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PubMed2026

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 = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + 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 = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p < 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 + PTX (HR: 0.40, 95% CI: 0.32-0.50; p < 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p < 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p < 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p < 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 + PTX may be more effective than RAM + 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 + PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult↗

PubMed2026

Effects of comprehensive oral care on nasogastric tube removal in long-term care residents with dysphagia: A multi-center randomized controlled trial.

Oral care is essential for residents in long-term care (LTC) facilities to reduce complications such as aspiration pneumonia. While routine oral hygiene is standard practice, comprehensive oral care (COC)-which includes facial and intraoral muscle massage, salivary gland stimulation, and oral moisturization-may further enhance swallowing function. However, evidence linking COC directly to nasogastric (NG) tube removal remains limited. This study evaluated the effectiveness of COC in facilitating NG tube removal and improving swallowing function among LTC residents with dysphagia. A multicenter, open-label randomized controlled trial was conducted across eight LTC facilities. The intervention group (n = 40) received daily one-on-one COC sessions lasting 30-40 min, while the control group (n = 37) received routine oral hygiene. Participants were followed for six months, with outcomes including NG tube removal, swallowing function, body weight, and pneumonia incidence. At six months, the COC group demonstrated a significantly higher NG tube removal rate, with eight participants achieving full oral intake (p = 0.005). Functional Oral Intake Scale scores were also significantly higher in the intervention group (p = 0.005). Time to NG tube removal ranged from 17 to 182 days. Under intention-to-treat principles, the NG tube removal rate remained significantly higher in the COC group (16.7%vs. 0%, p = 0.005). Competing risks analysis using the Aalen-Johansen estimator confirmed a 6-month cumulative incidence of NG tube removal of 14.6% in the COC group versus 0% in the control group (Gray's test: p = 0.005), with no significant between-group difference in mortality (p = 0.500). No significant differences were observed in body weight change or pneumonia incidence between groups. Among participants who successfully discontinued NG tube use, dementia was the most common underlying condition. These findings suggest that daily one-on-one COC is a feasible intervention in LTC settings and may improve swallowing function while facilitating NG tube removal in residents with dysphagia.

Humans↗

PubMed2026

The effect of monetary versus point-based rewards on effort-cost decision making in individuals at clinical high risk for psychosis.

OBJECTIVE: The dissemination of inexpensive computerized behavioral tasks indexing amotivation may enhance the assessment of clinical high risk (CHR) across settings. However, the impact of varying reward value in such tasks is unclear. If point-based rewards engage participants, this could improve the scalability of computerized assessments. We tested how point-based rewards versus money impacted effort-cost decision-making in CHR individuals. We further assessed how negative symptom severity and household income interacted with reward-type to impact behavior. METHODS: Participants completed the Effort Expenditure for Reward Task (EEfRT). Participants were randomly assigned to receive either money or points for their performance during the EEfRT. Data from a large sample of CHR (N = 233) individuals and healthy controls (HC; N = 157) were collected. RESULTS: Across diagnostic groups, we observed heightened effort expenditure when money was used as a reward (b = 0.13, p = 0.018). We did not find an interaction of CHR status (b = 0.07, p = 0.845) or negative symptoms (b = 0.01, p = 0.429) with reward-type. Within CHR individuals, heightened negative symptom severity was associated with reduced expended effort (b = -0.03, p = 0.016), regardless of reward type. In an exploratory analysis, we found that individuals in the money condition with relatively high household income expended less effort during high reward, high probability trials (b = -0.24, p = 0.046). CONCLUSIONS: Across CHR and HC individuals, individuals pursuing money expended greater effort. While we did not find a group by reward type interaction, CHR individuals with heightened negative symptom severity expended less effort across trials, replicating prior work. Present findings support further study of point-based rewards in tasks indexing amotivation.

Humans↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

PubMed2026

Evaluating a culturally adapted question prompt list to improve end-of-life communication among indonesian migrant caregivers: A randomized controlled trial with qualitative insights.

