SEARCH · Search PubMed

Results for “Blinding assessment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,064 records · Page 10Linked to original sources

PubMed2026

Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial.

BACKGROUND: Intravenous ketamine can provide short-term analgesia in chronic neuropathic pain but benefits often wane after treatment. We conducted a randomized pilot trial to assess the feasibility of combining ketamine infusions with psychotherapy to inform future efficacy trials. METHODS: In this single-center, randomized, outcome-assessor-blinded pilot trial at a Canadian tertiary pain clinic, adults with moderate-to-severe chronic neuropathic pain were randomly assigned in 1:1:1 ratio to the ketamine, psychotherapy, or combined ketamine plus psychotherapy arm. Ketamine was delivered as three intravenous infusions over 16 weeks; psychotherapy consisted of 16 weekly cognitive behavioral therapy and mindfulness-based meditation sessions. The primary outcome was feasibility, assessed using prespecified progression criteria. Exploratory outcomes included changes in pain interference (PROMIS 6a T-score), pain intensity, mood, and qualitative interview findings at week 20 (ClinicalTrials.gov: NCT05639322). FINDINGS: Between October 23, 2023, and March 31, 2025, 30 participants were randomized, and 26 (87%) completed 20-week follow-up. Most feasibility criteria, including consent, retention, data completeness, and absence of study-related serious adverse events, were met; adherence targets were partially met. Exploratory pain outcomes showed numerical improvement across groups, with clinically meaningful reductions observed for pain interference and pain intensity. Sixty-four adverse events were recorded, mostly mild and in ketamine-containing groups; no serious study-related adverse events occurred. CONCLUSIONS: Combined ketamine and psychotherapy was feasible and acceptably safe in this pilot trial, supporting evaluation in a larger efficacy-powered study. FUNDING: The study was funded by the St. Michael's Hospital Innovation Fund, The Canadian Pain Society Early Investigator Award and the Physician Services Incorporation Early Career Researcher Award.

Humans↗

PubMed2026

Biomimetic mesoporous silica nanosphere ameliorate experimental autoimmune uveitis by delivering sCD83.

Autoimmune uveitis (AU) is an autoimmune disease that may lead to blindness, but there are currently no precise targeted therapies for its prevention and treatment. Dendritic cell (DC) is key cell involved in the pathogenesis of AU, and specific regulation of their state can help improve AU. In this work, mesoporous silica nanospheres were loaded with the immunomodulator soluble CD83 (sCD83) and subsequently camouflaged with dendritic cell (DC) membranes to fabricate the nanocarrier DCM@MSN/sCD83 for treating experimental autoimmune uveitis (EAU). Research results show that DCM@MSN/sCD83 effectively alleviated the symptoms of uveitis in EAU, reduced the proportion of CD4+CD25-T cell/CD4+CD25+T cell and the percentage of DC in the eyes and cervical lymph nodes. It also decreased the expression of STING in Müller cell. Furthermore, the efficacy of DCM@MSN/sCD83 was found to be primarily targeting DC, and promoted the expression of IL-10 and TGF-β1 in DC by activating the phosphorylated HIF/STAT3 pathway, to induce the production of CD4+CD25+ T. This effect is superior to nanomedicine loaded with dexamethasone. Moreover，DCM enabled the nanocarriers to efficiently cross the blood-eye barrier and reach cervical lymph nodes, thereby regulating peripheral immunity. This research indicate that cell membrane-modified nanoparticles targeting homologous cells can effectively improve treatment efficiency and duration, which is potential therapy strategy for uveitis.

Animals↗

PubMed2026

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p = 0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference +28.0%, 95% CI 4.2-47.7; Fisher p = 0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks; +0.205 at 12 months; both p < 0.01). A modest between-group beta-diversity difference at 6 months (R2 = 0.035; p = 0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans↗

PubMed2026

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans↗

PubMed2026

Comparing Traditional Motor Speech Practice to Contextualized Speech Practice in Preschoolers With Childhood Apraxia of Speech.

