Efficacy of a portable BLT device on sleep and depressive symptoms in major depressive disorder: A double-blind randomized study.

Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial.

Giardiasis is a common protozoal infection in cats, often treated with nitroimidazole derivatives such as metronidazole and secnidazole. However, there are concerns about resistance to nitroimidazoles and their adverse effects. Recent in vitro studies suggest that omeprazole, a proton pump inhibitor, exhibits anti-giardial effects by inhibiting giardial triosephosphate isomerase. No clinical studies have evaluated its efficacy in naturally infected cats. This study aimed to assess and compare the anti-giardial efficacy of omeprazole, metronidazole, and secnidazole in cats naturally infected with Giardia duodenalis, based on faecal cyst shedding and clinical parameters. Forty-eight naturally infected cats were randomly assigned to four groups: omeprazole (1mg/kg/day for 7 days), metronidazole (25mg/kg twice daily for 7 days), secnidazole (30mg/kg single dose), and placebo. Faecal cyst shedding was evaluated using the zinc sulphate flotation technique on days 0, 7 and 14. Faecal consistency was scored daily, and haematological parameters were assessed on days 0, 7 and 14. By day 7, faecal cyst positivity was 50% in both the omeprazole and metronidazole groups, 58.3% in the secnidazole group, and 83.3% in the placebo group. The reduction observed in the omeprazole and metronidazole groups was statistically significant compared with the placebo (p < 0.05). By day 14, cyst positivity further decreased to 33.3% (omeprazole), 41.7% (metronidazole), and 50% (secnidazole), with omeprazole showing the lowest positivity rate among the treatments. Faecal scores improved significantly earlier in the omeprazole and metronidazole groups compared with secnidazole and placebo (p < 0.05). Omeprazole demonstrated promising anti-giardial efficacy, with reductions in cyst shedding and improvements in faecal consistency comparable to metronidazole. These findings suggest that omeprazole may serve as a potential alternative treatment option for feline giardiasis.

Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program. In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024. Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months. Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.

Effect of Persian traditional medicine based herbal vaginal gel in vaginal atrophy.

Shexiang Baoxin pill in patients with stable coronary artery disease and reduced eGFR: Subgroup analysis of phase IV randomized trial.

Stromal Keratitis in the Zoster Eye Disease Study: Lessons Learned.

Early maternal DHA supplementation fails to modify clinical phenotypes associated with impaired placentation: A randomized, double-blind, placebo-controlled trial (DEEPER trial).

Patients with persistent chylomicronaemia (PC) are at high risk for acute pancreatitis (AP). Plozasiran, a small interfering RNA, reduces hepatic apolipoprotein C-III, significantly lowers triglyceride (TG) levels and reduces risk of AP. To assess the effect of plozasiran on recurrent AP in patients with severe hypertriglyceridemia and history of pancreatitis. PALISADE was an international, multicentre, double-blind, placebo-controlled trial. Patients with extreme hypertriglyceridemia were randomised 2:1:2:1 to receive subcutaneous plozasiran (25- or 50-mg) or volume-matched placebo, quarterly for 12 months. This post hoc analysis involved participants with a history of at least one prior episode of AP. Primary and alpha-controlled secondary endpoints included the incidence of expert-adjudicated AP and pancreatitis-related hospitalisations. The analysis included 67 participants with median baseline TG > 22.6 mmol/L (2000 mg/dL). Plozasiran-treated participants experienced a > 75% reduction in median TG, with median levels falling below 5.65 mmol/L (500 mg/dL). Incident AP occurred in 5 of 22 in the placebo group versus 2 of 45 in the pooled plozasiran group, representing an 83% (HR, 0.17; 95% CI [0.03, 0.87], p < 0.017) reduction in risk for recurrent AP in the plozasiran group. AP severity, hospitalisation rates for abdominal pain, and length of hospital stay were lower in the plozasiran group. Plozasiran significantly lowered circulating TG levels, with substantial reduction in recurrent AP for participants with very severe hypertriglyceridemia and history of AP. Plozasiran is the first therapy to demonstrate a statistically significant reduction in recurrent AP in a prospective randomised trial of patients with familial chylomicronaemia syndrome (FCS). Clinicaltrials.gov identifier: NCT05089084.

