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Background and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke.Methods This randomized, open-label, controlled trial assigned patients with recent ischemic stroke P= 0.0003). LDL-C level P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (PP=0.0091). The adverse event rates did not differ between the two groups.Conclusion Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C

Background and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days.Conclusion This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).

There are limited studies on the association of COVID-19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID-19 vaccination and the occurrence of NA.We explored unexpected safety signals for NA related to COVID-19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database.On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (information component [IC]A weak association was observed between NA and COVID-19 vaccines. However, the risk did not surpass that of influenza vaccines.

People with depression and subjective cognitive complaints (SCC) may be at particularly high risk for developing dementia. However, to date, studies on depression and SCC are limited mainly to single high-income countries. Thus, the aim of the present study was to investigate the association between depression and SCC in adults from low- and middle-income countries (LMICs). Cross-sectional, community-based data were analyzed from the World Health Survey. Two questions on subjective memory and learning complaints in the past 30 days were used to create a SCC scale ranging from 0 (No SCC) to 100 (worse SCC). ICD-10 Diagnostic Criteria for Research was used for the diagnosis of subsyndromal depression, brief depressive episode, and depressive episode. Multivariable linear regression was conducted to explore the associations. Data on 237,952 individuals aged >= 18 years [mean (SD) age 38.4 (16.0) years; females 50.8%] were analyzed. After adjustment for potential confounders (age, sex, education, anxiety), compared to no depressive disorder, subsyndromal depression (b-coefficient 7.91; 95%CI = 5.63-10.18), brief depressive episode (b-coefficient 10.37; 95%CI = 8.95 11.78), and depressive episode (b-coefficient 13.57; 95%CI = 12.33 14.81) were significantly associated with higher mean SCC scores. The association was similar in all age groups (i.e., 18 44, 45 64, and >= 65 years), and both males and females. All depression types assessed were associated with worse SCC among adults in 47 LMICs. Future longitudinal studies are needed to investigate whether older people with depression and SCC are at higher risk for dementia onset in LMICs.

Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker for insulin resistance. Epidemiology studies have shown that insulin resistance is a risk factor for various infectious diseases. We evaluated the prognostic value of TyG index measured before the COVID-19 infection in COVID-19 infected patients.From a nationwide COVID-19 cohort dataset in Korea, we included COVID-19 patients diagnosed between Jan and Jun 2020. Based on the nationwide health screening data between 2015 and 2018, TyG index was calculated as ln [triglyceride (mg/dL) × fasting glucose level (mg/dL)/2]. Primary outcome is development of severe complications of COVID-19 defined as composite of mechanical ventilation, intensive care unit care, high-flow oxygen therapy, and mortality within two months after the diagnosis of COVID-19.This study included 3887 patients with COVID-19 confirmed by reverse transcription polymerase chain reaction. Mean ± standard deviation of TyG index was 8.54 ± 0.61. Severe complications of COVID-19 were noted in 289 (7.44%) patients. In the multivariate logistic regression, TyG index was positively associated with severe complications of COVID-19 (adjusted odds ratio: 1.42, 95% confidence interval [1.12-1.79]).In COVID-19 infected patients, high TyG index was associated with increased risk for severe complications. TyG index might be useful predictor for the severity of COVID-19 infection.

Dyslipidemia is a major risk factor for stroke, following hypertension, diabetes, and smoking. Treatment of dyslipidemia is important for the prevention and treatment of various vascular diseases, including stroke, coronary artery disease, and peripheral vascular disease. Statins, ezetimibe, and proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitors have been shown to reduce the risk of stroke and cardiovascular disease in previous studies. When prescribing dyslipidemia drugs for secondary prevention of stroke, the combination, type, and dose of dyslipidemia drugs should be appropriately selected according to the patient's comorbidity and stroke subtype. In the case of statins, highintensity statin administration should be considered, but it is essential to take into account side effects, comorbidities, and individual characteristics of each patient. If the target low density lipoproteincholesterol level is not reached or inappropriate drug dosing due to the side effects of statins, ezetimibe or a PCSK9 inhibitor may be considered. Finally, statin discontinuation due to improper judgment may be detrimental to the patient in the longterm view.

