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Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score ≥2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

Humans

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans

Acupuncture improves depressive symptoms and prefrontal cortical function in mild to moderate depressive disorder: A randomized sham-controlled trial and fNIRS study.

BACKGROUND: Depressive disorder is a common mental illness associated with substantial functional impairment. Although pharmacotherapy is widely used, its effectiveness is often limited by adverse effects and poor adherence. Acupuncture has been increasingly applied as a complementary treatment for depression, and its neurobiological characteristics remain unclear. OBJECTIVE: This randomized, sham-controlled trial aimed to evaluate the clinical efficacy of acupuncture for mild to moderate depressive disorder and to investigate its effects on prefrontal cortical function using functional near-infrared spectroscopy (fNIRS). METHODS: Patients with mild to moderate depressive disorder were randomly assigned to a real acupuncture (RA) group or a sham acupuncture (SA) group and received standardized treatment for 8 weeks. Clinical outcomes were assessed using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Short Form-36 Health Survey (SF-36), and a traditional Chinese medicine syndrome score. A subset of participants underwent fNIRS assessment during resting-state and task-based conditions to evaluate prefrontal cortical activation and functional connectivity. RESULTS: Compared with baseline, the RA group showed significant reductions in SDS and SAS scores and significant improvements in SF-36 emotional domains, with effects emerging at Week 4 and persisting up to 12 weeks after treatment. Improvements were greater and more stable in the RA group than in the SA group. fNIRS analyses revealed enhanced activation in dorsolateral and medial prefrontal regions and strengthened prefrontal functional connectivity following acupuncture, whereas neural changes in the SA group were limited. CONCLUSION: Acupuncture is effective for improving depressive and anxiety symptoms and quality of life in patients with mild to moderate depressive disorder. Modulation of prefrontal cortical activation and connectivity may underlie its antidepressant effects.

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 = 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

Understanding psychosocial adjustment in military-to-civilian transition: A latent profile analysis of ex-serving Australian Defence Force members.

Military-to-civilian transition is a critical life stage that can expose veterans to elevated risks of psychological distress, social difficulties, and reduced wellbeing. Although psychosocial factors are central to successful reintegration, little is known about distinct patterns of needs among ex-serving Australian Defence Force (ADF) members. This study used latent profile analysis (LPA) to identify psychosocial needs profiles across five domains of the Military-Civilian Adjustment and Reintegration Measure (M-CARM) in a sample of 725 ex-serving ADF members. The optimal three-class solution identified: a Low Adjustment Need (LAN) group (20.7%) reporting minimal reintegration challenges; a Cultural Adjustment Need (CAN) group (42.9%) characterized by cultural adaptation difficulties, particularly beliefs about civilians and regimentation; and a Cultural and Psychological Need (CPN) group (36.4%) showing broader challenges across beliefs about civilians, purpose and connection, regimentation, and resentment and regret. The CAN group was more likely to be male, have lower educational attainment, and have no combat deployment history. The CPN group was similarly male dominated with lower education, and was additionally characterized by Navy service, unemployment or not being in the labor force, and medical discharge. Compared with the LAN group, both CAN and CPN groups reported higher levels of depression, anxiety, posttraumatic stress, and nightmare distress, as well as poorer quality of life and greater functional impairment. These findings highlight persistent reintegration challenges among veterans and support the need for stratified support models, ranging from psychoeducation to intensive multidisciplinary care, to better address diverse psychosocial needs of ex-serving ADF members.

Australian defense force

Shared Medical Appointments for Substance Use Disorders: A Systematic Review.

BACKGROUND: Shared medical appointments (SMAs) integrate group-based clinical care with individual medical management and are increasingly used in the treatment of substance use disorders (SUDs) to improve access, engagement, and care coordination. However, their use, outcomes, and implementation in SUD care have not been systematically synthesized. METHODS: We conducted a systematic review registered with PROSPERO (CRD42025639504). MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Central were searched from database inception through September 2025. Randomized controlled trials, observational studies, and qualitative studies examining SMAs among adults with SUDs were included. Outcomes of interest included treatment engagement and retention, substance use outcomes, mental health and patient-reported outcomes, and implementation characteristics. Study quality was assessed across quantitative and qualitative designs, and findings were synthesized descriptively. RESULTS: Fourteen studies, representing approximately 578 participants, met inclusion criteria. Twelve studies focused exclusively on opioid use disorder, 1 included both alcohol and opioid use disorders, and 1 did not specify substance type. Treatment retention was reported in 6 studies, with a median 6-month retention of 72.9%. Three studies reported reductions in substance use outcomes, and 2 reported improvements in depression or anxiety. Qualitative studies consistently described high patient satisfaction, peer support, and shared accountability. Implementation studies demonstrated feasibility across diverse outpatient settings, with substantial heterogeneity across study designs and outcomes. CONCLUSIONS: SMAs appear feasible and acceptable for addiction care and may support treatment retention and patient experience. Evidence remains heterogeneous and largely observational, highlighting the need for rigorous comparative studies to better define effectiveness and implementation.