Augmentation of clozapine with dextromethorphan in treatment-resistant schizophrenia: A randomized, group sequential adaptive design, controlled clinical trial.

BACKGROUND Postoperative delirium (POD) is common in older surgical patients and increases morbidity and mortality. Oxiracetam, a nootropic agent, has not been evaluated for POD prevention. AIM To assess the efficacy of perioperative oxiracetam in reducing POD incidence. METHODS In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 173 elderly patients (age ≥ 65 years) scheduled for elective laparoscopic gastrointestinal surgery were enrolled and randomly assigned to the oxiracetam group (OG, n = 82) or the normal saline control group (SG, n = 91). The OG received intravenous Oxiracetam (4.0 g/day) from 30 minutes before anesthesia induction and for 6 consecutive days postoperatively, while the SG received an equal volume of normal saline. The primary outcome was the incidence of POD within 7 days postoperatively. Secondary outcomes included changes in perioperative cognitive function and dynamic levels of a panel of inflammatory factors. RESULTS POD incidence was lower in the OG [13.4% (11/82)] than in the placebo group [28.6% (26/91)] (P &lt; 0.01). Oxiracetam remained an independent protective factor after multivariate adjustment (adjusted odds ratio = 0.12, 95% confidence interval: 0.04-0.36, P &lt; 0.01). The OG also showed better preservation of cognitive function (Montreal Cognitive Assessment score). Inflammatory profiling revealed a distinct immunomodulatory pattern: Oxiracetam attenuated postoperative rises in interleukin (IL)-6, IL-8, and IL-1β while enhancing levels of IL-10 and IL-2. CONCLUSION Perioperative oxiracetam significantly reduces POD risk and preserves cognitive function in elderly surgical patients, potentially through a multi-target immunomodulatory mechanism rather than simple anti-inflammation.

Tralokinumab is approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 12years. Here, we examined clinical laboratory parameters in adolescents with moderate-to-severe AD who were treated with tralokinumab for up to 1 year. This analysis assessed data from adolescents in the ECZTRA 6 (NCT03526861) phase 3 trial initiated on tralokinumab (150mg or 300mg) or placebo for 16weeks. Additionally, pooled data from tralokinumab-treated patients who continued treatment beyond Week 16 were analyzed regardless of Week 16 response or tralokinumab dosing regimen (i.e., blinded 150mg or 300mg every 2 or 4weeks or open-label tralokinumab 300mg plus optional topical corticosteroids or calcineurin inhibitors). Median levels of most laboratory parameters were within respective reference ranges at baseline, Week 16, and Week 52, with comparable values across treatment groups at baseline and Week 16. Baseline levels for eosinophils and immunoglobulin E (IgE) were elevated across treatment groups. Few patients shifted from normal baseline eosinophil levels to moderate eosinophilia by Week 16 (150mg, 3.4%; 300mg, 2.0%; placebo, 0.0%). In tralokinumab-treated patients who continued treatment beyond Week 16, median eosinophil levels at Week 52 (0.48 × 109/L) were similar to baseline levels (P = 0.70). No adverse events of "eosinophilia" or "eosinophil count increased" were reported. IgE levels decreased from baseline to Week 16 in the tralokinumab groups but increased in the placebo group (median change: 150mg, -186IU/mL; 300mg, -105IU/mL; placebo: + 41IU/mL). Among tralokinumab-treated patients, median IgE was significantly lower at Week 52 (1183IU/mL) versus baseline (P < 0.01). Similar to previous findings in adults, tralokinumab treatment for up to 1 year did not have any clinically relevant impact on laboratory parameters in adolescents with moderate-to-severe AD, supporting its use without required laboratory monitoring. ClinicalTrials.gov identifier, NCT03526861 (ECZTRA 6); study start date: June 19, 2018; primary completion date: April 15, 2020; study completion date: March 16, 2021.

