Sex-based outcomes on unguided de-escalation from ticagrelor to clopidogrel in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention: a post-hoc analysis of the TALOS-AMI.

Background: The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear. Methods: This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization. Results: Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P = 0.001) (interaction P = 0.46). Conclusions: In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men.

Impact of the coronavirus disease 2019 pandemic on the incidence of other infectious diseases in the hematology hospital in Korea.

BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.

Associations of active and passive tobacco exposure with elevated blood pressure in Korean adolescents.

OBJECTIVES: To test the hypothesis that tobacco exposure is associated with elevated blood pressure (EBP) in Korean adolescents, and that the association is dose dependent. METHODS: This cross-sectional study used data from the 2011-2020 Korea National Health and Nutrition Survey (KNHANES). Subjects were eligible if they were 13-18 years at the time of participation in KNHANES. Tobacco exposure was defined by urine cotinine level. The main outcomes were EBP and hypertension. Statistical analyses were conducted using SAS version 9.4 with appropriate sampling weights to account for the complex survey design, stratification, and cluster variable. RESULTS: A total of 2,518 adolescents was included in the analysis, representing 2.5 million Korean adolescents. The mean± standard deviation participant age was 15.3±1.7 years, and 55.3% were male. The number of participants with active tobacco smoke exposure was 283 (11.2%), passive tobacco smoke exposure was 145 (5.8%), and no smoke exposure was 2,090 (83.0%). Analysis of the 2,518 urine-cotinine-verified participants showed that tobacco smoke exposure had a significant effect on EBP: with an odds of elevated blood pressure of 3.00 (95% confidence interval [CI], 1.14 to 7.89). The odds of hypertension were 3.61 (95% CI, 1.13 to 11.49) in the active smoking group compared with the no tobacco exposure group after adjustment for potential confounders. CONCLUSIONS: It is necessary to present a range of public health plans to reduce tobacco exposure that affects adolescents' blood pressure, and further research with a larger number of participants using urine cotinine as a biomarker is needed.

Analysis of the progression rate of idiopathic macular holes and the optimal cut-off for baseline minimum linear diameter and base diameter.

PURPOSE: To determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular holes (MHs) decreases before vitrectomy. STUDY DESIGN: A retrospective study. METHODS: We investigated the differences in MLD and BD between baseline and operation days in patients with stages 2, 3, and 4 MHs using optical coherence tomography (OCT). Each difference in OCT parameters was divided by the time interval to calculate the MH progression rates and the cut-off points of MLD and BD. RESULTS: Overall, 269 patients (282 eyes) were included. It took an average of 36.02 ± 24.69 (7-197) days from baseline to operation. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p < 0.001 and p = 0.007; BD: p < 0.001 and p = 0.019, respectively). Simple linear regression showed the relationship between baseline MLD and BD, and the progression rate; the progression rate decreased as baseline MLD (p = 0.004) and BD increased ( p < 0.001). For baseline MLD and BD, the cut-off points where the progression rate decreased were 306.0 and 470.0 µm, respectively. CONCLUSION: The group without PVD progressed faster than the group with PVD. Moreover, the progression rates were faster in MHs with MLD < 306.0 µm and BD < 470.0 µm. In these patients, vitrectomy without delay is expected to improve the visual prognosis.

The effectiveness of a suicide prevention program in primary care clinics supported by community public health resources: A difference-in-differences analysis.

The importance of appropriate and intensive follow-up management for individuals identified with suicide risk through screening is highlighted. The Link between Primary Care Clinic and Public Health Resources Intervention(LinkPC-PH), a suicide prevention program in primary care clinics supported by community public health resources, was implemented at the district level in 2017. The purpose of the present study is to evaluate the effectiveness of the LinkPC-PH intervention by comparing suicide rates before(2014-2016) and after(2017-2019) implementation of the intervention using a difference-in-differences design. The LinkPC-PH comprises several dimensions of intervention including screening, risk assessment of suicidality, and referral in primary care clinics and crisis contact within 24 hours, case management, and safety planning led by public health professionals. After adjustment for district-level confounders, an intervention-implemented district had 2.87 fewer suicide deaths per 100,000 people in a population sample at post-intervention than would have been expected from the same trend in suicide rates as non-implemented intervention districts. In other words, the suicide rate in the intervention area decreased by 25% following the intervention. These results empirically substantiate suicide prevention programs in primary care clinics by community public health resources for reduced suicide rates to support effective community-based suicide prevention interventions.

Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk: Post Hoc Analysis of the TALOS-AMI Randomized Clinical Trial.

