Observational evidence suggests both low and high iodine intakes in pregnancy are associated with poorer neurodevelopment in children. This raises concern that blanket recommendations for iodine supplementation in pregnancy may negatively impact child neurodevelopment in women with sufficient iodine intake from food alone.

PoppiE (Prenatal Iodine Supplementation and Early Childhood Neurodevelopment) is a multi-centre, parallel, two-arm, clinician, researcher and participant blinded randomised controlled trial. Seven hundred fifty-four consenting pregnant women ≤ 13 weeks of gestation with an iodine intake of > 165 μg/day from food will be randomised to receive a multivitamin and mineral supplement containing 20 µg/day (intervention) or 200 µg/day (control) of iodine from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age as assessed with the Cognitive Scale Score of the Bayley Scales of Infant Development, 4th Edition, to be analysed using linear regression with generalised estimating equations to account for multiple births. In this article, we comprehensively detail the planned statistical analyses of the PoppiE trial, including approaches to intercurrent events, methods for handling missing data and planned sensitivity analyses.

PoppiE is the first trial to examine the effect of prenatal iodine supplementation on early childhood development in women with sufficient iodine intake from food. At the time of writing (February 2025), recruitment into the trial is complete and data collection is due to conclude in July 2026. The statistical analysis plan was finalised before the database lock, which will ensure study conclusions are not subject to bias due to data-driven analyses.

ClinicalTrials.gov NCT04586348. Registered on October 14, 2020.

BACKGROUNDChronic nonspecific low back pain (CNLBP) is a leading cause of disability and remains a major burden for many public health systems. Acupuncture is a nonpharmacological treatment for CNLBP that can be effective in improving low back pain; nevertheless, its effect on improving back muscle endurance in patients with CNLBP and its duration of effect have not been studied.OBJECTIVEThe goal of this study was to assess the impact of acupuncture on lower back muscle activity in CNLBP patients.METHODSThis was a single-blind, randomized, crossover experimental study. Thirty female patients were randomized into Group A (15 patients) or Group B (15 patients). Patients in Group A were assigned to receive real acupuncture (RA) in the first phase and sham acupuncture (SA) in the second phase, while those in Group B received SA first and then RA, with a 1-week washout period between phases. Two-way repeated ANOVA was used to evaluate the effect of group and time on isokinetic parameters, Surface electromyography (sEMG) data, and blood data.RESULTSSignificant interaction effects were identified between group * time on the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels (all p < 0.05). Compared with those of the SA group, the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels of the RA group were significantly different (all p < 0.05).CONCLUSIONRA improves lumbar extensor endurance in patients with CNLBP and lasts approximately 9 minutes. RA can improve blood circulation to reduce blood lactic acid and blood ammonia produced during exercise.

The efficacy of tumor necrosis factor inhibitors for treating chronic low-back pain with Modic changes is uncertain. This study investigated the superiority of infliximab over placebo in patients with Modic type 1 changes.

In this multicenter, randomized, triple-blind, placebo-controlled trial, patients aged 18 to 65 years with moderate to severe chronic low-back pain and Modic type 1 changes were enrolled from five Norwegian public hospitals between January 2019 and October 2022. Participants were randomly assigned to four intravenous infusions of 5 mg/kg infliximab or placebo. The primary outcome was difference in change in the Oswestry Disability Index (ODI) score from baseline to five months. Secondary outcomes included changes in low-back pain intensity, disability, and health-related quality of life. A linear mixed model was used for efficacy analyses.

A total of 128 patients (mean age 43 years, 65.6% women) participated (64 in each group). All patients who received at least one dose of the allocated infusion were included in the primary analyses. The average ODI score (±SD) change was -7.0 (±9.7) in the group who received infliximab and -6.4 (±10.4) in the group who received placebo. The difference in the ODI score change between the two groups was 1.3 ODI points (95% confidence interval -2.1 to 4.6, P = 0.45). Analyses showed no effect of infliximab compared to placebo on secondary outcomes. Adverse event rates were similar between groups.

Infliximab did not demonstrate superiority over placebo in reducing pain-related disability in patients with moderate to severe chronic low-back pain with Modic type 1 changes at five months.

Pain and distress are frequently reported by people with HIV. Although pain is widely acknowledged to contribute to distress, distress may also contribute to pain and its persistence. Facilitation of nociceptive signalling in the spinal dorsal horn is one pathway by which distress could exacerbate pain. The current study investigated the relationships between distress, secondary hyperalgesia (SH), and persistent pain in people with HIV, reporting pain (n=19) or no pain (n=26). We hypothesised that self-reported distress would be positively associated with the surface area (primary measure) and magnitude (secondary measure) of induced SH, and that participants reporting persistent pain would display greater induced SH than those reporting no pain. We found that distress was positively associated with the surface area (p=0.02) and the magnitude (p=0.01) of induced SH. However, participants with persistent pain showed no difference in the surface area of SH compared to pain-free participants (p=0.87), and those with pain displayed a marginally lower magnitude of SH (p=0.05). These findings lay a foundation for testing whether reducing distress also reduces SH, but also raise questions about the relevance of heterotopic spinal facilitation mechanisms to clinical persistent pain, in people with suppressed HIV.

Transcranial direct current stimulation (tDCS) is a method of noninvasive brain stimulation. tDCS clinical efficacy is debatable, but it was proved to be effective at the neurophysiological level. tDCS has a very good safety profile in human subjects. Because the method has been more frequently studied in patients with schizophrenia, we wanted to analyze the safety and tolerability of tDCS treatment in this population. We also evaluated blinding quality of tDCS stimulations.

