94 research outputs found

    Molecular Dynamics Studies of PEGylated Antimicrobial Peptides with Lipid Bilayers

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    <p>(A) Emission spectrum of CaAl<sub>2</sub>O<sub>4</sub>:Eu<sup>2+</sup>, Nd<sup>3+</sup> crystals curves depending on H<sub>3</sub>BO<sub>3</sub> concentration. (B) Decay curves depending on H<sub>3</sub>BO<sub>3</sub> concentration. (C) Magnified views of the graph in (B). (D) Decay curves in log scale depending on H<sub>3</sub>BO<sub>3</sub> concentration. (E) Relative initial intensity measured at 5s (relative values where the value of control sample #1 is 1.0) depending on H<sub>3</sub>BO<sub>3</sub> concentration.</p

    Limaprost and the Risk of Bleeding: A Self-Controlled Case Series Study

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    Objective To investigate the association between the use of limaprost and the risk of bleeding. Methods A self-controlled case series analysis was conducted using the National Health Insurance Service-National Sample Cohort database in South Korea. We identified patients aged 18 years or older who had at least one prescription of limaprost and were diagnosed with at least one case of bleeding between 2003 and 2019. The incidence rate ratio (IRR) of bleeding was calculated by dividing the incidence rate in the exposed period to limaprost by that in the unexposed period and adjusted for age using conditional Poisson regression model. Results Among 72,860 patients with limaprost prescriptions and bleeding diagnoses, there were 184,732 events of bleeding. After adjusting for age, the IRR was 1.47 (95% confidence interval [CI], 1.43ā€“1.50), wherein the IRR was the highest during the 0ā€“7 days after limaprost initiation (IRR, 2.11; 95% CI, 2.03ā€“2.18). Risk of bleeding was higher when limaprost was concomitantly used with antithrombotics or other drugs for spinal stenosis treatment, and when higher daily doses of limaprost were administered. Conclusion Our findings suggest that the risk of bleeding increased by 1.5-fold in periods of limaprost exposure compared to unexposed periods, with particularly higher risks observed during the first week after limaprost initiation, with concomitant drugs related to bleeding, and with a higher daily dose. A careful risk-benefit assessment is warranted when initiating limaprost, especially when administered with other medications or in higher daily doses

    Association of sodium-glucose cotransporter 2 inhibitors with post-discharge outcomes in patients with acute heart failure with type 2 diabetes:a cohort study

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    BACKGROUND: Given the cumulative evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on chronic heart failure, demand is emerging for further information on their effects in patients who are hospitalized for acute heart failure. However, there is still limited evidence about the class effect of SGLT2is on acute heart failure. We investigated whether initiating treatment with SGLT2is after an episode of acute heart failure reduces the risks of post-discharge heart failure readmission or cardiovascular mortality among patients with type 2 diabetes. METHODS: A retrospective cohort study was conducted in a cohort of patients with type 2 diabetes who hospitalized for heart failure, using Korean Health Insurance Review & Assessment database (2015-2020). The exposure was defined as initiation of SGLT2is during hospitalization or at discharge. We assessed hazards of post-discharge heart failure readmission and cardiovascular death at 1-year, and 30-, 60-, and 90-day from the date of discharge in the SGLT2is users and non-users. Cox proportional hazards models with propensity score-based inverse probability of treatment weighting were used to estimate hazard ratios and 95% confidence intervals. RESULTS: Among 56,343 patients with type 2 diabetes hospitalized for heart failure, 29,290 patients were included in the study cohort (mean [SD] age, 74.1 [10.8] years; 56.1% women); 818 patients (2.8%) were prescribed SGLT2is during index hospitalization or at discharge. Patients with a prescription for SGLT2i vs. those without prescription had lower rates of heart failure readmission or cardiovascular death at 1 year (22.4% vs. 25.3%; adjusted hazard ratio, 0.90 [95% confidence interval, 0.87-0.93]), and also at 30 days (7.0% vs. 7.7%%; 0.74 [0.69-0.79]). CONCLUSIONS: Among patients with type 2 diabetes, initiating SGLT2i treatment after an episode of acute heart failure was significantly associated with a reduced combined risk of heart failure readmission and cardiovascular mortality in a nationwide cohort reflecting routine clinical practice

    Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study

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    Objective: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice. Design: A retrospective cohort study. Setting: Korean Health Insurance Review and Assessment database. Participants: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018. Interventions: Initiation of combination therapy with evogliptin. Primary and secondary outcome measures: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs. Results: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51). Conclusions: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population

    Machine learning prediction of incidence of Alzheimerā€™s disease using large-scale administrative health data

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    Nationwide population-based cohort provides a new opportunity to build an automated risk prediction model based on individualsā€™ history of health and healthcare beyond existing risk prediction models. We tested the possibility of machine learning models to predict future incidence of Alzheimerā€™s disease (AD) using large-scale administrative health data. From the Korean National Health Insurance Service database between 2002 and 2010, we obtained de-identified health data in elders above 65 years (Nā€‰=ā€‰40,736) containing 4,894 unique clinical features including ICD-10 codes, medication codes, laboratory values, history of personal and family illness and socio-demographics. To define incident AD we considered two operational definitions: ā€œdefinite ADā€ with diagnostic codes and dementia medication (nā€‰=ā€‰614) and ā€œprobable ADā€ with only diagnosis (nā€‰=ā€‰2026). We trained and validated random forest, support vector machine and logistic regression to predict incident AD in 1, 2, 3, and 4 subsequent years. For predicting future incidence of AD in balanced samples (bootstrapping), the machine learning models showed reasonable performance in 1-year prediction with AUC of 0.775 and 0.759, based on ā€œdefinite ADā€ and ā€œprobable ADā€ outcomes, respectively; in 2-year, 0.730 and 0.693; in 3-year, 0.677 and 0.644; in 4-year, 0.725 and 0.683. The results were similar when the entire (unbalanced) samples were used. Important clinical features selected in logistic regression included hemoglobin level, age and urine protein level. This study may shed a light on the utility of the data-driven machine learning model based on large-scale administrative health data in AD risk prediction, which may enable better selection of individuals at risk for AD in clinical trials or early detection in clinical settings

    Association of adverse respiratory events with sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in South Korea:a nationwide cohort study

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    BACKGROUND: Impaired respiratory function remains underrecognized in patients with type 2 diabetes (T2D), despite common pulmonary impairment. Meanwhile, there is little data available on the respiratory effects of sodium glucose cotransporter 2 inhibitors (SGLT2i). Hence, we examined the association between SGLT2i use and the risk of adverse respiratory events in a real-world setting. METHODS: We conducted a population-based, nationwide cohort study using an active-comparator new-user design and nationwide claims data of South Korea from January 2015 to December 2020. Among individuals aged 18 years or older, propensity score matching was done to match each new user of SGLT2is with dipeptidyl peptidase 4 inhibitors (DPP4is), with patients followed up according to an as-treated definition. The primary outcome was respiratory events, a composite endpoint of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure. Secondary outcomes were the individual components of the primary outcome and in-hospital death. Cox models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Of 205,534 patient pairs in the propensity score matched cohort, the mean age of the entire cohort was 53.8 years and 59% were men, with a median follow-up of 0.66 years; all baseline covariates achieved balance between the two groups. Incidence rates for overall respiratory events were 4.54 and 7.54 per 1000 person-years among SGLT2i and DPP4i users, respectively, corresponding to a rate difference of 3 less events per 1000 person-years (95% CIā€‰-ā€‰3.44 toā€‰-ā€‰2.55). HRs (95% CIs) were 0.60 (0.55 to 0.64) for the composite respiratory endpoint, 0.35 (0.23 to 0.55) for acute pulmonary edema, 0.44 (0.18 to 1.05) for ARDS, 0.61 (0.56 to 0.66) for pneumonia, 0.49 (0.31 to 0.76) for respiratory failure, and 0.46 (0.41 to 0.51) for in-hospital death. Similar trends were found across individual SGLT2is, subgroup analyses of age, sex, history of comorbidities, and a range of sensitivity analyses. CONCLUSIONS: These findings suggest a lower risk of adverse respiratory events associated with patients with T2D initiating SGLT2is versus DPP4is. This real-world evidence helps inform patients, clinicians, and guideline writers regarding the respiratory effects of SGLT2i in routine practice
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