Importance: In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking. Objective: To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI). Design, Setting, and Participants: This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022. Intervention: Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT. Main Outcomes and Measures: Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated. Results: Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32). Conclusions and Relevance: In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Health-related quality of life of Korean older adults according to age, sex, and living arrangements: a cross-sectional study.

Introduction: The number and proportion of older adults living alone is a significant issue. While the number of the oldest old people is also expected to increase, their health characteristics are poorly understood. This study aims to evaluate the health-related quality of life (HRQoL) of the oldest old people according to age, sex, and living arrangements. Methods: This study is based on the Korea Community Health Survey 2021. Among the survey's 229,242 observations, 73,617 observations aged 65 or higher were used for the analysis. The study participants were divided into 5-year age intervals (from 65-69 to 90+), sex, and living arrangements. The outcome variables are the EuroQol 5 Dimensions (EQ-5D) index score and the problem reporting rates of the five dimensions of EQ-5D. Results: The mean EQ-5D index scores were 0.896 at 65-69 and 0.741 at 90+. The mean EQ-5D index score decreased more rapidly as age increased. Women showed consistently lower mean EQ-5D index scores than men in all age intervals. The proportion of older adults living alone increased from 18.1% at 65-69 to 43.6% at 90+. The odds of reporting problems with anxiety/depression among older men living alone were estimated to be significantly higher than older men living with someone (aOR 1.22 95% CI 1.05-1.43). The odds of reporting problems in self-care and usual activity among older women living alone were estimated to be significantly lower than older women living with someone (aOR 0.88 95% CI 0.70-0.83 and aOR 0.88 95% CI 0.82-0.94). Conclusion: This study showed that older adults' HRQoL deteriorates as their age increases. Moreover, living alone may lead to different effects on older adults' HRQoL according to sex. More comprehensive studies and collaborative attention are needed to identify and provide customized care for older adults.

Gastric Cancer Incidence and Mortality After Endoscopic Resection of Gastric Adenoma: A Nationwide Cohort Study.

INTRODUCTION: Gastric adenoma is a precursor lesion of gastric cancer. We investigated whether the removal of gastric adenoma prevented gastric cancer incidence and its mortality. METHODS: Using the linkage of nationwide databases, we assessed gastric cancer incidence and mortality among patients who had gastric adenomas removed between 2011 and 2013 in Korea. These outcomes were compared primarily with those of the Korean general population by estimating the standardized incidence and mortality ratio and secondarily with internal control subjects who did not have gastric neoplasm after esophagogastroduodenoscopy and were matched for age, sex, and calendar year by calculating hazard ratios (HR) with the Cox proportional hazards model. RESULTS: We identified 44,405 adenoma removal patients. During a median follow-up of 8.4 years, 1,038 (2.34%) of them were given a diagnosis of gastric cancer and a total of 524 gastric cancers were expected for a standard incidence ratio of 1.98 (95% confidence interval [CI], 1.84-2.13). A total of 199 deaths from gastric cancer were expected and 99 were observed for a standard mortality ratio of 0.50 (95% CI, 0.40-0.60). Compared with the nonadenoma cohort (n = 39,826), the adenoma removal patients had a higher risk of gastric cancer (HR, 2.84; 95% CI, 2.51-3.21) and associated mortality (HR, 1.66; 95% CI, 1.19-2.31). DISCUSSION: Removal of gastric adenoma resulted in lower-than-expected mortality but higher-than-expected incidence due to gastric cancer than that in the general population. Our analyses indicated the importance of follow-up strategy after removal of gastric adenoma.

Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS: The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

Effectiveness of Psychotherapy on Prevention of Suicidal Re-Attempts in Psychiatric Emergencies: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Many psychological interventions aim to prevent suicide, but there is limited information regarding their comparative effectiveness. OBJECTIVES: We conducted a systematic review and network meta-analysis to evaluate the relative effects of psychological interventions for preventing suicide re-attempts in psychiatric emergencies. METHODS: We searched PubMed, Embase, Cochrane, and PsycINFO from inception to December 1, 2022. Selection and data extraction were conducted independently by two reviewers based on prespecified criteria. We evaluated the efficacy of interventions, potential effect moderators, and study quality both within individual studies and across studies. Global and local inconsistencies and publication bias were explored. The primary outcome was suicide re-attempt rate. The network meta-analysis was conducted using the "netmeta" package in R. The protocol was registered with PROSPERO (CRD42021291407). RESULTS: There were 3,155 participants from 26 randomized controlled trials included in the network meta-analysis. Cognitive behavioral therapy (CBT) was the only intervention that was more effective than a common comparator for reducing suicide re-attempts among psychological interventions in both direct and indirect comparisons (odds ratio: [95% confidence interval], 0.46 [0.25-0.85] vs. 0.47 [0.27-0.83]). CBT had the highest score (p score = 0.8727) across the various psychological interventions. Neither global nor local inconsistencies were significant. There was no clear evidence of violations of the transitivity assumption when comparing characteristics of studies across interventions. Publication bias was not suspected for the primary outcome. CONCLUSIONS: CBT may be regarded as a reasonable first-line psychological intervention to prevent re-attempts among people with previous suicide attempts. We observed a moderate quality of evidence supporting an 87% probability of CBT being the best treatment available for preventing suicide re-attempts.

