Development and Validation of a Machine Learning Model for Early Prediction of Delirium in Intensive Care Units Using Continuous Physiological Data: Retrospective Study

BACKGROUND: Delirium in intensive care unit (ICU) patients poses a significant challenge, affecting patient outcomes and health care efficiency. Developing an accurate, real-time prediction model for delirium represents an advancement in critical care, addressing needs for timely intervention and resource optimization in ICUs. OBJECTIVE: We aimed to create a novel machine learning model for delirium prediction in ICU patients using only continuous physiological data. METHODS: We developed models integrating routinely available clinical data, such as age, sex, and patient monitoring device outputs, to ensure practicality and adaptability in diverse clinical settings. To confirm the reliability of delirium determination records, we prospectively collected results of Confusion Assessment Method for the ICU (CAM-ICU) evaluations performed by qualified investigators from May 17, 2021, to December 23, 2022, determining Cohen kappa coefficients. Participants were included in the study if they were aged >/=18 years at ICU admission, had delirium evaluations using the CAM-ICU, and had data collected for at least 4 hours before delirium diagnosis or nondiagnosis. The development cohort from Yongin Severance Hospital (March 1, 2020, to January 12, 2022) comprised 5478 records: 5129 (93.62%) records from 651 patients for training and 349 (6.37%) records from 163 patients for internal validation. For temporal validation, we used 4438 records from the same hospital (January 28, 2022, to December 31, 2022) to reflect potential seasonal variations. External validation was performed using data from 670 patients at Ajou University Hospital (March 2022 to September 2022). We evaluated machine learning algorithms (random forest [RF], extra-trees classifier, and light gradient boosting machine) and selected the RF model as the final model based on its performance. To confirm clinical utility, a decision curve analysis and temporal pattern for model prediction during the ICU stay were performed. RESULTS: The kappa coefficient between labels generated by ICU nurses and prospectively verified by qualified researchers was 0.81, indicating reliable CAM-ICU results. Our final model showed robust performance in internal validation (area under the receiver operating characteristic curve [AUROC]: 0.82; area under the precision-recall curve [AUPRC]: 0.62) and maintained its accuracy in temporal validation (AUROC: 0.73; AUPRC: 0.85). External validation supported its effectiveness (AUROC: 0.84; AUPRC: 0.77). Decision curve analysis showed a positive net benefit at all thresholds, and the temporal pattern analysis showed a gradual increase in the model scores as the actual delirium diagnosis time approached. CONCLUSIONS: We developed a machine learning model for delirium prediction in ICU patients using routinely measured variables, including physiological waveforms. Our study demonstrates the potential of the RF model in predicting delirium, with consistent performance across various validation scenarios. The model uses noninvasive variables, making it applicable to a wide range of ICU patients, with minimal additional risk

국내 학술지에 게재된 환자보고형 건강평가 측정도구에 대한 체계적 고찰연구의 현황

Purpose: This study aimed to explore the current status of systematic review studies on patient-reported outcome measures (PROMS) published in Korean journals. Methods: Studies on the systematic review of PROMs, which applied the COnsensus-based Standards for selecting health Measurement Instruments (COSMIN) methodology. There were searched from the KoreaMed. The studies were evaluated based on the eight steps suggested by the COSMIN systematic review processes. Results: A total of eight systematic review studies were published in seven Korean journals. Patient-reported outcome measures (PROMS) measure for post-traumatic growth, social adjustment, physical impairment in post-intensive care syndrome, sleep quality, constipation, discharge readiness, post-traumatic stress disorder, and eHealth literacy. Conclusions: No studies adhered to the steps of the COSMIN systematic review guidelines. Among the steps, the weakest points were searching strategies and evaluating measurement properties

Discrepancies in Dapagliflozin Response in Terms of Glycemic Control and Body Weight Reduction

BACKGRUOUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin. METHODS: The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of >/= 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of >/=3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL-, GC-/WL+, and GC-/WL-. RESULTS: Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%+/-0.8% from baseline, while body weight had declined by 2.4+/-3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL. CONCLUSION: A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management

Risk of new-onset polymyalgia rheumatica following COVID-19 vaccination in South Korea: a self-controlled case-series study

