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Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

Humans

Implementation outcomes of a dementia-focused intervention for family care partners and clinicians in home hospice care.

OBJECTIVES: End-of-life care for persons living with dementia in home hospice relies heavily on coordination between family care partners (FCPs) and clinicians (e.g., hospice social workers and nurses). FCPs and clinicians have reported support and knowledge gaps in end-of-life dementia care. Interventions are needed to improve FCPs' support and clinicians' educational gaps. METHODS: A pilot randomized controlled trial was designed to examine implementation outcomes for a dementia-focused end-of-life intervention for FCPs (n = 37) and clinicians (n = 15). Data on survey completion and acceptability were collected at baseline, during 4 follow-up visits, and at the conclusion of the study. RESULTS: Twenty-eight (75%) caregivers completed the post-study survey, and 10 (27%) reported using the structured worksheet. Thirteen (87%) clinicians completed the post-training survey, 8 (53%) completed the post-study survey, and 8 (100%) used the worksheet. Clinicians (n = 8) were satisfied or highly satisfied with the instructional videos, and half (50%) used the information frequently with patients. Both groups reported the worksheet helpful, easy to use, and satisfactory, though clinicians rated helpfulness slightly higher (mean = 3.88 vs. 3.70 for FCPs). Clinicians liked the worksheet's structured guidance and the enhanced collaboration. SIGNIFICANCE OF RESULTS: This study provides preliminary evidence for implementation outcomes of a dementia-focused end-of-life intervention in home hospice. Findings suggest the intervention can be implemented in a hospice setting, with moderate worksheet uptake and perceived value among FCPs and clinicians.

Humans

Bioabsorbable vs. titanium screws in first metatarsophalangeal joint arthrodesis: a pilot randomized controlled trial with 2-year follow-up.

INTRODUCTION: To assess the feasibility and preliminary clinical outcomes of bioabsorbable screw fixation in first metatarsophalangeal joint arthrodesis compared to conventional titanium screw fixation. METHODS: In this prospective pilot randomized controlled trial, 30 patients were allocated 1:1 to bioabsorbable or titanium cannulated lag screw fixation. Arthrodesis was performed using a cup-and-cone technique at two Finnish hospitals. Full weight-bearing in an orthopaedic shoe was allowed after six weeks. Outcomes included AOFAS and VA-FAS FA-VAS scores, union rates, and complications assessed at 3, 6, 12, and 24 months. RESULTS: Both groups showed significant functional improvement with no between-group differences. At 24 months, mean AOFAS scores were 89.1 (SD 2.7) in the titanium group and 90.0 (SD 0.0) in the bioabsorbable group (p = 0.23). Mean FA-VAS total scores (sum of pain, function, and complaints subscales) were 1948 (SE 59.4) in the titanium group and 1914 (SE 61.4) in the bioabsorbable group (p = 0.655). Union rate was 90% overall; nonunion occurred in one titanium and two bioabsorbable patients, all requiring revision. No implant-related complications or hardware removal surgeries were recorded. Degradation of bioabsorbable screws caused no adverse clinical or radiographic reactions. CONCLUSIONS: Bioabsorbable screws appear safe and feasible in first metatarsophalangeal joint arthrodesis, with preliminary outcomes comparable to titanium fixation. These findings support the conduct of a larger confirmatory trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133039, registered 28 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133039.

Humans

Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.

