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Effects of Progressive Inspiratory Muscle Training on Lung Volume and Respiratory Strength in Patients With Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease can present changes in thoracic cavity volume and respiratory muscle weakness, even in the pre-dialysis stage. However, there is little evidence on the effects of inspiratory muscle training in these patients. METHODS: This was a randomized clinical trial which comprised patients with Chronic Kidney Disease in stages 3, 4, and 5 undergoing conservative treatment, allocated experimental group (EG) with progressive loading (up to 50% of maximal inspiratory pressure [MIP]) and control group (CG) with a fixed load (5 cmH2O) and no load progression performed daily for 8&#xa0;weeks. The outcomes assessed were thoracic cavity volumes, as measured by optoelectronic plethysmography, and inspiratory and expiratory respiratory muscle strength. RESULTS: A total of 30 patients completed the study. All volumes significantly increased at the end of the protocol with a large effect size, but only the pulmonary thoracic cavity volume showed a significant interaction (F&#xa0;=&#xa0;3.698; p&#xa0;=&#xa0;0.042). There was an increase in inspiratory muscle strength in the EG (73.88-90.35&#xa0;cmH2O; p&#xa0;<&#xa0;0.001) and in the CG (70.85-86.92&#xa0;cmH2O; p&#xa0;=&#xa0;0.001), as well as in expiratory muscle strength in the EG (97.71-108.53&#xa0;cmH2O; p&#xa0;=&#xa0;0.001) and in the CG (80.69-94.77&#xa0;cmH2O; p&#xa0;=&#xa0;0.004). CONCLUSION: Daily IMT increased thoracoabdominal volumes, particularly pulmonary rib cage volume in the progressive-load group, as well as respiratory muscle strength in patients with pre-dialysis CKD. However, progressive-load IMT was not superior to minimal-load training.

Humans

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (&#x3c7;), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA&#xa0;=&#xa0;5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated &#x3c7; in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific &#x3c7; alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans

Premature closure underlies bias in medical diagnosis in students: A randomised controlled experiment.

OBJECTIVE: The purpose of the study reported in this article was to shed light on the cognitive mechanism mediating between biasing information and diagnostic error. The literature suggests at least two different hypotheses: premature closure leading biased participants to spend less time on diagnosis or increased competition between diagnostic hypotheses. The latter hypothesis predicts that biased participants would spend more time reaching a diagnosis. METHOD: Using the salient distracting findings (SDF) experimental paradigm, we biased 58 fourth-year medical students while diagnosing 12 clinical vignettes in a within-group incomplete block design under three conditions: cases presented without SDF, with SDF at the beginning and with SDF at the end. For each of these conditions, diagnostic accuracy, the number of SDF-related mistakes and time per word needed to process the case were recorded. The data were analysed using linear mixed modelling. Estimated marginal mean scores were reported. RESULTS: Participants confronted with salient distracting features (SDFs) at the beginning of a clinical case demonstrated significantly lower diagnostic accuracy (mean 0.11) compared with the No-SDF condition (0.27), representing a 61% reduction (F2,693&#x2009;=&#x2009;11.995, p&#x2009;<&#x2009;0.001), and made more SDF-related mistakes (F2, 693&#x2009;=&#x2009;16.395, p&#x2009;<&#x2009;0.001). When SDFs were presented at the end of the case, diagnostic accuracy was also reduced (mean 0.17; 36% reduction), but processing time did not differ from the No-SDF condition. Only early presentation of SDFs was associated with reduced processing time per word (F2,636&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.01), consistent with premature closure. CONCLUSION: These findings demonstrate that biasing information increases diagnostic error in medical students and that only early bias is associated with reduced information processing. The data do not support the competition hypothesis for early bias, as processing time did not increase under biasing conditions. Premature closure can therefore be directly observed rather than inferred, inviting further research.

Humans

Comparison of analgesic efficacy of pericapsular group of nerve block versus anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty: A comparative randomized controlled trial.

BACKGROUND: Total hip arthroplasty is a painful surgical procedure; therefore, it is a challenge to manage effective pain control during the perioperative period. STUDY OBJECTIVES: We compared the analgesic efficacy of the pericapsular nerve group block and the anterior quadratus lumborum block in patients undergoing unilateral hip arthroplasty. DESIGN: Randomized controlled trial. SETTINGS: Operating room of a tertiary care center. PATIENTS: 92 adult patients of >18&#xa0;years who underwent elective, unilateral total hip arthroplasty under spinal anesthesia were randomized to either Group P (USG guided PENG block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) or Group Q (USG guided QL block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) 20&#xa0;min before surgery. MEASUREMENTS: We compared the total perioperative fentanyl consumption between the two groups in the first 24&#xa0;h as the primary outcome. Other outcomes included time to first rescue analgesia in the postoperative period, NRS scores at rest and on movement at 0, 2, 4, 6, 12, and 24&#xa0;h, incidence of intraoperative hemodynamic changes, and incidence of postoperative PONV. MAIN RESULTS: There was no significant difference in the total fentanyl consumption between the two groups: 237.5 (150-450) &#x3bc;g in the P group and 250 (125-400) &#x3bc;g in the Q group; p&#xa0;=&#xa0;0.617. The time to first rescue analgesia was similar in both groups: the P group (198 [123-268] minutes) and the Q group (241 [180-318] minutes); p&#xa0;=&#xa0;0.120. There was also no difference in pain scores, intraoperative hemodynamic changes, or PONV. CONCLUSION: There was no difference in the perioperative opioid consumption, pain scores, and adverse event rates between the pericapsular nerve group block and anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI number: CTRI/2023/08/057157).

