Therapeutic inertia has been extensively examined in chronic medical conditions but remains insufficiently conceptualized and empirically studied in psychiatry. This structured narrative review examines therapeutic inertia as a multilevel and potentially bidirectional phenomenon arising when clinically relevant care is not reconsidered or modified despite unmet therapeutic goals and the availability of a reasonable and feasible alternative. A targeted PubMed search was supplemented by backward and forward citation searching, prioritizing psychiatric evidence and foundational literature on clinical decision-making under uncertainty. The review distinguishes therapeutic inertia from appropriate caution, watchful waiting, informed refusal, structural non-access, therapeutic nihilism, medical futility, therapeutic obstinacy, and evidence-based deprescribing. Potential determinants include cognitive and emotional mechanisms, diagnostic and prognostic uncertainty, adverse-effect concerns, patient preferences and previous experiences, therapeutic relationships, resource constraints, fragmented care, guideline structures, workload, and medicolegal culture. Clozapine underutilization in treatment-resistant schizophrenia represents the most compelling psychiatric example, while direct but more limited evidence is available in major depressive and bipolar disorders; applications to anxiety, obsessive-compulsive, substance-use, and non-pharmacological care remain largely hypothesis-generating. Strategies include explicit therapeutic goals, planned reassessment, measurement-based and guideline-informed care, shared decision-making, multidisciplinary review, improved access, clinical decision support, and audit and feedback. Future research should use operational definitions, experimental and observational designs, patient-centered outcomes, and real-world data to determine when treatment non-modification is inappropriate and whether corrective interventions improve care without promoting indiscriminate escalation, coercion, polypharmacy, or premature discontinuation.
The term sepsis is commonly used in surgical and critical care settings, yet its linguistic and emotional impact on patients' families is underexplored. Misinterpretation can influence perception, critical decision, and heighten fear. This work examines how the diagnosis of sepsis functions as both a physiologic and communicative event, and to propose the SEPSIS Dialogue; a novel, structured framework for family-centered communication in acute surgical care. Narrative reflection and synthesis integrating surgical physiology, health literacy, and communication ethics. This framework was developed by mapping common communicative friction points in the ICU and perioperative setting against established principles of serious illness conversations. Families frequently interpret sepsis as a fixed, catastrophic outcome, whereas clinicians view it as a dynamic spectrum. In surgical contexts, this "comprehension gap" is often widest at critical decision points, such as the need for re-operation. The SEPSIS Dialogue (State mechanism, Explain source, Present the spectrum, Speak to uncertainty, Invite questions, Support emotions, Demonstrate understanding) provides a structured pathway to bridge the gap in ways that respect comprehension, emotional experience, and clinical context. Structured, plain-language communication can transform sepsis conversations from fear-driven moments into opportunities for partnership, clarity, and informed, values-based care.
So far, a full exocrine system survey exists for the major ant subfamilies but not yet for Pseudomyrmecinae. This study provides a morphological survey of the exocrine system in workers of Tetraponera ants using the large Tetraponera rufonigra and the smaller T. allaborans, T.penzigi and T. tessmanni. We found 20 glands of which the antennal bulb gland is a new exocrine structure in ants. The cardo base gland is well-developed in all species which is striking as this gland so far was mainly found in the subfamily Formicinae. Gland size is linked with worker size, in which larger workers clearly have more cells rather than bigger cells. A study of the exocrine system in other ant subfamilies often revealed differences that are relevant for species' lifestyle and communication system. In spite of the numerous glands described in the present paper, almost nothing is known about their function in Tetraponera as surprisingly poor literature data exist on the communication system in this genus. Our study hopefully inspires researchers to perform bioassay experiments using gland extracts to fill this gap in the social biology of these ants.
