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PubMed2026

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale ≥3.0, n = 12) and controls (n = 10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p = 0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p < 0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p < 0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans↗

PubMed2026

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma.

PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC. METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint. RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo. CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

Adult↗

PubMed2026

MIC-based tuberculosis drug susceptibility testing using Sensititre MYCOTB: a diagnostic accuracy meta-analysis.

Accurate drug susceptibility testing (DST) is crucial for designing effective regimens for multidrug-resistant (MDR) and pre-extensively drug-resistant tuberculosis (pre-XDR TB). Sensititre MYCOTB enables simultaneous determination of minimum inhibitory concentrations (MICs) for multiple drugs, but its diagnostic performance varies across studies. This meta-analysis evaluated the diagnostic performance of Sensititre MYCOTB for key MDR and pre-XDR TB drugs. The protocol was registered in PROSPERO (CRD420251230599). PubMed, Cochrane, Google Scholar, Scopus, ONOS, Web of Science, ScienceDirect, and registries were systematically searched for studies published between 2010 and 2025. Studies comparing the Sensititre MYCOTB with reference DST for Mycobacterium tuberculosis complex (MTBC) were included. Bias assessment and pooled diagnostic accuracy estimates were generated. Fourteen studies, including 1,728 isolates, were analyzed. Rifampicin and isoniazid demonstrated high sensitivity (0.976 [95% CI: 0.94-0.99] and 0.977 [95% CI: 0.95-0.99]) and specificity (0.958 [95% CI: 0.84-0.98] and 0.957 [95% CI: 0.83-0.99], respectively) with low heterogeneity. Amikacin, kanamycin, and ofloxacin demonstrate good diagnostic accuracy, with high specificity (>0.98 [95% CI]). Moderate diagnostic accuracy was observed for ethambutol, streptomycin, ethionamide, and rifabutin. Cycloserine, moxifloxacin, and para-aminosalicylic acid showed inconsistent performance despite excellent specificity (>0.97 [95% CI]). Sensitivity analysis partially improved pooled sensitivity for moxifloxacin 0.801 (95% CI: 0.585-0.924) and para-aminosalicylic acid 0.76 (95% CI: 0.518-0.894), whereas cycloserine remained at 0.436 (95% CI: 0.190-0.725), although heterogeneity persisted. Sensititre MYCOTB DST demonstrates high diagnostic accuracy for MDR-TB and pre-XDR-TB drugs, while caution is required with cycloserine, moxifloxacin, and para-aminosalicylic acid. These findings support the integration of MIC-based testing into clinical decision-making.

Microbial Sensitivity Tests↗

PubMed2026

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans↗

PubMed2026

Safety of insulin eye drops in the treatment of open angle glaucoma: a randomized phase I clinical trial.

OBJECTIVE: The progression of glaucoma despite adequate intraocular pressure (IOP) control highlights the need for neuroprotective and neuroregenerative therapies. Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans. We aim to assess the safety and tolerability of these two concentrations of insulin eye drops in patients with open-angle glaucoma (OAG). DESIGN: A phase I, randomized, double-blind, placebo-controlled, single-centre clinical trial. PARTICIPANTS: Patients with mild to moderate OAG were randomized 2:2:1 to receive once-daily topical insulin U-100, U-500, or placebo in 1 eye for 5 days, with follow-up visits at 1, 3, and 6 months. The primary safety outcomes include glycemia, serum potassium, ocular adverse events (AEs), and ocular tolerability scores. Secondary outcomes included IOP, best-corrected visual acuity (BCVA), retinal nerve fibre layer thickness, ganglion cell complex, visual field, and OCT angiography. RESULTS: Eighteen open-angle glaucoma patients were enrolled (mean age: 66.2 ± 10.1 years). No serious AEs related to insulin were observed. One asymptomatic, transient near-hypoglycemia event occurred in a fasting participant (3.9 mmol/L), with no recurrence after dietary adjustment. No significant changes were found in serum potassium, IOP, BCVA, visual fields, or OCT. Ocular symptoms in the insulin groups were limited to transient, mild burning sensation upon application. One participant experienced cystoid macular edema at 3 months, which was attributed to pre-existing ocular pathology. CONCLUSION: Topical insulin at 100 and 500 units/mL concentrations was well tolerated in patients for short-term use and did not result in significant systemic or ocular toxicity.

Aged↗

PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2026

No Efficacy of Dexamethasone Injections for Acute Sciatica: A Double-Blind Randomized Study Versus Saline.

