Femoral osteoporosis prediction model using autosegmentation and machine learning analysis with PyRadiomics on abdomen-pelvic computed tomography (CT).

Background: With the advancement of artificial intelligence technology and radiomics analysis, opportunistic prediction of osteoporosis with computed tomography (CT) is a new paradigm in osteoporosis screening. This study aimed to assess the diagnostic performance of osteoporosis prediction by the combination of autosegmentation of the proximal femur and machine learning analysis with a reference standard of dual-energy X-ray absorptiometry (DXA). Methods: Abdomen-pelvic CT scans were retrospectively analyzed from 1,122 patients who received both DXA and abdomen-pelvic computed tomography (APCT) scan from January 2018 to December 2020. The study cohort consisted of a training cohort and a temporal validation cohort. The left proximal femur was automatically segmented, and a prediction model was built by machine-learning analysis using a random forest (RF) analysis and 854 PyRadiomics features. The technical success rate of autosegmentation, diagnostic test, area under the receiver operator characteristics curve (AUC), and precision recall curve (AUC-PR) analysis were used to analyze the training and validation cohorts. Results: The osteoporosis prevalence of the training and validation cohorts was 24.5%, and 10.3%, respectively. The technical success rate of autosegmentation of the proximal femur was 99.7%. In the diagnostic test, the training and validation cohorts showed 78.4% vs. 63.3% sensitivity, 89.4% vs. 98.1% specificity. The prediction performance to identify osteoporosis within the groups used for training and validation cohort was high and the AUC and AUC-PR to forecast the occurrence of osteoporosis within the training and validation cohorts were 90.8% [95% confidence interval (CI), 88.4-93.2%] vs. 78.0% (95% CI, 76.0-79.9%) and 94.6% (95% CI, 89.3-99.8%) vs. 88.8% (95% CI, 86.2-91.5%), respectively. Conclusions: The osteoporosis prediction model using autosegmentation of proximal femur and machine-learning analysis with PyRadiomics features on APCT showed excellent diagnostic feasibility and technical success.

Evidence of the existence of multiple modules for the stroke-caused flexion synergy from Fugl-Meyer assessment scores.

Stroke-caused synergies may result from preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or muscle synergies, and accordingly the controllability of individual muscles is reduced. It is not clear whether the muscles involuntarily activated by abnormal synergy vary with the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from merging and re-weighting of synergies individuals without neurological deficit. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment (FMA) that could characterize the neuroanatomical architecture in individuals with a wide range of impairment. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% (8/57, 95%CI: [5.0%, 23.1%]) of the participants with severe impairment (total FM score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants undergo a different course of neural reorganization which enhanced abnormal synergies in comparison with individuals with mild impairment (p<0.05). These results evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.

Correlations in abnormal synergies between the upper and lower extremities across various phases of stroke.

BACKGROUND AND OBJECTIVES: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. METHODS: We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. RESULTS: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). DISCUSSION: These results suggest that preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension but a recovery of the CST functional and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.

Predictors of Burden for First-Ever Stroke Survivor's Long-Term Caregivers: A Study of KOSCO.

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

Components of the Chronic Obstructive Pulmonary Disease Assessment Test Associated with the Exacerbation of Severe Chronic Obstructive Pulmonary Disease Patients.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score is widely used for evaluating the health status of patients diagnosed with COPD. The aim of this study was to identify which components of the CAT are associated with exacerbations in severe COPD patients. METHODS: Using data from the Korean COPD Subgroup Study (KOCOSS), we identified 3,440 COPD patients, among which 1,027 patients are classified as having severe COPD based on spirometry results. The CAT scores on 8 items were evaluated and classified into respiratory and non-respiratory categories. We analyzed the association between CAT item scores and moderate-to-severe exacerbations during study enrollment and the following years. RESULTS: Patients with a history of moderate-to-severe exacerbations had higher scores on non-respiratory CAT components. Longitudinal CAT scores on all items after enrollment were higher in the moderate-to-severe exacerbation group. Additionally, the frequency of severe exacerbations was associated with specific CAT components related to limited activities, confidence leaving home, sleeplessness, and energy. CONCLUSIONS: This study revealed that the non-respiratory CAT component scores were statistically significant factors for predicting the moderate-to-severe exacerbation of severe COPD patients. Non-respiratory symptoms and functional limitations should be considered in patients with severe COPD. Interventions, such as pulmonary rehabilitation, may be needed to improve patients' overall well-being and prevent exacerbations.

