Search PubMedSearch

SEARCH · Search PubMed

Results for “Time to subsequent therapy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,910 records · Page 7Linked to original sources

A Smartphone-Based Ecological Momentary Intervention for Workplace Mental Health: Randomized Controlled Trial.

BACKGROUND: Work-related stress has been widely associated with an increased risk of various mental disorders and poor mental well-being. The fast-growing mobile health services industry has provided new opportunities for workplace mental health. OBJECTIVE: This randomized controlled trial examined the effectiveness of Neurum (Neurum Limited), a smartphone-based intervention tool featuring ecological momentary assessments and interventions that aims to reduce workplace stress in real-time and real-world settings. METHODS: A total of 201 working adults were recruited for a 4-week smartphone-based intervention that incorporated cognitive behavioral therapy, mindfulness exercises, and self-regulation exercises delivered on Neurum. A simple randomization procedure was used. Participants in the intervention group were encouraged to log mood journals, complete mental health exercises, and provide user feedback whenever applicable. The key outcome was measured by the Depression, Anxiety, and Stress Scale-21 items (DASS-21; Cronbach &#x3b1;=0.87). RESULTS: The intervention group consisted of 102 participants, while the control group consisted of 99 participants. More participants dropped out from the intervention group (n=21) than from the control group (n=2; &#x3c7;21=18.259; P<.001). The final sample consisted of 178 participants (male: 85/178, 47.8%; female: 93/178, 52.2%; mean age of 34.65, SD 7.67 y). Analyses revealed that after the 4-week intervention, the DASS-21 scores decreased in the intervention group (mean difference [MD]post-pre intervention=-14.518) but increased in the control group (MDpost-pre intervention=3.319; F1,176=59.358, P<.001; &#x3b7;2=0.252). This effect was largely led by stress reduction (F1,176=64.679, P<.001; for the intervention group, MDpost-pre intervention=-6.692, while for the control group, MDpost-pre intervention=2.000). On average, participants completed 6.27 (SD 9.4) exercises and provided 9.74 (SD 18.2) mood journal logs, with a daily engagement of 4.95 (SD 6.89) minutes. However, the associations between the changes in DASS-21 scores and the numbers of exercises or mood journal logs did not reach statistical significance. CONCLUSIONS: This study primarily established the effectiveness of Neurum in alleviating depression, anxiety, and stress symptoms in noninstitutionalized working adults, with a satisfactory user retention rate. Despite potential health-related culture differences, Neurum contributed to evidence-based digital health in nonclinical settings for timely needs and general accessibility as an alternative to traditional, face-to-face, and high-cost mental health services. Future directions involving a personalized approach in online mental health services were discussed.

Humans

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH&#x2082;O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO&#x2082;/FiO&#x2082;), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6&#x2009;>&#x2009;12.5), the PaO&#x2082;/FiO&#x2082; ratio and Cstat increased significantly after RM (PaO&#x2082;/FiO&#x2082;: 100.8&#x2009;&#xb1;&#x2009;30.3 vs. 125.4&#x2009;&#xb1;&#x2009;38.3&#xa0;mmHg, p&#x2009;<&#x2009;0.05; Cstat: 21.5&#x2009;&#xb1;&#x2009;5.8 vs. 28.0&#x2009;&#xb1;&#x2009;7.0&#xa0;mL/cmH&#x2082;O, p&#x2009;<&#x2009;0.001), Pdriv decreased (19.1&#x2009;&#xb1;&#x2009;3.5 vs. 15.6&#x2009;&#xb1;&#x2009;3.2 cmH&#x2082;O, p&#x2009;<&#x2009;0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6&#x2009;&#x2264;&#x2009;12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

Humans

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of &#x2265; 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer

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

The Effect of Robot-Assisted Gait Training on Balance, Gait and Kinesiophobia in Individuals With Post-Stroke Hemiparesis: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Robot-assisted gait training (RAGT) is well established for post-stroke gait rehabilitation, but its potential effects on psychological and behavioral outcomes are less clear. This study investigated the effects of adding RAGT to conventional rehabilitation on balance, gait, kinesiophobia, and movement confidence in individuals with post-stroke hemiparesis. METHODS: This single-blind, parallel-group randomized controlled trial included 60 individuals with post-stroke hemiparesis (50-75&#xa0;years), randomly allocated to an RAGT group (n&#xa0;=&#xa0;30) or control group (n&#xa0;=&#xa0;30). Ethical approval was obtained from the Clinical Research Ethics Committee of Istanbul Yeni Y&#xfc;zy&#x131;l University (Approval No. 20.01.2022/05; approval date: 20 January 2022). Both groups received conventional rehabilitation for 8&#xa0;weeks; the RAGT group additionally received 24 sessions of RAGT. Kinesiophobia was a prespecified study outcome assessed using the Kinesiophobia Causes Scale (KCS); balance, gait, and balance confidence were also assessed. All 60 randomized participants completed follow-up and were analyzed in their assigned groups. RESULTS: Significant group&#xa0;&#xd7;&#xa0;time interactions were observed for several outcomes, including BBS, TUG duration, 10MWT walking speed, ABC, and KCS total score (p&#xa0;<&#xa0;0.05). The between-group difference in change for KCS total score was -0.36 (95% CI: -0.51 to -0.21; partial eta squared&#xa0;=&#xa0;0.292). In post hoc analyses adjusting each outcome for its baseline value, significant group effects remained for BBS, TUG duration, 10MWT walking speed, ABC, KCS biological domain, and KCS total score (p< = 0.031), whereas 10MWT step count and the KCS psychological domain were no longer statistically significant. DISCUSSION: Adding RAGT to conventional rehabilitation was associated with greater improvements in several balance, mobility, walking-speed, balance-confidence, and kinesiophobia outcomes compared with conventional rehabilitation alone. These findings suggest potential additional physical and psychological benefits of incorporating RAGT into post-stroke rehabilitation. However, because the RAGT group received greater overall treatment exposure, the observed between-group differences cannot be attributed solely to the robotic component. The principal contribution of this study is the concurrent evaluation of kinesiophobia and movement confidence alongside physical outcomes.

Aged

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals

Sex differences in sleep and alcohol consumption outcomes following a digital insomnia intervention.

BACKGROUND: Poor sleep is a well-established risk factor for heavy drinking, and evidence suggests that sleep could serve as a potential treatment target for reducing alcohol consumption. The relationship between poor sleep and problematic drinking appears to be stronger among females, but no studies to date have assessed sex differences in alcohol consumption following insomnia treatment. Here, we combine the samples from two clinical trials to investigate sex differences in the effects of a digital cognitive behavioral therapy for insomnia (Sleep Healthy Using the Internet; SHUTi) on sleep and alcohol outcomes. METHODS: 184 heavy drinking individuals with insomnia (weekly binge episodes: 4/5&#x2009;+ drinks in one sitting for females/males; AUDIT score >7; ISI score >14) were randomly assigned to either the SHUTi program (n&#x2009;=&#x2009;102) or an active control program (n&#x2009;=&#x2009;82). Participants completed self-report assessments at baseline, immediately following the 9-week intervention period, and at 3 and 6-months post-intervention. RESULTS: Linear mixed effects models showed that SHUTi effects over time were stronger among females than males for improved sleep outcomes and reduced frequency of total and heavy drinking days (ps &#x2264; 0.038). Follow-up comparisons of within-group effect sizes revealed consistently larger reductions in alcohol consumption among SHUTi females (Cohen's d range = 0.92-2.23) than SHUTi males (Cohen's d range = 0.65-1.95). CONCLUSIONS: Findings suggest that SHUTi may be more efficacious in improving sleep and reducing drinking among females with insomnia compared to males. These results could have important implications for sex-specific prevention and treatment efforts for heavy drinking individuals with insomnia.

Humans

Assessment of Surgical Salvage Outcomes for Exposed Cranial Neuromodulating Devices.