To characterize the clinical features of patients with medication-overuse headache (MOH) according to the class of acute medications being overused.MOH is a common global health problem, severely disabling the majority of the patients affected. Although various medications can cause MOH, whether clinical features differ according to the overused medication type remains unclear.We analyzed data from a multicenter cross-sectional study in neurology clinics in Korea from April 2020 to June 2021.Among 229 eligible patients, MOH was documented in patients who overused multiple drug classes (69/229, 30.1%; most frequent occurrence), triptans (50/229, 21.8%), non-opioid analgesics (48/229, 21.0%), and combination-analgesics (40/229, 17.4%). Patients who overused multiple drug classes reported more frequent use of acute medications (median [25th-75th percentiles]: 25.0 [15.0-30.0] vs. 17.5 [10.0-25.5] days/month, p = 0.029) and fewer crystal-clear days (0.0 [0.0-9.5] vs. 9.0 [0.0-10.0] days/month, p = 0.048) than those who overused triptans. Patients who overused multiple drug classes also reported shorter intervals from chronic daily headache to the onset of MOH than patients who overused combination-analgesics (0.6 [0.2-1.9] vs. 2.4 [0.7-5.4] years, p = 0.001) or non-opioid analgesics (1.5 [0.6-4.3] years, p = 0.004). Patients who overused multiple drug classes reported more emergency room visits (1.0 [0.0-1.0] visits/year) than those who overused combination-analgesics (0.0 [0.0-1.0], p = 0.024) or non-opioid analgesics (0.0 [0.0-1.0], p = 0.030). Patients who overused triptans reported fewer headache days (21.0 [20.0-30.0] vs. 30.0 [20.5-30.0] days/month, p = 0.008) and fewer severe headache days (7.0 [4.0-10.0] vs. 10.0 [5.0-15.0] days/month, p = 0.017) than those who overused non-opioid analgesics.Some clinical characteristics of MOH significantly differed according to the class of overused medications. The findings from this study may contribute to the understanding of the clinical characteristics and pathophysiology of MOH.

Gamma-glutamyl transferase (GGT) is a biomarker of inflammation, and is known to be associated with stroke and atrial fibrillation. Venous thromboembolism (VT), a not uncommon thrombotic disorder, shares similar mechanisms with other thrombotic disorders including these stroke and atrial fibrillation. Given these associations, we intended to investigate the potential association between variability in GGT and VT. The study included data from the National Health Insurance Service-Health Screening Cohort, comprising 1,085,105 participants with health examinations 3 or more times from 2003 to 2008. Variability indexes were the coefficient of variation, standard deviation, and variability independent of the mean. The occurrence of venous thromboembolism (VT) was defined with more than one claim of the following ICD-10 codes: deep VT (I80.2–80.3), pulmonary thromboembolism (I26), intraabdominal venous thrombosis (I81, I82.2, I82.3), or other VT (I82.8, I82.9). To determine the relationship of quartiles of GGT with incident VT risk, Kaplan–Meier survival curve and logrank test were used. Cox’s proportional hazard regression was used to investigate the risk of VT occurrence by GGT quartile (Q1–Q4). A total of 1,085,105 subjects were incorporated in the analysis, and the average follow-up was 12.4 years (interquartile range 12.2–12.6). VT occurred in 11,769 (1.08%) patients. The GGT level was measured 5,707,768 times in this stud. Multivariable analysis showed that GGT variability were positively associated with the occurrence of VT. Compared to the Q1, the Q4 showed an adjusted HR of 1.15 (95% CI 1.09–1.21, p p p