All stimulations were performed using the DC-Stimulator PLUS (neuroCare, Germany) with the sham module installed. For all the stimulations, 2.0-mA current and 5 × 7-cm anode and cathode rubber electrodes in saline-soaked sponges were used.

We collected and evaluated safety data in a large dataset of 1139 tDCS stimulations in patients with schizophrenia. No serious adverse events were recorded. None of the subjects discontinued tDCS treatment due to side effects. All the reported events resolved spontaneously within 30 minutes after the tDCS session. In approximately 17% of all the stimulations, no side effects were reported by the patients. The 2 most frequent types of side effects were itching/tingling (reported by 68.4% of the subjects) and burning/warmth sensations (57.4%, when combined).

This study confirms that tDCS is safe and well tolerated by patients with schizophrenia. The most frequent side effects are itching/tingling and burning/warmth sensations, all of low severity. We found that blinding of tDCS stimulations is imperfect. We recommend that blinding assessment become a routine part of sham-controlled tDCS studies.

Senile pruritus (SP), characterized by idiopathic itch in individuals aged 60 years and older without primary skin lesions, significantly impacts sleep and quality of life. Effective alternative treatments are needed. Acupuncture has been suggested as a potential intervention to alleviate pruritus; however, its role in managing SP remains uncertain. This study aims to evaluate the efficacy and safety of acupuncture for SP.

This single-center, parallel, two-arm, randomized, sham-controlled trial will enroll 200 patients diagnosed with SP in a 1:1 ratio to either the acupuncture or sham acupuncture group, receiving acupuncture or sham acupuncture three sessions weekly for six weeks. Participants, outcome assessors, and the statisticians will be blinded. The primary outcome is the change from baseline in the Average Pruritus Numerical Rating Scale (AP-NRS) score at week 6. Secondary outcomes include changes in AP-NRS (at other timepoints), Peak Pruritus Numerical Rating Scale (PP-NRS), number of scratch episodes, itchy area of body surface, overall dry skin score (ODS), the Dermatology Life Quality Index (DLQI), the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale (HADS), and Patient Global Impression of Change (PGIC). Long-term effects of acupuncture will also be explored. Adverse events and additional treatments will be monitored throughout the study period. The modified intention-to-treat (mITT) population which includes participants who complete baseline assessments and receive at least one treatment session will be analyzed.

This trial represents the first rigorously designed, single-center, randomized, sham-controlled study assessing the effects and safety of acupuncture for senile pruritus. We used valid outcome measurements which can provide valuable insights into the patient's symptoms and facilitate tracking symptoms over time and evaluate treatment effectiveness. This study may provide valuable insights into the research topic and inform future research.

This study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-087-KY).

Registered with ClinicalTrials.gov (NCT06506240) on July 11, 2024.

Individual treatments for chronic low back pain (CLBP) have small magnitude effects. Combining different types of treatments may produce larger effects.

To (1) assess feasibility of conducting a factorial randomized controlled trial of these treatments; and (2) estimate individual and combined treatment effects of (a) lumbar radiofrequency ablation (LRFA) of the dorsal ramus medial branch nerves (vs. a simulated LRFA control procedure) and (b) Activity Tracker-Informed Video-Enabled Cognitive Behavioral Therapy program for CLBP (AcTIVE-CBT) (vs. an educational control treatment) on back-related disability at 3 months post-randomization.

Participants (n = 13) were randomized in a 1:1:1:1 ratio in a 2 × 2 factorial randomized controlled trial. Feasibility goals included an enrollment proportion ≥ 30%, a randomization proportion ≥ 80%, and a ≥ 80% proportion of randomized participants completing the 3-month Roland-Morris Disability Questionnaire (RMDQ) primary outcome end point. An intent-to-treat analysis was used.

The enrollment proportion was 62%, the randomization proportion was 81%, and all randomized participants completed the primary outcome. Though not statistically significant, there was a beneficial, moderate-magnitude effect of LRFA versus control on 3-month RMDQ (-3.25 RMDQ points [95% confidence interval [CI], -10.18 to 3.67]). There was a significant, beneficial, large-magnitude effect of AcTIVE-CBT versus control (-6.29 [95% CI, -10.97 to -1.60]). Though not statistically significant, there was a beneficial, large effect of LRFA+AcTIVE-CBT versus control (-8.37 [95% CI: -21.47, 4.74]).

We conclude that it is feasible to conduct a randomized controlled trial combining procedural and behavioral treatments for CLBP.

gov Registration: https://clinicaltrials.gov/ct2/show/NCT03520387.

Pre-incisional antibiotics are recommended for all patients having cesarean delivery, despite emerging concerns regarding effects on the infant. In this feasibility blinded randomized controlled trial we aimed to test research processes in low-risk women receiving cefazolin or placebo prior to elective cesarean delivery.

The trial was prospectively registered (ACTRN12619001705178). Eligible women were aged ≥ 18 and < 40 years, ≥ 37 weeks gestation, at low risk of surgical site infection (SSI) and recruited from a single tertiary centre. We reported proportions of women eligible and consenting; adherence to perioperative infection prevention; blinding adequacy of staff using Bang's blinding index; SSI surveillance and diagnosis according to the Centre for Disease Control definitions and patient reported outcome measures using validated questionnaires up to 90 days.