PURPOSE: Neoadjuvant chemotherapy (NACT) is a commonly recommended approach for treating several cancers, and improving patients' outcomes to this therapy is important. This systematic review and meta-analysis assessed the impact of exercise on pathologic complete response (pCR), a key short-term marker of treatment efficacy, in patients with solid tumors receiving NACT. METHODS: Four electronic databases were searched for randomized controlled trials with physical exercise during NACT as an intervention published until May 2025. Risk of bias was assessed using Cochrane RoB 2.0 and the TESTEX scale. A random-effect meta-analysis using the inverse variance method synthesized the results. Heterogeneity was assessed using I2 and chi2 statistics. Risk ratio estimated the effect size. RESULTS: Eight studies involving 504 patients with breast, esophageal, gastric, or rectal cancer were included in the final analysis. Exercise interventions consisted of aerobic and resistance exercise. Overall, there were no significant differences between exercise and control groups in the rate of pCR to NACT (pooled risk ratio: 1.08 (95% CI: 0.82 to 1.43) Z = 0.56, p = 0.58). However, meta-regression data from breast cancer (BC) studies (4 studies, 367 participants) suggest exercise may be associated with enhanced tumor response to NACT in HR + /HER2- subtypes (regression coefficient: 0.83 (95% CI: -0.00 to 1.67), p = 0.05). CONCLUSION: Exercise during NACT did not improve pCR across cancer types. Exploratory meta-regression findings suggest a possible benefit of exercise in BC patients with the HR + /HER2- subtype. These results should be interpreted with caution due to the small number of studies and low certainty of the evidence.

Humans

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans

Relational care in community mental health: Evaluating staff experiences in Intensive Community Care Services (ICCS) vs treatment as usual.

BACKGROUND: The quality of healthcare delivery relies heavily on building strong relationships between healthcare providers (HCPs) and clients. This study presents the results of a process evaluation for a Randomised Controlled Trial (RCT) examining the effectiveness of Intensive Community Care Service (ICCS) vs Treatment as Usual (TAU; inpatient or core community CAMHS). METHODS: Thirty-four semi-structured interviews were conducted with staff across various services, including 20 from ICCS and 14 other TAU services. A thematic decomposition analysis was conducted on the data, and specific themes relevant to staff experiences of young people's engagement with services and overall recovery. RESULTS: Three main themes were observed in the HCP data (1. Relational Ecologies: barriers and enablers to engagement, 2. flexibility of approach amidst systemic pressures and 3. the web of trust in the relationship-building process). HCPs highlighted the necessity of developing trust and rapport through non-clinical engagement strategies, such as informal visits and personalised interactions. HCPs emphasised that without trust, treatment effectiveness diminishes, necessitating a tailored approach rather than a one-size-fits-all model. The flexibility in duration of treatment and methods of engagement was noted as crucial in accommodating individual client needs and fostering an open, trusting environment necessary for long-term recovery. CONCLUSION: The findings highlight the vital importance of relational care models, especially ICCS, in addressing the complex needs of Children and Young People (CYP). Flexible, family-centred approaches improve trust, engagement, and long-term recovery outcomes. Recommendations include tackling systemic barriers and expanding relational care models within CAMHS to meet increasing mental health demands effectively. Further research should investigate scalable strategies for integrating these insights into wider mental health service frameworks.

Humans

Physicochemical effects of bicarbonate-buffered solution versus compound sodium lactate during major abdominal surgery: A randomized, open-label, non-inferiority trial.

INTRODUCTION: Bicarbonate-buffered crystalloids avoid exogenous lactate and have physicochemical properties distinct from compound sodium lactate (CSL), but direct comparative evidence during major abdominal surgery remains limited. METHODS: This single-center, open-label, randomized non-inferiority trial enrolled high-risk adults undergoing elective major abdominal surgery. Participants received bicarbonate-buffered solution or CSL as the allocated intraoperative crystalloid. The primary estimand was the arithmetic mean difference in standard base excess (SBE) at skin closure (bicarbonate-buffered solution minus CSL). The non-inferiority margin was -1.5 mEq/L. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001228178). RESULTS: Fifty participants were randomized (25 per group) and received their allocated intervention. End-of-surgery arterial blood gas data were missing for two CSL participants. In the intention-to-treat analysis using multiple imputation, the estimated mean difference in end-of-surgery SBE was -0.42 mEq/L (95% confidence interval [CI], -1.92 to 1.09 mEq/L). The complete-case per-protocol estimate was -0.48 mEq/L (95% CI, -2.02 to 1.06 mEq/L). In both analyses, the lower CI bound was below the prespecified non-inferiority margin; non-inferiority was not established. Secondary outcomes were exploratory; observed end-of-surgery lactate was lower with bicarbonate-buffered solution (median 0.9 vs 1.2 mmol/L; unadjusted P = 0.031), without a corresponding difference in SBE or pH. CONCLUSIONS: In this small trial of hemodynamically stable adults undergoing elective major abdominal surgery, the primary non-inferiority result was inconclusive. The data did not establish interchangeability, equivalence, superiority, or inferiority of the two fluids. As the trial was powered for a physiologic endpoint, no comparative inference can be made about organ dysfunction, postoperative complications, recovery, or mortality. Larger trials with standardized co-interventions and patient-important outcomes are required before routine substitution for CSL can be recommended.