Impact of the COVID-19 Pandemic on Gender Differences in Depression Based on National Representative Data.

BACKGROUND: Restrictions on daily life and changes in economic structure due to coronavirus disease 2019 (COVID-19) likely would have affected men and women differently. However, there is still a lack of research on the difference between men and women in the amount of change in depression during COVID-19 compared to before COVID-19. Therefore, the researchers investigated gender differences in the magnitude of increase in the prevalence of depression with its severity and individual symptoms during COVID-19 compared with pre-pandemic levels. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2016 and 2018 were used to assess depression levels pre-pandemic and the KNHANES 2020 for pandemic depression levels. Depression was evaluated using the Patient Health Questionnaire-9 (PHQ-9). To analyze the differences between men and women in the magnitude of the mental health impact of COVID-19, the researchers analyzed the weighted differences in depression prevalence, severity, and individual symptoms during the COVID-19 pandemic compared to before COVID-19 stratified by gender. RESULTS: In men, there were significant increases in weighted prevalence for depression (1.2% percentage point; 95% confidence interval [CI], 0.0-2.3) and severe symptoms of depression (2.6-fold; 95% CI, 1.2-5.7). Among the individual symptoms of depression, significant increases during the pandemic compared to before were: little interest or pleasure in doing things, 1.26-fold; feeling tired or having little energy, 2.2-fold; and suicidal thoughts, 1.7-fold. However, there was no significant difference in prevalence, symptoms severity, and any symptom before and during COVID-19 in women. CONCLUSIONS: Because the pandemic is likely to increase mental problems of the affected over time due to such problems as financial stress and joblessness or post-infection health issues, the researchers anticipate an increase in the prevalence of some mental illnesses. In particular, since the suicide rate of men is higher than that of women, from a public health perspective, active interventions are needed to prevent an increase in the suicide rate due to COVID-19. It is also necessary to establish national policies to overcome the psychological, social, and economic losses resulting from COVID-19.

The Change of Suicidal Ideation Over a 12-Week Naturalistic Treatment of Depression: Comparison Between Young People and Older Adults.

OBJECTIVE: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. METHODS: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. RESULTS: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. CONCLUSION: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Associations between digital media use and lack of physical exercise among middle-school adolescents in Korea.

OBJECTIVES: The reported effects of digital media overuse on physical activity among adolescents are inconsistent. This study examined the association between hours of digital media use and lack of moderate-intensity physical exercise (mPE) according to the type of digital media. METHODS: This study included 1,837 middle school students from the iCURE (Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence) study conducted in Korea. Hours spent using digital media were measured by self-reported daily usage time for Internet games, messengers, social media, and watching game streaming on weekdays. Lack of mPE was defined as performing a minimum of 30 minutes at a time less than twice weekly. Multivariable logistic regression analysis stratified by sex was performed. RESULTS: Among male students, the group with the highest hours of using either Internet games or watching game streaming was more likely to lack mPE than each non-user group. In contrast, among male students, the group using either messengers or social media had a higher rate of mPE compared to each non-user group. Female students showed no association between hours spent using Internet games, messengers, social media, or watching game streaming and a lack of mPE. CONCLUSIONS: Among male middle school students in Korea, the excessive use of Internet games or watching game streaming was associated with a lack of mPE. Thus, guidelines should be established regarding adolescent use of internet games and watching game streaming.

Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis.

BACKGROUND: It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). METHODS: In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1-4) was used to determine visit-to-visit HbA1c variability. RESULTS: Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients). The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0-6.9%]_Q1 (P = 0.006), HVS [6.0-6.9%]_Q2 (P = 0.013), HVS [6.0-6.9%]_Q3 (P = 0.018), and HVS [7.0-7.9%]_Q3 (P = 0.040). CONCLUSION: To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

Impact of the risk of malnutrition on bleeding, mortality, and ischemic events in patients with acute myocardial infarction.

