority margin of 6 percentage points. Noninferiority will be evaluated using one-sided 95% confidence interval of proportion difference between groups. Secondary endpoints include postintervention complications, recurrent appendicitis after the 30-day follow-up, duration of hospital stay, admission to hospital and reason for admission, readmissions to emergency department or hospitalization, VAS pain scores, quality of life, sick leave, and treatment costs. The follow-up after discharge from the ER includes a phone call at day 1, and at 3-4 days, 30 days, and 1, 3, 5, 10, and 20 years. Those eligible patients, who decline to undergo randomization, will be invited to participate in a concurrent observational cohort study with follow-up at 30 days, and 1 and 5 years. To our knowledge, APPAC IV trial is the first large randomized, double-blind, noninferiority multicenter clinical trial aiming to compare oral antibiotics and placebo for CT-diagnosed uncomplicated acute appendicitis in an outpatient setting. The study aims to bridge the major knowledge gap on whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated acute appendicitis. The study protocol has been approved by the Clinical Trials Information System (CTIS) of the European Medicines Agency (EMA), study number: 2023-506213-21-00 and the trial has been registered in ClinicalTrials.gov, NCT06210269.

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic

The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD). To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic. This double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no prepandemic mental health diagnoses but had moderate or severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle. One intervention episode consisted of 2 preparation visits, 1 medication session, and 3 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally. The primary outcome was a change from baseline (preparation 1 session) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. The secondary outcomes were a change in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]). A total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) participated, of whom 15 were randomly assigned to receive psilocybin and 15 to receive niacin. The mean change in symptoms of depression (MADRS scores) from preparation 1 session to day 28 was -21.33 (7.84) in the psilocybin arm compared with -9.33 (7.32) in the niacin arm, with a mean difference between arms of -12.00 (95% CI, -17.67 to -6.33; P < .001), a decrease in MADRS scores indicating improvement. The mean change in SPFI scores from preparation 1 session to day 28 showed a numerically larger improvement in symptoms of burnout in the psilocybin compared with the niacin arm (-6.40 [5.00] vs -2.33 [5.97]; P = .05) but was not statistically significant. Since the SPFI score change did not reach statistical significance, the PCL-5 score change was evaluated descriptively. The mean change in PCL-5 scores showed a numerically larger decrease in symptoms of PTSD from preparation 1 session to day 28 in the psilocybin vs the niacin arm (-16.67 [15.04] vs -6.73 [10.69]), but this difference was not statistically tested. This randomized clinical trial found that psilocybin therapy resulted in a significant, sustained reduction in symptoms of depression experienced by clinicians after frontline work during the COVID-19 pandemic. The findings establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition. ClinicalTrials.gov Identifier: NCT05163496.

Clinical evaluation of AYUSH-SL in patients receiving mass drug administration for the treatment of chronic inflammatory lymphedema, a double blind, placebo controlled, multicentric study.

A 2.5-year placebo controlled double blind trial was conducted to investigate the safety and efficacy of AYUSH- SL, a poly- herbal Ayurvedic formulation on filarial lymphedema in different endemic areas of India. Lymphatic filariasis (LF) is caused by parasitic nematodes from Wuchereria bancrofti, Brugia malayi, or B. timori that are transmitted through mosquitoes. In Ayurveda, LF has been elaborately narrated under the heading Shlipada, and the literature also includes detailed therapeutic measures. The multicenter, prospective, parallel group interventional study of a total of 180 participants were recruited within the duration through competitive enrollment. Diagnosed cases of grade I and grade II filarial lymphedema of Grade I and Grade II (lower extremities) were included in the trial. The study group was treated with MDA and AYUSH-SL or its placebo tablet. The control group had received MDA and a matching placebo. The primary outcome measure was the reduction in edema calculated for analysis by percentage reduction from baseline at the 4th, 12th and 24th week. Secondary outcome measures included improved quality of life (QoL), which was assessed using the Lymphatic Filariasis Specific QoL Questionnaire, and prevention of recurrence of acute episodes, which was evaluated by investigating the presence and severity of episodes in the past 4 weeks. The water displacement method for the evaluation of the efficacy of the intervention was shown to be highly significant compared to the baseline value (right leg; 3071.60 ± 970.482, 2828.40±829.339, p<0.001and Left leg; 3158.69 ± 1136.391, 2890.73 ±1077.475, p<0.001). There was significant improvement of Quality of Life in the LF QoL Questionnaire (p <0.001) at each follow-up visit in both groups. Safety estimations on hematologic and biochemical parameters were within limits and or changes were not significant. The results revealed that AYUSH- SL is safe and effective for FL due to its comprehensive anti-inflammatory, antimicrobial, and anti-allergic activities.