Humans

Protocol for project FIERCE: A randomized controlled trial to evaluate a positive emotion-focused meditation intervention for physicians with elevated stress.

INTRODUCTION: Nearly 80% of healthcare providers experience adverse psychological symptoms (e.g., depression, burnout, sleep disturbance) stemming from workplace stressors. Elevated levels of stress have been associated with unfavorable occupational, patient, and provider-related outcomes, imposing a heavy burden on a strained system. Given the impact of stress on both employee and patient health, effective interventions are urgently needed to reduce distress and promote well-being among healthcare professionals. Mindfulness-based interventions show promise for addressing these challenges. We developed a six-week, remotely delivered mindfulness intervention, the Building Emotional Strength Training (BEST) program, based on the Buddhist Four Immeasurables practice to cultivate the distinct emotional qualities of loving-kindness, compassion, joy, and equanimity. The present study aims to evaluate the feasibility and efficacy of a Four Immeasurables-based mindfulness intervention on perceived stress (primary outcome), burnout, depressive symptoms, and inflammatory biomarkers, while enhancing psychological well-being and sleep quality (secondary outcomes) in physicians. We will also investigate potential mediators of intervention effects, including compassion, positive affect, equanimity, and mindfulness. METHOD: We will enroll 90 full-time physicians in a remote, two-arm randomized controlled trial with 1:1 allocation to either the meditation intervention or waitlist control. Participants will complete self-report questionnaires and provide blood samples at baseline, mid-course, and post-intervention to assess outcomes and mediators. DISCUSSION: The project aims to advance the study of mindfulness-based interventions that reduce distress and promote well-being through practices that cultivate prosocial and altruistic feelings toward oneself and others. While mindfulness interventions have gained considerable interest, none have specifically drawn from the Four Immeasurables practice to target loving-kindness, compassion, joy, and equanimity. This novel investigation could expand our understanding of practices that foster kindness and compassion to reduce distress in an at-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT07283744, registered on 2025/10/14. The Open Science Framework, registered on 2026/06/26.

Humans

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans

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

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

Humans

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

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

Humans

Process evaluation of a nurse-led transitional care model (Cardiolotse) within a randomized controlled trial aiming to improve care coordination for patients with cardiovascular diseases in Germany.

BACKGROUND: Patients with higher age suffering from cardiovascular disease discharged from hospital are at greater risk of readmission within 30 days. We evaluated an innovative care program providing post-discharge support and helping patients to navigate through the healthcare system. This paper reports the findings of the process evaluation of the randomized controlled trial Cardiolotse, a nurse-led transitional care model improving care coordination for patients with cardiovascular diseases in Germany. METHODS: A process evaluation, following the guidelines of the Medical Research Council (MRC) Framework, was performed. Semi-structured interviews with all relevant target groups were conducted to gain more insight about implementation processes. Questionnaires and medical records were used to explore mechanisms of impact and understand how change was produced in the intervention. Qualitative data were analysed using content analysis with deductive and inductive categories. Descriptive statistics and subgroup analyses were utilized to explore quantitative data. RESULTS: Overall, the designed training programme was perceived positively by the study nurses, so called Cardiolotsen (CLs). Patients receiving support by the CLs reported positive satisfaction ratings. Interactions between CLs and patients were reported as trustworthy and reliable. A total of approximately 12,500 contacts were made over the course of the intervention. However, changes in satisfaction scores between intervention and control groups in terms of medical treatment or the interaction between medical health providers involved in the treatment could not be determined. Furthermore, data suggested reach issues with respect to office-based physicians, as regular CL contact could not be achieved with 90% of the participating general practitioners and cardiologists. CONCLUSIONS: The CLs served as an important source of support for the participating patients throughout the intervention. At regular intervals, they checked a patient's health status and their adherence to therapies after discharge. However, the process evaluation identified cross-sectoral communication and information exchange between CLs and office-based physicians as an implementation challenge. TRIAL REGISTRATION: The study was retrospectively registered at German Clinical Trial Register, http://www.drks.de/DRKS00020424 (Trial Registration Number DRKS00020424) on 18 June 2020.