We screened 1651 women, with 1245 (75%) ineligible based on body mass index or presence of diabetes. Of 287 eligible women, 30 were randomized (11%) with 15 in each group. Reasons for non-participation included "wanting antibiotics" (68, 27%), "no reason" (62, 25%) and lack of research staff (33, 13%). Compliance with perioperative infection prevention occurred in 5 of 7 steps. Spontaneous placental separation occurred in 25 (83%) and Comfeel dressing in 29 (97%). Blinding was adequate for all staff groups. SSI surveillance occurred in 156 of 210 (74%) timepoints. SSI occurred in two patients who received pre-incisional cefazolin and were successfully treated as outpatients. Patient reported outcome questionnaires were completed at 136 of 180 (76%) timepoints. There was no difference in maternal health-related quality of life between the groups.

Feasibility was impacted by the high-risk population and patient desire for antibiotics. Adherence to perioperative infection prevention practices were high but incomplete. These study processes could be effectively applied in a larger population, targeting low risk maternity patients.

Prospectively registered 4/12/2019 with the Australian New Zealand Clinical Trials Registry (ACTRN12619001705178).

Despite the use of multimodal analgesia regimens following video-assisted thoracoscopic surgery (VATS), acute postoperative pain persists. Electroacupuncture (EA) may alleviate acute postoperative pain following VATS; however, current evidence remains insufficient.

This trial will assess the feasibility and efficacy of EA as an adjunctive treatment compared with sham electroacupuncture (SA) for managing acute postoperative pain during coughing after VATS.

In this pilot randomized controlled trial, 60 patients with non-small-cell lung cancer who will undergo VATS will be randomly assigned to either the EA or SA group in a 1:1 ratio. Patients will receive standard care combined with four sessions of EA or SA within 72 h after surgery. The primary outcome will be the average postoperative pain score during coughing, measured using a numeric rating scale within 72 h after surgery. Secondary outcomes will include the average daily pain scores at rest, during coughing, and while mobilizing; incidence of chronic post-surgical pain; quality of life; cough symptom score; and analgesic consumption. All adverse events will be recorded in detail.

This study will determine whether EA as an adjunctive treatment can reduce acute postoperative pain during coughing following VATS.

ClinicalTrial.gov ITMCTR2024000170 (http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=f1a344f7-7e06-4665-ad9d-0917d588eba6).

This meta-research assessed methodologies used for evaluating peri-implant marginal bone levels on digital periapical radiographs in randomized clinical trials published between 2019 and 2023.

Articles were searched in four databases. Data on methods for assessing peri-implant marginal bone levels were extracted. Risk of bias assessment was performed.

During full-text reading, 108 out of 162 articles were excluded. Methodological issues accounted for these exclusions, including the absence of radiograph-type information, the lack of radiographic positioners, the missing anatomical references, and the use of panoramic radiographs or tomography. Fifty-four articles were included, most from Europe (70%) and university-based (74%). Radiographic positioners were specified in 54% of articles. Examiner calibration was unreported in 54%, with 69% lacking details. In 59%, no statistical measure assessed examiner agreement. Blinding was unreported or unused in 50%. Marginal bone level changes were the primary outcome of 61%. Most articles (59.3%) raised "some concerns" regarding bias, while 37% showed a high risk of bias, and only two articles (3.7%) demonstrated a low risk of bias.

Several limitations and areas for improvement were identified. Future studies should prioritize protocol registration, standardize radiographic acquisitions, specify examiner details, implement calibration and statistical measures for agreement, introduce blinding protocols, and maintain geometric calibration standards.

tVNS enhances various memory and learning mechanisms, but there is inconclusive evidence on whether probabilistic learning can be enhanced by tVNS. Here, we tested a simplified version of the probabilistic learning task with monetary rewards in a between-participants design with left and right-sided cymba conchae and tragus stimulation (compared to sham stimulation) in a sample of healthy individuals (n = 80, 64 women, on average 26.38 years old). tVNS enhances overall accuracy significantly (p = 4.09 x 10-04) and reduces response times (p = 1.1006 x 10-49) in the probabilistic learning phase. Reinforcement learning modelling of the data revealed that the tVNS group uses a riskier strategy, dedicates more time to stimulus encoding and motor processes and exhibits greater reward sensitivity relative to the sham group. The learning advantage for tVNS relative to sham persists (p = 0.005 for accuracy and p = 9.2501 × 10-27 for response times) during an immediate extinction phase with continued stimulation in which feedback and reward were omitted. Our observations are in line with the proposal that tVNS enhances reinforcement learning in healthy individuals. This suggests that tVNS may be useful in contexts where fast learning and learning persistence in the absence of a reward is an advantage, for example, in the case of learning new habits.

Sprint interval exercise can cause transient, intense exercise-induced pain (EIP) during and several minutes after the activity. A hypoalgesic strategy for high-intensity exercise, such as sprint interval exercise, against EIP is necessary to maintain exercise habituation and improve training quality/exercise performance. Preexercise caffeine supplementation, a well-known ergogenic strategy, may improve sprint performance and alleviate EIP as the hypoalgesic strategy. However, whether preexercise caffeine supplementation exhibits both the ergogenic effect on sprint interval performance and the hypoalgesic effect on intensive EIP during and several minutes after high intensity sprint interval exercise remains unknown, and thus we investigated to clarify those points. In this double-blind, randomized, crossover trial, sixteen male collegiate athletes performed 3 sets of 30-sec all-out Wingate pedaling exercises at 2-min intervals. Participants ingested 6 mg·kg-1 caffeine or placebo via capsules at 60 min prior to exercise. Quadriceps EIP was measured using a visual analogue scale during and up to 20 min after exercise. The results showed that caffeine did not significantly affect peak or mean power during sprint interval exercise (peak power: P = 0.196, ηp 2 = 0.11, mean power: P = 0.157, ηp 2 = 0.13; interaction). No significant interactions were also found for quadriceps EIP during (P = 0.686, ηp 2 = 0.03) and immediately after exercise (P = 0.112, ηp 2 = 0.12), nor for changes in physiological responses (blood lactate and ammonia concentrations) and caffeine-induced side effects (all P > 0.05). In conclusion, caffeine had no ergogenic or hypoalgesic effects on sprint interval exercise with intensive EIP.