Humans

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

Multi-omics panorama of glaucoma: Pathogenesis, biomarkers, and novel therapeutic strategies.

Glaucoma is a group of irreversible, blinding eye diseases characterized by progressive loss of retinal ganglion cells, leading to gradual visual field defects that severely impact patients' quality of life. Its complex pathophysiological mechanisms remain incompletely understood, limiting the development of early diagnostic and effective therapeutic strategies. Advances in omics technologies have provided new insights into elucidating the pathophysiology of glaucoma. We summarize specific alterations in genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics associated with glaucoma. We emphasize the systematic analysis of disease mechanisms, identification of clinically applicable biomarkers, and discovery of novel therapeutic targets through the integration of these data. This approach paves new pathways for glaucoma subtype diagnosis and personalized treatment, while also outlining future research directions and challenges.

Humans

Ictal electroencephalography and heart rate as treatment criteria in electroconvulsive therapy: a systematic review of the literature.

BACKGROUND: Decades before the emergence of precision medicine, psychiatrists raised the question of whether specific seizure characteristics could help optimize electroconvulsive therapy (ECT), as relationships between some of these characteristics and better outcomes were found. From 1990 onward, researchers focused on electroencephalography (EEG) and cardiovascular markers, which were broadly adopted by guidelines worldwide. However, the prognostic value of these markers is still controversial. Here, we provide a systematic summary of the studies on this topic. METHODS: We conducted a literature review on the use of ictal EEG and heart rate as outcome predictors in ECT using the PubMed, EMBASE, Cochrane and PsycINFO databases. RESULTS: Thirty-seven studies addressing more than 100 quality markers fulfilled our inclusion criteria. Single EEG markers were assigned to five categories (postictal inhibition, amplitude, coherence, regularity, and seizure duration). Heart rate and composite markers were considered separately. In contrast to single EEG markers, heart rate and composite markers could be consistently linked to better outcomes in patients with depression. Only a few studies on schizophrenia could be retrieved. CONCLUSION: Multiparametric markers outperformed single markers. Furthermore, changes in heart rate during seizures were related to better outcomes. Although clinical assessment remains the cornerstone of treatment guidance decisions, EEG and cardiac monitoring could help prevent insufficient seizures during the period preceding clinical improvement. Evidence on schizophrenia remains limited. More randomized trials are needed to analyze the role of composite markers as prognostic tools.

Humans

Patient and Public Involvement and Engagement in Pediatric Health Research: A Systematic Review.

BACKGROUND: Patient and public involvement and engagement (PPIE) can increase the relevance and efficiency of research projects. An overview of PPIE approaches and implementation in pediatric research studies is needed to facilitate learning from others' experiences. OBJECTIVE: We aimed to systematically review practices in PPIE across all pediatric health research disciplines regarding characteristics and recruitment of PPIE participants, timepoints and methods used for PPIE, levels of involvement, benefits and barriers of PPIE. SEARCH STRATEGY: We searched Pubmed, EMBASE, Cochrane and PsycInfo using a comprehensive set of terms based on the concepts 'Patient and Public Involvement,' 'Health Research' and 'Pediatrics.' INCLUSION CRITERIA: We included original research articles describing PPIE implementation in pediatric health research published in English or German between 01/2003-10/2024. DATA EXTRACTION AND SYNTHESIS: Data was extracted using predefined categories and synthesized by narrative summary and thematic synthesis. PPIE reporting quality was assessed using the GRIPP2 short form checklist. MAIN RESULTS: Out of 1910 references, we included 37 original research articles, representing 35 studies. PPIE participants were mostly children, adolescents or caregivers involved in all research stages, especially in study design (89%) and recruitment (51%). Key positive impacts of PPIE on research included enhanced recruitment and retention rates and personal benefits for PPIE participants. Barriers to PPIE were financial and time resources required and challenges in recruiting representative PPIE participants. The level of involvement and PPIE reporting quality varied highly between studies. DISCUSSION: Common benefits and barriers of PPIE exist across pediatric research disciplines. Reporting quality varied highly between studies. CONCLUSIONS: PPIE is valuable in pediatric health research. Adherence to guidelines for conducting and reporting PPIE is important to enhance mutual learning. PATIENT OR PUBLIC CONTRIBUTION: PPIE input contributed to the understandability of the lay summary. The findings of this review, together with parent and public input, will inform guidelines for future PPIE activities at the authors' institutions.

Humans

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

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

Humans

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&#x202f;=&#x202f;30) or the control group (n&#x202f;=&#x202f;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&#x202f;=&#x202f;.215 [-0.41, 0.44]) or communication selfefficacy (F = 0.83, p&#x202f;=&#x202f;.366 [-0.44, 0.79]). However, communication satisfaction was significantly higher in the intervention group (F = 4.19, p&#x202f;<&#x202f;.05 [0.04, 0.44]). The number of questions asked was also significantly higher in the intervention group (t&#x202f;=&#x202f;-4.35, p&#x202f;<&#x202f;.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

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12&#xa0;months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade&#xa0;&#x2265;&#xa0;2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade&#xa0;&#x2265;&#xa0;3 pulmonary adverse events following SBRT and in overall grade&#xa0;&#x2265;&#xa0;2 oesophageal adverse events among patients with clinical stage I-II and those aged >70&#xa0;years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes

Efficacy of Proton Pump Inhibitor Therapy for Nocturnal GERD Symptoms and Associated Sleep Disturbances: A Systematic Review of Randomized Controlled Trials.