OBJECTIVE: Indonesian caregivers serve as essential providers of end-of-life (EOL) care in Taiwan. But often face communication challenges due to language, cultural, and hierarchical barriers. This study evaluated the effectiveness of a culturally adapted Question Prompt List (QPL). METHODS: This study employed a two-arm randomized controlled trial design supplemented with qualitative interviews. The study was conducted in a hospice ward and home care setting within a medical center in Taiwan. A total of sixty Indonesian caregivers were recruited and randomly assigned to either the intervention group (n = 30) or the control group (n = 30). The intervention group received routine end-of-life (EOL) education along with a culturally adapted Question Prompt List (QPL), which consisted of 37 items covering domains including the dying process, emotional support, communication, symptom management, and care decision-making. The control group received routine EOL education. Outcome measures included caregiving preparedness, communication self-efficacy, satisfaction, and question-asking behavior. In addition, semi-structured interviews were conducted with eight participants, and the data were analyzed using thematic content analysis. RESULTS: Analysis of covariance revealed no statistically significant between-group differences in caregiving preparedness (F = 1.58, p = .215 [-0.41, 0.44]) or communication selfefficacy (F = 0.83, p = .366 [-0.44, 0.79]). However, communication satisfaction was significantly higher in the intervention group (F = 4.19, p < .05 [0.04, 0.44]). The number of questions asked was also significantly higher in the intervention group (t = -4.35, p < .001 [-5.41, -1.98]). Thematic analysis of qualitative data identified 4 themes and 14 subthemes, illustrating how the QPL reduced anxiety, clarified care needs, and improved confidence. CONCLUSIONS: A culturally adapted QPL can enhance communication engagement and satisfaction among migrant caregivers. PRACTICE IMPLICATIONS: Integrating culturally tailored QPLs into caregiver education and palliative care practice may promote more inclusive and effective communication.

Humans↗

PubMed2026

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans↗

PubMed2026

Evaluating the Effectiveness of an Intimate Partner Violence Training Intervention on Healthcare Providers' Preparedness, Knowledge, and Experiences: A Mixed-Methods Study From Nepal.

Intimate partner violence (IPV) places a considerable burden on health systems globally due to its profound effects on women's health, and women who experience violence often seek care from healthcare providers (HCPs). However, HCPs often lack the preparedness and confidence to respond effectively, resulting in missed opportunities for support and care. This study, conducted in Nepal, evaluated the impact of structured training intervention on HCPs' perceived preparedness, knowledge, and attitudes toward managing IPV and its mental health consequences, including self-harm and suicidal tendencies. The study was nested within a larger cluster randomized trial. A convergent mixed-methods design with a comparison group was conducted among 46 female HCPs in all public hospitals (except one) and 17 primary healthcare centers in Madhesh Province, Nepal. The intervention group (n = 24) received a 10-day intensive IPV and mental health training, while the control group (n = 22) completed 3-day training. Quantitative data were collected using a validated self-administered Physician's Readiness to Manage IPV questionnaire and IPV consequences scale. Paired and independent t-tests were applied to assess changes. Insights from key informant interviews were thematically analyzed to explore participant experiences and perceived impacts. At baseline, over 80% of participants had not received IPV management training. Post-intervention, significant improvements were observed in HCPs perceived preparedness (median change 2.1; 95% confidence interval (CI): 1.1- 2.9), knowledge (median change 2.7; 95% CI: 2.0-3.1), and awareness of IPV consequences (mean difference 1.2; 95% CI: 0.5-2.0), with greater gains in the intervention group. Qualitative findings revealed enhanced confidence in identifying IPV, addressing psychological impacts, and supporting survivors through safety planning and referral. The training significantly improved HCPs' knowledge, preparedness, and confidence to manage IPV and related mental health issues, underscoring the need to scale similar programs to frontline providers, particularly in rural and underserved settings, to strengthen health system's response to IPV.