Background d ‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d ‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d ‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d ‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results In the 170 patients, the median d ‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d ‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P d ‐dimer level was independently associated with poor outcome 3 months after EVT (odds ratio [OR], 4.399 [95% CI, 1.594–12.135]). Kaplan–Meier survival analysis showed that a high d ‐dimer level was independently associated with death within 6 months after EVT (OR, 5.441 [95% CI, 1.560–18.978]; log‐rank test, P d ‐dimer effect showed no heterogeneity across the subgroups for poor outcome 3 months after EVT or death within 6 months after EVT. The direction of effect was unfavorable for tertile 3 across all demographic strata. Conclusions High plasma d ‐dimer levels were predictive of early neurologic worsening, poor functional outcome 3 months after EVT, and death within 6 months after EVT. Registration URL: http://www.clinicaltrials.gov ; Unique identifier: NCT02964052.

Background: There is inadequate information on the validation of diabetic microvascular complications in the Korean National Health Insurance Service data set. We aimed to validate the diagnostic algorithms regarding the nephropathy, neuropathy, and retinopathy of diabetes.Methods: From various secondary and tertiary medical centers, we selected 6,493 patients aged ≥ 40 years who were diagnosed with diabetic microvascular complications more than once based on codes in the 10th version of the International Classification of Diseases (ICD-10). During 2019 and 2020, we randomly selected the diagnoses of 200 patients, 100 from each of two hospitals. The positive predictive value (PPV), negative predictive value, error rate, sensitivity, and specificity were determined for each diabetic microvascular complication according to the ICD-10 codes, laboratory findings, diagnostic studies, and treatment procedure codes.Results: Among the 200 patients who visited the hospital more than once and had the diagnostic codes of diabetic microvascular complications, 142, 110, and 154 patients were confirmed to have the gold standard of diabetic nephropathy (PPV, 71.0%), diabetic neuropathy (PPV, 55.0%), and diabetic retinopathy (PPV, 77.0%), respectively. The PPV and specificity of diabetic nephropathy (PPV, 71.0–81.4%; specificity, 10.3–53.4%), diabetic neuropathy (PPV, 55.0–81.3%; specificity, 66.7–76.7%) and diabetic retinopathy (PPV, 77.0–96.6%; specificity, 2.2–89.1%) increased after combining them with the laboratory findings, diagnostic studies, and treatment procedures codes. These change trends were observed similarly for both hospitals.Conclusions: Defining diabetic microvascular complications using ICD-10 codes and their related examination codes may be a feasible method for studying diabetic complications.

Infection is associated with the occurrence, recurrence, and progression of atrial fibrillation (AF), and is also closely related to poor prognosis. However, studies of the relationship between infectivity and severe complications of coronavirus infectious disease-19 (COVID-19) with a history of AF are limited. To estimate infectivity and severity of complications in COVID-19 patients with a history of AF, this study was done. From the Korean nationwide COVID-19 dataset, 212 678 participants with at least one severe acute respiratory syndrome coronavirus 2 (COVID-19) test were included between January 1 and June 4, 2020. AF was defined according to at least two outpatient hospital visits or one admission with an ICD-10 code of "I48" before the COVID-19 test. To investigate the association of AF with infectivity and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) was performed. Severe complications of COVID-19 were defined as a composite outcome of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. Among 212 678 participants who underwent the COVID-19 test, there were 7713 COVID-19 positive patients. After PSM, COVID-19 PCR positivity did not show a significant difference according to the presence of AF (odds ratio [OR]: 0.79, 95% confidence interval [CI]: [0.60-1.04]). Of 7713 COVID-19 patients, 62 (0.8%) had a history of AF and severe complications occurred in 444 (5.7%) patients. After PSM, AF was associated with the development of severe complications (OR: 2.04, 95% CI: [1.10-3.79]) and mortality (OR: 2.09, 95% CI: [1.01-4.31]) of COVID-19. We found that AF was associated with an increased risk of severe complications in COVID-19 infected patients.

