Sham Intervention Research Articles

Cerebral hemodynamics underlying ankle force sense modulated by high-definition transcranial direct current stimulation.

This study aimed to investigate the effects of high-definition transcranial direct current stimulation on ankle force sense and underlying cerebral hemodynamics. Sixteen healthy adults (8 males and 8 females) were recruited in the study. Each participant received either real or sham high-definition transcranial direct current stimulation interventions in a randomly assigned order on 2 visits. An isokinetic dynamometer was used to assess the force sense of the dominant ankle; while the functional near-infrared spectroscopy was employed to monitor the hemodynamics of the sensorimotor cortex. Two-way analyses of variance with repeated measures and Pearson correlation analyses were performed. The results showed that the absolute error and root mean square error of ankle force sense dropped more after real stimulation than after sham stimulation (dropped by 23.4% vs. 14.9% for absolute error, and 20.0% vs. 10.2% for root mean square error). The supplementary motor area activation significantly increased after real high-definition transcranial direct current stimulation. The decrease in interhemispheric functional connectivity within the Brodmann's areas 6 was significantly correlated with ankle force sense improvement after real high-definition transcranial direct current stimulation. In conclusion, high-definition transcranial direct current stimulation can be used as a potential intervention for improving ankle force sense. Changes in cerebral hemodynamics could be one of the explanations for the energetic effect of high-definition transcranial direct current stimulation.

Efficacy of heel lifts for mid-portion Achilles tendinopathy (the LIFT trial): study protocol for a randomised controlled trial

BackgroundMid-portion Achilles tendinopathy is a common condition, characterised by localised Achilles tendon load-related pain and dysfunction. Numerous non-surgical treatments have been proposed for the treatment of this condition, but many of these treatments have a poor or non-existent evidence base. Heel lifts have also been advocated as a treatment for Achilles tendinopathy, but the efficacy and mechanism of action of this intervention is unclear. This proposal describes a randomised controlled trial comparing the effectiveness of heel lifts versus sham heel lifts for reducing pain associated with mid-portion Achilles tendinopathy, with an embedded biomechanical analysis.MethodsOne hundred and eight men and women aged 18 to 65 years with mid-portion Achilles tendinopathy (who satisfy the inclusion and exclusion criteria) will be recruited. Participants will be randomised, using the website Sealed Envelope, to either a control group (sham heel lifts) or an experimental group (heel lifts). Both groups will be provided with education regarding acceptable pain levels to ensure all participants receive some form of treatment. The participants will be instructed to use their allocated intervention for at least 8 h every day for 12 weeks. The primary outcome measure will be pain intensity (numerical rating scale) at its worst over the previous week. The secondary outcome measures will be additional measures of Achilles tendon pain and disability, participant-perceived global ratings of change, function, level of physical activity and health-related quality of life. Data will be collected at baseline and the primary endpoint (week 12). Data will be analysed using the intention-to-treat principle. In addition, the acute kinetic and kinematic effects of the interventions will be examined at baseline in a subpopulation of the participants (n = 40) while walking and running using three-dimensional motion analysis.DiscussionThe LIFT trial (efficacy of heeL lIfts For mid-portion Achilles Tendinopathy) will be the first randomised trial to compare the efficacy of heel lifts to a sham intervention in reducing pain and disability in people with Achilles tendinopathy. The biomechanical analysis will provide useful insights into the mechanism of action of heel lifts.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12623000627651. Registered 7 June 2023.

High-definition transcranial direct current stimulation (HD-tDCS) in major depressive disorder with anxious distress—a study protocol for a double-blinded randomized sham-controlled trial

BackgroundComorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS.MethodsMDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects.DiscussionThe HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects.Trial registrationThe trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.

The Effects of Chiropractic Spinal Adjustment on EEG in Adults with Alzheimer's and Parkinson's Disease: A Pilot Randomised Cross-over Trial.