Humans↗

PubMed2026

Comparing the Effects of Push and Hold Isometric Training on Strength and Musculotendinous Adaptations: A Within-Subject Randomized Controlled Trial.

Lum, D, Oranchuk, DJ, Chen, SE, and Kong, PW. Comparing the effects of push and hold isometric training on strength and musculotendinous adaptations: A within-subject randomized controlled trial. J Strength Cond Res 40(9): 1050-1058, 2026-Despite recent interest in delineating pushing (PIMA) and holding (HIMA) isometric muscle actions, training-induced adaptations have not been examined. As such, we compared the strength and morphological adaptations between PIMA and HIMA training. Twenty limbs across 10 adults (5 men, 5 women, age: 31.4 ± 6.5 years) were randomly assigned to PIMA or HIMA conditions and underwent 12 training sessions over 6 weeks. PIMA required subjects to exert force against a fixed lever while the HIMA limb maintained a set joint angle while resisting an isotonic lever. During each contraction, subjects had to exert force at 70% of maximal voluntary contraction for 20 seconds at an 80° knee angle, for 4-6 repetitions. Subjects completed isometric, concentric, and eccentric knee extension assessments for both limbs before and after the intervention. Pre- and postintervention ultrasound scans were performed to determine quadriceps muscle architecture and patellar tendon thickness. Increased isometric torque was found following both conditions (p < 0.05, g = 0.30-0.36), while concentric (p < 0.05, g = 0.31) and eccentric (p < 0.01, g = 0.50) torque only increased following PIMA. Both conditions increased muscle thickness (p < 0.05, g = 0.27-0.88) and vastus lateralis fascicle length (p < 0.05, g = 0.20-0.31). Only HIMA increased patellar tendon thickness (p < 0.05, g = 0.12). The increase in total quadriceps (p < 0.05, g = 0.46) and especially rectus femoris (p < 0.05, g = 1.44) thickness was greater in HIMA. The results suggest that PIMA may be more effective at improving strength, while HIMA may be superior for inducing morphological adaptations. Larger sample sizes and more ecologically valid training programs are warranted to further elucidate potential differences between different isometric types.

Humans↗

PubMed2026

Effects of essential amino acid supplementation on musculotendinous recovery following eccentric plantar flexor exercise: a randomized controlled trial.

BACKGROUND: Exercise-induced muscle damage (EIMD) resulting from eccentric contractions leads to transient impairments in muscle function. Essential amino acids (EAAs) stimulate muscle protein synthesis and may support recovery following damaging exercise. However, limited research has examined the effects of EAAs on muscle function following eccentric plantar flexor exercise. The purpose of this study was to examine the effects of EAA supplementation on indirect markers of muscle and musculotendinous recovery following EIMD. METHODS: Thirty-six recreationally active males (age: 21.2 ± 2.7 years) were randomly assigned to an EAA group (10 g of EAAs), placebo (10 g of maltodextrin), or control (no supplementation). Supplements were consumed 30 minutes before and immediately after an eccentric plantar flexor protocol (4 × 50 repetitions followed by one set to failure) and during the 72 hours recovery period. Indirect markers of muscle damage were assessed pre-exercise, immediately post-exercise, and 24, 48, and 72 hours post-exercise, consisting of perceived soreness (NPRS), pain pressure threshold (PPT), calf muscle thickness and Achilles tendon thickness (ultrasound), and calf circumference. RESULTS: The eccentric protocol elicited responses consistent with EIMD, including increased soreness (p < 0.001), increased calf muscle thickness and circumference (p < 0.001), and reduced PPT (p = 0.018). EAA supplementation attenuated soreness at 24 hours compared with placebo. Calf muscle thickness increased following exercise in both groups; however, swelling returned to baseline by 72 hours in the EAA group but remained elevated in placebo (Condition × Time, p < 0.001). Achilles tendon thickness decreased immediately post-exercise (p = 0.005) but was not influenced by supplementation. CONCLUSIONS: EAA supplementation modestly reduced soreness and was associated with faster recovery of muscle swelling but did not influence tendon morphology within 72 hours.