Catheter-related bladder discomfort (CRBD) after perioperative catheterisation of the urinary bladder (COUB) is not uncommon. We evaluated the efficacy of both oral gabapentin and trospium in preventing CRBD during the early postoperative period in patients admitted to the surgical intensive care unit (S-ICU). 120 patients aged 20-65 years, ASA I, II or III who were admitted to S-ICU after undergoing elective spinal surgery (ESS) with COUB were included. They were randomly assigned to be administered either an oral 400 mg gabapentin capsule (Group G) or an oral 60 mg slow-release trospium chloride capsule (Group T) or nothing (Group C). The primary goal was the occurrence of CRBD and its severity at 1, 2, 6, 12, and 24 hours after the study drug administration (SDA). Group G and group T had a statistically significant lower incidence of CRBD than group C at 1, 2, 6, 12, and 24 hours after SDA, respectively. Both had considerably lower severity than group C in the first two hours only (P= 0.001 and 0.001, respectively). Group T had non-significantly lower incidence and severity of CRBD than group G. Group G had significantly lower mean total fentanyl requirements for up to 24 hours after SDA than group T and group C (P < 0.001). Both oral gabapentin capsules and slow release trospium chloride capsules administered postoperatively, significantly decreased both the incidence of CRBD and its severity in the early postoperative period amongst S-ICU patients, without significant differences between the two drugs.
Single-cell foundation models such as scGPT and Geneformer are large neural networks trained on human single-cell RNA-seq data. They were never shown chronological age during training. Do their internal representations nevertheless encode aging biology in a way that can be interpreted, and how should we test whether an apparent aging signal is real biology rather than an artifact of which donors and cell types happened to be sampled?. We applied a nine-step evaluation pipeline to two foundation models (frozen, no fine-tuning) and five PBMC datasets containing 4 to 5 million cells from ∼ 2,000 donors with chronological age. Each step is one specific test: can we read age out of the model's representation; does the representation place age along a clean axis; do sparse-feature decompositions surface aging-related programs; do the two models agree at the pathway level; do targeted perturbations of those features change predicted age in the expected direction; and finally, does the signal survive when we resample cells so that young and old donors have matched cell-type composition (removing the most obvious confound). (1) The foundation models encode age but do not predict it better than a 50-component PCA of gene expression: in all five cohorts the PCA baseline matches or exceeds the best foundation-model probe. What they add is a complementary interpretability mode-sparse-feature decomposition and activation-level intervention-rather than predictive power; a PCA of gene expression is itself interpretable through its loadings, so the contribution here is the evaluation framework that adjudicates such signals, not a claim that foundation models predict age better. Randomly reinitialising Geneformer's weights destroys most of its age signal ( - 0.107 balanced-accuracy points), while doing the same to scGPT's layer 9 changes essentially nothing-so the two models encode age asymmetrically. (2) Sparse autoencoders surface 132 robust aging-related features across the two models, of which 193 cross-model pairs match each other at pathway level, concentrated in inflammation. The shared inflammation signal resolves into specific submodules: TNF / NF- κ B classical and type-II IFN- γ (both models agree), complement (scGPT-specific). (3) The strongest aging signal is Geneformer's NF- κ B program in the AIDA phase 1 v2 cohort. Pushing those features in the "older" direction increases predicted age by 0.15 expected-age units; pushing them the opposite way decreases it; pushing along random unrelated directions does neither-a three-way directional check we call the "strict gate". When cells are resampled so that the age groups have matched cell-type composition (the strictest control), the directional effect shrinks ∼ 3 × but 7 of 8 resampling seeds still pass the strict gate. One in eight resamplings fully nullifies the effect. The directional aging signal therefore survives confounder removal on most realizations, at attenuated magnitude. An external check on the Yazar OneK1K cohort (981 donors, fully separate from AIDA) reproduces the workflow on a known-strong biological axis (sex), with results within 10% of the AIDA contrast-evidence that the test is calibrated and transfers off-cohort. The paper's primary contribution is an evaluation framework for deciding when an apparent aging signal in a single-cell foundation model is biology rather than sampling structure. Applied here, it shows that frozen foundation models carry a recoverable aging signal concentrated in NF- κ B and IFN- γ inflammation submodules-biology that is already established at the gene-expression level, recovered zero-shot from models never trained on age. Reporting both an unrestricted contrast and a composition-matched contrast as side-by-side specificity tests-not just the headline number-is the framework's central recommendation.
The United States National Institutes of Health (NIH) serves as the cornerstone of biomedical research funding. Yet, radiology departments receive a disproportionately small share of this support, concentrated among senior investigators at large academic institutions. Beginning in January 2025, the current administration proposed an approximately 40% reduction in federal research funding, equivalent to a $20 billion decrease, and implemented the termination or freezing of over 2500 grants, representing $1.4 billion in research loss, alongside a proposed 15% mandatory cap on indirect cost recovery. This perspective examines the potential consequences of these administrative changes on the radiology physician-scientist pipeline and the future of imaging research and innovation. Research Project Grant success rates are projected to decline from 18.5% in fiscal year (FY) 2024 to a historic low of 7.3% by FY 2026, compounding the already widening gap between established and early-career investigators. Radiology-specific training pathways remain critically undersubscribed, with the Holman Research Pathway averaging only 1.6 graduates per year over 20 years. The systematic erosion of NIH training grants and dropping funding success rates risk permanent structural collapse of the radiology physician-scientist workforce, and jeopardizing United States leadership in imaging science, artificial intelligence, and translational innovation.