Long-Term Functional Outcome in Patients With Isolated Thalamic Stroke: The KOSCO Study.

BACKGROUND: Information on the long-term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. METHODS AND RESULTS: Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (P<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability. CONCLUSIONS: Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long-term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.

Interactions in abnormal synergies between the upper and lower extremities in various phases of stroke: A cohort study.

Objective: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. Methods: In this study, we used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. Results: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). Interpretation: These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension, however a recovery of the CST or/and the functional fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.

Nanoplasmonic Detection of EGFR Mutations Based on Extracellular Vesicle-Derived EGFR-Drug Interaction.

Analysis of membrane proteins from extracellular vesicles (EVs) has emerged as an important strategy for molecular cancer diagnosis. The epidermal growth factor receptor (EGFR) is one of the most well-known oncogenic membrane proteins, particularly in non-small cell lung cancer (NSCLC), where targeted therapies using tyrosine kinase inhibitors (TKIs) are often addressed based on EGFR mutation status. Consequently, several studies aimed at analyzing oncogenic membrane proteins have been proposed for cancer diagnosis. However, conventional protein analysis still faces limitations due to the requirement for large sample quantities and extensive post-labeling processes. Here, we develop a nanoplasmonic detection method for EGFR mutations in the diagnosis of NSCLC based on interactions between EGFR loaded in EVs and TKI. Gefitinib is selected as a model TKI due to its strong signals in the surface-enhanced Raman spectroscopy (SERS) and mutation-dependent binding affinity to EGFR. We demonstrate an SERS signal attributed to gefitinib at a higher value in the EGFR exon 19 deletion, both in cells and EVs, compared to wild-type and exon 19 deletion/T790M variants. Furthermore, we observe a significantly higher gefitinib SERS signal in EGFR obtained from exon 19 deletion NSCLC patient plasma-derived EVs compared with those from wild-type and exon 19 deletion/T790M EVs. Since our approach utilizes an analysis of the SERS signal generated by the interaction between oncogenic membrane proteins within EVs and targeted drugs, its diagnostic applicability could potentially extend to other liquid biopsy methods based on EVs.

Inhalation Delivery of Interferon-λ-Loaded Pulmonary Surfactant Nanoparticles Induces Rapid Antiviral Immune Responses in the Lung.

The interferon-λ (IFN-λ)-regulated innate immune responses in the airway expand our understanding toward antiviral strategies against influenza A virus (IAV). The application of IFN-λ as mucosal antiviral therapeutic is still challenging, and advanced research will be necessary to achieve more efficient delivery of recombinant IFN-λs to the damaged respiratory mucosa. In this study, we examine the capability of IFN-λ to stimulate the innate immune response, promoting the swift elimination of IAV in the lungs. Additionally, we develop IFN-λ-loaded nanoparticles incorporated into pulmonary surfactant for inhalation therapy aimed at treating lung infections caused by IAV. We found that inhaled delivery of IFNλ-PSNPs significantly restricted IAV replication in the lungs from 3 days after infection (dpi), and IAV-caused lung histopathologic findings were completely improved in response to IFNλ-PSNPs. More significant and rapid attenuation of viral RNA was observed in the lung of mice with inhaled delivery of IFNλ-PSNPs compared to mice with recombinant IFN-λs. Inhalation treatment of IFNλ-PSNPs to IAV-infected mice can result in the increase of monocyte frequency in concert with restoration of T and B cells composition. Furthermore, the transcriptional profiles of monocytes shifted toward heightened IFN responses following IFNλ-PSNP treatment. These results imply that IFN-λ could serve as a robust inducer of innate immunity in the lungs against IAV infection, and inhalation of IFN-λs encapsulated in PSNPs effectively resolves lung infections caused by IAV through rapid viral clearance. PSNPs facilitated improved delivery of IFN-λs to the lungs, triggering potent antiviral immune responses upon IAV infection onset.

