rTMS for Poststroke Pusher Syndrome: A Randomized, Patient-Blinded Controlled Clinical Trial.

BACKGROUND: Patients with poststroke pusher syndrome (PS) require longer duration of rehabilitation and more supplemental care after discharge. Effective treatment of PS remains a challenge. The role of repetitive transcranial magnetic stimulation (rTMS) for PS has not been examined. OBJECTIVE: Assess the efficacy of rTMS for patients with poststroke PS in reducing pushing behavior, enhancing motor recovery and improving mobility. METHODS: A randomized, patient- and assessor-blinded sham-controlled trial with intention-to-treat analysis was conducted. Thirty-four eligible patients with poststroke PS were randomly allocated to receive either rTMS or sham rTMS for 2 weeks. Pushing behavior on the Burke lateropulsion scale and scale for contraversive pushing, motor function on Fugl-Meyer assessment scale-motor domain (FMA-m) and mobility on modified Rivermead mobility index were measured at baseline, 1 and 2 weeks after intervention. Repeated-measures analysis of covariance was used for data analysis. RESULTS: There was no significant interaction between intervention and time on Burke lateropulsion scale (F = 2.747, P = .076), scale for contraversive pushing (F = 1.583, P = .214), or change of modified Rivermead mobility index (F = 1.183, P = .297). However, a significant interaction between intervention and time was observed for FMA-m (F = 5.464, P = .019). Post hoc comparisons of FMA-m show better improvement in rTMS group with mean differences of 12.7 (95% CI -7.3 to 32.7) and 15.7 (95% CI -4.6 to 36.0) at post-treatment week 1 and week 2 respectively. CONCLUSIONS: rTMS did not demonstrate significant efficacy in improving pushing behavior and mobility in patients with PS. However, rTMS might have potential effect in enhancing motor function for patients with PS. REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200058015 at http://www.chictr.org.cn/searchprojen.aspx) on March 26, 2022.

A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.

BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).

Effectiveness of interventions on improving early-life dental care utilization: a systematic review and meta-analysis.

OBJECTIVES: Although early-life dental care is crucial for preventing early childhood caries and has numerous benefits, the utilization rate of such care remains remarkably low worldwide, especially in families of low socioeconomic status. The aim of this study was to systematically review the scientific evidence relating to the effectiveness of interventions on improving early-life dental care utilization of very young children. METHOD AND MATERIALS: We reviewed scientific evidence relating to these positive changes, with 7 randomized controlled trials after qualitative evaluation. Interventions assessed included prenatal oral health promotion, motivational interviewing, intraoral camera use alongside social work consultations to aid in decreasing barriers to care, monetary incentives for tooth brushing, fluoride varnish applications, and probiotic usage. RESULTS: The intervention was significantly effective in reducing the incidence of dental caries among children, especially in caries risk. Caries reduction was significant when oral health information was provided at frequent intervals prenatally. Caries increment was also reduced when probiotics were introduced when administered daily. Interventions that attempted to increase parental involvement in oral health care by increasing motivation and decreasing barriers had inconclusive results within the study groups. CONCLUSIONS: Considering high rates ECC, early establishment and preservation of a dental home should be a focus in public health measures. Continuous monitoring and parental involvement are key components to maintaining healthy oral conditions. Future studies could explore and test various innovative strategies that utilize technological platforms to engage with parents and promote early-life dental care utilization among the underserved population.

A Controlled Clinical Trial on the Effects of Aquatic Exercise on Cognitive Functions in Community-Dwelling Older Adults.

Several therapies have been developed to reduce cognitive decline associated with aging. Aquatic exercises, which are widely used to enhance functional capacity, may play a role in stimulating cognitive functions. This study investigated the effects of a 3-month aquatic exercise program on cognitive functions in community-dwelling older adults. In this prospective, single-blinded, controlled clinical trial, 31 participants were allocated to either the experimental (aquatic exercises) or control (no-exercise) group. The intervention program consisted of exercises conducted twice a week in a 1.2 m deep indoor pool. The main outcome measures were cognitive functions, assessed using Raven's Progressive Matrices test and the Wisconsin Card Sorting Test. A repeated-measures analysis of variance was used to assess the impact of the exercise program. The effect sizes (η2p) were reported when a level of significance was achieved (p < 0.05). Compared with the control group, the participants who underwent aquatic exercises showed positive outcomes in Raven's Progressive Matrices test (p = 0.046; η2p = 0.131) and the Wisconsin Card Sorting Test (p = 0.001, η2p = 0.589). Complementary analyses of the Wisconsin Card Sorting Test indicated that the benefits of the aquatic exercise were observed in terms of the number of trials (p = 0.001, η2p = 0.478), number of errors (p = 0.001, η2p = 0.458), and number of non-perseverative errors (p = 0.001, η2p = 0.302). The results indicate that a period of three months of aquatic exercise was beneficial for stimulating specific aspects of the cognitive function of community-dwelling older individuals. Aquatic exercise should be prescribed to this population.

Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial.

BACKGROUND: Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19. TRIAL DESIGN AND METHODS: A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups. RESULTS: Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 - 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000-65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load. CONCLUSION: Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms. TRIAL REGISTRATION NUMBER: SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021.

Implementation of a Comprehensive and Personalised Approach for Older People with Psychosocial Frailty in Valencia (Spain): Study Protocol for a Pre-Post Controlled Trial.

With ageing, the risk of frailty increases, becoming a common condition that exposes older people to an increased risk of multiple adverse health outcomes. In Valencia (Spain), the ValueCare project develops and applies a value-based care approach that addresses the multidimensional nature of frailty by implementing integrated and personalized care to tackle psychosocial frailty. A pre-post controlled design with a baseline measurement at inclusion, at the end of implementation and a follow-up measurement after 6 months of intervention. In Valencia (Spain), 120 participants over 65 years of age are recruited from primary care centres to receive the ValueCare comprehensive and personalised care plan according to the results and are compared with 120 participants receiving "usual care". An assessment questionnaire is designed using validated instruments, and a personalised care plan is developed specifically for each participant based on the results obtained. The study protocol has been registered under the ISRCTN registration number ISRCTN25089186. Addressing frailty as a multidimensional and multifactorial risk condition requires the development and implementation of comprehensive assessments and care. In this context, this study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people experiencing frailty.

Efficacy and Safety of Ensitrelvir for Asymptomatic or Mild COVID-19: An Exploratory Analysis of a Multicenter, Randomized, Phase 2b/3 Clinical Trial.

BACKGROUND: This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19). METHODS: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6-August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary. RESULTS: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein. CONCLUSIONS: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT2031210350.

Similar Efficacy of Mesalazine in Adult and Older Adult Ulcerative Colitis Patients: Post Hoc Analysis of a Randomized Noninferiority Trial of 1600 mg vs 400 mg Tablets.

BACKGROUND: The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age. AIM: We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine. METHODS: We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities. RESULTS: Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ±â€…0.486 in older adults vs 2.26 ±â€…0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38. CONCLUSIONS: We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.

We investigated the rates of clinical and endoscopic response in adult (≤60 years) and older adult (>60 years) ulcerative colitis patients treated with oral mesalazine; our results demonstrated that age did not influence the efficacy and safety.

Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety.

Rationale & Objective: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Study Design: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Setting & Participants: Patients with FSGS, excluding secondary FSGS. Intervention: Sparsentan (200, 400, and 800 mg/d). Outcomes: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. Results: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; P = 0.03) and in the first 2 years (-1.69 vs -6.46; P = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. Limitations: The open-label extension does not include a comparison group. Conclusions: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

There is substantial unmet clinical need for safe and effective treatments for focal segmental glomerulosclerosis (FSGS), a kidney lesion with varied causes. Sparsentan is being studied for treatment of FSGS and targets 2 important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function. In the 8-week randomized, double-blind DUET study in patients with FSGS, sparsentan reduced the amount of protein in the urine better than irbesartan (a blood pressure medicine often used to treat FSGS). We examined long-term treatment with sparsentan over >4 years in the DUET open-label extension. We found sustained proteinuria reduction in patients who continued treatment with sparsentan and a consistent safety profile with no new or unexpected adverse effects.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study.

Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.