BACKGROUND & AIMS: Data regarding the relationship between malnutrition and clinical outcomes of acute myocardial infarction (AMI) is limited. The study aims to evaluate the clinical impact of malnutrition in AMI patients after percutaneous coronary intervention (PCI). METHODS AND RESULTS: The COREA-AMI registries identified 10,161 AMI patients who underwent PCI from January 2004 to August 2014. Patients with geriatric nutritional risk index (GNRI) scores of <82, 82 to <92, 92 to <98, and ≥98 were categorized as having severe, moderate, mild malnutrition risk, and absence of risk, respectively. Associations of GNRI with Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding, all-cause death, and major cardiovascular events (MACEs; a composite of cardiovascular death, myocardial infarction, or ischemic stroke) were evaluated. Over 50% of AMI patients were malnourished, with 25.0%, 22.7%, and 4.9% having mild, moderate, and severe malnutrition risks, respectively. Over a median 4.9-year follow-up, patients with malnutrition risk had higher risks of BARC 3 or 5 bleeding (adjusted hazard ratios [aHRs], 1.27, 1.55, and 2.02 for mild, moderate, and severe, respectively; p < 0.001), all-cause death (aHRs, 1.26, 1.46, and 1.85 for mild, moderate, and severe, respectively; p < 0.001), and MACEs (aHRs, 1.14, 1.32, and 1.67 for mild, moderate, and severe, respectively; p < 0.001) than patients without risk. CONCLUSION: Elevated malnutrition risk was common among AMI patients undergoing PCI and was strongly associated with a higher risk of major bleeding, all-cause death, and major ischemic events.

Establishing Rationale for the Clinical Development of Cell Therapy Products: Consensus between Risk and Benefit.

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

Risk factors and outcomes of internet gaming disorder identified in Korean prospective adolescent cohort study.

Background and aims: Internet gaming disorder (IGD) is known to cause various psychological and physical complications. Through data collected from an adolescent prospective longitudinal cohort, we examined how IGD is related to lifestyle and physical symptoms, as well as the temporal relationship between them. Methods: This study was conducted as part of iCURE (Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence) in Korea between 2015 and 2019. Sleep and physical activity time, dry eye symptoms, musculoskeletal pain, and near-miss accidents were measured at baseline and followed-up after one year. IGD risk was evaluated using the Internet Game Use - Elicited Symptom Screen (IGUESS). The association between IGD risk and measured variables was analyzed, both at baseline and at follow-up after one year. Results: At baseline, the IGD risk group had significantly less physical activity time and sleep time and had more dry eye symptoms, musculoskeletal pain, and near-miss accidents than the IGD non-risk group. Additionally, in the IGD risk group at baseline, dry eye symptoms, musculoskeletal pain, and near-miss accidents occurred significantly more after one year of follow-up. Discussion and conclusion: The results of this study show that IGD is a significant risk factor that increases the probability of physical disease and trauma in adolescents. Therefore, interventions aimed at reducing IGD risk and protecting the physical and mental health of adolescents are imperative.

Long-Term Changes in HbA1c According to Blood Glucose Control Status During the First 3 Months After Visiting a Tertiary University Hospital.

BACKGROUND: We evaluated patients visiting a tertiary university hospital due to a diagnosis of diabetes with a goal of achieving blood glucose control and evaluated blood glucose persistence over 7 years according to the change in blood glucose evident at 3 months after the first visit. METHODS: Patients treated from 2009 to 2013 were categorized into four groups according to the change in HbA1c levels during the first 3 months of follow-up (Best_group, ≥ 1.6% decrease; Better_group, 0.5-1.5% decrease; Neutral_group, maintained at -0.4% to +0.4%; Worse_group, ≥ 0.5% increase). Each patient's blood glucose control status was then monitored for 7 years. The incidence of stroke and acute coronary syndrome during this period was confirmed. RESULTS: Overall, 9,776 patients were included. HbA1c values were lower in the Best_group than in the other groups at all time points (all P < 0.001). The rate of reaching targets of < 6.5% or < 7.0% HbA1c decreased over time; the rate at which the estimated glomerular filtration rate decreased to < 30 or < 60 mL/min/1.73m² increased over time (all trends, P < 0.01). CONCLUSION: Blood glucose control status in the first 3 months after initiating hospital care enabled estimation of the patient's glycemic control status for the next 7 years. In cases with poor initial blood glucose control, a new or more active method of blood glucose control should be sought.

The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017-2018.

Background: In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework. Materials and methods: We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment. Results: Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95-3.86). Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16-1.41). Conclusion: Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.