Systematic Review and Meta-Analysis of Second-Generation Sham-Controlled Randomized Trials of Renal Denervation Therapy for Patients with Hypertension.

INTRODUCTION: Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. AIM: We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. METHODS: Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. RESULTS: Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. CONCLUSION: Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

Efficacy of transcranial direct current stimulation in patients with dysphagia after stroke: a systematic review.

BACKGROUND: Swallowing is a complex function that can be disrupted after stroke. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation therapy that recently has been tested to treat stroke-related dysphagia. METHODS: The authors performed a search in the literature to review the described evidence of the use of tDCS in dysphagia after stroke. Three electronic databases were searched. The risk of bias evaluation was carried out through the RoB-2 tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was also implemented. RESULTS: Of 265 articles, only nine studies were included in this review. The most common location of the tDCS stimulation was the unaffected hemisphere (44%). Regarding the outcome measure, the Dysphagia Outcome and Severity Scale (DOSS) was the most commonly used (55%). However, due to the high heterogeneity of the protocols, and considering the differences between the types of stroke, the authors opted not to perform a metanalysis. Instead, a systematic review with a thorough analysis of each individual study and the impact of the differences to the outcomes was preferred. CONCLUSIONS: The final considerations are that even though the majority of studies described benefits from tDCS in post-stroke dysphagia, as they present too many methodological differences, it is not possible to compare them. In addition, many articles included patients with less than 6 months after stroke, which is an important bias as the swallowing function can be recovered spontaneously within this period, turning the certainty of the evidence really low.

Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

A general justification for hybrid functionals in DFT by means of linear response theory.

In the present work, resorting to linear response theory, we examine the plausibility of postulating Kohn-Sham (KS)-type equations which contain, by definition, an effective hybrid potential made up by some arbitrary mixture of local and non-local terms. In this way a general justification for the construction of hybrid functionals is provided without resorting to arguments based on the adiabatic connection, the generalized KS theory or the Levy's constrained search (or its variations). In particular, we examine the cases of single-hybrid functionals, derived from non-local exchange and of double-hybrid functionals, emerging from non-local second-order expressions obtained from the KS perturbation theory. A further generalization for higher-order hybrid functionals is also included.

Assessment of the Effectiveness of Transcranial Magnetic Stimulation in Subjective Tinnitus.

Introduction Increases in spontaneous activity in the neurons of the auditory cortex are presumed as the pathophysiology of tinnitus. Objective To investigate the effectiveness of transcranial magnetic stimulation (TMS) in the treatment of tinnitus. Methods A total of 62 patients between the ages of 22 and 74 with chronic subjective tinnitus were enrolled in the study. The inclusion criteria were normal findings on an otolaryngologic examination and normal ranges of complete blood count, routine biochemical parameter levels, thyroid function, air-bone gap on pure-tone audiometry, and middle-ear pressure and stapedial reflex on tympanometry. The patients were randomized into 2 groups: 40 patients were placed in the treatment for TMS (tTMS) group, and the rest (22 patients) were placed in the sham TMS group. The frequency and severity of the tinnitus, as well as the tinnitus handicap inventory (THI) score of each patient were measured before and one month after the treatment, and the values were statistically evaluated. Results We observed a statistically significant improvement in the tTMS group ( p < 0.05 and p < 0.05 respectively) regarding the THI and tinnitus severity scores. The sham TMS group showed no significant improvement in terms of the THI ( p > 0.05). However, the tinnitus severity showed a significant increase in this group ( p < 0.05). The comparison of differences in the changes in the THI and the tinnitus severity scores showed a significant statistical improvement in the tTMS group compared with the sham TMS group ( p < 0.05 and p < 0.05 respectively). Conclusion Transcranial magnetic stimulation was found to be effective in the treatment of tinnitus, and may be adopted as a treatment for tinnitus after further comprehensive studies.

Effect of Dry Cupping Therapy on Pain and Functional Disability in Persistent Non-Specific Low Back Pain: A Randomized Controlled Clinical Trial.

Background: Cupping therapy is used to treat musculoskeletal conditions, including low back pain. Objectives: The study assessed the effects of dry cupping on pain and functional disability from persistent nonspecific low back pain. Methods: This was a randomized controlled trial, where participants were allocated to a cupping therapy (n = 19) or sham (n = 18) group, for five 10-minute sessions of cupping therapy, twice a week, to stimulate the acupoints related to low back pain (GV4, BL23, BL24, BL25, and BL30, BL40 and BL58) and emotional aspects (HT3 and ST36). All participants were assessed at baseline, post-treatment and follow up (a finalization period of four weeks) using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Groups were compared using the analysis of covariance (ANCOVA) and the effect size was calculated using Cohen̓s d. Results: The cupping therapy group presented a lower mean VAS when compared to the sham, at post-treatment (mean difference: -2.36; standard error [SE]: 0.58; p < 0.001; "large" effect size: -0.94) and follow up (mean difference: -1.71; SE: 0.81; p < 0.042; 'large' effect size: -0.83). The cupping therapy group presented a lower mean ODI when compared to the sham post-treatment (mean difference: -4.68; SE: 1.85; p: 0.017; 'large' effect size: -0.87), although in follow-up, there was no difference between the groups (mean difference: 4.16; SE: 2.97; p: 0.17; "medium" effect size: -0.70). Conclusion: Dry cupping was more effective in improving pain and functional disability in people with persistent nonspecific low back pain when compared to the sham.

Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT – sham controlled trial

Abstract Background Thirty percent of schizophrenia patients are treatment-resistant. Objective This is a single-blinded sham-controlled trial to assess the efficacy of electroconvulsive therapy (ECT) as augmentation strategy in patients with clozapine-resistant schizophrenia. Methods Twenty three subjects were randomly assigned to 12 sessions of ECT (N = 13) or placebo (Sham ECT) (N = 10). The primary outcome was improvement on psychotic symptoms as measured by the mean reduction of the PANSS positive subscale. The assessments were performed by blind raters. Results At baseline both groups were similar, except for negative and total symptoms of the PANSS, which were higher in the Sham group. At the endpoint both groups had a significant decrease from basal score. In the ECT group the PANSS total score decreased 8.78%, from 81.23 to 74.75 (p = 0.042), while the positive subscale had a mean reduction of 19% (19.31 to 16.17, p = 0.006). In the Sham group, the mean reduction of PANSS total score was 15.27% (96.80 to 87.43; p = 0.036), and the PANSS positive subscale decreased 27.81% (22.90 to 19.14, p = 0.008). The CGI score in ECT group decreased 23.0% (5.23 to 4.17; p = 0.001) and decreased 24.31% in the Sham ECT group (5.80 to 4.86; p = 0.004). Discussion In this pilot study, we found no difference between the groups.

Acupuncture for Symptomatic Treatment of Fatigue in Parkinson's Disease: Trial Design and Implementation.

Background: Acupuncture use is increasing worldwide for many conditions, including movement disorders. Clinical research in acupuncture has also increased to test anecdotal reports of clinical benefits empirically and investigate potential mechanisms. Method: This article describes considerations for designing a double-blinded, randomized, placebo-controlled clinical trial of acupuncture for fatigue in Parkinson's disease (PD) and describes the current authors' experience in the implementation and early conduct of this trial. Relevant literature is also reviewed to provide guidance for other researchers seeking to perform clinical research relevant to PD and related disorders. Results: Trial design should be driven by a well-defined research question and sufficient detail to meet Standards for Reporting Interventions in Clinical Trials of Acupuncture criteria when a trial is complete. Important items for review include: randomization and blinding; recruitment and participant selection; sham methodology choice; staff training; and practical implementation of study procedures. Sample forms used for the current authors' trial are shared. Conclusions: High-quality clinical trials of acupuncture can provide valuable information for clinicians, patients, and policymakers. Acupuncture trials differ in critical ways from pharmaceutical trials and might require additional considerations regarding design and implementation. Adequate preparation for the unique challenges of acupuncture studies can improve trial implementation, design, efficiency, and impact.

A randomized, controlled, crossover study in patients with mild and moderate asthma undergoing treatment with traditional Chinese acupuncture

OBJECTIVES:This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma.METHODS:This was a randomized, controlled, crossover trial conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A total of 74 patients with mild/moderate, persistent asthma were randomized into two therapeutic groups: Group A - 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short- and long-acting β-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (α=0.05).RESULTS:In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation.CONCLUSION:Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma.

Reducing transcranial direct current stimulation-induced erythema with skin pretreatment: considerations for sham-controlled clinical trials.