Effect of Rural Trauma Team Development on the Outcomes of Motorcycle Accident-Related Injuries (Motor Registry Project): Protocol for a Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Injury is a global health concern, and injury-related mortality disproportionately impacts low- and middle-income countries (LMICs). Compelling evidence from observational studies in high-income countries shows that trauma education programs, such as the Rural Trauma Team Development Course (RTTDC), increase clinician knowledge of injury care. There is a dearth of such evidence from controlled clinical trials to demonstrate the effect of the RTTDC on process and patient outcomes in LMICs. OBJECTIVE: This multicenter cluster randomized controlled clinical trial aims to examine the impact of the RTTDC on process and patient outcomes associated with motorcycle accident-related injuries in an African low-resource setting. METHODS: This is a 2-arm, parallel, multi-period, cluster randomized, controlled, clinical trial in Uganda, where rural trauma team development training is not routinely conducted. We will recruit regional referral hospitals and include patients with motorcycle accident-related injuries, interns, medical trainees, and road traffic law enforcement professionals. The intervention group (RTTDC) and control group (standard care) will include 3 hospitals each. The primary outcomes will be the interval from the accident to hospital admission and the interval from the referral decision to hospital discharge. The secondary outcomes will be all-cause mortality and morbidity associated with neurological and orthopedic injuries at 90 days after injury. All outcomes will be measured as final values. We will compare baseline characteristics and outcomes at both individual and cluster levels between the intervention and control groups. We will use mixed effects regression models to report any absolute or relative differences along with 95% CIs. We will perform subgroup analyses to evaluate and control confounding due to injury mechanisms and injury severity. We will establish a motorcycle trauma outcome (MOTOR) registry in consultation with community traffic police. RESULTS: The trial was approved on August 27, 2019. The actual recruitment of the first patient participant began on September 01, 2019. The last follow-up was on August 27, 2023. Posttrial care, including linkage to clinical, social support, and referral services, is to be completed by November 27, 2023. Data analyses will be performed in Spring 2024, and the results are expected to be published in Autumn 2024. CONCLUSIONS: This trial will unveil how a locally contextualized rural trauma team development program impacts organizational efficiency in a continent challenged with limited infrastructure and human resources. Moreover, this trial will uncover how rural trauma team coordination impacts clinical outcomes, such as mortality and morbidity associated with neurological and orthopedic injuries, which are the key targets for strengthening trauma systems in LMICs where prehospital care is in the early stage. Our results could inform the design, implementation, and scalability of future rural trauma teams and trauma education programs in LMICs. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR202308851460352); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25763. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55297.

Comparative Evaluation of the Effectiveness of Innovative Periorbital Eye Massager and Virtual Reality Eyeglasses for Reducing Dental Anxiety during Dental Restorative Procedures in Children.

Background: Many behavior management techniques are employed to reduce the anxiety associated with dental procedures in children. One of the most commonly used methods comprises audiovisual distraction using virtual reality (VR) eyeglasses. In this study, an innovative device, a periorbital eye massager (PEM), is compared with VR to evaluate dental anxiety in children. Materials and methods: in this study, 22 children were divided into two groups, that is, group I consisting of PEM and group II consisting of VR. The participants were instructed to wear the device and then subjected to dental restorative procedures. After completion of the procedure, anxiety was measured using a validated questionnaire by the children and by using the modified behavior pain scale by the second investigator. Also, physiological parameters like heart rate and oxygen saturation were evaluated before and after a dental procedure. Results: The results were statistically insignificant for group I and group II when a validated questionnaire and modified behavior pain scale were used to measure the dental anxiety of children. Also, the data also shows no significant difference in heart rate and oxygen saturation between the two groups. Conclusion: The innovative PEM can also be used as an effective behavior management tool in managing dental anxiety in children, as there was no statistically significant difference between PEM and VR. Clinical significance: As a pediatric dentist, the methods for administering a patient present a novel challenge because behavior management varies from patient to patient. As a result, the prospects for augmenting various techniques of behavior therapy for pediatric patients are limitless. How to cite this article: Gala UP, Kalaskar R. Comparative Evaluation of the Effectiveness of Innovative Periorbital Eye Massager and Virtual Reality Eyeglasses for Reducing Dental Anxiety during Dental Restorative Procedures in Children. Int J Clin Pediatr Dent 2024;17(1):48-53.

Therapy effect of cochleural alternating acoustic beam therapy versus traditional sound therapy for managing chronic idiopathic tinnitus patients.

Idiopathic tinnitus is a common and complex disorder with no established cure. The CAABT (Cochleural Alternating Acoustic Beam Therapy CAABT), is a personalized sound therapy designed to target specific tinnitus frequencies and effectively intervene in tinnitus according to clinical tinnitus assessment. This study aimed to compare the effectiveness of the CAABT and Traditional Sound Therapy (TST) in managing chronic idiopathic tinnitus. This was a randomized, double-blind, parallel-group, single-center prospective study. Sixty adult patients with tinnitus were recruited and randomly assigned to the CAABT or TST group in a 1:1 ratio using a computer-generated randomization. The treatment lasted for 12 weeks, and participants underwent assessments using the tinnitus handicap inventory (THI), visual analog scale (VAS), tinnitus loudness measurements, and resting-state functional magnetic resonance imaging (rs-fMRI). Both groups showed significant reductions in THI scores, VAS scores, and tinnitus loudness after treatment. However, CAABT showed superiority to TST in THI Functional (p = 0.018), THI Emotional (p = 0.015), THI Catastrophic (p = 0.022), THI total score (p = 0.005) as well as VAS score (p = 0.022). More interesting, CAABT showed superiority to TST in the changes of THI scores, and VAS scores from baseline. The rs-fMRI results showed significant changes in the precuneus before and after treatment in both groups. Moreover, the CAABT group showed more changes in brain regions compared to the TST. No side effects were observed. These findings suggest that CAABT may be a promising treatment option for chronic idiopathic tinnitus, providing significant improvements in tinnitus-related symptoms and brain activity.Trial registration: ClinicalTrials.gov:NCT02774122.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Transcutaneous auricular vagus nerve stimulation for post-stroke depression: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: It is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial. METHODS: Patients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment. RESULTS: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05). CONCLUSIONS: The synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Dynamic salivary cytokine profile of recurrent aphthous stomatitis patients in thalidomide maintenance treatment.