Humans↗

PubMed2026

Precision targeting of teacher burnout using network-informed ecological momentary interventions.

Teacher well-being affects classroom functioning and workforce stability, yet generic digital programs rarely use person-specific affect dynamics to select support. This cluster-randomised trial evaluated whether micro-interventions selected from high expected influence (EI) nodes in teachers' contemporaneous affect networks produced larger changes in burnout-related EI and everyday happiness than content-matched random allocation. The objectives were to estimate allocation effects on changes in estimated network summaries and happiness, evaluate network change as a statistical mediator, examine personality moderation, and benchmark simpler allocation rules. A two-arm cluster randomised platform trial was conducted in 84 public schools across four urban districts in H Province. After a 14 day baseline of ecological momentary assessment (EMA), person specific partial correlation networks were estimated for happiness, exhaustion, detachment, efficacy and rumination. An optimisation engine prioritised three brief micro-intervention types per teacher according to baseline EI, while the active control received the same library without network information. EMA continued for 8 weeks; Bayesian multilevel models, permutation-based mediation, and benchmarking analyses were applied. EI-based targeting produced larger reductions in the composite EI-change index than active control (mean difference 0.11, 95% credible interval 0.08 to 0.14) and higher week 7 EMA happiness (4.4 points on a 0 to 100 scale, 95% credible interval 2.7 to 6.0), with a positive arm by week slope difference of 0.62 points per week (95% credible interval 0.39 to 0.85). Model-based mediation estimates were consistent with approximately one half of the happiness difference being statistically associated with change in the composite EI-change index (average conditional mediation estimate 3.5 points, 95% credible interval 2.0 to 5.2). Benchmarking showed smaller gains under severity, threshold, or group-level centrality rules. Effects were stronger among teachers higher in conscientiousness. The findings indicate that integrating EMA, network modelling, and EI-driven optimisation yields measurable gains beyond content-matched exposure, providing a proof of concept for district-scale precision mental health that requires prospective implementation testing. Replication in additional regions, expanded node sets, and longer follow up are warranted to assess durability and generalisability.

Female↗

PubMed2026

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans↗

PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed2026

Five-year outcomes in a randomised controlled trial of prolonged exposure therapy and supportive counselling for post-traumatic stress disorder in adolescents: a task-shifted intervention.

BACKGROUND: Cognitive-behavioural therapies with a trauma focus are effective in reducing posttraumatic stress disorder and other psychological distress in adolescents. Long-term follow-up data on adolescents treated for PTSD remain scarce, with few studies extending beyond 12 months after treatment completion. OBJECTIVE: To evaluate the maintenance of treatment gains in a comparative study of effectiveness of PE-A and SC up to 60 months post-treatment. METHOD: Sixty-three adolescents diagnosed with PTSD were randomly assigned to either treatment, provided by newly trained and supervised non-specialist health workers. The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale (CPSS). We report on the 60-month post-treatment follow-up, building on post-treatment, 3-month, 6-month, 12-month and 24-month post-treatment data that have been published previously. RESULTS: Participants in both treatment groups maintained a significant reduction in PTSD symptoms up to 60-months post-treatment (F (7, 343) = 2.86, p < .01). Participants receiving prolonged exposure experienced greater improvement on the CPSS at all follow-up assessment timepoints, except for the 60-month FU (p = .28; g = 0.33). CONCLUSION: Adolescents with PTSD continued to maintain treatment gains up to 60-months post-treatment. These data, along with findings from the original RCT, indicate that a brief treatment protocol (averaging 9 sessions of PE-A or SC) in a LMIC, task-shifted to be delivered by nurses without prior psychotherapy experience, led to lasting improvements in PTSD and comorbid symptoms for up to five years. The sustained benefits and improved functioning over the first few years post-treatment support expanding both treatments, especially PE-A, in community settings.