Self-help programs without therapist involvement for obsessive-compulsive disorder (OCD) are promising, but the high dropout rate is a significant issue. Our software, which incorporates entertainment elements, showed a completion rate of over 80% in a pre-post comparison study, with superior effectiveness. This is the protocol for a study that aims to evaluate the efficacy and tolerability of a video-based mobile application for OCD treatment through a randomized controlled trial.

This study is designed as a randomized controlled trial with two parallel group comparison, with assessors blinded to group allocation. The study will include outpatients aged 18 years or older diagnosed with OCD. The intervention group will receive a mobile-device-based intervention using an application grounded in cognitive behavioral therapy. The treatment period will be 8 weeks, during which 21 sessions will be conducted. Participants not allocated to the intervention group will be assigned to a waitlist control group for 8 weeks. The primary outcome for effectiveness will be the comparison of the Yale-Brown Obsessive Compulsive Scale. As the primary outcome for tolerability, participants in the intervention group who complete 80% or more of the sessions by the 8-week point will be defined as treatment completers, and the proportion of completers will be calculated. Assuming a 10% attrition rate, a total of 88 participants will be needed.

Results will be presented according to the protocol.

If this study demonstrates that OCD can be improved through mobile-based self-help treatment without therapist involvement, it will become an important treatment option for patients.

In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. Secondary outcomes included global impression of change, NP symptoms, sleep quality, quality of life, pain interference in daily activities, and mood. A larger number of responders were found in the methadone (68%), compared to the placebo (33%) arm; risk difference 33.6%; 95% confidence interval 13.0%-54.3%; P = 0.003; number needed to treat = 3.0. Methadone reduced pain intensity ( P < 0.001), burning ( P = 0.023), pressing ( P = 0.005), and paroxysmal dimensions ( P = 0.006) of NP. Methadone also improved sleep ( P < 0.001) and increased the patient's global impression of improvement ( P = 0.002). Methadone did not significantly impact quality of life, pain interference, or mood. Treatment-emergent adverse events occurred in all methadone- and in 73% of placebo-treated patients ( P < 0.001). No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterised by episodes of symptoms including rectal bleeding, increased stool frequency and abdominal pain, impacting quality of life significantly. Conventional treatments often come with potential side effects and may not be sufficient. Acupuncture is increasingly recognised for its potential benefits in UC. This study aims to assess the efficacy and safety of acupuncture for symptom relief in mild to moderate UC.

This single-centre, parallel-arm, randomised, sham-controlled, the two-step acupuncture (TSA)-UC trial, will involve 64 adults with mild to moderate UC, randomly assigned in a 1:1 ratio to either the acupuncture or sham acupuncture group. Participants will receive 20 sessions of two-step acupuncture or sham acupuncture therapy over 8 weeks. Blinding will be applied to participants, outcome assessors and statisticians. The primary outcome measure is the change in Patient-Reported Outcome 2 (PRO2) from baseline at week 8. Secondary outcomes include changes from baseline in the following scales: PRO2 at other time points, weekly average Numeric Rating Scale (NRS) for bowel urgency, weekly average NRS for abdominal pain (both associated and not associated with bowel movement), the 32-item Inflammatory Bowel Disease Questionnaire, Work Productivity and Activity Impairment Questionnaire-IBD, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. The Patient Global Impression of Change will also be assessed. Long-term effects of acupuncture will be explored. Adverse events and additional treatments will be monitored throughout the study. The modified intention-to-treat population including participants who complete baseline assessments and receive at least one treatment session will be analysed.

The study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-190-KY). The results will be published in a peer-reviewed medical journal.

NCT06615765.

Only 30%-40% of patients with first-episode depression recover after taking antidepressants. Acupuncture is a clinically recognized treatment for depression, but its effect on first-episode depression remains unknown. This randomized controlled trial is designed to investigate the efficacy and safety of electroacupuncture (EA) compared with escitalopram (ESC) in treating patients with mild to moderate first-episode depression.

This is a multi-site, single-blind, randomized controlled trial with two parallel arms. A total of 204 eligible patients will be randomly allocated to two groups: the EA group (receiving EA treatment with placebo drugs) and the ESC group (receiving escitalopram and sham acupuncture treatment). Treatment will last 12 weeks, with 3 sessions per week for the first 8 weeks, decreasing to 2 per week for the remaining 4 weeks. The primary outcome will be the score of the 17-item Hamilton Depression Rating Scale (HAMD-17), and the secondary outcomes will include depression recovery rate, depression remission rate, Patient Health Questionnaire-9 (PHQ-9), 36-Item Short Form Survey Instrument (SF-36), and the dose and frequency of ESC. The Treatment Emergent Symptom Scale (TESS) will be used to assess all adverse effects. Full details of the statistical analysis plan for the primary and secondary outcomes will be described in this article.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.

Cognitive processing therapy (CPT) is an evidence-based treatment for posttraumatic stress disorder (PTSD). However, there is little evidence on the efficacy of CPT in East Asia.

To evaluate whether CPT is effective in treating PTSD among outpatients in a Japanese medical setting.