Background: A phase III Rescue On reperfusion Damage in cerebral Infarction by Nelonemdaz (RODIN) trial has been launched since December, 2021 and patients are being enrolled. Rationale: Nelonemdaz (previously, neu2000) targets (1) selectively the 2B subunit of the N-methyl-D-aspartate glutamate receptor, the activation of which causes Na+ and Ca++ influx into neuronal cells and then induces downstream death-signaling pathways, and (2) free radical species, which are released both from the downstream pathways of glutamate receptors and from following reperfusion injury. Phase I and II trials showed its safety and a tendency of clinical outcome improvements. Methods: RODIN is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into nelonemdaz and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8 scores) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset. The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug, analyzed by the Cochran-Mantel-Haenszel shift test. Ongoing status: By August 23, 2022, 210 patients have been enrolled. It is expected that enrollment could be finalized until spring season of 2023. Conclusions: This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study was registered in ClinicalTrials.gov, number NCT05041010.

Retinal vascular occlusions are a common cause of visual loss. The association between oral health and the risk of retinal vascular occlusions remains unknown. We investigated whether oral health was associated with the risk of retinal vascular occlusions. We conducted a retrospective cohort study including 138,484 participants who completed a national health screening program with an oral health examination from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) 2002–2015. Oral health markers, such as the presence of periodontitis, tooth loss, and dental caries, and the frequency of daily tooth brushing, were evaluated. The primary outcome was the occurrence of retinal vascular occlusions up to December 2015. In total, 2533 participants developed retinal vascular occlusions (215 with retinal artery occlusion, 1686 with retinal vein occlusion, 632 with unspecified retinal vascular occlusion). In the multivariable Cox regression analysis, periodontitis was an independent risk factor for retinal vascular occlusions (adjusted hazard ratio: 1.18; 95% confidence interval: 1.02–1.36; p = 0.024). Frequent tooth brushing was negatively associated with the risk of retinal vascular occlusions (adjusted hazard ratio: 0.89; 95% confidence interval: 0.80–0.98; p = 0.022). Improving oral hygiene may contribute to the attenuation of the risk of retinal vascular occlusions.

ObjectiveTo investigate the association of oral health status and oral hygiene behaviors with cataract occurrence longitudinally.Materials and methodsBased on the National Health Screening cohort database of Korea, participants who underwent oral health screening by dentists in 2003 were included. Cataract was defined as two or more claims of disease classification for the International Classification of Diseases-10 (E10.34, E11.34, E12.34, E13.34, E14.34, H25, and H26) with cataract specific treatment or surgery procedure claim codes. The occurrence of cataract was analyzed with Cox proportional hazard model according to the presence of periodontitis and oral health examination findings, including missing teeth, caries, tooth brushing, and dental scaling.ResultsOverall, 103,619 subjects were included. During a median follow-up of 12.2 years, cataract developed in 12,114 (11.7%) participants. Poor oral health status such as the presence of periodontitis (adjusted hazard ratio [HR] 1.08, 95% CI [confidence interval] 0.99–1.17, p = 0.088) and increased number of missing teeth (adjusted HR = 1.74, 95% CI = 1.55–1.96, p < 0.001) was associated with the increased cataract risk. Better oral hygiene behaviors such as increased frequency of tooth brushing (adjusted HR = 0.84, 95% CI = 0.79–0.88, p < 0.001) and performed dental scaling within 1 year (adjusted HR = 0.90, 95% CI = 0.86–0.94, p < 0.001) were negatively associated with cataract occurrence.ConclusionPeriodontitis and increased number of missing teeth may increase the risk of cataract. However, maintaining good oral hygiene through tooth brushing and dental scaling may reduce the risk of future cataract occurrence. Further studies should be performed to confirm the association between chronic oral inflammation and cataract.