OBJECTIVE: To dynamically compare the longitudinal (time axis) and transverse (between groups) differences of the salivary cytokines during thalidomide maintenance treatment of recurrent aphthous stomatitis. METHODS: A randomized, controlled, clinical trial was performed. After the initial prednisone treatment, thalidomide (50 mg/d vs. 25 mg/d) was used as a maintenance drug for 4 or 8 weeks. The salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ were dynamically detected with a cytometric bead array. RESULTS: Overall, the level of six elevated salivary cytokines after prednisone treatment was significantly downregulated, remained low during thalidomide maintenance, and rebounded at recurrence. The effect of 50 mg/d thalidomide on the salivary cytokines was not superior to 25 mg/d medication. The relapse-free period following drug withdrawal was the longest in the subgroup using 25 mg/d thalidomide for 8 weeks. The order of magnitude of IL-6 was the most obvious, and at week 8, only the level of IL-6 in the group (25 mg/d thalidomide for 8 weeks) continued to decline compared with the other groups. CONCLUSION: Thalidomide maintenance treatment can effectively sustain low levels of salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ of recurrent aphthous stomatitis patients. IL-6 displayed a good correlation with the disease and is expected to become an index for diagnosis and follow-up. CLINICAL RELEVANCE: Low-dose long-term thalidomide maintenance treatment was supported for recurrent aphthous stomatitis. TRIAL REGISTRATION: Trial registration number of ChiCTR-IPR-16009759 at http://www.chictr.org/index.aspx .

Repeated local delivery of hyaluronic acid gel as adjunctive treatment of residual pockets in periodontitis patients undergoing supportive periodontal care. A randomized controlled clinical trial.

OBJECTIVES: To assess the effect of hyaluronic acid (HyA) application as adjunct to re-instrumentation of residual pockets in patients undergoing regular supportive periodontal care (SPC). METHODS: Chronic periodontitis patients (stage III and IV, grade B and C) with 4 interproximal residual pockets were randomly assigned to the test (HyA gel) or control (saline) group. After subgingival instrumentation, test or control substance was applied subgingivally, then daily supragingivally for 3 months, and if required a second time after subgingival re-instrumentation after 3 months. Clinical and patient reported outcome parameters were recorded every 3 months for 12 months. Pocket closure [probing pocket depth (PPD) ≤ 4mm with absence of bleeding on probing (BoP) at PPD = 4mm] was the main outcome parameter. RESULTS: Fifty-six patients (221 experimental sites) were analysed. Pocket closure was achieved in 56.8 and 46.6% of the experimental sites in the test and control group, respectively (p > 0.05), while median PPD and PPD distribution (< 5mm/5mm/ > 5mm) differed significantly between groups in favour of the test group, at 12 months. Further, significantly fewer sites in the HyA group required re-instrumentation at 3 months, and sites in the HyA group showed a tendency for lower odds to remain diseased compared to the control group (OR 0.48, 95%CI 0.22-1.06). The odds for a site to remain diseased after 12 months increased significantly in the presence of plaque (OR 7.94, 95%CI 4.12-15.28), but in general, decreased significantly over time (OR 0.48, 95%CI 0.28-0.81). CONCLUSION: Re-instrumentation of residual pockets in SPC patients, per se, leads to a significant increase in pocket closure over time; this was impeded by poor plaque control. Repeated local application of HyA results in fewer sites requiring re-instrumentation and might slightly improve the rate of pocket closure. (clinicaltrials.gov registration nr. NCT04792541). CLINICAL RELEVANCE: HyA gel is easy to apply, well accepted by patients, and may have some positive effect in terms of fewer sites requiring re-instrumentation at 3 months and higher pocket closure rate at 12 months.