Specific patient characteristics and certain cancer treatments increase the risk for postoperative complications in implant-based breast reconstructions. It is therefore essential to identify those risk factors and analyse their contribution to the outcome. Implant-based breast reconstruction with support of synthetic non-resorbable titanized polypropylene surgical mesh (TiLOOP® Bra) was performed in 269 patients during the prospective, multicentre PRO-BRA cohort trial (clinicaltrials.gov: NCT01885572, DRKS: DRKS00005342). Secondary endpoint was the evaluation of the postoperative complication rate 24 months after breast reconstruction. Univariable and multivariable logistic regression analyses were performed to identify specific factors (e.g. BMI, age, radiotherapy, chemotherapy, implant size) increasing the risk for complications. In 362 breast reconstructions the following factors were identified in univariable logistic regression to be associated with an increased risk for distinct complications: Implant volume, BMI (complication irrespective of type, seroma, wound complications), adjuvant radiotherapy (capsular fibrosis), Charlson Comorbidity Index (first complication, seroma), age (seroma), transverse/vertical incision (wound complications), and adjuvant chemotherapy (infection/inflammation). Multivariable logistic regression identified neoadjuvant chemotherapy as significant risk factor for the occurrence of complications. The following factors have been identified as increasing the risk of developing postoperative complications of implant-based breast reconstruction with a non-resorbable titanized polypropylene surgical mesh (TiLOOP® Bra): larger implants, age of 50 years or over, BMI of 25 kg/m2 or over, adjuvant radiotherapy, as well as neoadjuvant and adjuvant chemotherapy. These factors must be considered when selecting patients for this type of breast reconstruction and should form part of a thorough patient information.
Stent failure, including in-stent restenosis (ISR) and occlusion, remains a major challenge in femoropopliteal arteries. Since the underlying cause of stent failure, such as fibrin-rich thrombus versus organized fibrous plaque, likely dictates the optimal treatment strategy, accurate characterization of neointimal tissue is crucial. However, pathological validation for key intravascular imaging modalities in this setting is lacking. A total of 22 femoral arteries with an in-stent restenosis model in healthy swine after stent implantation were evaluated. One month later, intravascular imaging using intravascular ultrasound (IVUS), optical frequency domain imaging (OFDI), and angioscopy was performed. Diagnostic accuracy for characterizing neointimal tissue ≥ 1000 μm (thick neointima) was assessed using histology as the gold standard. For detecting fibrin/organizing thrombus, IVUS showed high specificity (96%) but poor sensitivity (13%), leading to underestimation. Conversely, OFDI offered relatively high sensitivity (60%) but a modest positive predictive value (PPV, 50%), risking overestimation. A paired use of IVUS and OFDI approach overcame these limitations, yielding significantly improved diagnostic accuracy (sensitivity 50%, specificity 96%, PPV 83%). While angioscopy showed excellent specificity (100%), its utility was limited by very low sensitivity (24%). Paired use of IVUS and OFDI may improve diagnostic confidence for neointimal tissue characterization. In contrast, the utility of angioscopy appears limited due to low sensitivity.
The optimal duration of dual antiplatelet therapy (DAPT) for high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) can vary based on individual clinical and lesion characteristics. As bifurcation lesions are associated with a greater risk of ischemic events, it is unknown whether HBR patients with bifurcation lesions can be safely treated with abbreviated DAPT. We examined ischemic and bleeding outcomes in patients with and without bifurcation lesions who underwent PCI with the Resolute Onyx zotarolimus-eluting stent (Medtronic) from the Onyx ONE Clear study. HBR patients free of events through 1 month were prescribed 1 month of DAPT. Outcomes from 1 month to 2 years were analyzed among patients with HBR who underwent successful PCI for at least 1 bifurcation lesion followed by 1-month DAPT. Of 1507 total HBR patients, 215 (14.3%) underwent PCI of a bifurcation lesion, with 86.6% treated with a provisional approach. Included patients had an average of 1.6 HBR criteria. Patients with bifurcation lesions treated had more stents implanted and longer total length of stents implanted. The composite of cardiac death or myocardial infarction was similar for patients with vs without bifurcation lesions (12.2% vs 11.6%, P = .92). There were no differences in any clinical or angiographic outcomes between groups, including BARC 3 to 5 bleeding events. In the Onyx ONE Clear study, HBR patients with bifurcation lesions treated with the Resolute Onyx zotarolimus-eluting stent and 1-month DAPT had comparable ischemic event rates at 2 years compared with patients without bifurcation lesions, despite greater lesion and procedural complexity.