OBJECTIVES: Transcranial direct current stimulation (tDCS)-induced erythema (skin reddening) has been described as an adverse effect that can harm blinding integrity in sham-controlled designs. To tackle this issue, we investigated whether the use of topical pretreatments could decrease erythema and other adverse effects associated with tDCS. MATERIALS AND METHODS: Thirty healthy volunteers were recruited, and four interventions were applied 30 min prior to tDCS in a Latin square design: placebo, ketoprofen 2%, hydroxyzine 1%, and lidocaine 5%. TDCS was applied for 30 min (2 mA, anode and cathode over F3 and F4, respectively) in two active sessions with a minimum 1-week interval. The Draize erythema scoring system scale was used to assess erythema intensity; a tDCS questionnaire was used to assess other adverse effects (e.g., tingling, itching, burning sensation, and pain). RESULTS: We found that ketoprofen (but not hydroxyzine or lidocaine) significantly attenuated tDCS-induced erythema regarding intensity and duration, with a medium effect compared with placebo. Erythema was overall mild, short-lived (lasting 18-24 min after tDCS ending), and more intense under the anode. Subjects with darker skin color also tended to present less intense tDCS-induced erythema. The prevalence of other adverse effects was low and did not differ between dermatological groups. CONCLUSIONS: Ketoprofen 2% topical pretreatment might be an interesting strategy to reduce tDCS-induced erythema and might be useful for blinding improvement in further sham-controlled tDCS trials.

Controladores del tiempo y el envejecimiento: núcleo supraquiasmático y glándula pineal / Aging process entrainment: suprachiasmatic nucleus and pineal gland

El núcleo supraquiasmático (NSQ) es el principal reloj biológico de los mamíferos y sincroniza la actividad de la glándula pineal al ciclo luz-oscuridad a través de una vía polisináptica. El efecto de asa de retroalimentación neuroendocrina se lleva a cabo por la melatonina. El presente trabajo pretende demostrar que la glándula pineal modula la sensibilidad a la luz en el NSQ. Se utilizaron ratas Wistar, y se asignaron a 3 grupos: grupo A (falsa pinealectomía -sham-, sin luz), grupo B (falsa pinealectomía -sham- + luz) y grupo C al cual se le realizó la pinealectomía + luz, después de la manipulación se sacrifican para realizar inmunohistoquímica para c-Fos y al final conteo celular por técnica de estereología. Se obtuvo una reducción del 46,8% del promedio de células inmunorreactivas a c-Fos en el grupo C en comparación del grupo B. Este trabajo muestra que la sensibilidad a la luz está modulada por la actividad de la glándula pineal.

The suprachiasmatic nucleus (SCN) is the main and major biological clock in mammals and is responsible for the synchronization of the pineal gland to the light/darkness cycle through a polysynaptic pathway. The neuroendocrine feedback loop effect is carried out by melatonin. This study was carried out to demonstrate that the pineal gland adjusts the sensibility to light in the suprachiasmatic nucleus. Wistar rats were allocated in 3 groups: Group A (sham pinalectomy, without light), group B (sham pinealectomy + light) and group C which underwent real pinalectomy + light. After the intervention the animals were slain to perform immunohistochemistry for c-Fos and cell counting by stereology technique. A 46.8% average reduction in c-Fos immunoreactive cells was achieved in-group C as compared with group B. The present work shows that sensibility to the light is modulate by the activity of the pineal gland.

DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet.

Dehydroepiandrosterone (DHEA) and the dehydroepiandrosterone sulfate (DHEA-S) are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX) female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS) and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

Swimming training prevents fat deposition and decreases angiotensin II-induced coronary vasoconstriction in ovariectomized rats.