BACKGROUND: The efficacy of caudal injections for patients with acute sciatica remains controversial. The DEXHIA study was designed to evaluate whether ultrasound-guided caudal injection of dexamethasone provides superior clinical outcomes compared with saline placebo. METHODS: This prospective, randomized, placebo-controlled, double-blind trial included adult patients with sciatica secondary to lumbar disc herniation of less than 3 months' duration. Participants were randomly assigned in a 1:1 ratio to receive either 16 mg of dexamethasone (4 mL) diluted with 16 mL of saline (DEXA group) or 20 mL of saline alone (PLACEBO group), administered by ultrasound-guided caudal epidural injection. The primary outcome was the change in the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcomes included leg pain and low back pain assessed by visual analogue scale (VAS), health-related quality of life (SF-36), need for repeat epidural injection, and need for lumbar surgery. Clinical assessments were performed at 3 weeks, 3 months, and 6 months. RESULTS: A total of 106 patients were randomized, with 53 participants assigned to each treatment group. The primary endpoint was not met, as the improvement in ODI at 3 weeks did not differ significantly between groups (mean change: -9.5 ± 4.4 in the DEXA group versus -13.8 ± 4.4 in the PLACEBO group; p = 0.18). No significant differences were observed for any relevant secondary outcome at any follow-up time point. During the 6-month follow-up, 34 patients in the DEXA group and 30 patients in the PLACEBO group underwent a second, non-blinded injection of dexamethasone (ns). Lumbar surgery was performed in 10 patients in the DEXA group and nine patients in the PLACEBO group (ns). Injection-related adverse events were mild and transient but occurred more frequently in the DEXA group. CONCLUSIONS: Caudal injection of soluble dexamethasone conferred no clinical benefit over saline placebo in patients with acute sciatica. SIGNIFICANCE STATEMENT: Epidural injections are widely used worldwide for the treatment of resistant sciatica and have been extensively studied in multiple meta-analyses. However, their clinical value remains debated due to the limited methodological quality of most available studies. We conducted a methodologically rigorous randomized, placebo-controlled trial, which yielded negative results. These findings question the efficacy of caudal epidural injection of a non-particulate corticosteroid administered via a remote (sacrococcygeal) approach for disc-related sciatica. TRIAL REGISTRATION: The trial was registered under European Clinical Trials No. 2021-001571-17 and ClinicalTrials.gov identifier NCT05000658.

Adult↗

PubMed2026

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n = 15) or red light placebo (n = 15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group × time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p = 0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p = 0.065), while sleep quality significantly improved at five weeks compared to placebo (p = 0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p < 0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p = 0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged↗

PubMed2026

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans↗

PubMed2026

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult↗

PubMed2026

Catheter ablation for symptomatic atrial fibrillation (PVI-SHAM-AF): a randomised, double-blind, sham-controlled, multicentre trial.

BACKGROUND: Guidelines recommend catheter ablation for symptom relief in patients with atrial fibrillation. The aim of this trial was to ascertain whether catheter ablation improves atrial fibrillation-related quality of life more than a sham procedure. METHODS: PVI-SHAM-AF was a double-blind, multicentre, randomised trial conducted at nine study sites in Germany and Poland. Patients aged 18 years or older with symptomatic paroxysmal or persistent atrial fibrillation were randomly assigned in a 2:1 ratio to catheter ablation or a sham procedure using an automated online randomisation system with variable block sizes, stratified by trial site. The primary endpoint was the between-group difference in change from baseline to 6 months in the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score. The prespecified primary analysis was done in the intention-to-treat population and included all randomly assigned patients, with missing data handled by multiple imputation. This trial is registered with ClinicalTrials.gov (NCT05119231) and 12-month follow-up is ongoing. FINDINGS: Between Nov 12, 2021, and Nov 3, 2025, 1199 patients were invited to participate in the study and 262 patients consented and were randomly assigned: 173 patients to catheter ablation and 89 to sham. The median age was 67 years (IQR 62-73); 134 (51%) were female and 128 (49%) were male. Median follow-up was 184 days (IQR 181-191). At 6 months, the mean AFEQT summary score had increased from 61·3 (SD 20·1) to 81·1 (16·6) in the catheter ablation group and from 59·2 (19·0) to 74·9 (19·5) in the sham control group. The Hodges-Lehmann estimate of the between-group difference in change was 2·6 (95% CI -2·7 to 8·0; p=0·36). One death occurred in each group; neither was considered related to the study procedure. Serious adverse events adjudicated as related or possibly related to the study procedure occurred in ten unique patients: six patients in the catheter ablation group and four patients in the sham control group. One of these was an ischaemic stroke occurred in the sham control group. INTERPRETATION: Catheter ablation did not demonstrate superiority over a sham procedure for improving atrial fibrillation-related quality of life at 6 months. FUNDING: Helios Gesundheit (Förderung Leipziger Herzmedizin).