PURPOSE: The aim of this study was to compare retention of real-word targets across practice conditions (contextualized vs. motor-only) within a modified integral stimulation treatment for preschoolers with childhood apraxia of speech (CAS). METHOD: A single-subject experimental design with alternating treatments was used with matched target sets randomly assigned to contextualized practice, motor-only practice, or no treatment. Three preschoolers with CAS completed 18 therapy sessions, each consisting of two 25-min blocks: one contextualized practice and one motor-only practice. Order of practice was randomized each visit. Changes in percent phonemes correct (PPC) and lexical stress accuracy, derived from blinded transcription, were explored with visual analysis and effect sizes (standardized mean difference, d statistic). RESULTS: Meaningful improvements (d > 1) were observed in PPC across words treated in contextualized practice for all three children immediately posttreatment and for two of three children at the 1-month follow-up. Meaningful improvements in the motor-only condition were observed in two of three children immediately posttreatment and at follow-up. No meaningful changes were observed in lexical stress across any conditions in any participant. CONCLUSIONS: This study provides preliminary support for the feasibility of a modified integral stimulation therapy that incorporates elements of linguistically grounded therapies (linguistic retrieval, recasts, expansions) that may facilitate target retention in some preschoolers with CAS. However, other elements should be explored in conjunction with integral stimulation to maximize clinical outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33228981.

Humans↗

PubMed2026

Impact of oxytocin discontinuation on fetal heart rate and uterine contractility: A pre-specified ancillary analysis embedded within a randomized trial.

INTRODUCTION: Oxytocin is widely used to augment uterine contractions during labor. However, its use has been associated with fetal heart rate (FHR) abnormalities and neonatal morbidity, which may be reduced by discontinuing oxytocin during labor. We aimed to assess the impact of oxytocin discontinuation at the onset of the active phase of labor on FHR patterns and uterine contractility. MATERIAL AND METHODS: This study is a pre-specified ancillary analysis of the STOPOXY trial, a multicenter, randomized, open-label, controlled superiority trial conducted in 21 French maternity units between January 2020 and January 2022, which aimed to assess the impact of oxytocin discontinuation during active labor on neonatal morbidity. Participants who received oxytocin before 4 cm dilation were randomly assigned (1:1) to either oxytocin discontinuation or oxytocin continuation. For the present analysis, we included women from the per-protocol discontinuation group of the parent trial. Inclusion was restricted to the six centers with electronic cardiotocography storage where valid cardiotocography recordings were available for at least 1 h before and 1 h after oxytocin discontinuation. Using a paired before-and-after design, FHR parameters (classified according to FIGO criteria) and uterine activity were compared during the 60 min preceding versus the 60 min following oxytocin discontinuation by independent obstetricians blinded to neonatal outcomes. Changes in FHR pattern were categorized as no change, improvement, or deterioration. RESULTS: 284 women fulfilled the eligibility criteria. Following oxytocin discontinuation, mean FHR increased (135 vs. 137.5 bpm; p < 0.002) and FHR variability significantly changed (p = 0.010), with a lower rate of reduced variability (3.9% vs. 2.5%) and a higher rate of normal variability (48.2% vs. 53.3%). The proportion of tracings with decelerations significantly decreased (64.1% vs. 48.6%; p < 0.001). Uterine activity decreased, with fewer uterine contractions (4.0 vs. 3.5 contractions per 10 min; p < 0.001). CONCLUSIONS: Among women receiving oxytocin during early labor, discontinuation at the onset of the active phase was associated with improved FHR patterns and reduced uterine activity, suggesting a lower fetal stress and tachysystole. Further studies are needed to assess whether these changes affect labor management or maternal experience.

Humans↗

PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans↗

PubMed2026

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum↗

PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗

PubMed2026

BLIS study: a feasibility randomised controlled trial assessing compliance, acceptability and colonisation with different dosing regimens of the probiotic supplement Streptococcus salivarius K12 (Bactoblis) in adults in England.