In this study, we explored the effects of chiropractic spinal adjustments on resting-state electroencephalography (EEG) recordings and early somatosensory evoked potentials (SEPs) in Alzheimer's and Parkinson's disease. In this randomized cross-over study, 14 adults with Alzheimer's disease (average age 67 ± 6 years, 2 females:12 males) and 14 adults with Parkinson's disease (average age 62 ± 11 years, 1 female:13 males) participated. The participants underwent chiropractic spinal adjustments and a control (sham) intervention in a randomized order, with a minimum of one week between each intervention. EEG was recorded before and after each intervention, both during rest and stimulation of the right median nerve. The power-spectra was calculated for resting-state EEG, and the amplitude of the N30 peak was assessed for the SEPs. The source localization was performed on the power-spectra of resting-state EEG and the N30 SEP peak. Chiropractic spinal adjustment significantly reduced the N30 peak in individuals with Alzheimer's by 15% (p = 0.027). While other outcomes did not reach significance, resting-state EEG showed an increase in absolute power in all frequency bands after chiropractic spinal adjustments in individuals with Alzheimer's and Parkinson's disease. The findings revealed a notable enhancement in connectivity within the Default Mode Network (DMN) at the alpha, beta, and theta frequency bands among individuals undergoing chiropractic adjustments. We found that it is feasible to record EEG/SEP in individuals with Alzheimer's and Parkinson's disease. Additionally, a single session of chiropractic spinal adjustment reduced the somatosensory evoked N30 potential and enhancement in connectivity within the DMN at the alpha, beta, and theta frequency bands in individuals with Alzheimer's disease. Future studies may require a larger sample size to estimate the effects of chiropractic spinal adjustment on brain activity. Given the preliminary nature of our findings, caution is warranted when considering the clinical implications. The study was registered by the Australian New Zealand Clinical Trials Registry (registration number ACTRN12618001217291 and 12618001218280).

The effects of co-designed physical activity interventions in older adults: A systematic review and meta-analysis.

Physical activity (PA) declines with age despite the knowledge that physical inactivity is a leading cause of disease, death, and disability worldwide. To better tailor PA interventions to older adults, researchers are turning to the collaborative principles of co-design. The purpose of this systematic review was to compare the effectiveness of co-designed PA interventions and standard care for increasing PA and other health outcomes (i.e., physical function, quality of life, mental health, functional independence, attendance and attrition rates) in older adults. A search was conducted in MEDLINE, AgeLine, CINAHL, Embase, and SPORTDiscus. Records were screened by independent pairs of reviewers. Primary research studies conducted among community-dwelling older adults (age 60+) comparing co-designed PA interventions to standard care were considered for inclusion. Controls included wait-list control, usual care, sham interventions, PA interventions without the use of co-design, and no intervention. A random effects meta-analysis was conducted, and the standardized mean difference (SMD) was used to report effect estimates. Quality of evidence was rated using GRADE. Of 16,191 studies screened, eight (N = 16,733) were included in this review. Most studies reported results favouring the effect of co-design on physical activity; however, only two studies (N = 433) could be pooled for meta-analysis resulting in a SMD of 0.28, (95% CI = -0.13 to 0.69; p = 0.19; I2 = 56%) immediately post-intervention. The GRADE quality of evidence was very low. The quantitative analysis of three studies reported improved physical function. This review did not demonstrate that co-designed PA interventions are more effective than standard care for increasing PA in older adults; however, evidence was limited and of very low quality. Further well-designed trials are warranted to better understand the impacts of co-designed PA interventions and how to best implement them into practice. PROSPERO registration number: CRD42022314217.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study

BackgroundTranscranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting.MethodsThirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition).DiscussionThis study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks).Trial registrationAustralia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Chlorhexidine is not effective at any concentration in preventing ventilator-associated pneumonia: a systematic review and network meta-analysis