Anxiety is a prevalent non-motor symptom of Parkinson's disease (PD), yet treatment options remain limited. This randomized, double-blind, placebo-controlled trial evaluated the effects of a 12-week probiotic supplement containing nine bacterial strains (Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, and Lactococcus lactis W19 and W58) on anxiety symptoms in 61 individuals with PD and clinically significant anxiety. Both the probiotic (n = 30) and placebo (n = 31) groups showed significant within-group improvements on the Parkinson Anxiety Scale, with no significant between-group differences. The probiotic group showed a statistically significant improvement on the Montreal Cognitive Assessment compared with placebo (adjusted mean difference of 1.1 points; 95% confidence interval: 0.04-2.1; p = 0.043). No treatment effects were seen on other secondary outcomes, including depression, constipation, or motor symptoms. No significant between-group differences in gut microbiota composition or systemic inflammatory markers were observed. While the multi-strain probiotic did not reduce anxiety more than placebo, its potential cognitive effects warrant further investigation in larger trials. This trial was registered on ClinicalTrials.gov (NCT03968133) on May 28, 2019.

The American Diabetes Association recommends achieving treatment goals (glycated haemoglobin ≤ 53 mmol/mol [7.0%], blood pressure < 130/80 mmHg, low-density lipoprotein cholesterol < 1.81 mmol/L and use of sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists), to reduce cardiovascular and kidney complications in people with chronic kidney disease and type 2 diabetes. This exploratory study assessed whether treatment effects of finerenone versus placebo were modified by the number of treatment goals met at baseline. FIDELITY, a prespecified pooled analysis, combined participant-level data from the randomized, double-blind, multicentre phase III FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) trials. Participants with type 2 diabetes and chronic kidney disease were randomized 1:1 to finerenone or placebo. Composite cardiovascular and kidney outcomes, hospitalization for heart failure or cardiovascular death, hospitalization for heart failure and treatment-emergent adverse events were assessed by subgroups based on the number of treatment goals achieved. At baseline, 29%, 40%, 24% and 7% of participants had met 0, 1, 2 and ≥ 3 treatment goals, respectively. Those with more treatment goals met had fewer composite cardiovascular outcomes (events per 100 patient-years in the placebo group: 6.0, 5.1, 4.3 and 3.5 for 0, 1, 2 and ≥ 3 treatment goals, respectively). Similar patterns were observed for other outcomes. There was no heterogeneity in the effect of finerenone versus placebo on outcomes between subgroups. The safety profile of finerenone (vs. placebo) was similar across subgroups. Finerenone demonstrated treatment benefits in people with chronic kidney disease and type 2 diabetes, irrespective of treatment goals achieved at baseline.

Introduction Limited longitudinal data exist regarding functional and patient-reported outcome (PRO) in symptomatic hemorrhage (SH) from cerebral cavernous malformation (CCM) enrolled in clinical trials. Methods We assessed functional outcome using the modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS), and PRO using European Quality of Life 5-dimension and visual-analogue scale (EQ-5D-3L and VAS) and PRO-measurement information system (PROMIS-29) at baseline, 1 year, and 2 years in patients randomized to atorvastatin and placebo in the prospective, double-blinded Atorvastatin Treatment of Cavernous Angioma Symptomatic Hemorrhage-Exploratory Proof-of-Concept (AT-CASH-EPOC) trial. Sensitivity analyses compared score change in cases with and without prospective SH and in those with or without a ≥6% increase in lesional iron content on quantitative susceptibility mapping (QSM), consistent with occult bleeding. Results Of 64 patients with paired QSM and outcome data, baseline characteristics were similar; baseline mRS distributions differed between groups but were similar at Years 1 and 2. No significant differences in functional and PRO appeared between the atorvastatin and placebo groups. While there was a decline in PROMIS-29 sleep disturbance (57.1% SH vs 7.7% no SH; p<0.01), fatigue (57.1% SH vs 21.2% no SH; p=0.06) and social role (44.4% SH vs 16% no SH; p=0.07) domains with prospective SH over 2 years, the small numbers of patients limit the generalizability. These functional and PRO declines were generally specific but poorly sensitive for identifying SH or occult bleeding. Discussion Despite more frequently reported side-effects with atorvastatin in the trial, there were no significant differences in functional or PRO. Functional and PRO decline were highly specific but poorly sensitive for identifying prospective SH or occult bleeding.