Obstructive sleep apnea (OSA), a common comorbidity in patients with stroke, has shown increasing prevalence over the past few decades. OSA is an important risk factor for stroke in addition to other well-known contributors, including hypertension, hyperlipidemia, atrial fibrillation, and diabetes mellitus. Moreover, OSA is an independent predictor of neurological outcomes and mortality. The pathological mechanisms underlying the association between OSA and stroke include autonomic dysfunction, hypertension, cardiac arrhythmia, dyslipidemia, impaired glucose tolerance, hypoxia, and inflammation. Continuous positive airway pressure (CPAP) therapy has proven clinical utility in improvement of neurological symptoms in patients with stroke. Findings from a CPAP withdrawal model have shown increased sympathetic activity in OSA with a consequent significant elevation in blood pressure, relevant cerebral hypoxia, and disturbed cardiac repolarization. In this review, we present an overview of the literature that describes an association between OSA and stroke in addition to the vascular risk factors, including hypertension, hyperlipidemia, atrial fibrillation, and diabetes mellitus. This study highlights the importance of early and accurate diagnosis and management of OSA for stroke prevention and care and will benefit physicians in clinical practice.

Oral health is reportedly associated with several systemic diseases, particularly cardiovascular diseases, through systemic inflammatory and thrombotic mechanisms. This study aimed to investigate the association between oral health status, oral hygiene behavior, and venous thromboembolism (VTE) in a nationwide, population-based cohort database in a longitudinal setting. Data of participants who underwent oral health screening by dentists between January and December 2003 (n = 2,415,963) were retrieved from the National Health Insurance Database of the Korean National Health Insurance Service. Periodontitis was identified using claims or oral health screening data. Periodontal pockets and the number of missing teeth were examined by dentists during oral health screenings. Data on oral hygiene behaviors (tooth brushing, dental visits, and dental scaling) were collected. VTE was defined as two or more claims of one of the following ICD-10 codes: deep (I80.2–80.3), pulmonary (I26, I26.0, I26.9), intra-abdominal (I81, I82, I82.2, I82.3), and other (I82.8, I82.9) VTE and concurrent medication (anticoagulants and antiplatelets). VTE was analyzed using the Cox proportional hazard model according to periodontitis, number of missing teeth, tooth brushing frequency, dental visits, and dental scaling. VTE occurred in 39,851 (1.8%) participants within a median of 17.0 (interquartile range 16.3–17.7) years. Periodontitis was associated with VTE (adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.15–1.28; p < 0.001). An increased number of missing teeth was associated with an increased risk of VTE; the adjusted HR (versus participants without missing teeth) was 1.58 (95% CI, 1.46–1.71; p < 0.001, p for trend < 0.001) for participants with ≥15 missing teeth. Furthermore, tooth brushing ≥3 times a day was negatively correlated with VTE (adjusted HR, 0.67; 95% CI, 0.65–0.69; p < 0.001, p for trend < 0.001). Dental scaling within one year was associated with a significantly lower risk of VTE (adjusted HR, 0.95; 95% CI, 0.93–0.98; p < 0.001). Improved oral hygiene, including tooth brushing and dental scaling, may be associated with a decreased risk of VTE. Periodontitis and an increased number of missing teeth may increase the risk of VTE.

Background Characteristics, disabilities, and optimal management of medication overuse headache remain uncertain. This study aimed to elucidate the clinical characteristics of patients with medication overuse headache enrolled in a medication overuse headache registry in Korea. Methods The Registry for Load and Management of MEdicAtion OveruSE Headache (RELEASE), a cross-sectional prospective observational study including seven referral headache centers in Korea, started enrolling adult patients with medication overuse headache in April 2020. Data included information on headache characteristics, burden on daily function, depression, anxiety, history of acute and preventive medications, and treatment strategies. Results A total of 229 patients (85.6% females; mean age, 45.5 ± 13.5 years) were enrolled by June 2021. The average durations of chronic headaches and medication overuse were 6.5 and 4.3 years, respectively. In the past month before enrollment, patients had headaches for 25 days and severe headaches for 12 days, and used acute medications for 20 days. Patients were disabled in 66.8 days in the past 3 months and had moderate/severe depression and anxiety in 56% and 35%, respectively. The proportion of patients on preventive treatments increased from 38% to 93% during the study period. Conclusions RELEASE study reflects the current management status and opportunities to improve the quality of care in patients with medication overuse headache.