Workers occupationally exposed to fuel vapors are at risk of contamination by heavy metals such as lead and cadmium. This study aimed to quantify blood levels of lead and cadmium and evaluate associated biochemical, hormonal, and oxidative stress alterations among fuel station workers. This cross-sectional study recruited 66 healthy males, comprising 33 workers with at least 2 years of direct fuel exposure and 33 non-exposed controls. Blood lead and cadmium were quantified using Flame Atomic Absorption Spectrophotometry (AAS). Biochemical markers, reproductive hormones, and oxidative stress indicators were analyzed. Statistical analyses were performed using independent t-tests to identify significant differences between groups, and Pearson's correlation test to assess associations. Mean blood lead (43.4±5.4 µg/dL vs. 23.6±1.6 µg/dL; P<0.05) and cadmium levels (10.1±1.2 µg/dL vs. 5.5±0.4 µg/L; P<0.05) were significantly higher in exposed workers. Biochemical markers were elevated including ALT (38.76±3.3 U/L vs. 24.39±3.6 U/L; P<0.05), AST (29.91±3.4 U/L vs. 16.55±4.0 U/L; P<0.05), ALP (82.82±12.4 U/L vs. 42.67±9.5 U/L; P<0.05), BUN (19.52±3.1 v mg/dL s. 9.82±2.0 mg/dL), and Creatinine (1.13±0.1 mg/dL vs. 0.72±0.1 mg/dL; P<0.05) in exposed group. Oxidative stress was evident with higher MDA (2.86±0.6 nmol/mL vs. 0.84±0.2 nmol/mL; P<0.05) and lower SOD and GSH (P<0.05). Testosterone decreased (3.77±0.9 ng/mL vs. 4.98±0.9 ng/mL; P<0.05) while FSH increased (P<0.05). Occupational exposure to lead and cadmium suggests adverse hepatic, renal, hormonal, and oxidative stress changes among fuel station workers. Regular monitoring of biochemical and hormonal markers is strongly recommended, along with preventive exposure-control measures.
Extended interval dosing (EID) of natalizumab is increasingly used in clinical practice for patients with multiple sclerosis, driven by growing evidence supporting its sustained efficacy and associated benefits. However, it remains unclear whether EID, particularly at dosing intervals beyond six weeks, affects treatment satisfaction. To investigate whether natalizumab dosing intervals of up to ten weeks are associated with patient-reported treatment satisfaction. Participants from the prospective NEXT-MS and SUPERNEXT trials, both evaluating concentration-guided EID while preserving therapeutic drug concentrations, completed longitudinal Treatment Satisfaction Questionnaire for Medication (TSQM) assessments. Associations between dosing interval and scores in the four TSQM domains (Effectiveness, Side effects, Convenience, and Overall satisfaction) were analyzed using linear mixed-effects models. A total of 427 participants were included. Most participants reported high treatment satisfaction. No overall association was observed between dosing interval and TSQM scores. However, additional effect-modification analyses suggested that the association between dosing interval and treatment satisfaction differed according to treatment duration, disease duration, baseline EDSS, and route of natalizumab administration. Treatment satisfaction was high and was not affected by longer dosing intervals in the majority of patients. However, additional effect-modification analyses indicated that the impact of dosing interval on treatment satisfaction may differ according to patient characteristics, highlighting the importance of individualized treatment decisions.