The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously reported as an enhancer of Parabacteroides, improves defecation frequency as the primary outcome. It also assessed holistic gut health and underlying microbiota-based mechanisms. In this randomized, double-blind, placebo-controlled trial, 50 healthy Japanese participants with a defecation frequency of five or fewer times per week were enrolled. The mean (±SE) weekly defecation frequency in the GLO group was 3.2 ± 0.2 at baseline, increasing to 5.8 ± 0.6 at week 4, whereas that in the placebo group was 3.4 ± 0.3 at baseline, increasing to 4.4 ± 0.3 at week 4. The time-dependent weekly defecation frequency was significantly higher in the GLO group than in the placebo group (p = 0.029). Changes in the relative abundance of the genus Parabacteroides significantly increased in the GLO group compared with in the placebo group. Changes in fecal bile acid composition were also confirmed in the GLO group compared with the placebo group, which was thought to be due to the unique features of Parabacteroides. Furthermore, changes in alpha diversity indices were significantly higher in the GLO group than in the placebo group (Simpson, p = 0.041; Pielou, p = 0.022). Additional analysis demonstrated that the increase in alpha diversity in the GLO group was significantly correlated with the increase in the relative abundance of Parabacteroides (p = 0.006), which tended to be associated with decreases in serum gamma-glutamyltransferase (p = 0.089) and serum triglyceride (p = 0.075) levels. These data suggest that GLO intake improved defecation status, selectively increased Parabacteroides, and harmonized the gut environment.

BackgroundBlood-pressure reduction is the only proven treatment to prevent stroke. Whether a single pill that combines three antihypertensive drugs at low doses, in addition to standard antihypertensive treatment, can lower blood pressure more than standard care alone and reduce the risk of recurrent stroke after intracerebral hemorrhage is uncertain.MethodsWe conducted a multinational, double-blind, randomized, placebo-controlled trial involving patients with a history of intracerebral hemorrhage. Patients were eligible for the trial if they had a systolic blood pressure of 130 to 160 mm Hg at baseline and were in clinically stable condition. After a 2-week active run-in phase during which all the patients received a once-daily pill containing three antihypertensive agents at low doses (telmisartan at 20 mg, amlodipine at 2.5 mg, and indapamide at 1.25 mg; the triple pill), the patients were randomly assigned to continue receiving the triple pill or to receive matching placebo. The primary outcome was the first recurrent stroke. Secondary outcomes included blood-pressure control, major cardiovascular events, death from cardiovascular causes, and safety.ResultsOf 1670 patients who underwent randomization, 833 were assigned to receive the triple pill and 837 to receive placebo. The mean age of the patients was 58 years. At a median follow-up of 2.5 years, recurrent stroke had occurred in 38 patients (4.6%) in the triple-pill group and 62 (7.4%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.41 to 0.92; P=0.02). The mean systolic blood pressure during follow-up was 127 mm Hg and 138 mm Hg, respectively. The incidence of major cardiovascular events was lower with the triple pill than with placebo (6.6% vs. 9.8%; P=0.04). Serious adverse events occurred in 23.2% of the patients in the triple-pill group and 26.0% of those in the placebo group. Early discontinuation of the trial regimen due to an adverse event occurred in 13.6% and 6.0%, respectively. The most common adverse event leading to discontinuation was an increase of 20% or more in the serum creatinine level.ConclusionsAmong patients with intracerebral hemorrhage, treatment with a combination of three low-dose antihypertensive agents in a single pill, in addition to standard care, was associated with a lower incidence of recurrent stroke and major cardiovascular events than placebo. (Funded by the National Health and Medical Research Council of Australia and the Brazilian Ministry of Health; TRIDENT ClinicalTrials.gov number, NCT02699645; Australian New Zealand Clinical Trials Registry number, ACTRN12616000327482.)

