Sham-controlled Trial Research Articles

Is low-intensity shockwave therapy for erectile dysfunction a durable treatment option?—long-term outcomes of a randomized sham-controlled trial

Is low-intensity shockwave therapy for erectile dysfunction a durable treatment option?—long-term outcomes of a randomized sham-controlled trial

A multi-center, randomized, double-blind, sham-stimulation controlled study of transcranial magnetic stimulation with precision navigation for the treatment of multiple system atrophy

BackgroundMultiple system atrophy (MSA) is recognized as an atypical Parkinsonian syndrome, distinguished by a more rapid progression than that observed in Parkinson’s disease. Unfortunately, the prognosis for MSA remains poor, with a notable absence of globally recognized effective treatments. Although preliminary studies suggest that transcranial magnetic stimulation (TMS) could potentially alleviate clinical symptoms in MSA patients, there is a significant gap in the literature regarding the optimal stimulation parameters. Furthermore, the field lacks consensus due to the paucity of robust, large-scale, multicenter trials.MethodsThis investigation is a multi-center, randomized, double-blind, sham-controlled trial. We aim to enroll 96 individuals diagnosed with MSA, categorized into Parkinsonian type (MSA-P) and cerebellar type (MSA-C) according to their predominant clinical features. Participants will be randomly allocated in a 1:1 ratio to either the TMS or sham stimulation group. Utilizing advanced navigation techniques, we will ensure precise targeting for the intervention, applying theta burst stimulation (TBS). To assess the efficacy of TBS on both motor and non-motor functions, a comprehensive evaluation will be conducted using internationally recognized clinical scales and gait analysis. To objectively assess changes in brain connectivity, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be employed as sensitive indicators before and after the intervention.DiscussionThe primary aim of this study is to ascertain whether TBS can alleviate both motor and non-motor symptoms in patients with MSA. Additionally, a critical component of our research involves elucidating the underlying mechanisms through which TBS exerts its potential therapeutic effects.Ethics and disseminationAll study protocols have been reviewed and approved by the First Affiliated Medical Ethics Committee of the Air Force Military Medical University (KY20232118-F-1).Trial registrationChinese Clinical Trial Registry ChiCTR2300072658. Registered on 20 June 2023.

36-month durability of ultrasound renal denervation for hypertension resistant to combination therapy in RADIANCE-HTN TRIO.

Endovascular ultrasound renal denervation (uRDN) reduced blood pressure (BP) compared to sham at 2 months in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial. This analysis evaluates longer-term outcomes of patients randomized to uRDN. Patients with resistant hypertension to a 3-drug combination pill were randomized to uRDN (n = 69) or sham (n = 67). From 2-5 months, patients followed a standardized anti-hypertensive medication (AHM) titration protocol. At 6 months, patients were unblinded and received AHM per standard of care. In the uRDN group, 71% (49/69) completed 36-month follow-up. Screening office BP was 159/103 on 3.9 AHM. Baseline office BP on the single-pill combination was 153/99 mmHg. At 36 months, office BP changed by -14.5 ± 26.1/-9.0 ± 14.8 mmHg from screening (p < 0.001 for both) and -8.0 ± 24.5/-5.0 ± 14.6 mmHg from baseline (p = 0.007; p = 0.022) on 3.7 AHM. The efficacy of uRDN was durable to 36 months in patients with resistant hypertension with no safety concerns.

Effects of online high-definition transcranial direct current stimulation over left dorsolateral prefrontal cortex on predominant negative symptoms and EEG functional connectivity in patients with schizophrenia: a randomized, double-blind, controlled trial.

Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design. Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity. All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network. High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting.

Effects of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: results of a randomized, sham-controlled pilot trial

AbstractDialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in borderline personality disorder (BPD). We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that provides unilateral stimulation to the left dorsolateral prefrontal cortex, would enhance the effects of DBT and reduce BPD-specific symptoms more than sham stimulation. We performed a single-blind, randomized, sham-controlled pilot study to evaluate iTBS as an add-on to 8-week DBT for BPD in routine inpatient treatment. A total of 53 BPD patients were randomly assigned to either iTBS (n = 25) or sham stimulation (n = 28) in weeks 4–8 of DBT; 40 patients were eligible for inclusion in the analyses according to pre-specified criteria (≥ 16 of 20 iTBS sessions). The primary endpoint was change on the 23-item Borderline Symptom List; secondary endpoints were changes in depressive symptoms and general level of functioning. A mixed model repeated measures analysis with a 2 × 2 factorial between-subjects design showed no significant effect of add-on iTBS treatment, but a distinct trend was observed in favor of iTBS (Cohen’s d = 0.23 for group difference). We found a main effect of DBT with and without iTBS over time, indicating efficacy of 8 weeks’ DBT (d = 0.89–1.12). iTBS may be beneficial as an add-on to DBT in the long term and warrants further evaluation in larger studies. Trial registration Registered at drks.de (no. DRKS00020413) on January 13, 2020.