Humans

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 &#xd7; 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

Joint association of sedentary behaviour and physical activity with cardiovascular disease: a systematic review and meta-analysis.

This systematic review and meta-analysis of cohort studies aimed to synthesize existing evidence on the joint association of physical activity (PA) and sedentary behaviour (SB) with cardiovascular disease (CVD) risk among adults. We searched PubMed, EMBASE, and Cochrane for English studies published between January 2010 and February 2025 that examined the joint association of PA and SB (fatal and non-fatal) CVD among adults and pooled their results through meta-analyses using study-level data. Using findings from 17 studies, the pooled effect size for the lowest PA + highest SB group was 1.78 (95% CI: 1.59-2.00), suggesting increased risk for CVD compared with the reference group (i.e. highest PA + lowest SB). Compared with the same reference group, we found an increased risk for CVD in the lowest PA + lowest SB (HR = 1.25, 95% CI: 1.12-1.40) and the highest PA + highest SB (HR = 1.16, 95% CI: 1.06-1.27) groups. Subgroup analyses according to domains or types of PA and SB exposure, outcome measures, and exposure measurement method revealed a similar pattern. In conclusion, individuals with the lowest PA combined with the highest SB may experience an increased risk for CVD events compared with those with the highest PA and lowest SB. There was also an increased risk for individuals with a combination of either low PA + low SB and high PA + high SB, albeit to a lesser extent. Although substantial study-level heterogeneity exists, the results highlight the potential value of considering both behaviours jointly in relation to CVD risk.

Humans

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n&#x2009;=&#x2009;146) or osimertinib monotherapy (n&#x2009;=&#x2009;148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P&#x2009;<&#x2009;.001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult

Presentation, management, and outcomes of anterior inferior cerebellar artery dissecting and fusiform aneurysms: a systematic review and institutional case series.

Dissecting and fusiform aneurysms of the anterior inferior cerebellar artery (AICA) are rare and poorly characterized lesions. This study provides a comprehensive patient-level synthesis to date, combining a systematic review with institutional data to describe their clinical presentation, diagnostic workup, management strategies, and outcomes.&#xa0;A systematic review was conducted according to PRISMA guidelines. Studies were included if they reported on dissecting or fusiform AICA aneurysms. Individual patient data were extracted and supplemented with a single-institution case series. Outcomes, complications, and radiological evolution were analyzed descriptively.&#xa0;Forty-nine patients from 36 studies and 6 patients from our institution were included in this study. In the systematic review cohort, most aneurysms presented with subarachnoid hemorrhage (n&#x2009;=&#x2009;38/49, 77.6%). Compressive cranial neuropathies, particularly including the vestibulocochlear system, were common in patients with unruptured aneurysms. Diagnosis often required digital subtraction angiography after the initial non-invasive imaging. Endovascular treatment, most commonly parent artery occlusion, was employed in 61.2% (n&#x2009;=&#x2009;30/49) of cases. However, ischemic complications occurred in 23.3% (n&#x2009;=&#x2009;7/30), especially in proximal (A1-A2) lesions. Bypass surgery was reported selectively for proximal aneurysms with inadequate collateral flow. As an alternative surgical approach, decompression or trapping was pursued based on aneurysm morphology or clinical context. Conservative management was typically reserved for select patients with poor-grade SAH, high procedural risk, or patient refusal of intervention. Overall, 81.4% (n&#x2009;=&#x2009;35/43) of patients with available follow-up achieved good functional outcomes.&#xa0;Management of AICA dissecting and fusiform aneurysms is highly individualized. Endovascular approaches were frequently used to secure ruptured lesions or lesions considered at high risk, but periprocedural ischemic risk in perforator-rich segments remains a notable concern. Bypass procedures were reported in selected proximal aneurysms with limited collateralization. Conservative management was reserved for highly selected high-risk or anatomically inaccessible cases. Clinical trial registration: This study is not a clinical trial.