This randomized clinical trial used a 16-week, single-center, assessor-blinded, parallel-group superiority design to examine the efficacy of CPT in conjunction with treatment as usual (CPT-TAU) vs waiting list with TAU (WL-TAU) from April 2016 through December 2022. The trial included adult patients with PTSD at a national psychiatric referral hospital in Tokyo, Japan. Analysis was based on intention to treat and per protocol and was performed from February 1 to April 30, 2024.

Participants were randomized 1:1 to CPT-TAU (n = 29), which consisted of 12 weekly individual CPT sessions, or WL-TAU (n = 31), which consisted of clinical monitoring and/or pharmacotherapy.

The primary outcome was the Clinician-Administered PTSD Scale (CAPS-5) score for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) at 17 weeks. Secondary outcomes included self-reported PTSD symptoms assessed by the PTSD Checklist-5 and responder status at 17 weeks. Adverse events were evaluated using the Japanese version of the Common Terminology Criteria for Adverse Events, version 4.0.

Among 60 eligible participants (all included in the intention-to-treat analysis), mean (SD) age was 36.9 (9.9) years; 54 (90.0%) were women. The CPT-TAU group showed a mean (SE) reduction in CAPS-5 scores of 14.00 (1.92) points, with a low dropout rate (2 of 29 [6.9%]). Patients in the CPT-TAU group showed superiority in all secondary and other outcomes. The mean change difference was observed in depression (8.83; 95% CI, 6.00-11.66), suicidal ideation (6.73; 95% CI, 1.25-12.22), disability (8.16; 95% CI, 3.90-12.43), clinical global impression (0.84; 95% CI, 0.41-1.26), and loss of principal PTSD diagnosis (59.09; 95% CI, 37.19-81.00). There were no serious adverse events in the CPT-TAU group and 3 serious adverse events in the WL-TAU group during the intervention period.

In this randomized clinical trial of CPT-TAU vs WL-TAU, CPT was superior in reducing PTSD symptoms. These results strengthen the evidence for use of CPT in East Asian populations.

Umin.Uc.Jp/Ctr Identifier: UMIN000021670.

Post herpetic neuralgia (PHN) is the most common complication of herpes zoster, also known as shingles. Amitriptyline has been postulated to prevent PHN. The objective is to determine whether prophylactic low-dose amitriptyline prevents PHN in patients newly diagnosed with shingles.

This is a multicentre, individually randomized, pragmatic, placebo-controlled superiority trial with health economic analysis and nested qualitative study. Patients with new-onset shingles are screened by treating clinicians in participating general practitioner surgeries. Key eligibility criteria are age ≥50 years, ≤6 days since rash onset and not already taking (and no contraindication to) amitriptyline. Participants are randomized 1:1 to amitriptyline 10 mg or matched placebo tablets (dose escalated as tolerated to a maximum of three tablets daily for 70 days). Resource-use data (including health, social and informal care, personal expenses and usual activities) are collected from electronic medical records and participant questionnaires. A sample of recruitment conversations are audio-recorded and interviews conducted with recruiters and patients, including those who decline to participate or who withdraw from the trial.

The primary outcome is the presence of PHN (≥3/10 worst pain on Zoster Brief Pain Inventory) at 90 days after rash onset. Primary health economic analyses will present cost per case of PHN prevented and cost per quality-adjusted life year. Qualitative data will be analysed to optimize trial delivery and to aid interpretation and implementation of the trial findings. This is the largest trial to date to evaluate the clinical/cost-effectiveness and acceptability of prophylactic low-dose amitriptyline for the prevention of PHN.

EudraCT 2021-001101-78 and ISRCTN14490832.

Chronic low back pain is associated with dysfunctions in endogenous analgesia mechanisms, as evaluated through conditioned pain modulation paradigms. Although mobilization with movement has demonstrated enhancements in conditioned pain modulation among patients with conditions such as knee osteoarthritis, its efficacy in chronic low back pain patients has yet to be established.

To investigate the effects of mobilization with movement compared to sham mobilization in conditioned pain modulation, mechanical hyperalgesia, and pain intensity in chronic low back pain patients.

Randomized controlled trial following CONSORT and TIDieR guidelines.

Fifty-eight patients with chronic low back pain (mean age 48.77 ± 13.92 years) were randomized into the experimental group, which received real mobilization with movement (n = 29), or the sham mobilization with movement group (n = 29). Only one intervention was performed. Patients were assessed before and after intervention. Conditioned pain modulation, mechanical hyperalgesia and pain intensity were assessed.

Mobilization with movement resulted in no statistically significant differences compared to sham mobilization for conditioned pain modulation (post-treatment difference: 0.023 [-0.299, 0.345], p = 0.158), mechanical hyperalgesia (post-treatment difference: -0.198 [-0.505, 0.109], p = 0.207), or movement-related pain intensity (post-treatment difference: 0.548 [-0.068, 1.236], p = 0.079) improvements post-intervention. Effect sizes were small for conditioned pain modulation (r = 0.126), mechanical hyperalgesia (r = 0.101), and pain intensity (r = 0.208).

Mobilization with movement resulted in no significant differences compared to sham mobilization with movement after one intervention for conditioned pain modulation, mechanical hyperalgesia or pain intensity, with small effect sizes. However, the findings should be interpreted with caution due to absence of screening for appropriately eligible patients.

The aim of this study was to analyze the characteristics and trends of publications in clinical trials on tooth bleaching through a bibliometric and altmetric analysis.

A search was conducted in September 2024 on Web of Science Core Collection (WoS-CC) and Scopus. Two researchers selected articles and extracted key study characteristics. VOSviewer was used to generate bibliometric networks. Dimensions was consulted to measure altmetric data.