We investigated the effects of chronic swimming training (ST) on the deposition of abdominal fat and vasoconstriction in response to angiotensin II (ANG II) in the coronary arterial bed of estrogen deficient rats. Twenty-eight 3-month old Wistar female rats were divided into 4 groups: sedentary sham (SS), sedentary-ovariectomized (SO), swimming-trained sham (STS) and swimming-trained ovariectomized (STO). ST protocol consisted of a continuous 60-min session, with a 5% BW load attached to the tail, completed 5 days/week for 8-weeks. The retroperitoneal, parametrial, perirenal and inguinal fat pads were measured. The intrinsic heart rate (IHR), coronary perfusion pressure (CPP) and a concentration-response curve to ANG II in the coronary bed was constructed using the Langendorff preparation. Ovariectomy (OVX) significantly reduced 17-ß-estradiol plasma levels in SO and STO groups (p<0.05). The STO group had a significantly reduced retroperitoneal and parametrial fat pad compared with the SO group (p<0.05). IHR values were similar in all groups; however, baseline CPP was significantly reduced in the SO, STS and STO groups compared with the SS group (p<0.05). ANG II caused vasoconstriction in the coronary bed in a concentration-dependent manner. The SO group had an increased response to ANG II when compared with all other experimental groups (p<0.05), which was prevented by 8-weeks of ST in the STO group (p<0.05). OVX increased ANG II-induced vasoconstriction in the coronary vascular bed and abdominal fat pad deposition. Eight weeks of swimming training improved these vasoconstrictor effects and decreased abdominal fat deposition in ovariectomized rats.

Acupuncture as an Adjunct Treatment for Primary Dysmenorrhea: A Comparative Study.

BACKGROUND: Primary dysmenorrhea occurs 40%-50% in women of reproductive age. Acupuncture may assist treatment of menstrual pain. OBJECTIVE: This study compared the effects of the acupuncture program Chongmai, or Thoroughfare Vessel (TV), to sham acupuncture on primary dysmenorrhea. METHODS: The current authors selected 3 groups of 10 patients each with primary dysmenorrhea for this comparative, prospective longitudinal study. The first group was treated at the TV points, the second group underwent sham acupuncture, and the third group (control) did not receive any kind of acupuncture. All groups were allowed to use steroidal anti-inflammatory drugs (NSAIDs). Menstrual pain was measured using a visual analogue scale (VAS). The results were analyzed using a Student's-t test in GraphPad Prism 5.0. Acupuncture needles were applied at the following TV acupuncture points: (1) Gongsun (SP 4); (2) Qichong (ST30); (3) Neiguan (PC 6); and (4) Baihuanshu (BL 30), the metameric action point of the pelvic area. Electrical stimulation was applied through each needle at 120 Hz for 40 minutes. RESULTS: TV acupuncture, sham acupuncture, and/or NSAIDs substantially reduced pain in all 10 patients in each respective group (100%). TV acupuncture treatment reduced the symptoms of primary dysmenorrhea, and symptoms were reduced for at least 6 months. Application of needles at simulated points away from the TV acupuncture program did not reduce pain significantly. CONCLUSIONS: TV acupuncture treatment can reduce the symptoms of primary dysmenorrhea, and the effect can last for 6 months.

A comparative study of pelvic floor muscle training in women with multiple sclerosis: its impact on lower urinary tract symptoms and quality of life

OBJECTIVE: To compare pelvic floor muscle training and a sham procedure for the treatment of lower urinary tract symptoms and quality of life in women with multiple sclerosis. METHODS: Thirty-five female patients with multiple sclerosis were randomized into two groups: a treatment group (n = 18) and a sham group (n = 17). The evaluation included use of the Overactive Bladder Questionnaire, Medical Outcomes Study Short Form 36, International Consultation on Incontinence Questionnaire Short Form, and Qualiveen questionnaire. The intervention was performed twice per week for 12 weeks in both groups. The treatment group underwent pelvic floor muscle training with assistance from a vaginal perineometer and instructions to practice the exercises daily at home. The sham group received a treatment consisting of introducing a perineometer inside the vagina with no exercises required. Pre- and post-intervention data were recorded. RESULTS: The evaluation results of the two groups were similar at baseline. At the end of the treatment, the treatment group reported fewer storage and voiding symptoms than the sham group. Furthermore, the differences found between the groups were significant improvements in the following scores in the treatment group: Overactive Bladder Questionnaire, International Consultation on Incontinence Questionnaire Short Form, and the General Quality of Life, and Specific Impact of Urinary Problems domains of the Qualiveen questionnaire. CONCLUSIONS: The improvement of lower urinary tract symptoms had a positive effect on the quality of life of women with multiple sclerosis who underwent pelvic floor muscle training, as the disease-specific of quality of life questionnaires demonstrated. This study reinforces the importance of assessing quality of life to judge the effectiveness of a treatment intervention.