IntroductionOral chlorhexidine has been widely used for ventilator-associated pneumonia prevention in the critical care setting; however, previous studies and evidence synthesis have generated inconsistent findings. Our study aims to investigate if different concentrations of oral chlorhexidine may be effective in preventing such complication in intensive care unit patients.MethodsAfter pre-registration (Open Science Framework: 8CUKF), we conducted a network meta-analysis with the following PICOS: adult patients (age > 18 years old) undergoing invasive mechanical ventilation admitted in ICU (P); any concentration of chlorhexidine used for oral hygiene (I); placebo, sham intervention, usual care, or no intervention (C); rate of VAP (primary outcome), mechanical ventilation length, ICU length of stay (LOS), hospital LOS, mortality (secondary outcomes) (O); randomized controlled trials (S). We used the following database: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and EMBASE without any limitation in publication date or language.ResultsChlorhexidine did not demonstrate any significant advantage over the control group in preventing ventilator-associated pneumonia or reducing mortality, duration of mechanical ventilation, length of stay in the intensive care unit, or overall mortality.ConclusionsChlorhexidine oral decontamination does not reduce the rate of ventilator-associated pneumonia in critically ill adult patients and its routine use could not be recommended.Trial registrationRegistration number: Open Science Framework: 8CUKF.

Home-Based Heat Therapy and Vascular Function of Adults Living with Type 2 Diabetes: Preliminary Analyses of a Randomized Controlled Trial

Background: Several studies indicate that various heat exposure interventions improve peripheral endothelial function and microvascular reactivity, as well as reduce central arterial stiffness and blood pressure in various populations. Nonetheless, few studies have considered the potential therapeutic effects of heat exposure for people living with type 2 diabetes mellitus (T2DM), who are at high cardiovascular risk. In addition, all heat therapy interventions investigated to date have been laboratory-based, which may limit long-term adherence. HYPOTHESES: This study aims is to determine the effects of a 12-week home-based heat therapy intervention on markers of vascular function in adults living with T2DM. The primary hypothesis is that heat therapy improves peripheral endothelial function relative to a sham intervention. Secondary hypotheses include improved microvascular reactivity, central arterial stiffness, and 24h blood pressure. METHODS: Thirteen adults (66 ± 10 years, 28.9 ± 6.0 kg/m2, 9 men/ 4 women) living with TD2M were randomized to 12 weeks of home-based heat therapy (n=7, lower leg immersion in 42°C water) or a thermoneutral sham intervention (n=6, lower leg immersion in 36°C water). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), microvascular reactivity (post-occlusive reactive hyperemia), arterial stiffness (carotid-femoral pulse wave velocity), and 24h blood pressure (ambulatory blood pressure monitoring), were measured before and after the intervention. RESULTS: Brachial artery FMD changed by 1.72% [95%CI, 0.06; 3.37] in response to heat therapy compared to 0.41% [-1.38; +2.20] in response to the sham intervention. Peak and total reactive hyperemia changed by 0.79 mL/min/mmHg [-0.27; 1.86] and by 1.77 mL/mmHg [0.73; 2.81], respectively, in response to heat therapy compared with 0.76 mL/min/mmHg [-0.38; 1.91] and 1.68 mL/mmHg [0.56; 2.80] in response to the sham intervention. Arterial stiffness changed by 0.55 m/s [-1.62; 2.71] in response to heat therapy compared with -1.60 m/s [-3.75; 0.57] in response to the sham intervention. The 24h-systolic and diastolic blood pressure changed by 6 mmHg [-1; +12] and 2 mmHg [-3; +7], respectively, in response to heat therapy compared with -2 mmHg [-10; +6] and -3 mmHg [-9; +3] in response to the sham intervention. CONCLUSION: These preliminary results suggest that 12 weeks of home-based lower leg hot water immersion improves brachial artery FMD in adults with T2DM. In contrast, the heat therapy intervention does not appear to improve microvascular reactivity, central arterial stiffness, or 24h blood pressure. Cardiometabolic Health Diabetes and Obesity Research Network and Diabète Quebec. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Temporal Dynamics of Adverse Effects across Five Sessions of Transcranial Direct Current Stimulation.

