Toward Sham Interventions for Behavioral Voice Treatment Outcome Research in Female Students Without Dysphonia.

OBJECTIVES/HYPOTHESIS: To develop sham voice treatment techniques to be used in voice treatment outcome research, and to investigate their effectiveness as sham. This entails that the techniques induce no changes in voice or voice physiology, yet still lead to a perception of efficacy. STUDY DESIGN: Prospective randomized blinded controlled study. METHODS: Three distinct sham intervention protocols (SIPs) were conceptualized as placebic comparators for three common voice treatment approaches with focus on vocalization (SIP1), respiration (SIP2), and manipulation (SIP3). Forty-eight female students participated in the study. Each participant attended ten 30-minute sessions over 5weeks, including a baseline evaluation, three sessions of one SIP, an inter-SIP voice assessment, three sessions of a second SIP, and a final post-SIP assessment. Auditory-perceptual and instrumental voice evaluations were used as voice treatment outcome measures. The participants' perception of voice-related quality of life was evaluated using the French Voice Handicap Index (VHIFR). Frequentist as well as Bayesian statistical methods were applied for group comparisons. The effects of combining two SIPs, the potential influence of SIP order, and experimenter/clinician effects, were also investigated. RESULTS: The respiration-based SIP2 showed changes only in sound intensity level on a sustained vowel across the three sham intervention sessions. In contrast, the vocalization-based SIP1 impacted sound intensity level on a sustained vowel, sound intensity level on read text, and maximum phonation time. The manipulation-based SIP3 affected smoothed cepstral peak prominence on read text, Acoustic Voice Quality Index, and Dysphonia Severity Index. SIP2 thus demonstrated the highest alignment with the study's objectives, followed by SIP1 and SIP3. GRBASI ratings revealed no statistical differences for any SIP. VHIFr decreased significantly after all three SIPs. Combining the SIPs generally replicated the effects observed when each SIP was used individually. There was no order effect or experimenter/clinician effect on the results. CONCLUSIONS: This study demonstrated significant changes in participants' perceived voice quality (measured with VHIFr) across various SIPs, despite minimal impact on objective voice function measures. Further investigation is necessary to establish one or more protocols as genuinely sham interventions.

Real-time fMRI neurofeedback of the anterior insula using arterial spin labelling.

Arterial spin labelling (ASL) is the only non-invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level-dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal-to-noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL-based neurofeedback study incorporating a double-blind, sham-controlled design. A pseudo-continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real-time post-processing pipeline. The real-time pipeline allows to monitor the ASL signal and provides real-time feedback on the neural activity to the subject. In total 41 healthy adults (19-56 years) divided into three groups underwent a neurofeedback-based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback.

The effect and safety of acupuncture as adjunctive therapy for STEMI patients after PCI: study protocol of a randomized controlled trial.

BACKGROUND: ST-elevation myocardial infarction (STEMI) is a common acute ischemia heart disease that causes serious damage to human health worldwide. Even though morbidity and mortality have significantly decreased by percutaneous coronary intervention (PCI), an additional cardiac protection strategy is still required. Acupuncture therapy has presented a dominant cardiac protection in many studies lately. Thus, we aim to evaluate the effect and safety of acupuncture as an adjunctive therapy in STEMI patients after PCI through a randomized controlled trial. METHODS/DESIGN: This study describes a protocol of multicenter, double-blinded, parallel-controlled, randomized controlled trial. Ninety-six patients with STEMI aged 18-85 years who undergoing PCI will be recruited from the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, The Affiliated Third Hospital of Chengdu Traditional Chinese Medicine University/Chengdu Pidu District Hospital of Traditional Chinese Medicine, and Zhaotong Municipal Hospital of Traditional Chinese Medicine. Participants will be randomly assigned (1:1 ratio) to the verum acupuncture plus basic therapy (i.e., treatment) group or the sham acupuncture plus basic therapy (i.e., control) group. These participants will be treated for 5 days and then will be followed up for 24 weeks. Any adverse events will be recorded throughout the study to evaluate safety. DISCUSSION: The present study aims to investigate the effect and safety of acupuncture for patients with STEMI after PCI and set up standardized treatment programs for acupuncture of these patients. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400081117]), on February 22, 2024.

Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study.

BACKGROUND: Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. OBJECTIVE: This study aimed to describe a phase 3 remote, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone app-based DTx (CT-152) in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT). METHODS: Participants aged 22-64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to CT-152 or a sham DTx. CT-152 is a smartphone app-based DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of CT-152 are the Emotional Faces Memory Task exercises, brief lessons to learn and apply key therapeutic skills, and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match CT-152 for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period of 4 weeks to assess the durability of the effect. Sites and participants had the option of an in-person or remote screening visit; the remaining trial visits were remote. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale, the Generalized Anxiety Disorder-7, Clinical Global Impression-Severity scale, the Patient Health Questionnaire-9, and the World Health Organization Disability Assessment Schedule 2.0. The durability of the effect was evaluated with the Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scale. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EQ-5D-5L, were summarized using descriptive statistics. RESULTS: This study was initiated in February 2021 and had a primary completion date in October 2022. CONCLUSIONS: This represents the methodological design for the first evaluation of CT-152 as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety end points. Novel considerations included the use of a sham comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of CT-152. TRIAL REGISTRATION: ClinicalTrials.gov NCT04770285; https://clinicaltrials.gov/study/NCT04770285. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/56960.

Home-based EEG neurofeedback for the treatment of chronic pain: A randomized controlled clinical trial.

This parallel, two-arm, blinded, randomized controlled superiority trial examined whether, when added to usual care, active- electroencephalography neurofeedback (EEG NFB) was safe and more effective than sham control-EEG NFB for chronic pain. 116 participants with chronic pain were randomly assigned (1:1) to usual care plus ≥ 32 sessions of active-EEG NFB upregulating relative alpha power over C4 or usual care plus ≥ 32 sessions of sham control-EEG NFB. Per protocol analyses revealed no significant between-group differences in the primary outcome, brief pain inventory (BPI) average pain (mean difference [95% CI]: -0.04 [-0.39 to 0.31], p=0.90), or any secondary outcomes. However, 44% of participants in the active-EEG NFB group and 45% in the control-EEG NFB group reported at least a moderate (≥30%), clinically important improvement in BPI average pain. The number of treatment emergent adverse events were similar in both groups (p = 0.83), and none were serious. Post-hoc analyses revealed similar upregulated relative alpha power in both groups during training, with concordant positive rewards delivered to the active-EEG group 100% of the time and the control-EEG group ~25% of the time, suggesting a partially active sham intervention. When added to usual care, the active-EEG NFB intervention used in this study was not superior to the sham control-EEG NFB intervention. However, a large proportion of participants in both groups reported a clinically important reduction in pain intensity. A partially active sham intervention may have obscured between-group differences. The intervention was free of important side effects, with no safety concerns identified. PERSPECTIVES: This study is the first attempt at an appropriately blinded, randomized, sham-controlled trial of alpha EEG NFB for the treatment of chronic pain. The findings may interest people living with chronic pain, clinicians involved in chronic pain management, and may inform the design of future EEG NFB trials. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000667819.

Case report: Tremor in the placebo condition of a blinded clinical trial of intermittent theta-burst stimulation for cocaine use disorder.

We report a case of a new-onset, persistent tremor that developed during a clinical trial (NCT02927236) of intermittent theta burst stimulation [iTBS, a form of repetitive magnetic transcranial magnetic stimulation (rTMS)] for cocaine use disorder. Although the participant exhibited an exceptionally strong clinical response, subsequent unblinding revealed that they received sham iTBS. This case highlights the potential for strong functional neurological placebo responses in rTMS trials, and functional disorders might be a marker of a placebo response. Additionally, we note the possibility that the weak e-fields produced by some sham rTMS systems may induce clinically relevant effects.

Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups.

Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham group is usually not included in the experimental design of these studies. In this study, we aimed to evaluate the relevance of the sham group by analyzing and comparing the brain protein profiles of the sham and MCAO groups. In the sham group, 98 dysregulated proteins were detected, compared to 171 in the ischemic group. Moreover, a comparative study of protein profiles revealed the existence of a pool of 57 proteins that appeared to be dysregulated in both sham and ischemic animals. These results indicated that the surgical procedure required for the intraluminal occlusion of the middle cerebral artery (MCA) induces changes in brain protein expression that are not associated with ischemic lesions. This study highlights the importance of including sham control groups in the experimental design, to ensure that surgical intervention does not affect the therapeutic target under study.

Evaluating repetitive transcranial magnetic stimulation for neurogenic overactive bladder management in stroke survivors: A randomized sham-controlled trial protocol.