The effect of the EXOPULSE Mollii Suit on pain and fibromyalgia-related symptoms-A randomized sham-controlled crossover trial.

Fibromyalgia pain and related symptoms are poorly managed by approved pharmacological and alternative interventions. This trial aimed to evaluate the effects of the EXOPULSE Mollii Suit-a multisite transcutaneous electrical nerve stimulation device-on fibromyalgia pain, fatigue, affective symptoms, disease impact, and quality of life. Adult patients with fibromyalgia were enrolled. Phase 1 implied a randomized, sham-controlled, cross-over, double-blind trial, applying daily 1 h sessions of active or sham intervention, over 2 weeks (2-week washout). In the open-label phase 2, all patients received daily active intervention for 4 weeks. Comparisons on pain, fatigue, disease impact, affective symptoms, quality of life, clinical impression, and comfort ratings were performed using Friedman, Wilcoxon signed rank, and Chi2 tests. Thirty-three patients completed the study (93.9% female, mean age: 51.3 years). Pain (primary endpoint assessed via a visual analog scale) was significantly reduced after the active (pre-active: 6.9 ± 1.4, post-active: 5.9 ± 1.8, pre-sham: 6.8 ± 1.4, post-sham: 6.6 ± 1.5) versus the sham intervention (X2 = 10.60, p = 0.014). This was also the case of other secondary endpoints (i.e., fatigue, anxiety, and disease impact), except depression and quality of life. The Clinical Global Impression of Change (CGI-C) was significantly different between the active and sham intervention periods (X2 p = 0.035), and the different proportions of categories were as follows: 'worsening' (sham: 18.2% vs. active: 0.0%), 'improvement' (sham: 48.5% vs. active 63.6%) or 'no change (sham: 33.3% vs. active 36.4%) respectively. After phase 2, significant positive effects were observed for most of the outcomes, and 78.8% of patients reported improvement according to CGI-C. This study suggests the clinical benefits of the EXOPULSE Mollii Suit in alleviating pain and fibromyalgia-related fatigue, emotional symptoms, and disease impact. It is worth noting that the study has several limitations related to the low number of participants, the short-term analysis of effects in the first blinded and controlled phase, and the open-label nature of phase 2. Future studies with a larger cohort and longer protocol treatment are needed, to further confirm the current results, and evaluate the long-term effects of this technique. Patients with fibromyalgia suffer from pain as well as fatigue, sleep impairment, emotional disturbances, and altered quality of life. Transcutaneous electrical nerve stimulation might help manage those symptoms, but the available systems are limited by the fact that they could be applied at best over two sites. This randomized controlled study is the first to apply a multi-site transcutaneous electrical nerve stimulation device, the EXOPULSE Mollii Suit, with significant effects on fibromyalgia pain and related symptoms.

Cognitive potency and safety of tDCS treatment for major depressive disorder: a systematic review and meta-analysis.

The benefits of transcranial direct current stimulation (tDCS) for patients with major depression disorders are well-established, however, there is a notable research gap concerning its comprehensive effects on both depressive symptoms and cognitive functions. Existing research is inconclusive regarding the cognitive enhancement effects of tDCS specifically in MDD patients. The present study aims to fill this knowledge gap by scrutinizing the most updated evidence on the effectiveness of tDCS in anti-depressive treatment and its influence on cognitive function. A systematic review was performed from the first date available in PubMed, EMBASE, Cochrane Library, and additional sources published in English from 1 January 2001 to 31 May 2023. We examined cognitive outcomes from randomized, sham-controlled trials of tDCS treatment for major depression. The evaluation process strictly followed the Cochrane bias risk assessment tool into the literature, and meta-analysis was performed according to the Cochrane System Reviewer's Manual. In this quantitative synthesis, we incorporated data from a total of 371 patients across 12 studies. Results showed significant benefits following active tDCS compared to sham for the antidepressant effect [SMD: -0.77 (-1.44, -0.11)]. Furthermore, active relative to sham tDCS treatment was associated with increased performance gains on a measure of verbal memory [SMD: 0.30 (-0.02, 0.62)]. These results did not indicate any cognitive enhancement after active tDCS relative to sham for global cognitive function, whereas there was a noticeable trend toward statistical significance specifically in the effect of verbal memory. Our study offers crucial evidence-based medical support for tDCS in antidepressant and dimension-specific cognitive benefits. Further well-designed, large-scale randomized sham-controlled trials are warranted to further validate these findings. https://inplasy.com/, identifier: INPLASY202360008.

Investigating the efficacy of acupuncture in treating patients with metabolic-associated fatty liver disease: a protocol for a randomised controlled clinical trial

IntroductionAcupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose...

Hand functioning in progressive multiple sclerosis improves with tDCS added to daily exercises: A home-based randomized, double-blinded, sham-controlled clinical trial

Background: Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. Objective: This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. Methods: Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). Results: The intervention had high rates of adherence and completion (98% of participants completed at least 18 of 20 sessions). The active tDCS group demonstrated significant improvement for the left hand compared with baseline in 9-HPT (−5.85 ± 6.19 vs −4.23 ± 4.34, p = 0.049) and DMMPUT (−10.62 ± 8.46 vs −8.97 ± 6.18, p = 0.049). The active tDCS group reported improvements in multiple sclerosis (MS)-related quality of life (mean increase: 5.93 ± 13.04 vs −0.05 ± −8.27; p = 0.04). Conclusion: At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity.

B - 36 Investigating High-Definition Transcranial Direct Current Stimulation for Remediating Word Finding Difficulty in Civilians with a History of Chronic Traumatic Brain Injury: a Pilot Study

Abstract Objective Verbal-retrieval deficits often occur after traumatic brain injury (TBI), but no effective treatment is available. In this study, High-Definition Transcranial Direct Current Stimulation (HD-tDCS) was applied to examine its potential effects on cognitive, especially verbal-retrieval, performance in individuals with chronic TBI. Method Four adults (mean age 48 years; 3 females) with self-reported word-finding difficulty confirmed by objective measures following mild to moderate non-military TBIs sustained over a year ago underwent a double-blind, cross-over, randomized, sham-controlled trial. Each participant received 10 sessions of active HD-tDCS and sham stimulation over the superior medial frontal cortex. A battery of neuropsychological tests was administered including verbal-retrieval measures (i. e. letter fluency, category fluency, Boston Naming Test/BNT) at baseline, immediately, and 8 weeks post-treatment. Post-treatment performance was compared to baseline using 2-tailed paired t-tests. Results Improvements on letter fluency were observed between baseline and immediate assessments post active HD-tDCS, approaching statistical significance (p = 0.076, Cohen’s d = 0.957, 7.5 ± 5.7 more items). No immediate effects with sham HD-tDCS (p &amp;gt; 0.10, 1.5 ± 3.5 more items) and no sustained effects (8 weeks after) were found with either active or sham HD-tDCS (ps &amp;gt; 0.10). Additionally, no significant changes were observed for category fluency or BNT (all ps &amp;gt; 0.10). Conclusion While our pilot study suggests a potential benefit for improved letter fluency immediately following active HD-tDCS compared to sham, the lack of sustained improvement after 8 weeks and the observed variability across different tests acknowledges the need for future larger-scale investigation across multiple cognitive domains.

Efficiency and safety of continuous theta burst stimulation for primary insomnia: A randomized clinical trial

ObjectivesPrimary insomnia is a substantial public health burden, but current treatments for this disorder have limited effectiveness and adherence. Herein, we aimed to investigate the efficacy and safety of continuous theta burst stimulation (cTBS) for the treatment of primary insomnia. MethodsThis two-armed, randomized, sham-controlled trial was conducted at Peking University Sixth Hospital and local community clinics. A total of 46 patients with primary insomnia were recruited and randomly allocated to either the cTBS group or sham group. Forty-one patients completed 10 sessions of cTBS or sham intervention and follow-up assessments. ResultsAfter the intervention, the severity of insomnia was significantly lower in the cTBS group than in the sham group, with a large effect size (Cohen's d = −1.938). Additionally, 52.4 % of patients in the cTBS group achieved a response (Insomnia Severity Index score reduction ≥8), whereas only 4 % of patients in the sham group achieved a response. The duration of objective total sleep time and slow-wave sleep were higher in the cTBS group than in the sham group. The degree of anxiety was lower in the cTBS group than in the sham group. There were no significant differences in depression, sleepiness, or cognitive function between the cTBS and sham groups. During follow-up, the sleep quality of the cTBS group significantly improved and remained stable at the 6-month follow-up. ConclusionIn this randomized clinical trial, cTBS improved insomnia symptoms and was generally well tolerated, thus supporting the further development of cTBS for the treatment of primary insomnia.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials

BackgroundThere is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF). MethodsThe REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up. ResultsAt 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041). ConclusionsWith up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up.Clinicaltrials.gov registration: NCT02600234, NCT03088033

Blinding effect of sham Fu's subcutaneous needling in a healthy population: 假浮针在健康受试者中的盲法效应

ObjectiveFu's subcutaneous needling (FSN) has been shown potential positive effectiveness in clinical practice. However, its specific effects are still not clear. This study aims to evaluate the blinding effect of a non-penetrating sham FSN needle, developed for the first time by the authors' research team in healthy participants. Furthermore, to provide a reliable control tool to assess the specific effects of FSN. MethodsWe conducted a randomized, sham-controlled trial in 60 healthy participants divided into FSN group and sham FSN group in a 1:1 ratio. The participants were assessed according to blinding index (BI), pain intensity, sensation type and acceptability of needling. ResultsThe James' BI was (0.56, 95 %CI [0.45, 0.67]) for two groups. The Bang's BI was (0.50, 95 % CI [0.24, 0.76]) in the FSN group and (−0.36, 95 % CI [−0.67, −0.07]) in the sham FSN group. There was no significant difference between needling pain intensity (P > 0.05) and type of needling sensation. A total of 96.6 % participants who received sham FSN and 86.6 % participants who received FSN considered the needling acceptable or better. ConclusionThis study confirmed the effective blinding capability of the sham FSN needles in healthy participants, indicating that the novel non-penetrating sham FSN needle can be served as eligible control to evaluate the specific effects of FSN.

A Multicenter Prospective Sham-controlled Trial Evaluating a Physiologic Closed-loop Wearable Tibial Neuromodulation System for Overactive Bladder

ObjectiveTo evaluate the effectiveness and safety of a home-based, physiologic closed-loop wearable tibial neuromodulation system in comparison to a sham control for the treatment of Overactive Bladder (OAB). MethodsThis multicenter, prospective, randomized, double-blind, sham-controlled trial included 125 adult subjects with OAB who were randomized 1:1 to receive either active therapy with the Vivally System or sham therapy. Patients were allowed to continue concomitant OAB medications if therapy was stable and the remained on a consistent regimen throughout the study. The primary efficacy endpoint was a responder rate, defined as ≥50% reduction in daily urgency leaks or a ≥30% reduction in daily voids from baseline recorded on an electronic voiding diary. Safety was evaluated through adverse event (AE) reporting and patient satisfaction with the system was recorded. ResultsIn the the modified Intent-to-Treat (mITT) population (n=107) the responder rate was significantly higher in the active therapy arm (83.6%) compared to the sham arm (57.7%; p=0.032). The system demonstrated a favorable safety profile with no serious AE. Patient satisfaction with the device and mobile application was high with 90/92 (97.8%) reporting they were moderately to extremely satisfied and therapy compliance was above 92% for both therapy and sham groups. ConclusionThe Vivally System showed significant improvement in OAB symptoms compared to sham therapy, demonstrating a high responder rate and excellent safety profile. The combination of physiologic closed-loop neuromodulation and a behavior-tracking application may offer an effective and user-friendly option for OAB management.

The effect of ABM on attentional networks and stress-induced emotional reactivity in a mixed clinical sample with depression: A randomized sham-controlled trial

Research on the efficacy of Attention Bias Modification for depressive symptoms has predominantly yielded unfavorable outcomes. Despite adhering to rigorous conventions in randomized controlled trials, findings from these studies have indicated minimal effect sizes, thereby raising concerns about their limited clinical significance. This may be attributed to the overlapping mechanisms in ABM and the sham comparator, both affecting attentional processes. Participants with a diagnosis of major depressive disorder, with and without comorbid anxiety (N = 101) were randomized to a two-week preregistered randomized trial of ABM compared to sham. Attentional networks were assessed prior to and after the intervention by the Attention Network Task (ANT), and emotional reactivity was assessed in response to a lab-stressor. Irrespective of condition, participants improved their performance on the alerting and executive attentional networks, but not orienting, and stress-induced emotional reactivity was marginally decreased. Changes in attentional networks predicted post-intervention depression scores. It is imperative to reconsider the employment of a sham comparator in the exploration of the clinical efficacy of ABM.

Effect of Dry Needling Plus Static Stretching on Plantar Flexors Spasticity in Chronic Stroke Patients.