(1) Background: Transcranial direct current stimulation (tDCS) is a safe intervention, only producing mild and transient adverse effects (AEs). However, there is no detailed analysis of the pattern of adverse effects in an application transferable to the clinic. Therefore, our objective is to describe the AEs produced by tDCS and its temporal evolution. (2) Methods: A total of 33 young volunteers were randomized into a tDCS or sham group. Participants performed a hand dexterity task while receiving the tDCS or sham intervention (20 min and 1 mA), for five consecutive days. AEs were assessed daily after each intervention and classified as somatosensory, pain, or other effects. (3) Results: The number of AEs was generally increased by tDCS intervention. Specifically, tDCS led to more frequent somatosensory discomfort, characterized by sensations like itching and tingling, alongside painful sensations such as burning, compared to the sham intervention. Additionally, certain adverse events, including neck and arm pain, as well as dizziness and blurry vision, were exclusive to the tDCS group. Interestingly, tDCS produced similar AEs across the days; meanwhile, the somatosensory AEs in the sham group showed a trend to decrease. (4) Conclusions: tDCS produces mild and temporary somatosensory and pain AEs during and across sessions. The different evolution of the AEs between the tDCS and sham protocol could unmask the blinding protocol most used in tDCS studies. Potential solutions for improving blinding protocols for future studies are discussed.

The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis

BackgroundCystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis.MethodsUp to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach.ResultsSix studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects.ConclusionsThis systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training.Trial registrationThe protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

ObjectiveThe study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. MethodsWe performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. ResultsBetween October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. ConclusionsBilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Repetitive Transcranial Magnetic Stimulation for Working Memory Deficits in Schizophrenia: A Systematic Review of Randomized Controlled Trials.

Working memory (WM) deficits are a significant component of neurocognitive impairment in individuals with schizophrenia (SCZ). Two previous meta-analyses, conducted on randomized controlled trials (RCTs), examined the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in addressing WM deficits in individuals diagnosed with SCZ. However, the conclusions drawn from these analyses were inconsistent. Additionally, the commonly used random effects (RE) models might underestimate statistical errors, attributing a significant portion of perceived heterogeneity between studies to variations in study quality. Therefore, this review utilized both RE and quality effects (QE) models to assess relevant RCTs comparing TMS with sham intervention in terms of clinical outcomes. A comprehensive literature search was conducted using PubMed and Scopus databases, resulting in the inclusion of 13 studies for data synthesis. Overall, regardless of whether the RE or QE model was used, eligible RCTs suggested that the TMS and sham groups exhibited comparable therapeutic effects after treatment. The current state of research regarding the use of rTMS as a treatment for WM deficits in patients with SCZ remains in its preliminary phase. Furthermore, concerning the mechanism of action, the activation of brain regions focused on the dorsolateral prefrontal cortex and alterations in gamma oscillations may hold significant relevance in the therapeutic application of rTMS for addressing WM impairments. Finally, we believe that the application of closed-loop neuromodulation may contribute to the optimization of rTMS for WM impairment in patients with SCZ.

Application of transcranial alternating current stimulation to improve eSports-related cognitive performance.