BACKGROUND: Neurogenic overactive bladder (OAB) is a distressing condition in stroke. Existing neurogenic OAB management is expensive, unstandardized regimens, or invasive. Evaluating the effectiveness of repetitive transcranial magnetic stimulation (rTMS) remains crucial. We aimed to (1) compare the effectiveness of active-rTMS with sham-rTMS on neurogenic OAB symptoms, (2) analyze whether rTMS is cost-effective, and (3) explore the rTMS's experiences on participants' symptoms. METHODS: This is a randomized, sham-controlled, double-blinded trial with embedded qualitative and cost-effectiveness studies. A total of 110 stroke survivors with neurogenic OAB symptoms were screened for eligibility; 60 participants were eligible for inclusion and were randomly assigned to either the active (n = 30) or sham-rTMS (n = 30) groups using a computer-generated randomization schedule. The active-rTMS group received low-frequency rTMS of 1200 pulses per session lasting 20 min thrice weekly to pelvic floor muscle representation at the contralesional primary motor cortex. The sham-rTMS group received low-frequency stimulation at a 20 % resting motor threshold using the same coil as the active-rTMS but was configured to reduce the TMS-induced electrical fields significantly. The primary and secondary outcome measures were assessed at baseline, post-intervention (week 4) and follow-up (week 8). The analysis of covariance (ANCOVA) analysis compared changes in the study groups. Quality-adjusted life-years (QALY) were measured to evaluate the cost-effectiveness while EQ-5D-5L estimated QALY changes. Additionally, the focus group discussion data were thematically analyzed. CONCLUSIONS: The findings from this rTMS intervention study will be useful in alleviating neurogenic OAB symptoms and enhancing patient satisfaction in a cost-effective way.

The placebo effect of sham rhinologic procedures in randomized controlled trials: A systematic review and meta-analysis.

KEY POINTS: Sham procedures produce a clinically significant impact on patient-reported outcome measures This effect should be considered when designing and interpreting the results of RCTs.

Effects of renal denervation on blood pressure in patients with hypertension: a latest systematic review and meta-analysis of randomized sham-controlled trials.

The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. DISCUSSION: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42023410645.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II.

BACKGROUND: The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, "responders" (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. OBJECTIVES: This study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. METHODS: The study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. RESULTS: In 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). CONCLUSIONS: At 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033).

A systematic review of sham acupuncture validation studies.

BACKGROUND: Acupuncture is widely used worldwide; however, studies on its effectiveness have been impeded by limitations regarding the design of appropriate control groups. In clinical research, noninvasive sham acupuncture techniques can only be applied through validation studies. Therefore, this systematic review aimed to evaluate the scope of existing literature on this topic to identify trends. METHODS: We queried Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials databases from inception to July 2022 for relevant articles. Author names were used to identify additional relevant articles. Two independent reviewers assessed the identified articles based on the inclusion and exclusion criteria. The following data were extracted: study design, information regarding acupuncturists and participants, general and treatment-related characteristics of the intervention and control groups, participants' experience of acupuncture, and research findings. RESULTS: The database query yielded 673 articles, of which 29 articles were included in the final review. Among these, 18 involved the use of one of three devices: Streitberger (n = 5), Park (n = 7), and Takakura (n = 6) devices. The remaining 11 studies used other devices, including self-developed needles. All the included studies were randomized controlled trials. The methodological details of the included studies were heterogeneous with respect to outcomes assessed, blinding, and results. CONCLUSIONS: Sham acupuncture validation studies have been conducted using healthy volunteers, with a focus on blind review and technological developments in sham acupuncture devices. However, theren may be language bias in our findings since we could not query Chinese and Japanese databases due to language barriers. There is a need for more efforts toward establishing control groups suitable for various acupuncture therapy interventions. Moreover, there is a need for more rigorous sham acupuncture validation studies, which could lead to higher-quality clinical studies.

BomMDH1 regulates malate-mediated oxidative stress in tobacco BY-2 suspension cells.

Programmed cell death (PCD) is a genetically regulated process of cell suicide essential for plant development. The 'malate valve' is a mechanism that ensures redox balance across different subcellular compartments. In broccoli, the BomMDH1 gene encodes malate dehydrogenase in mitochondria, a critical enzyme in the 'malate circulation' pathway. This study investigates the functional role of BomMDH1 in malate (MA)-induced apoptosis in bright yellow-2 (BY-2) suspension cells. Findings revealed that transgenic cells overexpressing BomMDH1 showed enhanced viability under MA-induced oxidative stress compared to wild-type (WT) cells. Overexpression of BomMDH1 also reduced levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), and malondialdehyde (MDA), while increasing the expression of antioxidant enzyme genes such as NtAPX, NtAOX1a, NtSOD, and NtMDHAR. Additionally, treatment with salicylhydroxamic acid (SHAM), a characteristic inhibitor of mitochondrial respiration, further improved the anti-apoptotic activity of BY-2 cells. Overall, these results highlighted the function of the BomMDH1 gene and the potential of SHAM treatment in mitigating oxidative stress in BY-2 suspension cells.

Combined EEG-tDCS approach in resting state to reduce comorbid anxiety and depressive symptoms in affective disorders: A sham-controlled pilot study.