Color evaluation of a one-shade used for restoration of non-carious cervical lesions: an equivalence randomized clinical trial

BackgroundObtaining a perfect color match with resin composite presents a significant challenge. The chameleon effect has enabled resin composite to mimic the color of the adjacent tooth structure in vitro. This double-blind, split-mouth and equivalent randomized clinical trial evaluated the color matching of one-shade resin composite with chameleon effect versus multi-shade resin composite in non-carious cervical lesion restorations (NCCLs).MethodsOne hundred twenty restorations were performed on NCCLs with two restorative materials (n = 60). After prophylaxis, the teeth were isolated with rubber dam and one universal adhesive was applied in the selective enamel etching strategy. For both groups, the restorations were inserted incrementally. The values of ΔEab and ΔE00 in the cervical and middle third were evaluated using a digital spectrophotometer before vs. after the restorations. The restorations were evaluated at baseline and after 7 days, 6-, 12- and 18-month of clinical performance according to the FDI criteria (Word Federation Criteria). Statistical analysis was performed using Chi-square test for all parameters. Color change was analyzed by two one-sided t-tests for paired samples (α = 0.05).ResultsRegarding the color measurement no significant difference was observed when Vittra APS (FGM Dental Products, Joinville, SC, Brazil) was compared to Vittra Unique (FGM Dental Products, Joinville, SC, Brazil) for any of the comparisons performed (p > 0.05). However, the ΔEab and ΔE00 values for the cervical third, both before and after the restorations, were higher compared to the ΔEab and ΔE00 values observed when comparing the cervical and middle thirds after the restorations. After 18 months, five restorations exhibited minimal discrepancies in terms of marginal adaptation or marginal discoloration (p > 0.05). In all other criteria, including retention rate, no changes were detected at the 18-month recall.ConclusionsThe one-shade resin composite used achieve the same color match when compared to a multi-shade resin composite after a period of 7 days in NCCLs. Overall, the restorations scored clinically very good (FDI) at baseline and after 18 months for all outcomes.Clinical SignificanceThe use of a one-shade resin composite in NCCLs can be recommended because it has the ability to simplify the restoration procedure and maintaining an excellent clinical performance.Registration of clinical trialsRBR-8txr4fw: 26/05/2022.

Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.

Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19. To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia. This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023. Participants were adults aged 18 years or older hospitalized with acute SARS-CoV-2 infection and hypoxemia. Data were analyzed between January 10 and March 8, 2024. Fostamatinib, 150 mg orally twice daily for 14 days, or placebo. The primary outcome was oxygen-free days, an ordinal outcome classifying a participant's status at day 28 based on mortality and duration of supplemental oxygen use. An adjusted odds ratio (AOR) greater than 1.0 was considered to indicate superiority of fostamatinib over placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included elevated transaminase values, neutropenia, and hypertension. Of the 400 participants randomized (median age, 67 years [IQR, 58-76 years]; 210 [52.5%] men), 199 received fostamatinib and 201 received placebo. The mean (SD) number of oxygen-free days was 13.4 (12.4) in the fostamatinib group and 14.2 (12.1) in the placebo group (unadjusted mean difference, -1.26 days [95% CI, -3.52 to 1.00 days]; AOR, 0.82 [95% credible interval (CrI), 0.58-1.17]). Mortality at 28 days occurred in 22 of 195 patients (11.3%) in the fostamatinib group and 16 of 197 (8.1%) in the placebo group (AOR, 1.44; 95% CrI, 0.72-2.90). Aspartate aminotransferase elevation occurred more commonly in the fostamatinib group (23 [11.6%]) than in the placebo group (11 [5.5%]; AOR, 2.28; 95% CrI, 1.07-4.84). Other safety outcomes were similar between groups. In this randomized clinical trial of adults hospitalized with COVID-19 and hypoxemia, fostamatinib did not increase the number of oxygen-free days compared with placebo. These results do not support the hypothesis that fostamatinib improves outcomes among adults hospitalized with hypoxemia during the Omicron era. ClinicalTrials.gov Identifier: NCT04924660.

Comparison of Ultrasound-Guided Hydrodissection with Various Volumes of 5% Dextrose for Carpal Tunnel Syndrome: A Prospective Randomized Controlled Double-Blind Trial.

Ideal volume of 5% dextrose (D5W) for median nerve hydrodissection (HD) for treating carpal tunnel syndrome (CTS) is still unknown. This study assessed the efficacy of nerve hydrodissection using varying volumes of D5W for treating mild to moderate CTS. Eighty participants with unilateral mild to moderate CTS were randomized into groups to receive either 5 ml of normal saline (NS), 5 ml of D5W, 10 ml of NS, and 10 ml of D5W, with each group undergoing one session of ultrasound-guided HD. Visual Analogue Scale (VAS), Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), grip and pinch strength, cross-sectional area (CSA) of median nerve, and electrophysiological assessment were performed at baseline and weeks 4 and 12. In the 10 ml D5W group, VAS scores considerably improved compared with those in the NS groups. Although nerve CSA values decreased in all groups during follow-ups, the 10 mL D5W group showed a statistically significant improvement compared to the NS groups by the 12th week (p ≤ 0.01). Ultrasound-guided median nerve HD with 10 ml D5W was more effective in reducing pain and nerve size than the NS groups at the 12th week.

Efficacy and Safety of Dose Increase From 40 mg/d to 80 mg/d of Lurasidone in Patients With Schizophrenia: A Post Hoc Analysis of Extension Trial.

The primary objective of this study was to evaluate the efficacy and safety of increasing the dose of lurasidone from 40 mg/d to 80 mg/d in patients with schizophrenia. This post hoc analysis focused on patients who completed a 6-week double-blind, placebo-controlled trial of lurasidone and transitioned to a subsequent 12-week open-label extension trial. Patients initially assigned to lurasidone (40 mg/d) or placebo during the double-blind trial (DBT-LUR group or DBT-PLA group, respectively) received lurasidone (40 mg/d) during the extension. Clinicians could increase the dose to 80 mg/d based on clinical judgment. The efficacy outcomes included the change in the Positive and Negative Syndrome Scale (PANSS) total score from the start to the end of the lurasidone (80 mg/d) treatment period. Safety outcome was the rate of newly emergent adverse events. Of 287 patients in the intention-to-treat population, 153 received an increased dose of lurasidone from 40 mg/d to 80 mg/d. Significant reductions in the PANSS total scores were observed in both groups (all P values, ≤0.001). Additionally, 35.9% of the DBT-LUR group and 40.0% of the DBT-PLA group achieved a ≥20% reduction in the PANSS total score. New adverse events emerged in 47.4% of the DBT-LUR group and 48.0% of the DBT-PLA group during the lurasidone (80 mg/d) treatment period. Increasing the dose of lurasidone from 40 mg/d to 80 mg/d may be effective and well tolerated in patients with schizophrenia. Because of the lack of a control group and blinding, the results should be interpreted with caution.