Humans↗

PubMed2026

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

Humans↗

PubMed2026

Delphi study robot consenso: Strategies for the implementation of robotic surgery in general surgery in the Spanish hospital network.

INTRODUCTION: The implementation of robotic surgery in public hospitals presents multiple logistical, educational, and organizational challenges. In the absence of unified guidelines, a national consensus is required to optimize its safe and efficient adoption. This study aimed to establish a set of consensus-based and measurable recommendations for the implementation of robotic surgery programs in hospitals within the Spanish National Health System, based on the experience of centres with established robotic programs and intended to serve as guidance for hospitals that are initiating or planning their implementation. METHODS: A national Delphi study was conducted with the participation of robotic surgery experts from 26 public hospitals. The expert panel was composed exclusively of digestive surgeons with experience in robotic surgery. Three iterative rounds of expert panel evaluation were conducted between March 2024 and March 2025. The questions were grouped into five thematic blocks. Consensus was defined as an agreement level of ≥66.7%. Kendall's W coefficient was used to assess concordance. RESULTS: High levels of consensus were achieved on key aspects related to infrastructure, structured training, cost evaluation, and quality assurance mechanisms. Areas of disagreement were also identified, such as the need for a dedicated anaesthesiologist, purchase of accessory instruments during the initial phase, and official accreditation pathways. CONCLUSIONS: This study provides a guideline for developing a national robotic surgery strategy focused on patient safety, program sustainability, and standardized training of surgical teams. These recommendations can guide hospitals at different stages of robotic technology adoption. Given that the consensus was reached from an exclusively surgical perspective, the recommendations focus on patient safety, program sustainability, and standardized training of the surgical team, and should be interpreted in an adaptable manner according to each centre's context, case volume, and available resources.

Cirugía Asistida por Robot↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed2026

Substance use and co-occurring mental health conditions among adolescents and young adults in North America: a systematic review.

BACKGROUND: Substance use and co-occurring mental health conditions are common among adolescents and young adults and represent an important clinical and public health concern in North America. Trauma exposure, psychiatric symptoms, and social adversity frequently co-occur with substance-related problems in this population. This systematic review aimed to synthesize evidence on prevalence patterns, associated clinical and psychosocial factors, and care-related implications described in the literature on adolescents and young adults with substance use and co-occurring mental health conditions. METHODS: This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024581685). A systematic search was conducted in MEDLINE (Ovid), Embase, PsycINFO, and Google Scholar. Eligible studies examined adolescents and young adults (≤ 25 years) in North America. A combination of subject headings, keywords, and synonyms for the concepts "adolescents," "young adults," "substance use disorders," and "co-occurring mental health conditions" was used. Of 1,882 records identified, 29 studies met the inclusion criteria. Given the heterogeneity of the literature, findings were synthesized narratively. RESULTS: The included studies showed heterogeneity in population, setting, denominator, and ascertainment method. Across the literature, depressive, anxiety-related, trauma-related, and externalizing mental health presentations were frequently reported alongside substance-related problems in adolescents and young adults. Trauma exposure, adverse childhood experiences, and broader social adversity were also commonly reported in association with substance-related problems across studies. Care-related implications were more limited and were largely derived as future directions mentioned across studies rather than direct evaluations of youth-specific service models. CONCLUSION: Co-occurring mental health and substance-related problems were frequently reported among adolescents and young adults in high-risk and service-engaged populations in North America. Trauma and social adversity were prominent across the reviewed literature, while direct evidence for evaluated, integrated, youth-specific care models remains limited. These findings support the relevance of developmentally appropriate, integrated, and trauma-informed approaches to care and highlight the need for further research directly evaluating improved service delivery models for this population. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