OBJECTIVES: Implanted neuromodulating devices (NMDs) such as cochlear implants (CIs) and deep brain stimulators (DBSs) are commonly used in modern medicine. Rarely, complications arise post-operatively, including hardware exposure. Traditional teaching suggests that these devices require removal if exposed; however, surgical salvage is a high risk, high reward alternative. We review our single institution experience managing NMD exposure with surgical salvage. METHODS: Retrospective chart review was performed on individuals who had a NMD implanted and underwent an attempt at surgical salvage for exposure during the study period (January 01, 2021 through December 31, 2023). Study outcome success was defined as maintaining a functional NMD 1&#x2009;year after salvage was attempted. Surgical techniques associated with successful salvage were compared. RESULTS: Nine of 729 patients (1.2%) implanted with NMDs experienced hardware exposure during this 2-year study period. Nine subjects were referred for NMD salvage; however, only 6 of 9 subjects (66.7%, CI&#x2009;=&#x2009;3; DBS&#x2009;=&#x2009;3) underwent NMD salvage attempts. Four of the subjects had successful salvage demonstrated successful salvage with a functioning NMD and without wound healing concerns 1&#x2009;year after their salvage procedure. CONCLUSIONS: Classic teaching states that exposed NMDs require explantation. However, this approach necessarily imposes time without benefit from the NMD between explantation and reimplantation. Our experience demonstrates that surgical salvage can be a successful alternative for the majority (66.7%) of individuals.

Humans

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy.

OBJECTIVE: To evaluate the utility of compound muscle action potential (CMAP) amplitudes as biomarkers of disease severity in newborn screening (NBS)-positive infants with spinal muscular atrophy (SMA). METHODS: We conducted a retrospective review of 21 infants identified through SMA NBS (11 with 2 SMN2 copies and 10 with 3 SMN2 copies). Baseline and serial right median, ulnar, and fibular motor nerve CMAP amplitudes (millivolts, mV) were obtained during the study. Functional outcomes were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). RESULTS: At baseline, infants with 2 SMN2 copies demonstrated significantly lower median, ulnar, and fibular CMAP amplitudes compared with infants with 3 SMN2 copies (p&#xa0;<&#xa0;0.05). In contrast, baseline CHOP-INTEND scores did not differ significantly between the two groups. Prior to genetic confirmation, a right median CMAP amplitude&#xa0;&#x2265;3.2&#xa0;mV predicted&#xa0;&#x2265;3 SMN2 copies. Following treatment, right median and fibular CMAP amplitudes demonstrated significant improvement over time, including in analyses accounting for SMN2 copies number. CONCLUSION: CMAP amplitudes obtained from multiple upper- and lower-extremity motor nerves provided objective electrophysiological measures that distinguished infants with two versus three SMN2 copies, despite similar baseline CHOP-INTEND scores. Furthermore, CMAP abnormalities were detectable in some cases before confirmatory genetic testing results became available. Serial CMAP measurements demonstrated significant longitudinal changes following treatment, whereas functional assessments approached ceiling values, supporting the potential value of electrophysiological monitoring in the era of disease-modifying therapies. SIGNIFICANCE: CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS.

Humans

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans

Safety and efficacy of immune checkpoint inhibitors as a bridge to allogeneic hematopoietic stem cell transplantation in classical Hodgkin lymphoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for relapsed or refractory classical Hodgkin lymphoma (cHL); however, a substantial subset of patients ultimately requires allogeneic hematopoietic stem cell transplantation (allo-HCT) to achieve long-lasting disease control. The use of ICIs as a bridge to allo-HCT has therefore gained increasing clinical interest, though concerns persist regarding post-transplant complications and incompletely-defined safety profiles. Accordingly, this systematic review and meta-analysis was conducted to evaluate outcomes of ICIs administered prior to allo-HCT in cHL. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through January 2026. Eligible studies included observational designs reporting survival and transplant-related outcomes in cHL patients treated with ICIs followed by allo-HCT. Pooled proportions for overall survival, progression-free survival, non-relapse mortality, and graft-versus-host disease (GVHD) incidence were calculated using a random-effects model. Seven studies comprising 739 patients were included. Post-transplant survival outcomes were favorable, with high pooled estimates across timepoints. Transplant-related mortality remained low, with NRM rates consistently within an acceptable range through long-term follow-up. Acute GVHD was observed at a meaningful frequency, including a smaller subset of severe cases, while chronic GVHD occurred in approximately one-quarter of patients at follow-up. Overall, these findings suggest that ICI therapy prior to allo-HCT in cHL is associated with encouraging survival and disease control and does not appear to confer excessive non-relapse mortality, supporting its use as a feasible and effective bridging strategy, while underscoring the need for future prospective studies to clarify optimal timing, risk mitigation strategies, and patient selection.