Protecting hippocampal structures, such as the cornu ammonis 3 and dentate gyrus (CA3/DG), that are tied to mnemonic discrimination could be a promising approach to mitigate the age-related decline in episodic memory. This study examines the potential benefits of cognitive and physical engagement, specifically language learning and moderate aerobic exercise, for maintaining hippocampal subfield integrity and memory performance. In a randomized controlled trial involving 142 healthy older adults (aged 63-78 years), we investigated the effects of a 6-month regime comprising language learning, aerobic exercise, and their combination. Participants were assigned to one of four groups: an active control, language-only, exercise-only, or combined language and exercise group. CA3/DG volume remained stable in the language-only and combined groups, while the non-language groups showed a significantly greater decrease in volume, suggesting that foreign language learning may protect against normal aging-related CA3/DG volume loss. Comparatively, the exercise-only and combined groups showed significant improvements in mnemonic discrimination performance, while the non-exercise groups did not, indicating that aerobic exercise can improve this aspect of memory in older adults. Notably, the combined group was the only group to exhibit both preserved CA3/DG volume and improved mnemonic discrimination. No evidence for a boosting effect of the combined intervention on either outcome was observed. This suggests that, while the effects of language learning and aerobic exercise may be independent at the level of measured outcomes, they provide complementary benefits when combined. Finally, the initial volume of the subiculum was found to predict changes in mnemonic discrimination performance across all groups, indicating that this region may play a potential role in episodic memory changes over time. Contrary to our expectations, changes in hippocampal subfields were not directly associated with changes in mnemonic discrimination. In conclusion, this study highlights the potentially separate roles of foreign language learning and aerobic exercise in enhancing aspects of episodic memory in older adults; future research may address whether their combination may yield broader functional benefits than either intervention alone.
Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs), including tryptophan-derived metabolites such as kynurenine (KYN), indoxyl sulfate (IS), and indole-3-acetic acid (IAA). IS has been identified as a potential contributor to cognitive impairment (CI), whereas less is known about the other tryptophan metabolites. We aimed to evaluate the association between these toxins related to tryptophan metabolism and CI in patients with CKD. Three thousand thirty-three patients with CKD stages 2-5 enrolled in CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort. Patients with both UT measurement and cognitive function screening [with mini-mental state examination (MMSE)] were included. CI was defined as an MMSE score ≤ 26/30. Logistic regression was used to assess the association between the studied UTs and MMSE. Of the 2389 included patients [mean (SD) age: 66.5 (12.8) years, 66% males, mean (SD) estimated glomerular filtration rate (eGFR) 34.8 (13.4) ml/min/1.73 m2], 858 patients (35.9%) had an MMSE score ≤26/30. After adjustment for sociodemographic factors, cardiovascular risk factors, cerebrovascular disease, current depression, eGFR, urinary albumin-to-creatinine ratio, and UTs known to be associated with CI, no significant association was found between KYN or IAA and MMSE ≤26/30, whereas IS was significantly associated [Odds Ratio (OR), 95% confidence interval: 1.11 (1.00-1.21)]. Among tryptophan-derived metabolites studied, IS was associated with CI in patients with CKD, in contrast to KYN and IAA. Despite sharing a common origin, the UTs studied follow distinct metabolic pathways with different effects, highlighting the need for further investigation of the tryptophan pathway on CI in CKD.
This study aimed to evaluate the long-term effects of lobeglitazone on renal function, glycemic control, metabolic parameters, and safety in Korean patients with type 2 diabetes mellitus (T2DM) treated for over 1 year. This retrospective, non-interventional, multicenter observational study was conducted at 30 institutions in South Korea. Patients with T2DM who had received lobeglitazone for at least 1 year and had available estimated glomerular filtration rate (eGFR) data were included. Primary outcomes were changes in eGFR and urinary albumin-creatinine ratio (UACR). Secondary outcomes included changes in HbA1c, body weight, lipid profiles, insulin resistance, β-cell function, and adverse events (AEs). Of the 2743 enrolled patients, 2648 and 2500 were analyzed for safety and efficacy, respectively. Of 2648 patients analyzed for safety, 1655 (62.5%) were male and 993 (37.5%) were female. Baseline eGFR (82.0 ± 22.0 ml/min/1.73 m2) remained stable over 6 years across all chronic kidney disease (CKD) stages. UACR was unchanged in 77-83% of patients throughout follow-up. HbA1c significantly decreased from baseline (- 0.99% at year 1 to - 0.93% at year 6; all p < 0.0001), indicating sustained glycemic control. Lipid profiles and HOMA-IR improved, while HOMA- β remained stable. Overall, 1165 AEs occurred in 531 patients (20.05%), mostly consistent with the established safety profile; events of special interest were rare (< 1%). Long-term lobeglitazone treatment was not associated with deterioration of renal function or worsening of albuminuria status across all CKD stages, while demonstrating sustained glycemic efficacy and a favorable safety profile in real-world clinical practice. These findings support lobeglitazone as a clinically relevant long-term treatment option for patients with T2DM, including those with pre-existing CKD.