Continuous challenges have been imposed on mental health science by Anxiety and Depression disorders as the most prevalent and debilitating psychiatric conditions worldwide. Pharmacologic and cognitive behavioral therapies, either alone or in combination, have been considered as the first-line therapies, however, resistant symptomatology is prevalent in comorbid conditions with symptoms remaining after interventions. The demand for new therapeutic solutions has given space to the development of non-invasive brain stimulation techniques (NIBS), and the transmagnetic direct current stimulation (tDCS) has been reported as a safe and well-tolerated technique for the treatment of several mental health conditions, including Anxiety and Depression disorders. Relying on quantitative electroencephalography(qEEG)- tDCS approach, the current study aims to inspect the effect of tDCS intervention on patients who suffer from anxiety-depression comorbidity, in particular, the impact of tDCS intervention on qEEG spectral power activity and resting-state connectivity organization during eyes closed and eyes open protocols. QEEG data were acquired from eight patients suffering from moderate to severe anxiety-depression comorbid symptoms along with poor coping skills to manage stress and negative affect. Twelve control subjects allocated in the control group exhibiting low to moderate symptoms in both anxiety and depression conditions went also through the qEEG data acquisition. In addition, a sham-controlled study was conducted, and the patient group went through resting-state qEEG-tDCS neuromodulation once a week for ten weeks. Various-stage qEEG recordings were performed to inspect the efficacy of tDCS treatment during the modulation of brain regions involved in the regulation of affective responses. Our results demonstrated that after tDCS neuromodulation, the patients' groups exhibited decreased absolute power abnormalities over the left anterior cingulate cortex and reduced abnormal activity in the alpha band over posterior regions; improved functional connectivity indexes; decreased anxiety and depressive scores while positive affect score was improved. Besides the promising improvements, our study did not find a significant tDCS effect on perceived stress and negative affect scores. Consistently, significant differences in absolute spectral power over the left anterior cingulate cortex were detected among the patient group, as compared to the controls, as expected. Therefore, our study offers preliminary data to understand the neuroplasticity changes that potentially result from the manipulation of cortical excitability during affective regulation protocols followed by the consequent decrease of comorbid anxiety and depressive symptomatology. The pilot study was followed by prospective registration with ChiCTR2200062142.

Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials.

OBJECTIVE: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. METHODS: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors' effect was explored in meta-regression and stratified models with pain as the dependent variable. RESULTS: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of -0.51 (95% confidence interval -0.61 to -0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. CONCLUSION: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO REGISTRATION ID: CRD42022298984.

Effect of chewing gum in reducing postoperative ileus after gastroduodenal perforation peritonitis surgery: A prospective randomised controlled trial.

Chewing gum reduces the duration of postoperative ileus and early recovery of bowel function following elective abdominal surgery. However, its role has not been studied in cases of gastroduodenal perforation peritonitis, prompting us to conduct this study. Patients were randomised into two groups, 39 patients received chewing gum (study group) and 43 patients were in the control group. Sensation of hunger, appearance of first bowel sound, and passages of flatus and faeces were significantly early in the study group; their hospital stay was also shorter. Chewing gum reduces the duration of postoperative ileus in cases of gastroduodenal perforation peritonitis.Registration number: IEC/2020-23/3359 dated 13 December 2020, Institutional Ethics Committee, Netaji Subhash Chandra Bose Medical College, Jabalpur, India.

Inappropriate study inclusion in meta-analysis of sham-controlled rTMS for treatment-resistant depression.

Dr. Vida and colleagues have published an important meta-analysis on a critical topic in psychiatry: the efficacy of double-blind, sham-controlled rTMS in treatment-resistant depression (TRD) [1]. The primary reported finding was a significant effect of rTMS on remission and response (RR 2.25 and 2.78 respectively) compared to sham rTMS. A close evaluation of the studies included in this meta-analysis raises concerns about the accuracy of these findings.

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study.

Background: Previous studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. Methods: Twenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. Results: The EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. Conclusion: EA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

Overcoming Methodological Challenges for Advancing Stem Cell Therapies in Parkinson's Disease.

The quest for new and improved therapies for Parkinson's disease (PD) remains of paramount importance, despite previous trial failures. There is a current debate regarding the potential of stem cell research as a therapeutic approach for PD. The studies of dopaminergic fetal stem cells for PD treatment, their design, and the results of the initial surgical placebo-controlled trials were reviewed in this study. Some of the fundamental methodological challenges and possible strategies to resolve them were proposed. In this article, we argue that the most important impact lies in the proof-of-principle demonstrated by clinical trials for cell replacement strategies in reconstructing the human brain. While some researchers argue that the considerable technical challenges associated with cell therapies for PD warrant the discontinuation of further development using stem cells, we believe that the opposing viewpoints are instrumental in identifying a series of methodological misunderstandings. Here, we propose to expose key challenges to ensure the advancement of the field and unlock the potential of stem cell therapies in PD treatment. Overall, this review underscores the need for further research and innovation to overcome the hurdles in realizing the potential of stem cell-based therapies for PD.