Humans

Improving Community-Based Care for Adolescents with ADHD: a Randomized Controlled Trial of Artificial Intelligence-Assisted Fidelity Supports.

Cognitive-behavioral treatments (CBTs) for adolescents with ADHD demonstrate promise of long-term effects on outcome. However, their implementation in routine care community clinics faces barriers that impact quantity, efficiency, and quality of delivery, as well as client outcomes. This study is a randomized controlled trial designed to evaluate the impact of an AI-assisted service delivery model on therapist implementation of Supporting Teens' Autonomy Daily (STAND), a CBT blended with Motivational Interviewing (MI) for adolescents with ADHD. Adolescents with ADHD (N&#x2009;=&#x2009;51), who were clients at three community mental health agencies, received treatment from 23 therapists. There was randomization of adolescents and therapists to AI-assisted or standard implementation supports. In addition to standard supports (i.e., training, standard facilitation resources, technical assistance, case supervision), AI-assisted support package included digitized facilitation resources housed in a clinical dashboard (Care4), feedback on content fidelity, and AI-generated feedback on MI implementation quality. The AI-assisted group was associated with more efficient treatment delivery and lower number of appointments attended by the adolescent. There was also a significant decrement in MI quality over time in the AI-assisted group compared to the standard support group. Feedback in focus groups indicated that therapists perceived a task-oriented mindset to be associated with receipt of the AI-assisted support package, leading therapists to prioritize efficiency over relational aspects of therapy. Following the results of this trial, a future, larger RCT should examine the impact of the AI-assisted implementation model on mental health outcomes and cost savings to organizations, third party payers, and clients. Trial registration number: NCT05135065; https://www.clinicaltrials.gov ; Registered September 2021.

Humans

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM.&#xa0;A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events.&#xa0;Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16&#xa0;Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%.&#xa0;SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans

Beyond survival: Testicular tissue cryopreservation for fertility preservation during childhood cancer, experiences from a single center.

INTRODUCTION: Approximately 30% of all male childhood cancer survivors receive gonadotoxic therapy increasing their risk for infertility. The only current option for potential fertility preservation in prepubertal males is through testicular tissue cryopreservation (TTC), available through clinical trials. Our aim was to evaluate our experience and identify barriers to enrollment in the TTC study. METHODS: A retrospective review was conducted to describe a single center experience with TTC, including an assessment of factors impacting the decision to enroll or not enroll in the TTC trial. RESULTS: A total of 61 patients were found to be eligible for enrollment in the TTC trial, with 23 patients (34%) choosing to enroll and undergo testicular tissue cryopreservation including 19 (83%) oncology patients. In patients who underwent TTC there were no unexpected delays in starting disease directed therapy. For families that declined enrollment, many did not see fertility preservation as a priority at the time of counseling. (n = 17, 44%). Other barriers included concerns about post-operative complications and a feeling of being overwhelmed at the time of counseling. DISCUSSION: Despite being the only preservation option for pre-pubertal boys facing risk of infertility, TTC enrollment was not pursued by a majority of eligible patients and families. Identifying potential barriers or misconceptions, particularly in regard to post operative complication risks, offer opportunities for improved counseling and education. Early introduction of the Fertility Navigation team allows for procedural coordination success and access for patients that are interested. Success is not measured in how many patients proceed with TTC, rather that all patients have the opportunity for counseling and discussion. CONCLUSION: TTC can be offered and completed safely without delays in disease-directed treatment timelines. A Fertility Navigation Program allows for equal opportunity for education and enrollment on TTC protocol which should be the goal for pediatric institutions, though is not pursued by many patients. A majority of those who declined the study did not see fertility as a priority at the time of treatment while others were concerned regarding peri-operative risks.

Humans

Closed-loop insulin delivery for glycaemic control in hospitalised and perioperative adults: A systematic review and meta-analysis of randomised controlled trials.