Gestational diabetes (GDM) is a frequent health problem associated with both short- and long-term adverse outcomes for mother and child. Standard management includes lifestyle interventions and, when necessary, pharmacologic therapy. However, the effectiveness and timely initiation of pharmacological therapy depend on accurate glucose monitoring. Continuous glucose monitoring (CGM) systems have emerged as valuable tools in diabetes care, providing real-time information on glycemic variability and enabling more individualized therapeutic interventions. In this narrative review, we explore the role of CGM in the early detection of dysglycemia, its diagnostic and prognostic value, and its ability to identify specific glycemic patterns during pregnancies complicated by GDM. We also assess its role in optimizing lifestyle interventions and guiding pharmacotherapeutic strategies. Current evidence suggests that CGM supports clinical decision-making and patient engaging by providing real-time glucose data. This facilitates earlier identification of hyperglycemic patterns, more precise treatment changes and improved glucose control. Furthermore, CGM use has been associated with improved neonatal and maternal outcomes. Despite these promising findings, barriers such as cost and limited access persist. Although the existing evidence remains relatively limited, it supports the integration of CGM into routine care of women with GDM as part of a comprehensive and personalized treatment strategy. Larger clinical trials are needed to fully understand the benefits and optimal use of CGM in GDM, as well as its impact on pregnancy outcomes, glycemic control and psychological well-being.
Newer, more comprehensive treatment endpoints in the clinical management of patients with inflammatory bowel disease necessitate a robust, accurate, and reproducible approach during the histologic examination of disease activity in specimens from these patients. Pathologists are increasingly being asked to evaluate and report histologic parameters that will enable more specific and focused treatment decisions in the quest for more complete disease remission. This review will summarize the terminology used, available scoring systems, use context, and appropriate interpretation of findings during this endeavor. Limitations and future concerns in this evolving landscape will also be considered.
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Whether hypoxia during popular high-altitude travel negatively affects cerebral oxygenation in vulnerable patients with pulmonary vascular disease (PVD) is unknown. We studied overnight cerebral tissue oxygen saturation (CTO) and desaturation index (cODI) in PVD-patients at 2500 m and effects of supplemental oxygen therapy (SOT). In this randomized-controlled crossover trial, stable PVD-patients diagnosed with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) had CTO and cODI (decrease in CTO ≥ 4%) assessed overnight at 470 m and 2500 m along with fingertip pulseoximetry (SpO2) and desaturation index (aODI). For safety, SOT was given if SpO2 dropped < 80% for > 30 min and stratified analysis accordingly. Primary endpoint was the difference in CTO between 470 and 2500 m. 16 PVD-patients (7 women; 13 PAH, 3 CTEPH), (mean ± SD) 56 ± 14 years old, were included per-protocol. At 470 m, the mean nocturnal CTO was 66.3 ± 1.6% and SpO2 90.3 ± 0.8%. At 2500 m on ambient air, CTO was unchanged 65.9 ± 1.6% (mean difference -0.4%; 95% CI -4.0 to 3.2) despite a lower SpO2 of 83.6 ± 0.8; -6.7 (-8.7 to -4.6%). At 2500 vs. 470 m, cODI increased by 3.1 events/hour (-0.3 to 6.6). SOT needed by 50% of PH-patients improved SpO2 by +7.5 (4.9 to 10.0), but not CTO and cODI (+3.6% (-1.0 to 8.2)) and -3.8 events/hour (-8.1 to 0.5). In PVD-patients on ambient air at 2500 m, nocturnal CTO remained unchanged compared to 470 m despite lower SpO2. SOT promptly improved SpO2 without affecting cerebral oxygenation. These findings suggest sufficient nocturnal cerebral protection at 2500 m in PVD.