OBJECTIVE Studies on the association of oral hygiene indicators with cardiovascular disease in hypertensive patients have been lacking. Oral hygiene is directly or indirectly associated with systemic inflammation, one of the essential mechanisms of cardiovascular disease. Therefore, we hypothesized that oral hygiene would be related to the risk of cardiovascular diseases in hypertensive patients. METHODS We included 52 677 hypertensive participants who completed oral health checkups from the Korean National Health Insurance Service-National Health Screening Cohort between 2003 and 2004. We collected data on periodontitis diagnosis and treatment history, number of teeth loss, number of dental caries, and frequency of tooth brushing from medical records of health claims and oral health examination. The primary outcome was defined as composite outcomes of stroke and myocardial infarction. Follow-up was done until the date of primary outcome, or 31 December 2015. RESULTS During the 11.26 ± 2.39 years (mean ± standard deviation) of the study follow-up, 3292 participants developed primary outcomes [stroke (n = 2430), myocardial infarction (n = 862)]. In multivariable Cox regression analyses, participants with dental caries (≥ 5) were independently associated with occurrence of a primary outcome [adjusted hazard ratio: 1.37; 95% confidence interval (CI):1.10-1.72; P = 0.006]. Frequent tooth brushing (≥ 2 times/day) was significantly related to lower risk of primary outcomes (adjusted hazard ratio: 0.88; 95% CI: 0.81-0.96; P = 0.002). CONCLUSION Our study demonstrated that multiple dental caries were related to the risk of cardiovascular diseases in hypertensive patients. Better oral hygiene may attenuate the risk of cardiovascular events in hypertensive patients.

ObjectivesGamma-glutamyl transferase (GGT) is related to inflammation, osteoporosis, and vascular diseases. Recently, changes in metabolic parameters have been proposed as disease biomarkers. We aimed to assess longitudinally the association of GGT variability with osteoporotic fractures.MethodsFrom the National Health Insurance Service-Health Screening Cohort database, participants who underwent three or more health examinations between 2003 and 2008 were included (n=1,072,432). Variability indexes were as follows: (1) coefficient of variation (CV), (2) standard deviation (SD), and (3) variability independent of the mean (VIM). The primary outcome was occurrence of osteoporotic fracture, defined as identification of one of the following international classification of diseases-10 codes: vertebral fracture (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, M49.5), hip fracture (S72.0, S72.1), distal radius fracture (S52.5, S52.6), or humerus fracture (S42.2, S42.3).ResultsDuring a median of 12.3 years (interquartile range 12.1 – 12.6), osteoporotic fractures occurred in 49,677 (4.6%) participants. In multivariable analysis, GGT variability based on CV positively correlated with the occurrence of osteoporotic fracture (adjusted hazard ratio [HR] of the highest quartile compared with the lowest quartile 1.15, 95% confidence interval [CI] 1.12-1.18,P< 0.001). These results were consistent even when GGT variability was defined by SD (adjusted HR 1.22, 95% CI 1.19-1.25,P< 0.001) and VIM (adjusted HR 1.12, 95% CI 1.09-1.15,P< 0.001).ConclusionsIncreased GGT variability is associated with an increased risk of osteoporotic fractures in the Korean population. Maintaining constant and stable GGT level may help reduce the risk of osteoporotic fractures.