Electronic Sports (eSports) is a popular and still emerging sport. Multiplayer Online Battle Arena (MOBA) and First/Third Person Shooting Games (FPS/TPS) require excellent visual attention abilities. Visual attention involves specific frontal and parietal areas, and is associated with alpha coherence. Transcranial alternating current stimulation (tACS) is a principally suitable tool to improve cognitive functions by modulation of regional oscillatory cortical networks that alters regional and larger network connectivity. In this single-blinded crossover study, 27 healthy college students were recruited and exposed to 10 Hz tACS of the right frontoparietal network. Subjects conducted a Visual Spatial Attention Distraction task in three phases: T0 (pre-stimulation), T1 (during stimulation), T2 (after-stimulation), and an eSports performance task which contained three games ("Exact Aiming," "Flick Aiming," "Press Reaction") before and after stimulation. The results showed performance improvements in the "Exact Aiming" task and hint for a prevention of reaction time performance decline in the "Press Reaction" task in the real, as compared to the sham stimulation group. We also found a significant decrease of reaction time in the visual spatial attention distraction task at T1 compared to T0 in the real, but not sham intervention group. However, accuracy and inverse efficiency scores (IES) did not differ between intervention groups in this task. These results suggest that 10 Hz tACS over the right frontal and parietal cortex might improve eSports-related skill performance in specific tasks, and also improve visual attention in healthy students during stimulation. This tACS protocol is a potential tool to modulate neurocognitive performance involving tracking targets, and might be a foundation for the development of a new concept to enhance eSports performance. This will require however proof in real life scenarios, as well optimization.

Exploring the Differential Effects of Transcranial Direct Current Stimulation: A Comparative Analysis of Motor Cortex and Cerebellar Stimulation

BackgroundTranscranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique. Constant electric current is passed through the patient's scalp with the aim of modulating cortical excitability. Stroke is a cerebrovascular disease characterized by hemorrhage or cerebral ischemia. This systematic review and meta-analysis are aimed at comparing the efficacy of motor cortex stimulation with that of cerebellar stimulation by using transcranial direct current stimulation. MethodGoogle Scholar, PubMed, EMBASE, Cochrane CENTRAL, and Physiotherapy Evidence Database (Pedro) databases were searched for studies. The extracted qualitative data was synthesized systematically. Cochrane RevMan software was used to conduct a meta-analysis of quantitative data. The fixed effects mean difference of the collected data was calculated at a 95% confidence interval (CI) for the changes in balance and side effects. ResultsThis research included 10 articles with seven studies assessing changes in balance (outcome measured in CoP and FMA scores) and side effects (tingling and itching were the most prevalent). There was no significant difference between the efficacy levels of m1-tDCS versus ctDCS (P = 0.18), m1-tDCS versus sham (P = 0.92), and ctDCS versus sham (P = 0.19). Itching and tingling sensation were the most common and were significantly prevalent in sham interventions (P < 0.00001). ConclusionWe found that motor cortex and cerebellar stimulations are both effective in improving motor function in stroke patients. There are no adverse effects to using the interventions besides mild itching and tingling experienced during the stimulation.

Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson's disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson's disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as "good" in three trials, "fair" in one trial, and "poor" in one trial. Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

Impact of Transcranial Direct Current Stimulation in Pain, Fatigue, and Health Quality of Life of Patients with Idiopathic Inflammatory Myopathies: A Randomized, Double-Blind, Sham-Controlled Crossover Clinical Trial

Objectives. To assess the effectiveness of transcranial direct current stimulation (tDCS) for pain, fatigue, physical function, and health-related quality of life in patients with idiopathic inflammatory myopathy (IIM). Methods. This randomized, double-blind, sham-controlled, crossover clinical trial enrolled IIM patients with fatigue and pain who received tDCS (20 min, 2 mA) or sham stimulation for 10 daily sessions. Electrodes were placed according to the 10/20 EEG system. Both the groups underwent aerobic exercise training during the intervention period. The patients were evaluated for disease perception, pain, and fatigue using uni-multidimensional questionnaires and physical tests in the periods before and after the first and second interventions and after 12 weeks of follow-up. Results. After the tDCS intervention, a reduction in the general score of multidimensional pain of 32.0 (1.5-38.0) vs. 0.0 (0.0-13.4) with effect size (ES) of -0.78 was noted, and after sham intervention, a reduction of 26.0 (0.0-37.0) vs. 5.0 (0.0-19.2) with ES of -0.54 (P=0.047) was also noted. Similar results were evidenced with fatigue (22.5 (15.4-33.2) vs. 5.5 (0.0-14.6) with ES of -0.82) and sham intervention (21.0 (15.8-29.5) vs. 4.0 (4.0-17.5) with ES of -0.80 (P=0.012)). There were no differences in the domains of the fatigue and pain questionnaires. Adherence was observed in 88.8% of the patients without adverse events. Conclusion. The association of tDCS with aerobic training promoted additional effects in relation to the group subjected to placebo stimulation on general pain and fatigue scores, as well as on pain intensity, without changes in the subdomains of the pain and fatigue questionnaire. This trial is registered with NCT04678635.