To translate, culturally adapt, and validate the Thai Hot Flash-related Daily Interference Scale for assessing interference from vasomotor symptoms. In this cross-sectional psychometric validation study, the Hot Flash-related Daily Interference Scale was translated using forward-backward translation, expert review, and cognitive debriefing. Women in the menopause transition or postmenopause at the menopause clinic in Bangkok completed the Thai Hot Flash-related Daily Interference Scale, the Thai Menopause Rating Scale, and the Thai Menopause-Specific Quality of Life questionnaire. Psychometric evaluation included content validity, structural validity, internal consistency, test-retest reliability using the intraclass correlation coefficient, construct validity evidence, floor and ceiling effects, and exploratory receiver operating characteristic analyses to support score interpretation. Of 336 enrolled women, 330 were analyzed (164 symptomatic and 166 asymptomatic controls). Content validity was high (scale-level content validity index=0.960). Reliability was excellent (Cronbach's alpha=0.963; intraclass correlation coefficient=0.981; 95% CI: 0.971-0.987). Factor analyses supported a predominantly unidimensional structure. Construct validity evidence was supported by a strong correlation with the vasomotor domain of the Thai Menopause-Specific Quality of Life Questionnaire (Spearman's correlation coefficient=0.716; P<0.001) and by known-groups differences between symptomatic and asymptomatic women (mean, 3.67 vs. 0.43; P<0.001). In exploratory supplementary analyses, scale scores showed good discrimination between Menopause Rating Scale-defined symptom-burden groups. The Thai Hot Flash-related Daily Interference Scale demonstrated reliability and validity and provides a brief measure of vasomotor symptom-related interference for Thai-speaking women in clinical practice and research.
Multidrug-resistant (MDR) Gram-negative pneumonia is associated with high mortality and substantial healthcare resource utilization. Ceftazidime-avibactam (CAZ-AVI) is an important option, yet real-world experience in Chinese pneumonia cohorts is limited and the associated inpatient costs are seldom reported. This study aimed to describe the clinical response to CAZ-AVI in routine practice, to identify the factors associated with 14-day and with 30-day all-cause mortality separately so as to examine how they differ over time, and to characterize inpatient costs. We retrospectively studied 693 adults with MDR pneumonia who received at least 3 days of CAZ-AVI at eight hospitals in Hubei, China, between August 2022 and August 2025. Factors associated with 14-day and 30-day all-cause mortality were examined by univariable and multivariable logistic regression, with LASSO-penalized regression and cross-validation as a sensitivity analysis. Acute kidney injury (AKI) was recorded as a safety observation, and pneumonia-related inpatient costs were summarized descriptively. The study is reported in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Overall, 480 patients (69.3%) had a favorable response (cure, 356 [51.4%]; improvement, 124 [17.9%]). A higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score was independently associated with mortality at both 14 days (adjusted OR 1.20; 95% CI 1.14-1.26) and 30 days (1.27; 1.18-1.37). At 14 days, death was further associated with bacteremia (4.76; 2.39-9.66), carbapenem-resistant organisms (CRO; 5.93; 2.60-13.60), and septic shock (3.30; 1.32-8.39). At 30 days, the associated factors were Klebsiella pneumoniae (15.19; 3.25-78.94; the wide confidence interval warrants caution) and septic shock (5.74; 1.34-24.97), while a later rise in serum albumin accompanied lower mortality (0.89; 0.82-0.95). AKI occurred in 15 of 693 patients (2.2%). The median total inpatient cost was USD 14,982 (IQR 8462-25,136), of which CAZ-AVI accounted for a median of USD 3901 (IQR 2069-6159). In routine practice, CAZ-AVI for MDR pneumonia was associated with a favorable response, and the factors linked to early death differed from those linked to later death. These associations are hypothesis-generating; together with the cost description, they may help inform time-stratified management and the controlled studies needed to confirm these findings. Multidrug-resistant Gram-negative pneumonia carries significant morbidity and mortality, often requiring resource-intensive care. Ceftazidime–avibactam is an essential therapeutic option for these resistant infections. This retrospective, multicenter study evaluated the real-world clinical response to ceftazidime–avibactam in 693 adult patients across central China. Overall, 69.3% of patients achieved a favorable clinical response. Notably, the clinical factors associated with early mortality (within 14 days) differed from those linked to later mortality (up to 30 days). Early mortality was primarily associated with acute infectious dissemination, such as bacteremia and septic shock, whereas later mortality correlated with sustained inflammation, poor nutritional status, and specific pathogens such as Klebsiella pneumoniae. While lacking a comparator group to establish comparative efficacy, these findings highlight the necessity of time-stratified clinical management and provide real-world inpatient cost data to inform future controlled trials.