We evaluated whether closed-loop insulin delivery improves glycaemic control in hospitalised and perioperative adults. PubMed/MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to 29 June 2026 for randomised controlled trials comparing closed-loop or automated insulin delivery with usual care or conventional insulin therapy. Random-effects meta-analyses were conducted; risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Seven trials involving 375 analysed participants were included. Closed-loop insulin delivery increased time in target glucose range by 23.91 percentage points (95% CI 19.40 to 28.43; I2&#xa0;=&#xa0;0%) and reduced mean glucose by 1.79&#xa0;mmol/L (95% CI 1.06 to 2.53 lower; I2&#xa0;=&#xa0;36.3%); certainty was moderate for both outcomes. Two trials involving 69 participants reported compatible participant-level data for clinically significant hyperglycaemia, and both estimates favoured closed-loop insulin delivery, although the evidence was exploratory and imprecise. No severe hypoglycaemic events occurred in either group, precluding reliable estimation of comparative safety. Closed-loop insulin delivery may improve glycaemic process measures, but larger pragmatic trials are needed to establish clinical benefits, safety, and implementation feasibility.

Humans

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15&#x2009;mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8&#x2009;&#x3bc;g/m3 (5.9), and exposures ranged from 1.3 to 46.8&#x2009;&#x3bc;g/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7&#x2009;&#x3bc;g/m3, 0.1&#x2009;&#x3bc;g/m3, and 0.7&#x2009;&#x3bc;g/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9&#x2009;&#x3bc;g/m3) performed poorly (R2&#x2009;=&#x2009;0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans

Single-center experience with isolated male epispadias: Outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs by anatomical subtype.

BACKGROUND: Isolated male epispadias (IME) is a rare congenital malformation. Surgical repair aims to improve urinary function, correct penile curvature, reconstruct the urethra and glans, and preserve future sexual function. Because available series are small, the influence of anatomical subtype and operative technique on outcome remains incompletely defined. OBJECTIVE: To report single-center outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs for IME, with attention to anatomical subtype, complications, and age-appropriate continence outcomes. METHODS: We retrospectively reviewed boys with IME who underwent primary urethral reconstruction in my hospital, Capital Medical University, from May 2005 to June 2024. Data were locked on 30 June 2024. Primary outcomes were postoperative complications graded by the Clavien-Dindo system and urinary continence at last follow-up in patients aged 5 years or older. Secondary outcomes included improvement of preoperative incontinence, ICIQ score, subsequent bladder neck reconstruction, penile appearance/residual curvature when documented, and patient/parent-reported sexual function. RESULTS: Sixty-seven patients were included: 35 underwent modified Cantwell-Ransley repair and 32 underwent Thiersch-Duplay repair. The cohort included 26 glanular (38.8%), 23 penile (34.3%), and 18 penopubic (26.9%) cases. Median age at surgery was 28 months in both groups. Median age at last follow-up was 92.8 months (IQR 63.9-108.4) after modified Cantwell-Ransley repair and 137.9 months (IQR 77.9-172.6) after Thiersch-Duplay repair (P = 0.011). Procedure distribution differed by meatal location (P = 0.036), although penopubic cases were treated with both procedures. Total complications occurred in 5/35 and 5/32 patients, respectively. Formal continence analysis included 26 modified Cantwell-Ransley patients and 27 Thiersch-Duplay patients aged 5 years or older. Postoperative urinary incontinence persisted in 14/26 (53.8%) and 12/27 (44.4%), respectively. Among age-eligible patients with preoperative incontinence, any improvement was documented in 13/20 (65.0%) and 14/17 (82.4%), and complete remission occurred in 6/20 (30.0%) and 5/17 (29.4%), respectively. Three patients, all with penopubic epispadias treated with Thiersch-Duplay repair, subsequently underwent bladder neck reconstruction for persistent incontinence. Erectile function data were available in 37/67 patients (55.2%). CONCLUSIONS: In this large single-center retrospective cohort, Thiersch-Duplay and modified Cantwell-Ransley repairs had comparable overall complication rates. Continence and reoperation patterns were strongly influenced by anatomical subtype, with penopubic epispadias representing the highest-risk group. These findings support individualized, anatomy-conscious operative planning and prospective evaluation of standardized selection criteria, rather than a single prescriptive algorithm. CLINICAL/TRANSLATIONAL IMPLICATION: This series supports standardized reporting of anatomical subtype, age-appropriate continence outcomes, and graded complications when counseling families and comparing outcomes across centers. LEVEL OF EVIDENCE: Level III.

Humans