Noninvasive Neuromodulation Combined With Rehabilitation Therapy Improves Balance and Gait Speed in Patients With Stroke: A Systematic Review and Network Meta-analysis.

This study aimed to determine repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial nerve noninvasive neuromodulation affect functional balance, gait speed, and walking cadence in stroke patients. We searched PubMed, Embase, Cochrane, and Scopus (June 22, 2022) for randomized controlled trials. Three reviewers independently performed data extraction and assessed the risk of bias. Network and pairwise meta-analyses were performed to assess indirect and direct comparisons. We included 34 studies ( N = 915 patients). Sixty percent had moderate-to-high methodological quality. The meta-analyses showed positive effects of repetitive transcranial magnetic stimulation combined with rehabilitation therapy compared with sham on gait speed, walking cadence, and balance function with weighted mean differences and 95% confidence interval of 0.08 (0.03 to 0.13), 7.16 (3.217 to 11.103), and 3.05 (0.52 to 5.57), respectively. Transcranial direct current stimulation showed improvement on the time up and go test (-0.88 [-1.68 to -0.08]). From the surface under the cumulative ranking analyses, repetitive transcranial magnetic stimulation is the best ranked treatment for gait speed and functional balance improvement compared with transcranial direct current stimulation and sham interventions. There were not enough studies to include cranial nerve noninvasive neuromodulation in the meta-analysis. Walking cadence and speed, functional balance significantly improved after repetitive transcranial magnetic stimulation with short-term effects, which were superior to that of transcranial direct current stimulation and sham treatments. Transcranial direct current stimulation showed short-term beneficial effects on the Time Up and Go test.

Effects on pain of kinesiology tape in patients with plantar fasciitis: a randomized controlled study

Purpose. Plantar fasciitis is the most frequent cause of heel pain. Custom-made plantar supports are a common treatment solution, while the application of kinesiology tape (KT) can be an effective measure to alleviate pain. The objective was to evaluate the effects of KT on the pain of patients with plantar fasciitis. Methods. Randomized controlled trial including participants with plantar fasciitis. There was an experimental group (n = 17), whose participants underwent a KT treatment, and a control (sham tape) group (n = 17). The pain, measured with a visual analog scale (VAS), was the primary outcome and was assessed daily until the fifth day of wearing the tape and 24 h after removing it. Inferential statistics looked for time, group, and time per group differences with CI at 95%. Results. The greatest between-group VAS difference was 3.5 points, and occurred at the 2-day follow-up assessment. Then, pain differences decreased over time until the last assessment point. Statistically significant time, group, and time*group differences were found with p < 0.001. Conclusion. This study supports that KT is effective in reducing pain in the short term in patients with plantar fasciitis, and more effective than a sham intervention with tape.

Effect of different non-pharmacologic placebo treatments on migraine prevention: a network meta-analysis of randomized controlled trials.

Placebo control plays an important role in evaluating the effectiveness of interventions. Specifying differential effects of various placebo controls on migraine prevention would be essential in the explanation of preventive treatment for migraine and the indirect comparison between different prophylactic therapeutics. To access the impact of different non-pharmacologic placebo types on different outcomes in migraine patients. We searched PubMed, Cochrane Controlled Register of Trials, Embase, and Web of Science databases from the date of creation to June 19, 2023. Randomized controlled trials of migraine that included sham intervention of acupuncture or cognitive behavioural therapy (CBT) or non-invasive Vagus Nerve Stimulation (nVNS) or repetitive Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation (tDCS) were conducted. The primary outcome was the migraine days, and the secondary outcomes were the number of migraine attacks, headache days, headache frequency, and responder's rate. Placebo effects were assessed using five individual placebos for network meta-analysis, using mean differences to measure the relative effect of pair-wise comparisons between interventions. A total of 50 trials with 4880 subjects were included. Twenty-seven trials were evaluated for low risk of bias. The results of indirect comparisons show that sham rTMS and sham tDCS had optimal and similar effects in reducing migraine days; sham acupuncture has the greatest effect on reducing the number of migraine attacks and relieving headache frequency; sham rTMS had a highly significant advantage in reducing headache days compared with the other placebo controls. Based on the network meta-analysis results, we found that sham acupuncture had the greatest effect on migraine prophylaxis. The strong placebo effect of sham acupuncture should be considered when assessing the therapeutic effect.

Efficacy and safety of multiple external therapies in patients with insomnia: a systematic review and network meta-analysis.

The annual incidence of insomnia continues to increase owing to changes in lifestyle habits, increased work pressure, and increased environmental pollution. In recent years, an increasing number of external therapies have been proven effective in treating insomnia and have been widely used. However, the relative benefits and harms of external therapies remain uncertain, and an optimal treatment strategy has not yet been determined. A network meta-analysis was performed to evaluate and compare the efficacy and safety of multiple external therapies for patients with insomnia. Eight electronic databases were comprehensively searched from their inception to June 2023 for relevant literature. We also searched the grey literature and reviewed the reference lists of related systematic reviews. Two independent reviewers performed the study selection, data extraction, and bias assessment of the included randomized controlled trials (RCTs) using the Cochrane Reviewers' Handbook, and a network meta-analysis was conducted using Stata and RevMan software. In total, 14,826 studies were identified. Of these, 83 studies, including 9 external therapies and 6,100 patients, were deemed eligible for the present network meta-analysis. Except for the SL outcome, each external therapy was better than conventional medicine and the sham intervention (SI) in improving sleep quality. In terms of improving the psychological state indices of insomnia patients, each external therapy was superior to the SI; each external therapy had a better effect on the regulation of monoamine neurotransmitters. Tuina may be the most effective intervention in improving the total effective rate, Pittsburgh sleep quality index score, and SL. Repetitive transcranial magnetic stimulation (rTMS) perhaps resulted in the best improvement in total sleep time and awakening time (surface under the cumulative ranking curve [SUCRA] = 78.3 and 75.4%, respectively); and moxibustion (MB) and hyperbaric oxygen (HBO) were the most effective in reducing Self-rating Anxiety Scale and Self-rating Depression Scale scores. In terms of improving the monoamine neurotransmitters 5-hydroxytryptamine, norepinephrine, and dopamine, the best interventions were acupoint catgut embedding, electroacupuncture, and Tuina (SUCRA = 82.0, 69.9 and 90.3%, respectively). Safety results showed that the three safest interventions were the SI, Tuina, and foot bath. No serious adverse events were reported across the studies, and the most common minor adverse events included drowsiness, pain, excessive thirst, and hematoma. Both Tuina and rTMS have significant effects on improving sleep quality, but the safety of rTMS is low. Therefore, Tuina can be recommended as the first line of treatment to improve sleep quality. If a patient's anxiety and depression symptoms are evident, MB or HBO can be selected for treatment based on the actual situation. External therapy to improve sleep quality may be related to the regulation of monoamine neurotransmitters, which may be a potential mechanism of action. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=440882.