416 studies were included, published between 1990 and 2024. The most cited study obtained 164 citations on WoS-CC and 201 on Scopus. The studies predominantly investigated bleaching efficacy (n = 232), often employing double-blind designs (n = 146), conducted in adults (n = 403), randomized (n = 307), and mainly using hydrogen peroxide (n = 200) for at-home vital dental bleaching (n = 199). The majority of the articles were published by Brazilian authors (n = 165), with Loguercio AD (n = 70) and Reis A (n = 56) being the most frequent authors. The manufacturer FGM led with the highest number of investigated products (n = 153), particularly highlighting Whiteness HP Maxx 35 % (n = 40). VOSviewer revealed significant collaborations among authors and keywords. According to Dimensions, users of Mendeley and news outlets have shown great interest in whitening clinical trials.

This study highlighted a growing trend in clinical trials on tooth bleaching over 30 years, with a strong predominance of studies conducted in Brazil that primarily investigated bleaching efficacy through double-blind designs in adults using hydrogen peroxide.

Clinical trials on tooth bleaching represent one of the highest levels of scientific evidence guiding clinical practice, thus requiring thorough evaluation.

The objective was to examine the adjuvant effect of active pulsed electromagnetic field (PEMF) versus microwave (MW) therapy, as well as sham PEMF, in addressing pain and improving functionality for treating knee osteoarthritis (KOA).

This was a double-blind, placebo-controlled, randomized clinical trial. Individuals diagnosed with KOA were assigned to an intervention combining an exercise program (EX) with active PEMF, MW, or sham PEMF. The main outcomes were pain, reported on a visual analogue scale (VAS), and functionality, assessed using the Western Ontario and McMaster Universities Arthritis (WOMAC) questionnaire, and the Timed Up and Go test (TUG). The outcomes were measured preintervention, immediately postintervention, and at 1 and 4 months of follow-up (FU).

Sixty individuals (n = 83 knees) were evaluated. Significant between-group differences were found in WOMAC stiffness (rmMANOVA (F(2,77) = 4.33, P = .017, partial η2 = 0.10)). A notable interaction effect between group and time was found for the WOMAC pain score (rmMANOVA (F(2, 77) = 3.14, P = .049, partial η2 = 0.07)). After 4 months, the PEMF + EX group demonstrated superior pain relief compared to the sham PEMF + EX (WOMAC pain "mean difference ± standard error between-groups": -3.2 ± 1.2, P = .028) and MW + EX (VAS pain: -2.1 ± 0.9, P = .042) groups. PEMF + EX perceived less stiffness than did the sham PEMF + EX in both the pre-FU (WOMAC stiffness: -1.6 ± 0.6, P = .047), 1-month FU (-1.7 ± 0.6, P = .015) and 4-month FU (-1.4 ± 0.6, P = .038), with no changes in the MW + EX group. WOMAC function score showed greater improvement in the PEMF + EX group compared to the MW + EX group at 4-month of FU (-9.0 ± 3.6, P = .039). Only PEMF + EX showed a positive effect on the TUG score at 1-month FU (-1.7 ± 0.5, P = <.001) and 4-month of FU (1.9 ± 0.5, P = .020).

The application of PEMF could be a useful adjuvant treatment to exercise programs to further decrease pain and improve knee stiffness and function in individuals with KOA in the medium term compared to MW and sham PEMF.

Although various sham acupuncture techniques have been employed to ensure blinding in randomised controlled trials (RCTs) of acupuncture, the effectiveness of blinding in these trials and its influence on trial effect size estimates remain unclear. The objectives of this study are the following: (1) to investigate the proportion and study characteristics of sham-controlled trials reporting on blinding assessment, (2) to assess the blinding effectiveness of different types of sham acupuncture, (3) to investigate the relationship between blinding effectiveness and effect sizes in acupuncture RCTs.

We will search PubMed and EMBASE from inception to 1 January 2025 to identify RCTs that compared acupuncture with sham acupuncture in humans with any disease or symptom, with no restrictions on language. Paired investigators will independently determine eligibility and use pilot-tested standardised forms for data extraction. We will calculate the proportion of sham-controlled trials that assessed and reported blinding success and conduct descriptive analyses of general study characteristics, acupuncture treatment details, sham acupuncture details and blinding assessments for included trials. We will assess the effectiveness of blinding success using the James blinding index (BI) and Bang BI, and pool data from included trials using random-effects models. We will use Hedges' g, a standardised mean difference, with its 95% CI, to calculate treatment effects. We will use Pearson's r correlation coefficient to assess the relationship between blinding effectiveness and trial effect sizes when variable distributions meet the assumptions of normality and linearity; otherwise, we will consider employing non-parametric tests. When sufficient data are available, we will also use random-effects meta-regression to explore the relationship.

Ethical approval is not required. The findings of this study will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for clinicians, health policymakers and guideline developers regarding the design, conduct, analysis and interpretation of blinded assessment of sham acupuncture RCTs.

Open Science Framework (https://doi.org/10.17605/OSF.IO/B3U7K).

The postpartum period can be emotionally challenging for parents, with documented levels of anxiety, stress, and depression. While the benefits of skin-to-skin contact (SSC) are well-known, its impact on the mental health of parents of full-term newborns has been less studied.

We aimed to assess the effects of SSC in mental health outcomes in the parents of full-term newborns.

In this systematic review, a comprehensive search was conducted to identify randomized clinical trials (RCTs) comparing SSC versus no SSC and assessing mental health outcomes. Meta-analyses were performed whenever possible, and the GRADE approach was used to rate the certainty of evidence.

We included 9 RCTs with 1201 participants. Regarding the risk of bias, the most affected domains were selective reporting, blinding, and allocation concealment. Regarding parental anxiety, SSC may reduce it at short-term, while it is unsure its effect at mid-term and it may not have any effect at long-term. Regarding Psychological stress, SSC may not have an impact at mid- and long-term. Regarding delivery-related post-traumatic stress symptoms, SSC may not have an impact at short-, mid-, and long-term. Regarding depressive symptoms, the evidence is uncertain at short- and mid-term.

For the assessed outcomes, certainty of the evidence was low or very low.

SSC may reduce parental anxiety at short-term, while it may not have an impact in psychological stress and delivery-related post-traumatic stress symptoms. Moreover, the evidence is uncertain regarding its effect in long-term anxiety and depressive symptoms.

Blinding is essential for mitigating biases in trials of low back pain (LBP). Our main objectives were to assess the feasibility of blinding: (1) participants randomly allocated to active or placebo spinal manual therapy (SMT), and (2) outcome assessors. We also explored blinding by levels of SMT lifetime experience and recent LBP, and factors contributing to beliefs about the assigned intervention.

A two-parallel-arm, single-centre, placebo-controlled, blinding feasibility trial. Adults were randomised to active SMT (n = 40) or placebo SMT (n = 41). Participants attended two study visits for their assigned intervention, on average seven days apart. The primary outcome was participant blinding (beliefs about assigned intervention) using the Bang blinding index (BI) at two study visits. The Bang BI is arm-specific, chance-corrected, and ranges from - 1 (all incorrect beliefs) to 1 (all correct beliefs), with 0 indicating equal proportions of correct and incorrect beliefs. Secondary outcomes included factors contributing to beliefs about the assigned intervention.

Of 85 adults screened, 81 participants were randomised (41 [51%] with SMT lifetime experience; 29 [39%] with recent LBP), and 80 (99%) completed follow-up. At study visit 1, 50% of participants in the active SMT arm (Bang BI: 0.50 [95% confidence interval (CI), 0.26 to 0.74]) and 37% in the placebo SMT arm (0.37 [95% CI, 0.10 to 0.63]) had a correct belief about their assigned intervention, beyond chance. At study visit 2, BIs were 0.36 (0.08 to 0.64) and 0.29 (0.01 to 0.57) for participants in the active and placebo SMT arms, respectively. BIs among outcome assessors suggested adequate blinding at both study visits (active SMT: 0.08 [- 0.05 to 0.20] and 0.03 [- 0.11 to 0.16]; placebo SMT: - 0.12 [- 0.24 to 0.00] and - 0.07 [- 0.21 to 0.07]). BIs varied by participant levels of SMT lifetime experience and recent LBP. Participants and outcome assessors described different factors contributing to their beliefs.

Adequate blinding of participants assigned to active SMT may not be feasible with the intervention protocol studied, whereas blinding of participants in the placebo SMT arm may be feasible. Blinding of outcome assessors seemed adequate. Further methodological work on blinding of SMT is needed.

NCT05778396.

During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder. Preliminary evidence also supports efficacy in other psychiatric disorders (e.g., tobacco and alcohol use disorders). Notwithstanding the interest and promise of psychedelics, concerns have arisen with respect to the interpretability and translatability of study results. For example, aspects related to short- and long-term safety, abuse liability, and the essentiality of the psychedelic "trip" and psychological support are, inter alia, insufficiently characterized with psychedelic agents. The overarching aims in this overview are 1) to review methodological aspects that affect inferences and interpretation of extant psychedelic studies in psychiatric disorders, and 2) to provide guidance for future research and development of psychedelic treatment in psychiatry, critical to study interpretation and clinical implementation.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 years) treatment. tDCS consisted of five sessions per week for 3 weeks then three sessions per week for 7 weeks in a 10-week trial, followed by a 10-week open-label phase. Each session lasted 30 min; the anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right dorsolateral prefrontal cortex (active tDCS 2 mA and sham tDCS 0 mA, with brief ramp up and down to mimic active stimulation). As the primary outcome, depressive symptoms showed significant improvement when measured using the Hamilton Depression Rating Scale: active 9.41 ± 6.25 point improvement (10-week mean = 9.58 ± 6.02) and sham 7.14 ± 6.10 point improvement (10-week mean = 11.66 ± 5.96) (95% confidence interval = 0.51-4.01, P = 0.012). There were no differences in discontinuation rates. In summary, a 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety. ClinicalTrials.gov registration: NCT05202119.

Sham acupuncture is a widely accepted control in acupuncture clinical trials. Given the nature of acupuncture, it is warranted to assess the blinding of sham-controlled trials. Despite the sham acupuncture design having been widely used, the overall blinding of sham acupuncture and the characteristics of blinding assessment in acupuncture trials are unclear. This research aims to assess the blinding status of acupuncture clinical trials and explore the blinding assessment characteristics in acupuncture trials.

This meta-analysis included all the acupuncture clinical trials published in English that performed blinding assessments and reported the results. We searched PubMed, Embase, and Web of Science for randomized controlled trials (RCTs) from inception to April 2024. The primary outcome is Bang's Blinding Index (Bang's BI) and 95% credibility interval (CrI) was pooled using a Bayesian hierarchical model. The study adheres to the PRISMA guidelines.