Stroke is a leading cause of disability worldwide and is often accompanied by complications such as spasticity. Static stretching (SS) is a common physiotherapy intervention for reducing spasticity, whereas dry needling (DN) is a novel approach. However, the combined effects of DN and SS on spasticity have not been thoroughly investigated. Given the pivotal effect of spasticity on daily activities, mitigating spasticity can significantly contribute to restoring patient independence. This study will explore the impact of DN plus SS on spasticity, alpha motor neuron excitability, overall function, and quality of life in patients with chronic stroke. A double-blind, randomized, sham-controlled trial will be conducted in patients with post-stroke spasticity in the plantar flexor muscles. Twentyeight participants will be randomly assigned to either an intervention or control group. The intervention group will receive DN (60s × 3 days/week; 1 week) plus SS (20 min × 5 days/ week; 1 week). The control group will undergo sham DN (60s × 3 days/week; 1 week) and SS (20 min × 5 days/week; 1 week). DN plus SS or sham DN plus SS. Both groups will be assessed at baseline, immediately post-treatment, and after 1 week of follow-up. Outcome measures will include the Modified Modified Ashworth Scale, H-reflex latency, Hmax/Mmax ratio, active and passive ankle dorsiflexion range of motion, timed up and go test, and the EuroQol questionnaire. Results from this randomized, sham-controlled study will provide evidence for the effectiveness of DN in combination with SS for spasticity. The additional impact of DN in conjunction with SS, a widely used method for reducing muscle tone, remains unclear and warrants investigation. This study, with a high level of evidence, aims to address this knowledge gap.

The Effects of Auricular Acupressure Therapy on Obesity and Sleep in Korean Middle-Aged Women: A Randomized Single-Blind Sham-Controlled Trial.

This study aimed to evaluate the impact of auricular acupressure therapy on obesity and sleep quality in middle-aged Korean women. The single-blind, randomized, sham-controlled trial included participants aged 40-65years with a Body Mass Index (BMI) of 25-34 kg/m2, divided into an experimental group (n=30) and a control group (n=29). The intervention involved 8weeks of auricular acupressure using ear seeds on five acupoints associated with obesity and sleep. Obesity outcomes were assessed using anthropometric indices (body weight, BMI, waist circumference, body fat mass, body fat percentage), while sleep outcomes were evaluated using the Pittsburgh Sleep Quality Index and actigraphy. Measurements were taken thrice: before the intervention, and at 4 and 8weeks post-intervention start. The experimental group demonstrated a significant reduction in obesity measures and improvement in sleep quality over time compared to the control group. The findings suggest that auricular acupressure may serve as an alternative nursing intervention for managing obesity and improving sleep quality in middle-aged women.

Effects of renal denervation on the incidence and severity of cardiovascular diseases.

Renal denervation (RDN) is a neuromodulation therapy performed in patients with hypertension using an intraarterial catheter. Recent randomized sham-controlled trials have shown that RDN has significant antihypertensive effects that last for more than 3 years. Based on this evidence, the US Food and Drug Administration has approved two devices, the ultrasound-based ReCor ParadiseTM RDN system and the radiofrequency-based Medtronic Symplicity SpyralTM RDN system, as adjunctive therapy for patients with refractory and uncontrolled hypertension. On the other hand, there have been no randomized sham-controlled prospective outcome trials on RDN, and the effects of RDN on cardiovascular events such as myocardial infarction, heart failure, and stroke have not been elucidated. This mini-review summarizes the latest findings focusing on the effects of RDN on organ protection and physiological function and symptoms in both preclinical and clinical studies. Furthermore, the feasibility of using blood pressure as surrogate marker for cardiovascular outcomes is discussed in the context of relevant clinical studies on RDN. A comprehensive understanding of the beneficial effects of RDN on the incidence and severity of cardiovascular diseases with their underlying mechanisms will enhance physicians' ability to incorporate RDN into clinical strategies to prevent cardiovascular events including myocardial infarction, heart failure, and stroke. This mini-review focuses on the effects of RDN on organ protection and physiological function and symptoms in preclinical and clinical studies. RDN is expected to reduce the onset and progression of cardiovascular diseases including myocardial infarction, heart failure, and stroke in clinical practice.LV left ventricular, LVEF left ventricular ejection fraction, VO2max maximal oxygen uptake, VT ventricular tachycardia, VF ventricular fibrillation, 6MWD 6-min walk distance, NT-proBNP N-terminal pro-B-type natriuretic peptide, NYHA New York Heart Association, BBB blood-brain barrier, BP blood pressure.

A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study

BackgroundInfectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322–5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy.MethodsThis international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT.DiscussionWe anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request.Trial registrationNCT, NCT05110001, Registered on November 5, 2021.