Efficacy of Oxygen Treatment Using Home Oxygen Concentrators for the Treatment of Cluster Headaches: A Randomized, Crossover, Multicenter Study.

BACKGROUND AND PURPOSE: Oxygen treatment is the first-line acute treatment for cluster headaches (CHs), but this can be impeded by insurance coverage and oxygen-tank maintenance. Oxygen concentrators filter nitrogen from ambient air to produce oxygen-rich gas, and can therefore be an alternative to conventional oxygen therapy using a tank. We investigated the effectiveness and safety of using two home oxygen concentrators and compared them with using oral zolmitriptan for the acute treatment of CHs. METHODS: Forty patients with episodic CHs in an active cluster period were enrolled in this randomized, crossover, multicenter study. Two attacks during the cluster period were treated using oxygen delivered by connecting two home oxygen concentrators, whereas the other two attacks were treated using oral zolmitriptan (5 mg) in a random sequence. The primary endpoint was substantial pain reduction (0 or 1 on a five-point rating scale from 0 to 4 points) at 15 min after treatment. RESULTS: In total, 125 attacks among 32 patients were randomized and treated (63 attacks using oxygen and 62 using zolmitriptan) according to the study protocol. More attacks treated using oxygen reached the primary endpoint than did those treated using zolmitriptan (31.7% [20/63] vs. 12.9% [8/62], p=0.013). After 30 min, 57.1% of the patients who received oxygen and 38.7% who received zolmitriptan reported pain relief (p=0.082). All patients treated using oxygen reported an improvement in pain, and 61.3% preferred oxygen while only 9.7% preferred zolmitriptan. No adverse events occurred during the oxygen treatment. CONCLUSIONS: Oxygen treatment administered using two home oxygen concentrators resulted in better pain relief than oral zolmitriptan in patients with episodic CHs. Our results suggest that home oxygen concentrators are capable of efficiently supplying oxygen in a similar manner to using an oxygen tank.

Incidence of Altered Level of Consciousness in Hemorrhagic Stroke Survivors: Associated Factors From a Korean Nationwide Study.

OBJECTIVE: This study aimed to demonstrate the incidence of altered level of consciousness after hemorrhagic stroke and identify factors associated with altered level of consciousness at 3 mos after stroke. DESIGN: This study used data from a prospective multicenter cohort study conducted in nine hospitals in Korea and included 1677 patients with first-ever hemorrhagic stroke. Patients were dichotomized into those with and without altered level of consciousness at 3 mos after stroke. Multivariate logistic regression analysis was performed to identify factors associated with subacute to chronic stage altered level of consciousness. RESULTS: Among patients with hemorrhagic stroke (age: 20-99 yrs, female 50.21%), the prevalence of altered level of consciousness at admission was 38.58% (25.4% [drowsy], 6.38% [stupor], and 6.8% [coma]) and 17.29% 3 mos after stroke. Multivariate logistic regression analysis revealed that independent factors associated with altered level of consciousness at 3 mos after stroke included late seizure (odds ratio [95% confidence interval], 5.93 [1.78-20.00]), stroke progression (3.84 [1.48-9.64]), craniectomy (2.19 [1.19-4.00]), history of complications (1.74 [1.18-2.55]), age at stroke onset (1.08 [1.07-1.10]), and initial Glasgow Coma Scale score category (0.36 [0.30-0.44]). CONCLUSIONS: The factors associated with altered level of consciousness at 3 mos after stroke should be considered when explaining long-term consciousness status and focused management of modifiable factors in acute care hospitals could help ameliorate altered level of consciousness and promote recovery after stroke.

Effect of a Mismatched Vaccine against the Outbreak of a Novel FMD Strain in a Pig Population.

In December 2014, a novel foot and mouth disease (FMD) virus was introduced to a pig farm in South Korea, despite the animals being vaccinated. A marginal antigenic matching between the novel and vaccine strains potentially led to the infection of the vaccinated animals. To understand the impact of using an FMD vaccine on the transmission dynamics of an unmatched field strain, simulation models were employed using daily reported data on clinical cases from the farm. The results of this study indicated that immunisation with the FMD vaccine reduced the shedding of the novel FMD virus in pigs. However, there was no evidence to suggest that the immunisation had a significant effect in reducing the development of clinical signs. These findings highlight that the use of an unmatched FMD vaccine can confound the outbreak by altering the disease dynamics of the novel virus. Based on this study, we emphasise the importance of continuous testing to ensure antigenic matching between the circulating strains and the vaccine pool.

Modulation of immune cells with mRNA nanoformulations for cancer immunotherapy.

The global adaptation of mRNA vaccines to protect against the COVID-19 pandemic was a major interdisciplinary milestone, demonstrating the potential of combining mRNA applications with nanotechnology. This innovative strategy holds great promise as an improved therapeutic modality for cancer immunotherapy, as further development could facilitate targeted mRNA delivery to specific immune cells and enable manipulation of effector functions. Toward this, researchers have made substantial efforts to modulate various immune cell types, including lymphoid organ dendritic cells for cancer vaccines, peripheral blood lymphocytes for in situ T-cell therapy, and macrophages in the tumor microenvironment to restore antitumor functions. Here, we highlight recent advances in mRNA nanoformulations for cancer immunotherapy, emphasizing strategies for target cell engagement in different immunological sites.

Predictors of quality of life at 6 months in patients with mild stroke: A prospective observational cohort study.

OBJECTIVES: This study aimed to analyze the factors affecting the long-term quality of life of patients with mild stroke and evaluate the differences according to age and sex. MATERIALS AND METHODS: The Korean Stroke Cohort for functioning and rehabilitation data was used, and patients with mild stroke with a National Institute of Health Stroke Scale score of < 5 were included. Quality of life after 6 months was analyzed using EuroQol-5 dimensions. Demographic and clinical characteristics were evaluated, and factors affecting the quality of life at 6 months were analyzed. RESULTS: Age, current drinking, marital status, length of stay, and modified Rankin Scale, Fugl-Meyer assessment, Functional Independence Measure, and Geriatric Depression Scale scores affected the quality of life at 6 months in patients with mild stroke. Fugl-Meyer assessment score was a predictor for those aged < 65 years, while the functional ambulatory category was a predictor for those aged ≥ 65 years. Predictors of quality of life, excluding alcohol consumption, were comparable between male and female. CONCLUSIONS: Among patients aged <65 years, individuals who consumed alcohol, and those who showed better motor function and fewer comorbidities had a higher quality of life. Among patients aged ≥65 years, quality of life was higher in males, younger age, married individuals, those with diabetes, and those with a better walking ability. Among male, individuals who consumed alcohol had a higher quality of life. Rehabilitation treatment should prioritize improving modifiable factors to enhance the quality of life in patients with mild stroke.

Which obesity index is the most useful marker for predicting hepatic steatosis in children and adolescents with obesity? A cross-sectional study using quantitative magnetic resonance imaging.

INTRODUCTION: We aimed to evaluate the relationships between hepatic steatosis and various indices of obesity, and to identify the most useful index for the prediction of hepatic steatosis in children and adolescents with obesity. METHODS: A total of 226 children and adolescents with a mean body mass index (BMI) z-score of 2.65 and a mean age of 11.4 years were subjected to anthropometric and body composition measurements, laboratory testing, abdominal fat mass assessment, and hepatic fat accumulation by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). The participants were divided into quartiles according to the severity of their hepatic steatosis, and the presence of hepatic steatosis was defined using an MRI-PDFF ≥ 5%. RESULTS: The multivariate ordinal regression analysis showed that the severity of hepatic steatosis was positively associated with BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, fat mass, fat-free mass, visceral adiposity, and abdominal subcutaneous adiposity. Higher activities of liver enzymes and higher concentrations of triglyceride, C-reactive protein, fasting insulin, and leptin were associated with more severe hepatic steatosis, whereas high-density lipoprotein-cholesterol and adiponectin were negatively associated with hepatic steatosis. The indices of obesity with areas under the receiver operating characteristic curves (AUCs) > 0.8 for the prediction of hepatic steatosis were liver enzymes, visceral adipose tissue area, waist-to-hip ratio, and waist-to-height ratio. CONCLUSION: The severity of hepatic steatosis significantly correlated with various indices of obesity and cardiometabolic markers in children and adolescents with obesity. The indices of abdominal obesity would be the most useful for the prediction of hepatic steatosis.

Association Between Internet Searches Related to Suicide/Self-harm and Adolescent Suicide Death in South Korea in 2016-2020: Secondary Data Analysis.

BACKGROUND: Previous studies have investigated the association between suicide and internet search volumes of terms related to suicide or self-harm. However, the results varied by people's age, period, and country, and no study has exclusively investigated suicide or self-harm rates among adolescents. OBJECTIVE: This study aims to determine the association between the internet search volumes of terms related to suicide/self-harm and the number of suicides among South Korean adolescents. We investigated gender differences in this association and the time lag between the internet search volumes of the terms and the connected suicide deaths. METHODS: We selected 26 search terms related to suicide and self-harm among South Korean adolescents, and the search volumes of these terms for adolescents aged 13-18 years were obtained from the leading internet search engine in South Korea (Naver Datalab). A data set was constructed by combining data from Naver Datalab and the number of suicide deaths of adolescents on a daily basis from January 1, 2016, to December 31, 2020. Spearman rank correlation and multivariate Poisson regression analyses were performed to identify the association between the search volumes of the terms and the suicide deaths during that period. The time lag between suicide death and the increasing trend in the search volumes of the related terms was estimated from the cross-correlation coefficients. RESULTS: Significant correlations were observed within the search volumes of the 26 terms related to suicide/self-harm. The internet search volumes of several terms were associated with the number of suicide deaths among South Korean adolescents, and this association differed by gender. The search volume for "dropout" showed a statistically significant correlation with the number of suicides in all adolescent population groups. The correlation between the internet search volume for "dropout" and the connected suicide deaths was the strongest for a time lag of 0 days. In females, self-harm and academic score showed significant associations with suicide deaths, but academic score showed a negative correlation, and the time lags with the strongest correlations were 0 and -11 days, respectively. In the total population, self-harm and suicide method were associated with the number of suicides, and the time lags with the strongest correlations were +7 and 0 days, respectively. CONCLUSIONS: This study identifies a correlation between suicides and internet search volumes related to suicide/self-harm among South Korean adolescents, but the relatively weak correlation (incidence rate ratio 0.990-1.068) should be interpreted with caution.

Clustering and prediction of long-term functional recovery patterns in first-time stroke patients.

Objectives: The purpose of this study was to cluster long-term multifaceted functional recovery patterns and to establish prediction models for functional outcome in first-time stroke patients using unsupervised machine learning. Methods: This study is an interim analysis of the dataset from the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO), a long-term, prospective, multicenter cohort study of first-time stroke patients. The KOSCO screened 10,636 first-time stroke patients admitted to nine representative hospitals in Korea during a three-year recruitment period, and 7,858 patients agreed to enroll. Early clinical and demographic features of stroke patients and six multifaceted functional assessment scores measured from 7 days to 24 months after stroke onset were used as input variables. K-means clustering analysis was performed, and prediction models were generated and validated using machine learning. Results: A total of 5,534 stroke patients (4,388 ischemic and 1,146 hemorrhagic; mean age 63·31 ± 12·86; 3,253 [58.78%] male) completed functional assessments 24 months after stroke onset. Through K-means clustering, ischemic stroke (IS) patients were clustered into five groups and hemorrhagic stroke (HS) patients into four groups. Each cluster had distinct clinical characteristics and functional recovery patterns. The final prediction models for IS and HS patients achieved relatively high prediction accuracies of 0.926 and 0.887, respectively. Conclusions: The longitudinal, multi-dimensional, functional assessment data of first-time stroke patients were successfully clustered, and the prediction models showed relatively good accuracies. Early identification and prediction of long-term functional outcomes will help clinicians develop customized treatment strategies.

Gender differences in mortality and long-term functional outcomes after first-ever ischemic stroke: A prospective cohort study.

BACKGROUND: Although many studies about survival rates and functional outcomes after stroke have been published, studies on gender differences have reported conflicting results. AIMS: To determine whether there are differences in mortality and functional outcomes during the first 5 years after a first-ever ischemic stroke in Korean males and females. METHOD: This is an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation, a prospective multicenter cohort study. Multifaceted functional assessments were performed repeatedly from 7 days to 60 months after stroke onset to test motor, ambulatory, cognitive, language, and swallowing functions as well as activities of daily living (ADLs) in patients with first-ever stroke. Of 10,636 first-ever-stroke patients admitted to nine representative hospitals in Korea, 8210 were ischemic stroke patients included in the mortality analysis. Among them, 6258 patients provided informed consent and 3508 completed functional assessments for 60 months. Gender-related differences in 5-year mortality and functional recovery were analyzed. RESULT: Women showed a significantly higher 5-year mortality rate than men after correction for possible covariates (p < 0.05). In terms of functional outcomes, women showed worse ambulatory, cognitive, language, and ADL outcomes than men after adjusting for covariates (all p < 0.05). The 5-year recovery pattern differed significantly between genders only for ADL function (ß-coefficient estimate = 0.34; p = 0.03). CONCLUSION: Five-year mortality rate, functional outcomes, and recovery patterns after first-ever ischemic stroke differed significantly by gender. These results suggest the need for gender-specific stroke care and long-term management strategies.

Contributing Factors to the Burden on Primary Family Caregivers of Stroke Survivors in South Korea.

The purpose of this study is to identify the factors associated with the burden on primary family caregivers of stroke patients at home without care services. For this study, the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) data were used. Of the total 8010 caregivers, 1133 family caregiver burden was assessed with the shortened Caregiver Burden Inventory (CBI) 3 months after stroke. Patient and caregiver-related factors affecting the heavier burden of caregivers were identified by comparing the heavier caregiver burden group and the lighter caregiver burden group, which divided according to the CBI scores. The 719 (63.5%) family caregiver cared for patients at home without care services. Logistic regression analysis showed that four or more comorbidities (p = 0.002), neurological impairment at early onset (p < 0.001), dependence on daily life (p < 0.001), aphasia (p = 0.024), and depression(p < 0.001) were associated with a heavier burden of care. According to the shortened CBI, caregivers tended to be concerned more about psychological stress than physical strain. The findings suggest the importance of proactively guiding the emotional support services to caregivers who are at high risk of the heavier burden of patient care.

Comment regarding: what is the efficacy of aerobic exercise versus strength training in the treatment of migraine? A systematic review and network meta­analysis of clinical trials.

In Woldeamanuel and Oliveira (2022)'s article about the efficacy of exercise in the treatment of migraine, the ranking of the efficacy of strength training (mean difference, - 3.55), aerobic exercise (mean difference, - 2.18 to - 3.13), topiramate (mean difference, - 0.98), and amitriptyline (mean difference, 3.82) using network meta-analysis can mislead readers. First, the inclusion criteria were reported at a monthly frequency of migraine and the end of the intervention, but some article did not meet the inclusion criteria or had data inconsistency. Second, there was an inconsistency in the placebos used in the included studies, which can be problematic in network meta-analysis. Third, all three articles on strength training were rated as high-risk or exhibited some risk of bias. Finally, the effectiveness of this statistical method is questionable for assessing physical activities because strength training, aerobic exercise, and preventive medications can be simultaneously recommended for possible synergistic effects in the prevention of migraine.