Cervicogenic headache (CeH) is a common secondary headache type arising from a disorder or lesion of the cervical spine and its soft tissues. This study aimed to evaluate the effect of osteopathic manipulative treatment (OMT) in patients with CeH. A total of 413 patients with CeH were treated by 30 osteopaths and allocated by block randomization to an OMT group (n=226) or a placebo group (n=187). The primary outcome was the Neck Disability Index (NDI) score; the secondary outcome was upper cervical rotation measured with the Flexion-Rotation Test (FRT) utilizing a cervical range of motion (CROM) device. Patients received two treatments over 4weeks (standardized sham vs. findings-based OMT). Two-factor analyses of variance (ANOVAs) were utilized for the NDI score and CROM_FRT_sum, and Cohen's d was calculated for all clinical outcomes. A severity-based subgroup analysis of the NDI was performed. The NDI improved by 5.9 points (11.8 %) in the OMT group and by 2.5 points (5.1 %) in the placebo group from baseline to final follow-up. Only the OMT group reached the established minimal clinically important difference (MCID) of 5.5 points. Effect sizes in the OMT group were large (Cohen's d=0.74 short-term and 0.87 at follow-up). OMT reduces pain and improves functional disability in patients with CeH in a clinically meaningful way. Patients with higher initial NDI scores benefit more from OMT than others.

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder in which early bioenergetic dysfunction is increasingly implicated in its pathogenesis. Transcranial photobiomodulation (tPBM), a non-invasive neuromodulation using near-infrared light, has shown promise in improving cerebral metabolism and cognitive function.ObjectiveTo assess the safety and efficacy of a home-administered tPBM intervention in individuals with mild cognitive impairment (MCI) due to AD.MethodsIn this randomized clinical trial, 80 participants meeting the NIA-AA criteria for MCI due to AD were recruited. Participants self-administered a tPBM device emitting 808 nm near-infrared light over the bilateral dorsolateral prefrontal cortex, six times weekly for 12 weeks. The primary outcome was the change in MoCA-K score from baseline to week 13. Secondary outcomes included K-MMSE2, CERAD-K, and GDepS scores.ResultsActive tPBM significantly improved cognitive performance compared with the placebo. Mean MoCA-K scores increased by 3.87 ± 2.51 points in the active group versus a 0.74 ± 2.85 point decline in the placebo group (p < 0.001). K-MMSE2 scores improved significantly (p < 0.001). CERAD-K showed a significant between-group difference at week 13 (p < 0.001), while GDepS scores remained unchanged. No device-related adverse events occurred, and adherence to home-based treatment was high.Conclusions12 weeks of home-administered tPBM safely and significantly improved cognitive function in individuals with MCI due to AD. The observed benefits are consistent with enhanced mitochondrial metabolism, cerebral perfusion, and synaptic efficiency. These findings support tPBM as a promising, non-pharmacological treatment for MCI due to AD and as a preventative strategy against AD.Trial RegistrationKorean Clinical Research Information Service (CRiS), https://cris.nih.go.kr, KCT0011155.

Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity. We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the Days to Recovery Scale through Day 60 (DRS-60), analyzed using a Van Elteren test. From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (p=0.19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; p<0.001). There was no difference in secondary clinical outcomes or pre-specified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively. Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness severity in the Omicron era compared to earlier periods in the COVID-19 pandemic, and high use of remdesivir and corticosteroids, may have contributed to the lack of clinical benefit.