Humans↗

PubMed2026

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n = 12) or the sucrose group (CON; n = 11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p = 0.38) or mean interstitial glucose concentration (p = 0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p < 0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7 ± 1.9 vs. CON: 16.7 ± 4.6 mg/dL; d = 0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p < 0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans↗

PubMed2026

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24 mg single dose; MAD: 12 mg once daily (QD) for 7 days in healthy subjects) and phase IIa studies (0.75 to 6 mg once or twice daily for 4 weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24 h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5 h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12 h post-administration, with FEV1 peaking at approximately 2 h post-dose and returning to baseline levels by 12 h, which supports a twice-daily dosing regimen for the future, and peak FEV₁ improvements ranging from 186 to 272 ml across dose groups after 4 weeks of treatment. Moreover, twice-daily 3 and 6 mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult↗

PubMed2026

Nursing students' perspective of dignity: A systematic review.

AIM: This review synthesizes research on nursing students' perceptions of dignity shaped by education and clinical experiences. BACKGROUND: Respect for human dignity is central to nursing ethics. While dignity is well studied in patient care, less focus has been given to how nursing students perceive and experience dignity during their education. DESIGN: A systematic review of quantitative, qualitative, and mixed-methods studies. METHODS: A comprehensive search was conducted across the Medline, PubMed, ScienceDirect, Scopus, and Web of Science databases for English-language studies published from 2000 to 2025. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Mixed Methods Appraisal. Tool. Data were synthesized thematically. Reporting followed PRISMA guidelines. RESULTS: A total of 24 articles were included. Students viewed patient dignity as linked to respect, privacy, and autonomy. Although students had solid theoretical knowledge, they encountered institutional and professional barriers in delivering dignified care. Supportive environments and participation in decision-making enhanced their sense of dignity. Finally, educational strategies such as role-playing, simulations, and empathy exercises enhanced emotional and psychosocial awareness. CONCLUSIONS: These findings indicate that dignity is crucial in shaping nursing students' professional identity and ethical awareness throughout their education. Reinforcing ethical values and dignity in nursing education is essential for high-quality care.

Humans↗

PubMed2026

Effectiveness of passive vs. assistive robotic gait training on functional recovery and neuroplasticity post-stroke: A randomized controlled trial.

OBJECTIVE: This study seeks to compare the impacts of various robotic gait training (RAGT) modes on lower limb motor function recovery in stroke patients while exploring the corresponding neural mechanisms. DESIGN: A single-blind, randomized controlled trial. SETTING: Inpatient Rehabilitation Facility. PARTICIPANTS: Forty-eight patients aged 18-80 who had experienced their first unilateral subacute stroke accompanied by walking impairments were included. INTERVENTIONS: Participants were randomly assigned to: (1) assistive mode training, (2) passive mode training, or (3) control group receiving only traditional rehabilitation. Clinical and neurological outcomes were assessed at pre-intervention (T0), and post-2-week intervention (T1). MAIN OUTCOME MEASURES: Outcomes were evaluated using the Fugl-Meyer Assessment for Lower Extremity, Berg Balance Scale, Modified Barthel Index, the Functional Ambulatory Category, and functional near-infrared spectroscopy. RESULTS: Among the 48 patients recruited, significant time effects were observed across all groups in FMA-LE scores (p < 0.001). Notable improvements were detected in the conventional group (MD = 2.69, p＜0.01) and the passive group (MD = 3.67, p < 0.001), with the assistive mode also demonstrating a significant effect (MD = 1.79, p < 0.05). BBS scores improved across all groups; however, no significant differences were noted between the groups (p = 0.11). Similarly, MBI scores showed a significant time effect (p < 0.001), without notable group differences (p = 0.29). CONCLUSION: All training modalities effectively enhanced motor function, balance, and daily living skills in stroke patients. Distinct cortical activation and connectivity patterns were observed between training modalities, which may reflect different neuroplastic mechanisms. These preliminary neural differences may help inform personalized rehabilitation strategies, although no clinical superiority of one mode over another can be concluded from the present data.

Humans↗

PubMed2026

Pain outcomes of pediatric circumcision patients following administration of pre-operative ketorolac: A randomized clinical trial.