Humans

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p&#x202f;>&#x202f;0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p&#x202f;=&#x202f;0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p&#x202f;=&#x202f;0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1&#x2009;year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1&#x2009;year occurred in 44% of the MDT group vs 75% in the OBS group (P&#x2009;=&#x2009;0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4&#x2009;months) compared to the OBS arm (2.9&#x2009;months, P&#x2009;=&#x2009;0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans

Sleep disturbances in children and adolescents with iron deficiency: Questionnaire-based and actigraphic findings.

OBJECTIVE: Iron deficiency (ID), without or with anemia (IDA), has been linked to restless sleep and sleep-related movement disorders in childhood, but objective correlates are incompletely defined. We aimed to describe caregiver-reported sleep disturbances, restless legs syndrome (RLS) - related symptoms, and actigraphic sleep patterns in children and adolescents with ID/IDA, and to compare these findings with available sleep-asymptomatic control datasets. We finally explored short-term changes after iron supplementation. METHODS: In this single-center pilot observational study, 31 children with ID/IDA underwent baseline clinical/laboratory assessment and caregiver-reported sleep evaluation with the Sleep Disturbance Scale for Children (SDSC) plus RLS-oriented items. Sixteen also completed home actigraphy, and 8 had follow-up after iron treatment prescribed in routine care. Baseline findings were compared with historical healthy control datasets without reported sleep disturbances; iron-status data were not available for the questionnaire control group; within-subject changes were explored in the follow-up subgroup. RESULTS: Compared with healthy controls, the ID/IDA cohort had higher SDSC total scores (43.97&#x202f;&#xb1;&#x202f;9.63 vs 34.61&#x202f;&#xb1;&#x202f;7.50; p&#x202f;<&#x202f;0.001), with significant differences in the subscales difficulty in initiating and maintaining sleep (DIMS), sleep-wake transition disorders (SWTD), and sleep hyperhidrosis (SHY). Ten of 31 screened children (32.25%) had clinically plausible RLS-related symptoms and higher SWTD scores. Actigraphy showed shorter sleep duration, lower sleep efficiency, longer wake after sleep onset, and greater fragmentation. After iron treatment, parent reported restlessness improved, whereas actigraphic parameters showed only partial normalization. CONCLUSIONS: Pediatric ID/IDA was associated with caregiver-reported and actigraphic sleep disruption, characterized by restless and fragmented sleep. These findings support systematic sleep assessment in children with low iron stores and consideration of iron status in the work-up of restless or nonrestorative sleep.

Humans

Granger connectivity and graph-theoretical analysis of scalp EEG across the preictal to ictal transition for presurgical evaluation.

OBJECTIVE: To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. METHODS: Adults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. RESULTS: Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. CONCLUSIONS: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. SIGNIFICANCE: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Humans

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n&#x200a;=&#x200a;70) or cefoxitin (n&#x200a;=&#x200a;70), 2&#x2005;g every 8&#x2005;h for 5&#x2005;days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P&#x200a;=&#x200a;0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P&#x200a;=&#x200a;0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P&#x200a;=&#x200a;0.753), and mortality was 15.7% and 12.9%, respectively (P&#x200a;=&#x200a;0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of &#x2264;8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score &#x2264;4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans

[Analysis of a Chinese pedigree affected with Townes-Brocks syndrome due to a novel variant of SALL1 gene and a literature review].

OBJECTIVE: To analyze a novel exonic variant of the SALL1 gene and its impact on the binding site of SALL protein. METHODS: Clinical data of three children diagnosed with Townes-Brocks syndrome and their family members who had presented at the First Affiliated Hospital of Shandong First Medical University in April 2022 were retrospectively collected. The pathogenic variant was identified through whole-genome sequencing (WGS) and validated by Sanger sequencing. Protein structural prediction was performed using AlphaFold and PyMOL software to construct three-dimensional models of the wild-type and mutant proteins. Additionally, previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-386). RESULTS: The proband was one of triplet sisters born at 34+4 gestational weeks. All three cases had presented with anal atresia and rectovaginal fistula, and case 3 also had toe malformation of left foot. WGS revealed a novel heterozygous c.757C>T (p.Gln253*) variant in the SALL1 gene, which was predicted to be pathogenic. Sanger sequencing confirmed co-segregation of the variant with the disease within the family. Protein structural modeling demonstrated that the variant has introduced a premature stop codon at position 253, resulting in a truncated protein. CONCLUSION: Above finding has enriched the mutation spectrum of the SALL1 gene in association with Townes-Brocks syndrome, which also represented a rare case of anal atresia in triplets, and provided a basis for molecular diagnosis, genetic counseling, and further research.

