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Randomized controlled trials: explore 798 source-linked works published from 2025 to 2026, with original documents and citations.

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Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76&#xa0;years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0&#xa0;&#xb1;&#xa0;31.9 vs. 95.0&#xa0;&#xb1;&#xa0;25.3&#xa0;min/week, p&#xa0;=&#xa0;.003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p&#xa0;=&#xa0;.069). Depressive symptom severity decreased over time in both groups (p&#xa0;<&#xa0;.001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p&#xa0;<&#xa0;.001), without group differences (6MWT: MD -1.08&#xa0;m, 95% CI -20.04 to 17.89; FLX: MD 5.69&#xa0;mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

Humans

A hybrid effectiveness-implementation trial to integrate precision skin cancer risk feedback in federally qualified health centers.

BACKGROUND: Skin cancers are the most common type of cancer in the United States, occur in all segments of the population, and are preventable. Our previous research with primary care patients' demonstrated interest in and efficacy of a precision prevention intervention providing feedback on MC1R risk level (higher versus average) in combination with prevention education materials relative to a standard educational intervention. Our current study is a hybrid type 1 effectiveness-implementation trial deployed at six federally-qualified health centers. This paper presents the study protocol. METHODS: A community advisory panel will guide development of study materials and measures. Staff training at each clinic will be completed in-person. Patients will be approached and screened in-person. Those completing genetic testing and the baseline survey will be randomized to the precision versus standard intervention for each risk level with a target sample size of 286 for each combination. Primary outcomes of effectiveness, assessed at 6 and 12&#xa0;months, include a tanning score (5 items assessing intentional and unintentional tanning), number of sunburns, conduct of a skin self-examination, and electronic health record documentation of clinician-patient communication about skin cancer prevention. Effectiveness comparisons will focus on the precision relative to the standard intervention among higher risk participants. Implementation data will be collected to identify barriers and facilitators. RESULTS: Effectiveness and implementation outcomes will be evaluated following study completion. CONCLUSIONS: Results will guide subsequent scale-up of the precision intervention, including modifications of the intervention as well as methods for implementation. CLINICAL TRIALS IDENTIFIER: NCT07222995.

Humans

Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged&#xa0;&#x2265;&#xa0;75&#xa0;years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30&#xa0;mg/m2) or weekly carboplatin (area under the curve, 2&#xa0;mg&#xb7;min/mL) plus nab-paclitaxel (30&#xa0;mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1&#xa0;months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p&#xa0;=&#xa0;0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6&#xa0;weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p&#xa0;=&#xa0;0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 &#xb1; 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 &#xb1; 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans

Effect of a 6-month low-carbohydrate diet on the circulating fatty acid composition in patients with type 2 diabetes: a secondary analysis of an open-label randomized controlled trial.

BACKGROUND: Circulating fatty acid profiles are linked to cardiovascular disease risk and mortality. Short-term interventions suggest that low-carbohydrate diets (LCDs) promote cardioprotective shifts in circulating fatty acids in obesity. OBJECTIVES: We examined whether a 6-mo, non-calorie-restricted, LCD high in fat similarly improves circulating fatty acid composition in adults with type 2 diabetes. METHODS: In an open-label, randomized, controlled trial, 71 individuals with type 2 diabetes were randomly assigned 2:1 to an LCD [maximum of 20 E% (energy per cent) carbohydrates] or a control diet (50-60 E% carbohydrates) for 6 mo with no restriction in energy intake. The prespecified secondary outcomes were the mean difference in change between groups in serum phospholipid fatty acids in weight percentage (wt%) measured by gas chromatography and reported as 95% confidence intervals (CIs) and significance adjusted for multiple comparisons (q value). RESULTS: LCD reduced total saturated [-0.6 (CI: -0.9, -0.2)] and monounsaturated fatty acids [-0.9 (CI: -1.4, -0.3)] and increased total polyunsaturated fatty acids [1.3 (CI: 0.6, 2.0)] compared with the control diet (all q < 0.05). Importantly, LCD reduced palmitoleic acid (16:1n-7) [-0.13 (CI: -0.21, -0.06)], a marker of de novo lipogenesis, by 23% and dihomo-&#x3b3;-linolenic acid (20:3n-6) [-0.38 (CI: -0.67, -0.09)] by 12%, whereas it increased arachidonic acid (20:4n-6) [1.1 (CI: 0.3, 2.0)] by 9% compared with the control diet (all q < 0.05). Moreover, the LCD improved estimated desaturase activities by lowering stearoyl-coenzyme A desaturase 1 [-0.5 (CI: -0.7, -0.2)] and &#x394;6 desaturase [-0.6 (CI: -0.9, -0.2)] and increasing &#x394;5 desaturase [1.05 (CI: 0.3, 1.79)] activities, respectively (all q < 0.01). These changes occurred despite a 2.6-fold higher intake of saturated fatty acids in the LCD group. CONCLUSIONS: A 6-mo, non-calorie-restricted LCD modified the circulating composition of fatty acids in adults with type 2 diabetes in a manner consistent with a potentially favorable cardioprotective profile. This trial was registered at www. CLINICALTRIALS: gov as NCT03068078.

Humans

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide&#xae;) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N&#x202f;=&#x202f;663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide&#xae;. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide&#xae; significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p&#x202f;<&#x202f;0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p&#x202f;<&#x202f;0.001). The direct effect on AQoL-6D was non-significant (p&#x202f;=&#x202f;0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n&#x202f;=&#x202f;563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p&#x202f;=&#x202f;0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans

Outcomes and Associated Prognostic Factors for Orthograde Canal Obturation Using Ortho MTA III: A Randomised Prospective Clinical Trial.

AIM: To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY: Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n&#x2009;=&#x2009;120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI&#x2009;&#x2265;&#x2009;3) were randomly assigned to two groups (n&#x2009;=&#x2009;60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12&#x2009;months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p&#x2009;<&#x2009;0.05). RESULTS: The median recall period was 30&#x2009;months (14-48&#x2009;months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p&#x2009;>&#x2009;0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR&#x2009;=&#x2009;5.735, 95% CI: 1.286-25.577, p&#x2009;=&#x2009;0.022), periapical lesion size (OR&#x2009;=&#x2009;6.596, 95% CI: 1.397-31.138, p&#x2009;=&#x2009;0.017) and PAI score (OR&#x2009;=&#x2009;2.081, 95% CI: 1.047-4.136, p&#x2009;=&#x2009;0.036) were significant predictors of treatment failure. CONCLUSIONS: Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION: cris.nih.go.kr registration number: KCT00099939.

Humans

Memantine Augmentation for Obsessive-Compulsive Symptoms in Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Obsessive-compulsive symptoms are frequently observed in patients with bipolar disorder and present a significant therapeutic challenge. This study evaluated the efficacy and safety of memantine as an adjunctive therapy for obsessive-compulsive disorder in patients with bipolar disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, 46 patients with bipolar disorder and obsessive-compulsive disorder, stabilized on quetiapine and lithium, were randomly assigned to receive either memantine (n = 23) or placebo (n = 23) for 6 weeks. RESULTS: The memantine group showed a significant reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with the placebo group (Cohen d = 1.57 vs 0.42, P < 0.001). Nausea was the most common side effect, but overall adverse effects were minimal. CONCLUSION: Memantine appears to be a safe and effective adjunctive treatment for obsessive-compulsive disorder in patients with bipolar disorder, warranting further investigation.

Humans

BRAIN-Diabetes: Acceptability of an adapted FINGER multidomain intervention among adults living with type 2 diabetes in rural border regions across the island of Ireland.

BackgroundIndividuals with type 2 diabetes mellitus (T2DM) face increased risk of cognitive decline and dementia. Multidomain lifestyle interventions offer a non-pharmacological strategy to support brain health in this high-risk group.ObjectiveThis study examined the acceptability of a culturally adapted FINGER-based intervention among adults living with T2DM in rural border regions of Ireland (BRAIN-Diabetes Trial).MethodsA 6-month pilot randomized controlled trial was conducted. The intervention group received a multidomain program targeting diet, physical activity, and computerized cognitive training (CCT). The control group received standard care. Acceptability was assessed using questionnaires (all participants) and semi-structured interviews (intervention participants). Quantitative data were analyzed descriptively and qualitative data using template analysis, guided by four a-priori themes: trial participation and engagement, dietary behavior change, exercise behavior change, and CCT behavior change.ResultsQuestionnaire data (intervention: n&#x2009;=&#x2009;28; control: n&#x2009;=&#x2009;36) indicated high overall acceptability. Dietary and exercise components were rated most positively, while CCT component was less well received. Interviews (n&#x2009;=&#x2009;25) highlighted facilitators to trial engagement, including perceived health improvements, and social connection, with time constraints and limited personalization as barriers. Dietary change was supported by tailored guidance but hindered by cost and availability. Facilitators for exercise included accessible resources and perceived benefits, with barriers including competing priorities. CCT engagement was mixed, with challenges including digital access and repetitiveness.ConclusionsThe Brain-Diabetes intervention was acceptable and feasible among adults with T2DM. Personalized support and accessible resources were key to engagement. Future work should refine delivery to enhance scalability and long-term adherence among high-risk groups.

Humans

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

Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.

Humans

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged &#x2265;18 years) with type 2 diabetes (HbA1c &#x2265;8&#xb7;0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3&#xb7;9-5&#xb7;0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9&#xb7;57% for IcoSema and 9&#xb7;50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3&#xb7;32 vs -2&#xb7;44 percentage points; estimated treatment difference [ETD] -0&#xb7;88 percentage points [95% CI -1&#xb7;12 to -0&#xb7;63]), confirming superiority of IcoSema (p<0&#xb7;001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0&#xb7;79 vs 3&#xb7;81 kg; ETD -4&#xb7;61 kg [95% CI -5&#xb7;46 to -3&#xb7;75]), confirming superiority of IcoSema (p<0&#xb7;001). Rate of combined clinically significant (blood glucose <3&#xb7;0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0&#xb7;29 vs 0&#xb7;59 episodes per person-year of exposure; estimated rate ratio 0&#xb7;56 [95% CI 0&#xb7;32 to 0&#xb7;97]; p=0&#xb7;04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19&#xa0;weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19&#xa0;weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Humans

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased &#x3bc;-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based&#xa0;patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety&#x2011;four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5&#x2009;mg, PCIA 0.55&#x2009;mg/kg) or sufentanil group (loading dose 10&#x2009;&#x3bc;g, PCIA 3&#x2009;&#x3bc;g/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9&#x2009;&#xb1;&#x2009;3.1 versus 177.5&#x2009;&#xb1;&#x2009;3.9, p&#x2009;<&#x2009;0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3&#x2009;days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p&#x2009;>&#x2009;0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p&#x2009;=&#x2009;0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N&#xa0;=&#xa0;703) and aggregated data from the RAINBOW-Asia study (N&#xa0;=&#xa0;440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO&#xa0;+&#xa0;PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size&#xa0;=&#xa0;564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq&#xa0;+&#xa0;PTX significantly improved PFS compared with RAM&#xa0;+&#xa0;PTX (HR: 0.70; 95% CI: 0.51-0.96; p&#xa0;=&#xa0;0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18&#xa0;months at 20&#xa0;months (95% CI: 0.08-2.27; p&#xa0;=&#xa0;0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p&#xa0;=&#xa0;0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p&#xa0;<&#xa0;0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq&#xa0;+&#xa0;PTX (HR: 0.40, 95% CI: 0.32-0.50; p&#xa0;<&#xa0;0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p&#xa0;<&#xa0;0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p&#xa0;<&#xa0;0.05). For grade &#x2265;3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq&#xa0;+&#xa0;PTX than with RAM&#xa0;+&#xa0;PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p&#xa0;<&#xa0;0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq&#xa0;+&#xa0;PTX may be more effective than RAM&#xa0;+&#xa0;PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq&#xa0;+&#xa0;PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult

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&#x2009;<&#x2009;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&#x2009;<&#x2009;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

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans
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Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.2026-08-12PMID 42583940pubmed
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.2026-08-12PMID 42584170pubmed
Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.2026-08-12PMID 42584383pubmed

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