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. Methods: This prospective registry–based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41–3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics. Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Objectives: The purpose of our study is to investigate the effects of apolipoprotein B (APOB) and APOE gene polymorphisms on bleeding complications in patients receiving direct oral anticoagulants (DOACs). Methods: A total of 16 single nucleotide polymorphisms (SNPs) in 468 patients were genotyped. Six SNPs of ABCB1 (rs3842, rs1045642, rs2032582, rs1128503, rs3213619, and rs3747802), one SNP of CYP3A5 (rs776746), seven SNPs of APOB (rs1042034, rs2163204, rs693, rs679899, rs13306194, rs13306198, and rs1367117), and two SNPs of APOE (rs429358 and rs7412) were analyzed by a TaqMan genotyping assay. Multivariable logistic regression analysis with selected variables was performed for the construction of a risk scoring system. Two risk scoring systems were compared (demographic factors only vs. demographic factors and genetic factors). Results: In the multivariable analyses, two models were constructed; only demographic factors were included in Model I and both demographic factors and genetic factors in Model II. Rivaroxaban and anemia showed significant association with bleeding in both models. Additionally, ABCB1 rs3842 variant homozygote carriers (CC) and APOB rs13306198 variant allele carriers (AG, AA) had a higher risk of bleeding risk compared with that of wild-type allele carriers (TT, TC) and wild-type homozygote carriers (GG), respectively. Whereas the area under the receiver operating characteristic curve (AUROC) value using demographic factors only was 0.65 (95% confidence interval (CI): 0.56–0.74), the AUROC increased to 0.72 by adding genetic factors (95% CI: 0.65–0.80). The predicted bleeding risks of bleeding in patients with 0, 1, 2, 3, 4, 5, 6, 7 and 8 points from the logistic regression curve were 0.8%, 2.0%, 5.4%, 5.2%, 12.5%, 26.9%, 47.0%, 64.3% and 82.3%, respectively. Conclusions: The study results can be used for enhancing individualized treatment strategies in patients taking DOACs, helping clinicians predict the bleeding risk.

BackgroundThis study describes the global epidemiology and trends associated with neck pain. Global Burden of Disease data collected between 1990 and 2019 were used to determine the global burden of neck pain in the general populations of 204 countries.MethodsGlobal, regional, and national burdens of neck pain determined by prevalence, incidence, and years lived with a disability (YLD) from 1990 to 2019 were comprehensively analyzed according to age, gender, and socio-demographic index using the Global Burden of Disease Study 1990 and 2019 data provided by the Institute for Health Metrics and Evaluation.ResultsGlobally, in 2019, the age-standardized rates for prevalence, incidence, and YLD of neck pain per 100,000 population was 2,696.5 (95% uncertainty interval [UI], 2,177.0 to 3,375.2), 579.1 (95% UI, 457.9 to 729.6), and 267.4 (95% UI, 175.5 to 383.5) per 100,000 population, respectively. Overall, there was no significant difference in prevalence, incidence, or YLD of neck pain between 1990 and 2019. The highest age-standardized YLD of neck pain per 100,000 population in 2019 was observed in high-income North America (479.1, 95% UI 323.0 to 677.6), Southeast Asia (416.1, 95% UI 273.7 to 596.5), and East Asia (356.4, 95% UI 233.2 to 513.2). High-income North America (17.0, 95% UI 9.0 to 25.4%) had the largest increases in YLD of neck pain per 100,000 population from 1990 to 2019. At the national level, the highest age-standardized YLD of neck pain was found in the Philippines (530.1, 95% UI 350.6 to 764.8) and the highest change age-standardized YLD between 1990 and 2019 was found in the United States (18.4, 95% UI 9.9 to 27.6%). Overall, the global burden of neck pain increased with age until the age of 70–74 years, and was higher in women than men. In general, positive associations between socio-demographic index and burden of neck pain were found.ConclusionsBecause neck pain is a major public health burden with a high prevalence, incidence, and YLD worldwide, it is important to update its epidemiological data and trends to cope with the future burden of neck pain.

Rationale Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain. Aim We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment. Sample-size estimates We aim to randomize 668 patients (334 per arm), 1:1. Methods and design We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP Study outcomes The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0–2 vs. 3–6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months. Discussion The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP Clinical trial registration ClinicalTrials.gov Identifier: NCT04205305.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.