BACKGROUND: While several studies have reported some cases of polymyalgia rheumatica (PMR) following COVID-19 vaccination, studies using large databases are lacking. OBJECTIVES: To investigate the risk of PMR after COVID-19 vaccination using self-controlled case series (SCCS) analysis METHODS: We used the National Health Insurance Database, linked with the COVID-19 registry between February 2021 and August 2023, to identify adults aged 50 years or older who received at least one dose of COVID-19 vaccine and subsequently diagnosed with PMR within the observation period, defined as 240 days after the first dose of vaccine. The risk window was defined as 28 days after each dose of COVID-19 vaccination, and the control window encompassed the remainder of the observation period. Incidence rate ratios (IRRs) were estimated using conditional Poisson regression with 95% CIs, stratified by dose and vaccine type. RESULTS: Among 44 818 078 COVID-19 vaccine recipients, 376 patients were diagnosed with PMR. The analysis indicated that COVID-19 vaccination was not associated with an increased risk of PMR (IRR, 0.74; 95% CI 0.59 to 0.94). Rather, the risk of PMR was slightly reduced after the first dose (0.52; 0.34 to 0.79), with no significant association with other doses of COVID-19 vaccine (0.83; 0.59 to 1.16 for second dose, 0.77, 0.48 to 1.25 for third dose). CONCLUSION: In this nationwide SCCS, there was no association with the increased risk of PMR following COVID-19 vaccination. While these findings support the safety of COVID-19 vaccines, interpretation of the decreased risk of PMR should be cautious

A prevalent MOCS2 variant in the Roma population is associated with a novel mild form of molybdenum cofactor deficiency

Xanthinurias are rare inherited disorders of purine metabolism. Xanthinuria type III is caused by molybdenum cofactor deficiency (MoCD) due to pathogenic variants in MOCS1, MOCS2, MOCS3, or GEPH genes. Here, we described five Roma patients from four unrelated families with hypouricemia, accumulation of xanthine/hypoxanthine, deficiency of xanthine oxidase activity, variable age of diagnosis, and only asymptomatic or mild clinical course. Whole exome sequencing was performed on all probands, aged 3 to 43 years, due to lack of genetic confirmation for xanthinuria types I and II. The causality of the putative pathogenic variant was confirmed by analysis of sulfite and related metabolites and in vitro functional characterization of metal-binding pterin (MPT) synthesis and protein complex formation. Considering the rarity of the condition and recessive inheritance, 34 candidate variants were identified after filtering out allele frequency threshold in non-Finnish Europeans. An ultra-rare MOCS2 variant rs776441627 in two overlapping reading frames (c.244A > T (NM_176806.4; p.Ile82Phe) = c.57A > T (NM_004531.5; p.Leu19Phe)) segregated with the disease in all five patients (four homozygotes, one compound heterozygote). The variant has an allele frequency of 3.6% in a Roma population control group. Functional characterization revealed the significantly decreased MPT synthesis activity and confirmed the causality of rs776441627 in MoCD. CONCLUSION: The rs776441627 is a functional variant for MoCD with a mild to asymptomatic clinical phenotype and fully penetrant biochemical phenotype. Hypouricemia should be considered in the differential diagnostic algorithm of pediatric and adult patients with neurological symptoms, and MOCS2 should be considered in gene panels for xanthinuria screening. WHAT IS KNOWN: * Xanthinuria type III is caused by molybdenum cofactor deficiency (MoCD) due to pathogenic variants in MOCS1, MOCS2, MOCS3, or GEPH genes. * The majority of patients with xanthinuria III present with classical early-onset MoCD due to autosomal recessive variants in the MOCS1 gene, manifesting severe progressive neurological complications during the first postnatal days. * To date, approximately 40 patients with MoCD due to pathogenic MOCS2 variants have been reported; most were diagnosed during the neonatal period with intractable seizures and feeding disorders. WHAT IS NEW: * A novel ultra-rare variant, rs776441627, located in two overlapping reading frames of the MOCS2, was identified in five Roma patients presenting a mild to asymptomatic clinical MoCD phenotype and a fully penetrant biochemical phenotype. * Functional studies of p.Ile82Phe (small MOCS2A subunit) and p.Leu19Phe (large MOCS2B subunit) demonstrate a strong reduction in molydopterin synthase complex formation and activity, consistent with the changes in biomarkers of MoCD observed in affected individuals. * The rs776441627 variant shows significantly elevated frequency among the Roma population, highlighting the importance of considering ethnic background in the differential diagnosis of MoCD. * Hypouricemia may provide an initial, generally available biochemical key marker indicator of molybdenum cofactor deficiency

Increase of α-Synuclein in the Peripheral Blood of Subjects with Methamphetamine Use Disorder

OBJECTIVE: Methamphetamine (MA) use has created significant public health problems worldwide. Its chronic abuse causes neurotoxicity resulting in disruption of neural plasticity and early onset of neurodegenerative diseases. Therefore, there is need for a biomarker to evaluate the neurotoxicity caused by MA. This study investigates the expression levels of alpha-synuclein (alpha-Syn), brain-derived neurotrophic factor (BDNF), and neuron-specific enolase (NSE) in the blood of patients with MA use disorder to identify potential biomarkers. METHODS: We collected blood samples from 60 subjects (30 normal healthy controls and 30 patients with MA use disorder [MA group]). We used multiplex assay kits to analyze the expression levels of alpha-Syn, BDNF, and NSE in the blood of these subjects. RESULTS: Beck Depression Inventory and Beck Anxiety Inventory scale scores were significantly different between the control and MA groups. The expression level of alpha-Syn in the MA group was significantly increased compared to that in the control group (z value=-1.986, p=0.0473). In contrast, BDNF in the MA group tended to increase as the duration of MA use increased (r=0.323, p=0.082). CONCLUSION: We identified an increase of alpha-Syn in the blood of the MA group. This finding suggests that the alpha-Syn level increases in the brain after exposure to MA by passing through the blood brain barrier. This result provides useful information for potential biomarkers in diagnosis of neurodegenerative diseases caused by MA abuse

Delayed central nervous system progression with atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer (LU23-15)

BACKGROUND: The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases. METHOD: We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003). CONCLUSION: Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era

Revascularisation patterns and characteristics after erythropoietin pretreatment and multiple burr holes in patients who had acute stroke with perfusion impairment

BACKGROUND: Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals. METHODS: We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups. RESULTS: Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform. CONCLUSIONS: Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies

Age-related eye diseases and subsequent risk of mental disorders in older adults: A real-world multicenter study

BACKGROUND: The relationship between age-related eye diseases and the subsequent risk of dementia and depressive disorders remains inconsistent. Furthermore, the effects on anxiety disorders and sleep disorders have been underexplored. This study aims to comprehensively examine the impact of age-related eye diseases on common mental disorders in older adults, thereby enhancing our understanding of the mental health implications in these conditions. METHODS: The electronic health records of 1,522,036 patients aged over 60 from ten institutions in South Korea were analyzed. Patients with and without age-related eye diseases were identified, and 1:4 propensity score matching (PSM) was implemented. A 10-year longitudinal analysis was conducted using the Cox proportional hazards model to calculate the hazard ratios (HR). A meta-analysis was performed to combine the results from different institutions. Subgroup analyses were conducted to explore the impact of specific age-related eye diseases (cataract, glaucoma, age-related macular degeneration) on mental disorders. RESULTS: A total of 41,637 patients with age-related eye disease were matched with 134,908 patients without such conditions. Patients with age-related eye disease showed a significantly higher risk of mental disorders (dementia, HR: 1.21 [95 % CI: 1.14-1.27]; depressive disorders, HR: 1.28 [95 % CI: 1.20-1.36]; anxiety disorders, HR: 1.31 [95 % CI: 1.22-1.41]; sleep disorders, HR: 1.29 [95 % CI: 1.22-1.37]). In subgroup analyses, each of the three age-related eye diseases was significantly associated with an increased risk of mental disorders. (cataract, HR: 1.25-1.33; glaucoma, HR: 1.15-1.49; age-related macular degeneration, HR: 1.18-1.37). CONCLUSION: Age-related eye diseases increase the risk of developing mental disorders in older adults, highlighting the need for a multidisciplinary approach to patient care in these conditions

A single-cell RNA sequencing dataset of peripheral blood cells in long COVID patients on herbal therapy

Following the coronavirus disease 2019 (COVID-19) pandemic, the rise of long COVID, characterized by persistent respiratory and cognitive dysfunctions, has become a significant health concern. This leads to an increased role of complementary and alternative medicine in addressing this condition. However, our comprehension of the effectiveness and safety of herbal medicines for long COVID remains limited. Here, we present a single-cell RNA sequencing (scRNA-seq) dataset of peripheral whole blood cells derived from participants in a clinical study involving three commercially available herbal medicines, targeting fatigue and brain fog in long COVID. The dataset comprises 181,205 quality control (QC)-passed cells, along with clinical metadata, enabling a comparative analysis of immune cell populations before and after treatment. To ensure the technical validity of our dataset, we implemented rigorous quality checks throughout stages of the study, including sample preparation, sequencing, and bioinformatic data analysis levels. This transcriptomic data may serve as a resource to deepen our insights into the role of herbal medicines in management of long COVID