OBJECTIVES: Streptococcus salivarius K12 (SsK12) is a bacterium used as a probiotic with some evidence for preventing acute sore throat/tonsillitis, but the optimal dosing strategy is unclear. This study aimed to evaluate two dosing regimens of SsK12 to establish (a) the prevalence and duration of colonisation with SsK12 and (b) the acceptability and feasibility of these regimens. DESIGN: A randomised, non-blinded feasibility trial. SETTING: Primary care in the south of England. PARTICIPANTS: Adults with ≥2 episodes of sore throat within the 3 years before recruitment. INTERVENTIONS: Participants were randomised to take SsK12 lozenges once weekly or daily over 14 days. MAIN OUTCOME MEASURES: The primary outcome was the prevalence and duration of colonisation with SsK12. This was determined by real-time PCR conducted on self-taken whole-mouth swabs provided by participants at baseline and on days 2, 7, 14, 21 and 35. Secondary outcomes were the compliance and acceptability of the two SsK12 dosing regimens, based on questionnaire data. RESULTS: 53 participants were recruited (26 randomised to weekly and 27 to daily dosing) between 26 April and 5 December 2023. All swabs were returned by 65.4% (17/26) and 70.4% (19/27) of the weekly and daily groups respectively. Swabs at all timepoints from participants with PCR positives observed at baseline (two and four from the weekly and daily group, respectively) were excluded. Therefore, swabs from 23 participants in the weekly and 22 in the daily group did not have evidence of baseline colonisation and were included in the microbiology analysis. SsK12 colonisation was found in 59.1% (13/22, 95% CI 38.6% to 79.6%) of samples in both groups on day 2; in 13.6% (3/22, 95% CI 0.0% to 28.0%) and 85.7% (18/21, 95% CI 70.8% to 100.0%) of the weekly and daily groups, respectively, on day 7; in 19.1% (4/21, 95% CI 2.3% to 35.8%) and 59.1% (13/22, 95% CI 38.6% to 79.6%), respectively, on day 14; and in only one participant (weekly group) on days 21 and 35. The dosing regimen was reported as easy to follow by 85.0% (17/20, 95% CI 69.4% to 100.0%) of the weekly and 96.2% (25/26, 95% CI 88.8% to 100.0%) of the daily dosing groups. CONCLUSIONS: SsK12 colonisation was more prevalent with daily dosing; however, colonisation was not maintained when dosing stopped. Both dosing regimens were acceptable to participants. These findings support the use of daily dosing in a future trial to evaluate the efficacy of SsK12 in preventing recurrence of sore throat/tonsillitis. TRIAL REGISTRATION NUMBER: NCT04297878.

Humans↗

PubMed2026

Autophagy activation in granulosa cells as a mechanism of astaxanthin action: evidence from a pilot randomised trial in PMOS-associated infertility.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Female↗

PubMed2026

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans↗

PubMed2026

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans↗

PubMed2026

Effect of brewers' yeast or beta-glucan derived from Saccharomyces cerevisiae on breast milk supply following preterm birth: the BLOOM randomised controlled trial.

OBJECTIVE: Breast milk is the optimal source of nutrition for preterm infants; however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers' yeast or beta-glucan improves daily expressed breast milk volume. DESIGN: Randomised, blinded, parallel, placebo-controlled trial. SETTING: Three Australian tertiary-level neonatal units. PATIENTS: Mothers with a singleton or twin pregnancy who gave birth at <34 weeks' gestation. INTERVENTIONS: Mothers were randomised within 72 hours of birth into three parallel groups in a 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for 7 days. MAIN OUTCOME MEASURE: Total expressed breast milk volume over a 24-hour period on day 7 of intervention. RESULTS: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94 mL/day (95% CI -51 mL/day to 239 mL/day) between the brewers' yeast and placebo groups and -25 mL/day (95% CI -173 mL/day to 123 mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. CONCLUSION: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. TRIAL REGISTRATION NUMBER: ACTRN12622000968774.

Intensive Care Units, Neonatal↗

PubMed2026

International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial.

BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes. METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist. RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only). CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449. UNIQUE IDENTIFIER: NCT04674449.

Humans↗

PubMed2026

Effects of erector spinae plane block on postoperative pain in patients undergoing implant-based breast reconstruction for breast cancer: a randomized controlled trial.

BACKGROUND: Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE: To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN: Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING: Tertiary cancer center in China. PATIENTS: 100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION: Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 μg/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES: Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS: ESPB did not significantly reduce resting pain at 6 h at the median (τ =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (τ = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS: Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06143020.

Humans↗

PubMed2026

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had ≤US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans↗