INTRODUCTION: Circumcision is a common surgical intervention, and pain is the most common complaint. Poorly managed pain can increase morbidity and reduce patient and parent satisfaction. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), provides analgesia and may be effective in reducing pain after circumcision in pediatric patients. STUDY OBJECTIVES: The primary objective was to determine the effect of pre-operative intravenous ketorolac versus normal saline placebo on parental perception of postoperative pain at 24 h. We also explored the effect of ketorolac on postoperative pain scores, incidence of bleeding, incidence of vomiting, and analgesic use. MATERIALS AND METHODS: A prospective, randomized, single-blinded trial was conducted at a single tertiary children's hospital. Patients aged 1-17 presenting for circumcision were included and randomized to either normal saline injectate or ketorolac (0.5 mg/kg, maximum 30 mg). Postoperative delirium and pain scores were recorded in the post-anesthetic care unit. Parents completed the parents' postoperative pain measure (PPPM) at 24 h. The CONSORT criteria and checklist were used to guide reporting of this randomized controlled trial. RESULTS: A total of 100 participants were included. 50 participants were in each group. Mean (SD) PPPM score 24 h after normal saline and ketorolac was 6.1 (3.4) and 5.5 (3.3), respectively for a mean difference of -0.55 points [95% CI: -1.9 to 0.83; p = 0.427]. The mean (95% CI) fixed effect size of ketorolac on post anesthetic care unit reported Face, Leg, Activity, Cry, Consolability score was -0.17 (-0.77 to 0.43, p = 0.585) points, while the mean (95% CI) effect size of ketorolac on numerical rating scale was -1.2 (-2.2 to -0.18, p = 0.026) points. DISCUSSION: Pre-operative intravenous ketorolac, compared to normal saline placebo, did not result in a difference in parental perception of postoperative pain at 24 h after circumcision surgery. As part of exploratory analyses, those receiving ketorolac had modestly lower mean immediate postoperative pain scores, likely not of clinical importance. Ketorolac has often been avoided due to concerns of increased bleeding risk, however it is important to consider that there is no substantial evidence to support this. This is the first study to our knowledge evaluating the effect of ketorolac in pediatric circumcision patients. While the PPPM score is a family centered outcome, it is an indirect measurement of pediatric pain. CONCLUSIONS: Pre-operative intravenous ketorolac was not associated with lower parental reported pain scores at 24 h compared to normal saline placebo after pediatric circumcision surgery. CLINICAL TRIAL REGISTRATION: NCT02973958.

Humans↗

PubMed2025

Worldwide prevalence of haemorrhoids: a systematic review and meta-analysis.

BACKGROUND: Haemorrhoidal disease (HD) is one of the most common anorectal disorders globally, significantly impacting individuals' quality of life and productivity. Despite its importance, global prevalence remains unclear due to limited population-specific studies. This study aimed to systematically assess the global prevalence of HD through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Embase, Web of Science, and Google Scholar up to March 31, 2025, without language restrictions. Studies reporting prevalence of haemorrhoids in general, clinical, or high-risk populations were included. Exclusion criteria comprised studies lacking total sample size, focusing on other anorectal conditions, or using duplicate or insufficient data. Four independent reviewers extracted and appraised study quality using the Joanna Briggs Institute tool. The primary outcome was pooled point prevalence of HD, analyzed using a random-effects model with 95% confidence intervals (CIs). The study was registered in PROSPERO (CRD420251045600). RESULTS: From 6,312 records, 150 studies (210 datasets) comprising 8,960,338 individuals were included. The global pooled point prevalence was 25.92% (95% CI: 22.62-29.22). Lifetime prevalence was 27.19% (95% CI: 14.77-39.60), and one-year prevalence was 21.65% (95% CI: 14.33-28.97). Prevalence was higher in women (27.33%, 95% CI: 21.84-32.82) than in men, and highest in the African region 28.07% (95% CI: 15.34-40.79). Invasive diagnostic methods (28.05%, 95% CI: 23.86-32.26) yielded higher prevalence estimates than non-invasive methods. Also, factors showing associations with HD in unadjusted analyses include older age, obesity, pregnancy, diabetes, family history, constipation, and hypertension. CONCLUSION: HD remains a prevalent condition globally, with minor variation across regions. The burden is consistent regardless of socioeconomic context. Diagnostic method and population characteristics influence prevalence estimates. These findings underscore the importance of targeted prevention and early intervention strategies, especially for at-risk groups.

Humans↗

PubMed2026

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine + UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4 mg/day, 16 mg/day) for 8 weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC + UDS and cocaine + UDS during treatment. RESULTS: Participants (n = 301) averaged 46 (SD = 8.64) years of age, were majority male (78.41 %), non-Hispanic (89.70 %), and African American (66.45 %). GEE results indicated that patients who submitted THC + UDS had significantly higher odds of submitting cocaine + UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR = 1.47, 95 % CI = 1.21-1.79, p = 0.00). Time (OR = 0.9998, 95 % CI: 0.9997, 0.9999, p = 0.018) and the covariate of sex assigned at birth (OR = 1.77, 95 % CI = 1.13-2.77, p = 0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine + UDS over time for all patients and 77 % higher odds of submitting cocaine + UDS for females. CONCLUSION: THC + UDS was associated with increased odds of submitting a cocaine + UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans↗