Humans

Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.

STUDY OBJECTIVES: To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (&#x2265;18&#xa0;years) with severe OSA without insomnia. In each period, daridorexant 50&#xa0;mg or placebo was administered every evening for 5&#xa0;days. Primary and secondary endpoints were the treatment differences (daridorexant-placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI &#x2265;10 events/h and mean decrease in nocturnal SpO2 &#x2264;-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO). RESULTS: Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were&#x2009;-3.7 events/h (one-sided 95% CI&#x2009;&#x2264;&#x2009;+4.2) and&#x2009;-&#x2009;0.12 % (one-sided 95% CI&#x2009;&#x2265;&#x2009;-0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5&#xa0;min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3&#xa0;min [90% CI: -20.6, -0.02]) and a trend towards reduced WASO (-15.2&#xa0;min [-31.2, 0.9]). Four adverse events were reported (daridorexant n&#x2009;=&#x2009;3; placebo n&#x2009;=&#x2009;1), all of mild intensity and none related to respiratory function. CONCLUSION: Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193. Statement of Significance Obstructive sleep apnea (OSA) is highly prevalent and associated, in 30%-50% of cases, with insomnia-related symptoms, yet the safety of insomnia medications in OSA remains unclear. Daridorexant, a dual orexin receptor antagonist for the treatment of adults with insomnia disorder, previously showed no negative effect on sleep-disordered breathing in participants with mild/moderate OSA. This randomized, double-blind, placebo-controlled, crossover trial evaluates daridorexant 50&#xa0;mg (maximum therapeutic dose) in participants with severe OSA without insomnia. Repeated dosing (5 nights) did not impair nighttime respiratory function, as assessed by apnea/hypopnea index and nocturnal oxygen saturation. Moreover, improvements in sleep characteristics were observed with daridorexant, extending evidence that daridorexant 50&#xa0;mg is safe and well-tolerated and may improve sleep in adults with severe OSA.

Humans

Effectiveness of a digi-physical tool and working method for paediatric obesity treatment in Abu Dhabi: a non-inferiority intervention study using an external historical comparator.

BACKGROUND: Effective paediatric obesity treatment requires high intensity, scalable interventions. A digi-physical tool for paediatric obesity treatment has shown positive results in Stockholm, Sweden. This study evaluates whether the same treatment method is effective in a different cultural setting. METHODS: This non-inferiority intervention study, using an external historical comparator, included 60 consecutively recruited children aged 6-15.9 years with obesity who initiated treatment at Sheikh Shakhbout Medical City in Abu Dhabi between June and December 2023. Patients were treated with Evira, a digi-physical tool and working method enabling high intensity individualized care, real-time monitoring, and interactive patient-clinician communication. The primary outcome was BMI z-score change at 26 weeks. Non-inferiority was assessed using a predefined margin of 0.10 BMI z-score, with outcomes compared to a prior published trial in Stockholm (n&#x2009;=&#x2009;107). RESULTS: A total of 112 children were included in the analysis (Abu Dhabi cohort, n&#x2009;=&#x2009;35; Stockholm cohort, n&#x2009;=&#x2009;77). The adjusted mean change in BMI z-score was -&#x2009;0.20 (95% CI: -&#x2009;0.28, -&#x2009;0.12) in the Abu Dhabi cohort and -&#x2009;0.20 (- 0.26, -&#x2009;0.14) in the Stockholm cohort (p&#x2009;=&#x2009;0.88). Non-inferiority was confirmed, (predefined margin 0.10 was not exceeded). A clinically significant BMI z-score reduction (&#x2265;&#x2009;0.20 units) was achieved by 45.7% of participants in Abu Dhabi and 36.4% in Stockholm (p&#x2009;=&#x2009;0.35). Non-retention rates at 26 weeks were 41.7% vs. 28.0%, respectively (p&#x2009;=&#x2009;0.07). CONCLUSIONS: The findings provide promising evidence that treatment outcomes achieved with the digi-physical treatment tool were comparable in the Abu Dhabi and Stockholm cohorts, supporting its feasibility in a second cultural and healthcare setting.

Humans

Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n&#x2009;=&#x2009;1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n&#x2009;=&#x2009;7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

Humans

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 &#xb1; 0.17 vs. 4.65 &#xb1; 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 &#xb1; 15.69 vs. 8.64 &#xb1; 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 &#xb1; 0.09 vs. 0.06 &#xb1; 0.10 mm; P = 0.43) or mPII (0.10 &#xb1; 0.12 vs. 0.10 &#xb1; 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans