Recording of elapsed time and temporal information about biological events using Cas9.

DNA has not been utilized to record temporal information, although DNA has been used to record biological information and to compute mathematical problems. Here, we found that indel generation by Cas9 and guide RNA can occur at steady rates, in contrast to typical dynamic biological reactions, and the accumulated indel frequency can be a function of time. By measuring indel frequencies, we developed a method for recording and measuring absolute time periods over hours to weeks in mammalian cells. These time-recordings were conducted in several cell types, with different promoters and delivery vectors for Cas9, and in both cultured cells and cells of living mice. As applications, we recorded the duration of chemical exposure and the lengths of elapsed time since the onset of biological events (e.g., heat exposure and inflammation). We propose that our systems could serve as synthetic "DNA clocks."

Association Between Frequency of Rehabilitation Therapy and Long-Term Mortality After Stroke: A Nationwide Cohort Study.

BACKGROUND: Previous studies have demonstrated conflicting results regarding the effects of rehabilitation therapy on poststroke mortality. We aimed to investigate the association between rehabilitation therapy, including both inpatient and outpatient treatment, within the first 6 months after stroke and long-term all-cause mortality in patients with stroke using the Korean National Health Insurance System data. METHODS: A total of 10 974 patients newly diagnosed with stroke using the International Classification of Diseases, Tenth Revision, codes (I60-I64) between 2003 and 2019 were enrolled and followed up for all-cause mortality until 2019. Follow-up for mortality began 6 months after the index event. Poststroke patients were categorized into 3 groups according to the frequency of rehabilitation therapy: no rehabilitation therapy, ≤40 sessions and >40 sessions. Cox proportional hazards models were used to assess the mortality risk according to rehabilitation therapy stratified by disability severity measured based on activities of daily living 6 months after stroke onset. RESULTS: Within 6 months after stroke, 6738 patients (61.4%) did not receive rehabilitation therapy, whereas 2122 (19.3%) received ≤40 sessions and 2114 (19.3%) received >40 sessions of rehabilitation therapy. Higher frequency of rehabilitation therapy was associated with significantly lower poststroke mortality in comparison to no rehabilitation therapy (hazard ratio [HR], 0.88 [95% CI, 0.79-0.99]), especially among individuals with severe disability after stroke (mild to moderate: HR, 1.02 [95% CI, 0.77-1.35]; severe: HR, 0.74 [95% CI, 0.62-0.87]). In the context of stroke type, higher frequency of rehabilitation therapy was associated with reduced mortality rates compared with no rehabilitation therapy only in patients with hemorrhagic stroke (ischemic: HR, 1.04 [95% CI, 0.91-1.18]; hemorrhagic: HR, 0.60 [95% CI, 0.49-0.74]). CONCLUSIONS: We found a positive association between rehabilitation therapy within 6 months after stroke onset and long-term mortality in patients with stroke. A higher frequency of rehabilitation therapy would be recommended for poststroke patients, especially those with hemorrhagic stroke and severe disability.

Signal detection statistics of adverse drug events in hierarchical structure for matched case-control data.

The tree-based scan statistic is a data mining method used to identify signals of adverse drug reactions in a database of spontaneous reporting systems. It is particularly beneficial when dealing with hierarchical data structures. One may use a retrospective case-control study design from spontaneous reporting systems (SRS) to investigate whether a specific adverse event of interest is associated with certain drugs. However, the existing Bernoulli model of the tree-based scan statistic may not be suitable as it fails to adequately account for dependencies within matched pairs. In this article, we propose signal detection statistics for matched case-control data based on McNemar's test, Wald test for conditional logistic regression, and the likelihood ratio test for a multinomial distribution. Through simulation studies, we demonstrate that our proposed methods outperform the existing approach in terms of the type I error rate, power, sensitivity, and false detection rate. To illustrate our proposed approach, we applied the three methods and the existing method to detect drug signals for dizziness-related adverse events related to antihypertensive drugs using the database of the Korea Adverse Event Reporting System.

Depressive Symptoms and the Subsequent Risk of Parkinson's Disease: A Nationwide Cohort Study.

OBJECTIVE: Only a few studies have focused on depressive symptoms and Parkinson's disease (PD) risk. As a time lag exists from the onset of depressive symptoms to the diagnosis of depression, elucidating the association between depressive symptoms and PD development might be helpful for the early prediction of PD. We investigate the association between depressive symptoms and subsequent PD risk using nationwide population-based cohort database. DESIGN AND SETTING: Cohort study using the Korean National Health Insurance Service data between 2007 and 2017, with longitudinal follow-up until 2019. PARTICIPANTS: A total of 98,296 elderly people responded to a self-reported questionnaire from the National Health Screening Program on depressive symptoms. MEASUREMENTS: The association between depressive symptoms such as 1) decreased activity or motivation, 2) worthlessness, and 3) hopelessness and PD risk was analyzed. RESULTS: During median 5.06-year follow-up, 839 PD cases occurred: 230 in individuals with depressive symptoms and 609 in those without symptoms. Results showed an increased risk of PD development in those with depressive symptoms (HR = 1.47, 95% CI, 1.26-1.71), with dose-response association between the number of depressive symptoms and PD risk. Even in those already diagnosed with depression, combined depressive symptoms were linked to a higher risk compared to those without symptoms (with symptoms, HR = 2.71, 95% CI, 2.00-3.68; without symptoms, HR = 1.84, 95% CI, 1.43-2.36). CONCLUSION: Individuals with depressive symptoms were at an increased risk of developing PD, and there was a dose-response association between the number of depressive symptoms and PD risk.

Salivary Cortisol and Melatonin, Sleep, and Behavioral Patterns in Older Adults Living With Dementia.

BACKGROUND: Over half of the older adults living with dementia have behavioral and psychological symptoms of dementia (BPSD), including sleep disturbance; however, little is known about physiological markers. Salivary cortisol and melatonin have been identified as potential biomarkers of BPSD, with evidence suggesting a relationship between these biomarkers and various behavioral factors, as well as sleep and activity patterns. OBJECTIVES: The aim of this study was to investigate the time-dependent changes in salivary cortisol and melatonin levels in older adults with dementia, their relationship with the sleep-wake cycle, and their correlation with BPSD symptoms and behavioral factors. METHODS: This observational study conducted in Seoul and Gyeonggi-do, South Korea, used data from 172 older adults with dementia, measuring sleep and activity patterns for 2 weeks using a wearable device, in addition to administering questionnaires for neuropsychiatric and psychological symptoms-the Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Salivary cortisol and melatonin levels were measured at four time points and divided into four groups based on a dual-trajectory model. Differences among the groups were analyzed using one-way analysis of variance. RESULTS: The participants showed normal but heterogeneous patterns of salivary cortisol and melatonin levels. Dual-trajectory pattern analysis showed that higher levels of melatonin during the daytime were correlated with poor nighttime sleep efficiency and decreased disinhibited behaviors, and higher levels of cortisol at all four time points were associated with decreased physical activity. DISCUSSION: Measuring and analyzing periodic changes in cortisol and melatonin levels can predict various behavioral symptoms (e.g., sleep disturbances, activity counts, and disinhibition) in older adults with dementia. A study with an experimental design is needed to discover the direct physiological interactions between cortisol, melatonin, and these symptoms.

Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Assessing the Feasibility and Efficacy of Pre-Sleep Dim Light Therapy for Adults with Insomnia: A Pilot Study.

Background: Insomnia is increasingly recognized for its marked impact on public health and is often associated with various adverse health outcomes, including cardiovascular diseases and mental health disorders. The aim of this study was to investigate the efficacy of pre-sleep dim light therapy (LT) as a non-pharmacological intervention for insomnia in adults, assessing its influence on sleep parameters and circadian rhythms. Methods: A randomized, open-label, two-arm clinical trial was conducted over two weeks with 40 participants aged 20-60 years, all of whom had sleep disorders (CRIS, KCT0008501). They were allocated into control and LT groups. The LT group received exposure to warm-colored light, minimizing the blue spectrum, before bedtime. The study combined subjective evaluation via validated, sleep-related questionnaires, objective sleep assessments via actigraphy, and molecular analyses of circadian clock gene expression in peripheral blood mononuclear cells. Baseline characteristics between the two groups were compared using an independent t-test for continuous variables and the chi-squared test for categorical variables. Within-group differences were assessed using the paired t-test. Changes between groups were analyzed using linear regression, adjusting for each baseline value and body mass index. The patterns of changes in sleep parameters were calculated using a linear mixed model. Results: The LT group exhibited significant improvements in sleep quality (difference in difference [95% CI]; -2.00 [-3.58, -0.43], and sleep efficiency (LT: 84.98 vs. control: 82.11, p = 0.032), and an advanced Dim Light Melatonin Onset compared to the control group (approximately 30 min). Molecular analysis indicated a significant reduction in CRY1 gene expression after LT, suggesting an influence on circadian signals for sleep regulation. Conclusions: This study provides evidence for the efficacy of LT in improving sleep quality and circadian rhythm alignment in adults with insomnia. Despite limitations, such as a small sample size and short study duration, the results underscore the potential of LT as a viable non-pharmacological approach for insomnia. Future research should expand on these results with larger and more diverse cohorts followed over a longer period to validate and further elucidate the value of LT in sleep medicine. Trial registration: The trial was registered with the Clinical Research Information Service (KCT0008501).

Effect of Smoking Cessation on the Risk of Subarachnoid Hemorrhage: A Nested Case-Control Study in Korean Men.

BACKGROUND: Smoking is a well-established risk factor for subarachnoid hemorrhage (SAH), and current smokers have an increased risk of SAH. However, there are insufficient data on whether smoking cessation in current smokers reduces the risk of SAH. METHODS: A nested case-control study was conducted based on the National Health Insurance Service-National Health Screening Cohort, which comprises nationwide health claims data and a national health screening program in Korea (2002-2019). We constructed a cohort of current male smokers without a history of stroke at the baseline health screening (2002-2003). From this cohort, cases were defined as individuals who experienced a nontraumatic SAH during the follow-up period up to 2019. Five controls were matched to each case using incidence density sampling. Smoking status (continuation or cessation) before the occurrence of SAH was evaluated using the repeated national health screening program. We conducted a multivariable conditional logistic regression analysis, adjusting for alcohol consumption, physical activity, body mass index, systolic blood pressure, and fasting blood glucose levels, to evaluate the association between SAH risk and smoking cessation. RESULTS: At baseline, there were 112 142 current male smokers. After excluding individuals with prior stroke or insufficient data, the cohort consisted of 105 223 eligible participants (mean age, 50.3±8.5 years). Among them, we identified 318 cases of SAH and 1590 matched controls. Those who quit smoking had a significantly lower risk of SAH compared with current smokers (adjusted odds ratio, 0.55 [95% CI, 0.41-0.73]). The risk of SAH decreased with a longer period of smoking cessation. The risk reduction with smoking cessation was consistent even among prior heavy smokers. CONCLUSIONS: Smoking cessation in current male smokers reduced the risk of SAH, and the risk reduction was greater as the cessation period increased. These findings warrant intensive efforts to encourage smokers, even heavy smokers, to quit.

Impact of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction and Chronic Kidney Disease.

BACKGROUND: In the setting of acute myocardial infarction (AMI), there are no data regarding the benefits of intravascular ultrasound (IVUS) for chronic kidney disease (CKD) patients.Methods and Results: This study used data from the Korea Acute Myocardial Infarction Registry, a large, multicenter prospective cohort. We evaluated 1,759 patients with AMI and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and patients were classified into 2 groups: with and without IVUS. The primary outcome was target lesion failure (TLF) at 3 years. The hazard ratio (HR) of TLF according to eGFR was also analyzed. A total of 1,759 patients with AMI and CKD who underwent IVUS-guided PCI (19.2%) had a significantly lower risk of TLF at 3 years (8.9% vs. 15.3%; HR 0.55; 95% confidence interval [CI]: 0.38 to 0.81; P=0.002) than those who underwent angiography-guided PCI, regardless of their eGFR and the presence of end-stage renal disease (ESRD). The results were consistent after confounder adjustment and inversed probability weighting. CONCLUSIONS: In patients with CKD and AMI who underwent PCI with 2nd-generation DES implantation, the use of IVUS guidance was associated with a significant reduction in 3-year TLF and showed consistently favorable outcomes regardless of eGFR and ESRD.

Mohs Micrographic Surgery With Digital Pathology Improves Surgical Quality and Efficiency: A Retrospective Cohort Study.

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.

The Epidemiological and Clinical Characteristics of the Largest Outbreak of Enterohemorrhagic Escherichia coli in Korea.

BACKGROUND: The largest outbreak of enterohemorrhagic Escherichia coli (EHEC) O157:H7 occurred at a preschool in South Korea from June 12 to 29, 2020. This study aimed to analyze the epidemiological and clinical characteristics of EHEC infection in this outbreak. METHODS: Epidemiological investigation was performed on all 184 children and 19 workers at the preschool using a standard questionnaire to assess symptoms, food intake, attendance, and special activity history. Pulsed-field gel electrophoresis analysis of confirmed cases was performed to determine genetic relevance. RESULTS: During this outbreak, 103 children were affected, whereas only one infection was identified in adults. Of the 103 pediatric patients, 85 had symptoms (82.5%), including diarrhea, abdominal pain, bloody stool, fever, and vomiting. Thirty-two patients (31.1%) were hospitalized, 15 (14.6%) were diagnosed with hemolytic uremic syndrome, and 4 (3.9%) received dialysis treatment. Pulsed-field gel electrophoresis analysis identified 4 genotypes with high genetic relevance (92.3%). Epidemiological investigation revealed that this outbreak might have occurred from ingesting foods stored in a refrigerator with a constant temperature above 10°C, which was conducive to bacterial growth. Despite several measures after outbreak recognition, new infections continued to appear. Therefore, the preschool was forced to close on June 19 to prevent further person-to-person transmission. CONCLUSION: Our findings from the response to the largest outbreak will help prepare countermeasures against future EHEC outbreak.

Effects of registered nurses' staffing levels, work environment and education levels on nursing home residents' quality of life and nurse outcomes.

AIMS AND OBJECTIVES: To examine the effects of registered nurse staffing levels, work environment and education levels on the residents' quality of life and nurses' job dissatisfaction, burnout and turnover intention. BACKGROUND: Registered nurse staffing status and work environment are suboptimal in nursing homes worldwide. Nursing home care aims to maximise residents' quality of life. However, evidence on the impact of registered nurse staffing levels, work environment and education levels on the residents' quality of life and nurse outcomes in nursing homes is limited. DESIGN: This is a cross-sectional observational study. METHODS: A total of 513 residents and 117 registered nurses from 39 nursing homes in South Korea participated in surveys. The main measures included registered nurses' staffing levels, work environment, education levels, residents' quality of life, registered nurses' job dissatisfaction, burnout and turnover intention. We analysed data using the generalised estimating equations and reported the study using the STROBE checklist. RESULTS: Overall, the residents' quality-of-life score was 13.7 ± 2.6 (out of 17). Residents in nursing homes with a higher number of registered nurses or with work environment evaluated as 'mixed' or 'better' (compared with 'poor') had a higher quality of life. Regarding nurse outcomes, 74.4% of the registered nurses were dissatisfied with their current jobs, 12.0% had burnout and 18.8% had a turnover intention. Registered nurses working in 'mixed' or 'better' work environment were less likely to have job dissatisfaction. Registered nurses' education levels did not have a statistically significant effect on the resident and nurse outcomes. CONCLUSIONS: Registered nurse staffing levels and work environment should be considered important for improving residents' quality of life and nurses' job satisfaction. RELEVANCE TO CLINICAL PRACTICE: Regulation and policy reforms are needed to increase the registered nurse staffing levels and to create a good work environment in nursing homes. PATIENT OR PUBLIC CONTRIBUTION: Nursing home residents and registered nurses participated in the surveys of this study. Registered nurses facilitated resident recruitment by identifying and introducing the study to residents who were eligible for study participation. TRIAL REGISTRATION: Not applicable.

The Potential Role of an Adjunctive Real-Time Locating System in Preventing Secondary Transmission of SARS-CoV-2 in a Hospital Environment: Retrospective Case-Control Study.

BACKGROUND: There has been an increasing demand for new technologies regarding infection control in hospital settings to reduce the burden of contact tracing. OBJECTIVE: This study aimed to compare the validity of a real-time locating system (RTLS) with that of the conventional contact tracing method for identifying high-risk contact cases associated with the secondary transmission of SARS-CoV-2. METHODS: A retrospective case-control study involving in-hospital contact cases of confirmed COVID-19 patients, who were diagnosed from January 23 to March 25, 2022, was conducted at a university hospital in South Korea. Contact cases were identified using either the conventional method or the RTLS. The primary endpoint of this study was secondary transmission of SARS-CoV-2 among contact cases. Univariate and multivariable logistic regression analysis comparing test positive and versus negative contact cases were performed. RESULTS: Overall, 509 and 653 cases were confirmed by the conventional method and the RTLS, respectively. Only 74 contact cases were identified by both methods, which could be attributed to the limitations of each method. Sensitivity was higher for the RTLS tracing method (653/1088, 60.0%) than the conventional tracing method (509/1088, 46.8%) considering all contact cases identified by both methods. The secondary transmission rate in the RTLS model was 8.1%, while that in the conventional model was 5.3%. The multivariable logistic regression model revealed that the RTLS was more capable of detecting secondary transmission than the conventional method (adjusted odds ratio 6.15, 95% CI 1.92-28.69; P=.007). CONCLUSIONS: This study showed that the RTLS is beneficial when used as an adjunctive approach to the conventional method for contact tracing associated with secondary transmission. However, the RTLS cannot completely replace traditional contact tracing.

Factors Associated With Behavioral and Psychological Symptoms of Dementia: Prospective Observational Study Using Actigraphy.

BACKGROUND: Although disclosing the predictors of different behavioral and psychological symptoms of dementia (BPSD) is the first step in developing person-centered interventions, current understanding is limited, as it considers BPSD as a homogenous construct. This fails to account for their heterogeneity and hinders development of interventions that address the underlying causes of the target BPSD subsyndromes. Moreover, understanding the influence of proximal factors-circadian rhythm-related factors (ie, sleep and activity levels) and physical and psychosocial unmet needs states-on BPSD subsyndromes is limited, due to the challenges of obtaining objective and/or continuous time-varying measures. OBJECTIVE: The aim of this study was to explore factors associated with BPSD subsyndromes among community-dwelling older adults with dementia, considering sets of background and proximal factors (ie, actigraphy-measured sleep and physical activity levels and diary-based caregiver-perceived symptom triggers), guided by the need-driven dementia-compromised behavior model. METHODS: A prospective observational study design was employed. Study participants included 145 older adults with dementia living at home. The mean age at baseline was 81.2 (SD 6.01) years and the sample consisted of 86 (59.3%) women. BPSD were measured with a BPSD diary kept by caregivers and were categorized into seven subsyndromes. Independent variables consisted of background characteristics and proximal factors (ie, sleep and physical activity levels measured using actigraphy and caregiver-reported contributing factors assessed using a BPSD diary). Generalized linear mixed models (GLMMs) were used to examine the factors that predicted the occurrence of BPSD subsyndromes. We compared the models based on the Akaike information criterion, the Bayesian information criterion, and likelihood ratio testing. RESULTS: Compared to the GLMMs with only background factors, the addition of actigraphy and diary-based data improved model fit for every BPSD subsyndrome. The number of hours of nighttime sleep was a predictor of the next day's sleep and nighttime behaviors (odds ratio [OR] 0.9, 95% CI 0.8-1.0; P=.005), and the amount of energy expenditure was a predictor for euphoria or elation (OR 0.02, 95% CI 0.0-0.5; P=.02). All subsyndromes, except for euphoria or elation, were significantly associated with hunger or thirst and urination or bowel movements, and all BPSD subsyndromes showed an association with environmental change. Age, marital status, premorbid personality, and taking sedatives were predictors of specific BPSD subsyndromes. CONCLUSIONS: BPSD are clinically heterogeneous, and their occurrence can be predicted by different contributing factors. Our results for various BPSD suggest a critical window for timely intervention and care planning. Findings from this study will help devise symptom-targeted and individualized interventions to prevent and manage BPSD and facilitate personalized dementia care.

Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

Extended multi-item gamma Poisson shrinker methods based on the zero-inflated Poisson model for postmarket drug safety surveillance.

Bayesian signal detection methods, including the multiitem gamma Poisson shrinker (MGPS), assume a Poisson distribution for the number of reports. However, the database of the adverse event reporting system often has a large number of zero-count cells. A zero-inflated Poisson (ZIP) distribution can be more appropriate in this situation than a Poisson distribution. Few studies have considered ZIP-based models for Bayesian signal detection. In addition, most studies on Bayesian signal detection methods include simulation studies conducted assuming a gamma distribution for the prior. Herein, we extend the MGPS method using the ZIP model and apply various prior distributions. We evaluated the extended methods through an extensive simulation using more varied settings for the model and prior than existing methods. We varied the total number of reports, the number of true signals, the relative reporting rate, and the probability of observing a true zero. The results show that as the probability of observing a zero count increased, methods based on the ZIP model outperformed the Poisson model in most cases. We also found that using the mixture log-normal prior resulted in more conservative detection than other priors when the relative reporting rate is high. Conversely, more signals were found when using the mixture truncated normal distributions. We applied the Bayesian signal detection methods to data from the Korea Adverse Event Reporting System from 2012 to 2016.

Duration of dual-antiplatelet therapy after stent-assisted coil for unruptured intracranial aneurysm: A nationwide cohort study.

BACKGROUND: Stent-assisted coil (SAC) is increasingly used to treat unruptured intracranial aneurysm (UIA). However, the optimal duration of dual-antiplatelet therapy (DAPT) after SAC insertion remains unknown. AIM: To assess the time-dependent effect of DAPT on the risk of ischemic and hemorrhagic complications after SAC. METHODS: This is a retrospective cohort study among patients with UIA treated with SAC using the nationwide health claims database in South Korea between 2009 and 2020. Multivariate Cox regression analysis was used, which included the use of DAPT as a time-dependent variable. The effect of DAPT was investigated for each period of "within 90 days," "91 to 180 days," "181 to 365 days," and "366 to 730 days" after SAC. The primary outcome was a composite of ischemic stroke and major bleeding in each period within two years after SAC. RESULTS: Of the 15,918 patients, mean age at SAC was 57.6 ± 10.8 years, and 3815 (24.0%) were men. The proportion of patients on DAPT was 79.4% at 90 days, 58.3% at 180 days, and 28.9% at 1 year after SAC. During the 2 years after SAC, the primary composite outcome occurred in 356 patients (2.2%). DAPT significantly reduced the primary composite outcome within 90 days after SAC (adjusted hazard ratio (aHR), 0.44; 95% confidence interval (CI), 0.28-0.69; p < 0.001); however, this was not the case after 90 days (all p > 0.05). DAPT reduced ischemic stroke risk within 90 days (aHR, 0.31; 95% CI 0.18-0.54; p < 0.001), and 91 to 180 days after SAC (aHR 0.40; 95% CI 0.18-0.88; p = 0.022); however, after 180 days, DAPT was no longer beneficial. CONCLUSIONS: In patients with UIA treated with SAC, 3 months of DAPT was associated with a decreased risk of the composite of ischemic and hemorrhagic complications.

Effectiveness of the triglyceride-glucose index and triglyceride-glucose-related indices in predicting cardiovascular disease in middle-aged and older adults: A prospective cohort study.

BACKGROUNDS: Cardiovascular disease (CVD) risk assessment is a crucial component of public health. We aimed to determine the predictive value of the triglyceride-glucose (TyG) index and TyG-related indices for new-onset CVD. METHODS: This prospective study included 7,808 participants aged 40-69 years from the Ansung-Ansan cohort database. Our analysis was stratified by diabetes status. The hazard ratio (HR) with a 95% confidence interval (CI) for incident CVD was computed using multiple Cox proportional-hazards regression models. To evaluate the predictive performance of these indices for new-onset CVD, we calculated the Harrell's C-index (95% CI). RESULTS: In this study, a total of 6,890 participants did not have diabetes at baseline, while 918 participants had diabetes. In participants without diabetes, compared to the lowest tertile, fully adjusted HR and 95% CI for new-onset CVD in the highest tertile were as follows: TyG (HR 1.42, 95% CI 1.06-1.90), TyG-body mass index (BMI) (HR 1.92, 95% CI 1.19-3.10), TyG-waist circumference (WC) (HR 2.37, 95% CI 1.61-3.49), and TyG-waist-to-height ratio (WHtR) (HR 2.20, 95% CI 1.47-3.28). However, no significant associations were observed between TyG, modified TyG indices, and new-onset CVD in participants with diabetes. Notably, the C-indice of TyG-WC and TyG-WHtR were significantly higher than those of TyG and TyG-BMI in participants without diabetes. CONCLUSIONS: TyG-BMI, TyG-WC, and TyG-WHtR were associated with an increased risk of new-onset CVD in participants without diabetes. Furthermore, TyG-WC and TyG-WHtR showed better predictive performances for new-onset CVD than TyG and TyG-BMI in participants without diabetes.

Secular trends in dietary energy, carbohydrate, fat, and protein intake among Korean adults, 2010-2020 KHANES.

OBJECTIVES: The composition and balance of macronutrient intake play key roles in promoting a longer lifespan. In this study, we aimed to investigate the secular trends in carbohydrate, fat, and protein intakes in South Koreans from 2010 to 2020. METHODS: We examined the dietary nutritional intake of South Koreans using data from the Korean National Health and Nutrition Examination Survey. A total of 60,190 adults aged ≥19 y who completed the 24-h dietary recall interviews in a single day on all survey periods were included in this study. The outcomes included changes in macronutrient intake according to subgroups, such as age; sex; and the presence of diabetes, dyslipidemia, stroke, or heart disease, as well as energy intake from macronutrients. RESULTS: The study population showed a significant decrease in total energy intake from 2010 to 2020, with a corresponding decrease in the percentage of energy intake from carbohydrates (p-values for trend < 0.001). Conversely, the proportions of energy intake from proteins and fats increased during the same period (p < 0.001). Subgroup analyses revealed variations in macronutrient intake trends according to age, sex, obesity status, and underlying diseases. The analysis of trends in energy intake from various fat subtypes, total sugar, and fiber revealed a decrease in the energy intake percentage of total sugar from 2016 to 2020 and an increase in the energy intake percentage of all fat subtypes and fiber from 2013 to 2020. CONCLUSIONS: In the past 10 y, the dietary patterns in Korea have shifted toward the consumption of high-fat and high-protein diets with reduced carbohydrate intake.