Sixty-four eligible studies published from 1999 to 2024 were included. The mean of Bang's BI was - 0.24 (95% CrI - 0.34 to - 0.14, tau2 = 0.13) for the sham acupuncture group and 0.41 (95% CrI 0.32 to 0.49, tau2 = 0.10) for the verum acupuncture group. The characteristics of blinding showed that 62.50% of the trials had a Bang's BI greater than 0 in the verum group and less than 0 in the sham group; in 28.15% of the trials, the Bang's BI was greater than 0 in the verum group and greater than 0 in the sham group. Subgroup analysis revealed that area, number of research centers, treatment sessions, acupoints number, and evaluation timepoint can influence blinding results.

Overall blinding status in current acupuncture clinical trials shows a majority correctly guessing for the verum group and opposite guessing for the sham group. However, in some acupuncture trials, the blinding of sham acupuncture might be compromised. Factors such as the Asian population, penetrating sham needling, and querying participants about their group assignment during the study increase the risk of unblinding and warrant careful consideration in sham acupuncture control design. Furthermore, researchers should closely monitor the blinding status of sham acupuncture and transparently report details of blinding assessments.

PROSPERO CRD42023403595.

Blinding is an essential part of many randomized controlled trials. However, its quality is usually not checked, and when it is, common measures are the James index and/or the Bang index. In the present paper we discuss these two indices, providing examples demonstrating their considerable weaknesses and limitations, and propose an alternative method for measuring blinding. We argue that this new approach has a number of advantages. We also provide an R-package for computing our blinding index.

Randomized clinical trials provide reassurances that confounding factors are balanced at baseline whereas blinding is essential to assure the balance of extraneous factors thereafter. This article provides a three-part taxonomy of pitfalls that can arise because of inadequate blinding in clinical trials. We introduce a cautionary framework for readers interpreting a blinded randomized trial for evidence-based medicine. Each pitfall is illustrated with a relevant example of a potential bias resulting from knowledge of group assignment. Several pitfalls occur during the conduct of the study including inadequate blinding of the intervention group, control group, or responsible clinicians. Additional pitfalls relate to data analysis including unsubstantiated assertions of blinding and subverted tests for blinding. Further pitfalls arise due to surrounding oversight including unblinding of research ethics boards and scientific reviewers. These caveats are sources of misunderstanding when observing the apparent connection between a clinical intervention and patient outcomes. An awareness of specific pitfalls might help advance the interpretation and application of blinded randomized clinical trials to inform evidence-based medical care.

Ileus is characterized by a period of intestinal dysmotility after surgery, leading to vomiting and constipation. In preclinical models, vagus nerve stimulation reduces intestinal inflammation and prevents smooth muscle dysfunction, accelerating the return of gut function. This study explored the feasibility of a definitive trial of non-invasive vagus nerve stimulation (nVNS) along with an early assessment of efficacy.

A multicentre, randomized feasibility trial (IDEAL Stage 2B) of self-administered nVNS was performed. Patients undergoing colorectal surgery were randomized to nVNS or sham before and after surgery. Feasibility outcomes comprised assessments of recruitment, compliance, blinding and attrition. Clinical outcomes were measures of intestinal function and adverse events. All participants were followed up for 30 days. Interviews with patients and health professionals explored barriers to feasibility and perspectives around implementation.

In all, 125 patients were approached about the study and 97 (77.6%) took part. Across all randomized groups, the median compliance to treatment was 19 out of 20 stimulations (interquartile range 17-20). The incidence of adverse events was similar across groups. In this unpowered feasibility study, the time taken for the return of gut function (such as first passage of stool) was similar between nVNS and sham treatments. According to interviews, patients were highly motivated to use the device because it provided them with an opportunity to engage actively in their care. Health professionals were highly driven to tackle the problem of ileus.

Powered assessments of clinical efficacy are required to confirm or refute the promise of nVNS, as already demonstrated in preclinical models. This feasibility study concludes that a definitive randomized assessment of the clinical benefits of nVNS is desired and feasible.

Caffeine consumption can elicit improvements in aspects of physical function in older adults but also, negatively modify standing balance, potentially increasing fall risk. However, balance alterations and changes in physical function induced by commonly consumed caffeine vehicles such as coffee have not been investigated. Therefore, this study investigated coffee ingestion providing 3 mg·kg BW-1 caffeine on balance performance and physical function, in a group of older adults. In a randomised, crossover design, 22 older adults (Male n = 10, Age: 68 ± 6 years) completed bipedal standing balance and physical function assessments (Senior Fitness Test) under one of the following conditions: caffeinated coffee (COF), decaffeinated coffee (DEC), placebo (PLA) or a control (CON) (no fluid ingestion). Centre of pressure (COP) root mean square and power frequency were calculated to characterise postural performance and strategy, respectively. The complexity (i.e., regularity) of the COP signal was also determined by calculating sample entropy. Caffeinated coffee had limited effects on COP outcomes. Frequency of the COP in the anteroposterior direction was greater following COF compared to DEC (P = 0.047;g = 0.29) but there were no statistical differences between COF and PLA or CON (P > 0.05). Furthermore, there were no significant performance differences between any conditions in all tests of physical function (P > 0.05). This suggests that coffee has limited effects on balance performance or physical function but may influence both balance complexity and the strategy utilised to maintain upright stance. Overall, a strong cup of coffee does not significantly influence balance and measures of functional performance in healthy older adults.

This parallel, 2-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. In total, 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 average pain (mean difference [95% confidence interval]: -.04 [-.39 to .31], P = .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 Brief Pain Inventory average pain. The number of treatment-emergent adverse events were similar in both groups (P = .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. PERSPECTIVE: 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.