Humans

Effect of Various Types of Remineralizing Agents on the Remineralization of Mild and Moderate Defects Caused by Molar-Incisor Hypomineralization in Mexican Schoolchildren: A 12-month Follow-up Randomized Clinical Trial.

PURPOSE: Using Laser-Induced Fluorescence (LIF), this study aimed to evaluate the effect of three remineralizing agents on permanent molars and incisors with both mild and moderate Molar-Incisor Hypomineralization (MIH) in 8-to-12-year-old Mexican schoolchildren. MATERIALS AND METHODS: In this randomized clinical trial, 104 children were selected to participate and then divided randomly into four groups: Group I: control, Oral-B kids (toothpaste); Group II: Fluor Protector (varnish); Group III: Clinpro White Varnish; and Group IV: MI Paste (CCP-ACP). Both varnishes were applied once every four weeks for twelve months for each group. Remineralization was evaluated by LIF at intervals of 1, 3, 6, 9, and 12 months. Paired-sample t-tests and repeated-measures ANOVA were performed, while the Greenhouse-Geisser correction was used to evaluate sphericity. RESULTS: The three test agents used increased the level of remineralization observed at the site of mild and moderate MIH defects over the course of twelve months (p0.001). A similar decrease in average LIF values was observed across the three treatment groups. CONCLUSIONS: The use of both fluoride varnishes and the CPP-ACP toothpaste was observed to promote the remineralization of both mild and moderate MIH defects.

Humans

Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.

To evaluate the efficacy and safety of the flexible ureteroscopy (fURS) with a flexible and negative suction ureteral access sheath (FANS) versus traditional sheath for patients with infectious upper urinary tract stones (IUUTS). A total of 185 patients were enrolled, with 93 assigned to the FANS group and 92 to the traditional UAS group. The primary outcome was the stone-free rate (SFR) at the first postoperative day. Secondary outcomes included the SFR at 30 days postoperatively, operative time, hemoglobin reduction, length of hospital stay, quality of life (QoL) improvement, incidence of ureteral stricture at 3 months, and surgery-related complications. No significant differences were observed between the two groups in baseline demographics or preoperative clinical characteristics (P&#x2009;>&#x2009;0.05). The FANS group had significantly lower white blood cell count, C-reactive protein, and procalcitonin levels at 6 and 24&#xa0;h postoperatively (all P&#x2009;<&#x2009;0.05). Mean operative time was significantly shorter (P&#x2009;<&#x2009;0.001), QoL improvement was obviously greater (P&#x2009;<&#x2009;0.001), and average hospital stay was shorter in the FANS group (P&#x2009;<&#x2009;0.001). The SFRs on postoperative day 1 and at 30 days were both significantly higher in the FANS group (both P&#x2009;<&#x2009;0.05). At 3 months, ureteral strictures occurred in three patients in the traditional UAS group and one in the FANS group, a difference that was not statistically significant (P&#x2009;>&#x2009;0.05). The overall complication rate was significantly lower in the FANS group (P&#x2009;<&#x2009;0.05). For patients with IUUTS, fURS combined with FANS effectively improves stone clearance efficiency and reduces the risk of postoperative infection.

Humans
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Effect of Various Types of Remineralizing Agents on the Remineralization of Mild and Moderate Defects Caused by Molar-Incisor Hypomineralization in Mexican Schoolchildren: A 12-month Follow-up Randomized Clinical Trial.2026-09-08PMID 42709059pubmed
Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.2026-09-08PMID 42709214pubmed

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