GOALS: A systematic review was conducted to evaluate the efficacy and safety of proton pump inhibitor (PPI) therapy in relieving nocturnal reflux symptoms and sleep disturbances. BACKGROUND: Nocturnal gastroesophageal reflux disease (GERD) is commonly associated with sleep disturbances. The benefits of PPI therapy for GERD-related nocturnal reflux and sleep disturbance remain unclear. STUDY: We searched the MEDLINE, EMBASE, and Cochrane CENTRAL databases from inception to March 1, 2026, for randomized controlled trials (RCTs) in adults with GERD and sleep disturbances that compared any PPI to placebo or an alternative therapy. The primary outcome was the proportion of patients experiencing relief from nighttime heartburn. Secondary outcomes included relief from GERD-related sleep disturbances, changes in subjective sleep quality, work productivity, and treatment-emergent adverse events (TEAEs). RESULTS: Five RCTs involving 1495 patients met the inclusion criteria. Three placebo-controlled trials consistently showed that PPI therapy improved nighttime heartburn relief and GERD-related sleep disturbances compared with placebo. Subjective sleep quality and sleep-related daytime functioning also generally improved with PPI therapy. However, the findings were more heterogeneous across trials because of differences in study populations, comparators, and outcome measures. Across the placebo-controlled studies, TEAEs were generally similar between the PPI and placebo groups. CONCLUSIONS: PPI therapy was associated with improvement in nighttime heartburn and reflux-related sleep disturbances, especially in patients with reflux-driven nocturnal symptoms. The available evidence also suggests potential improvement in subjective sleep quality and sleep-related daytime functioning.

Humans

Functional constipation in pregnancy and its association with dietary intake and physical activity: a cross-sectional study.

BACKGROUND: Functional constipation (FC) is a common complaint during pregnancy and has been reported to be associated with physical activity and dietary intake. However, previous studies have reported inconsistent findings. Therefore, this study aimed to determine the prevalence of FC and examine its association with physical activity and dietary intake among pregnant women. METHOD: In this cross-sectional study, 381 healthy pregnant women attending urban health centres in Tabriz, Iran, between January 2024 and February 2025, were selected using a multistage cluster sampling method. FC was diagnosed according to the Rome IV criteria. Data were collected through face-to-face interviews using the International Physical Activity Questionnaire (IPAQ) and the Food Frequency Questionnaire (FFQ). Multivariable Generalised Estimating Equations (GEE) analysis was performed to identify factors associated with FC. RESULTS: The overall prevalence of FC throughout pregnancy was 37%. In the first trimester, 41 out of 73 women (56%) had FC, while in the second trimester 53 out of 146 women (36%), and in the third trimester 47 out of 162 women (29%) were affected. Multivariate GEE indicated that both higher dietary fibre intake (aOR= 0.88, 95%CI 0.86-0.91, p&#x2009;<&#x2009;0.001) and higher fluid intake (aOR= 0.59, 95%CI 0.52-0.67, p&#x2009;<&#x2009;0.001) were associated with a reduced risk of FC. A normal BMI was associated with a lower risk of FC (aOR= 0.35, 95% CI 0.16-0.77, p&#x2009;=&#x2009;0.009), whereas, secondary education was associated with a higher risk (aOR= 2.81, 95%CI 1.33-5.95, p&#x2009;=&#x2009;0.007). Physical activity (aOR= 1.00; 95%CI 1.00 to 1.01; p&#x2009;=&#x2009;0.168), and other demographic characteristics (p&#x2009;>&#x2009;0.05) were not independently associated with FC after adjustment. CONCLUSION: FC is highly prevalent during pregnancy and may adversely affect women's quality of life. Higher dietary fibre and fluid intake were associated with lower odds of FC, highlighting the importance of healthy lifestyle behaviours during pregnancy. Prospective longitudinal studies are warranted to confirm these findings.

Humans

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3&#xa0;mg&#xa0;g-1 for myricetin and 112.1&#xa0;mg&#xa0;g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08&#xa0;mg&#xa0;g-1, respectively. Moreover, the affinity constants (KL&#xa0;=&#xa0;0.760-0.950&#xa0;L&#xa0;mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59&#xa0;ng&#xa0;mL-1 and limits of quantification (LOQs) of 1.10-1.96&#xa0;ng&#xa0;mL-1, and excellent linearity over the concentration range of 5.0-5500&#xa0;ng&#xa0;mL-1 (R2&#xa0;>&#xa0;0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids