In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation ...strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.
In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.
From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority<0·001; HR 0·55 95% CI 0·40–0·76, psuperiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42–1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35–0·77, p=0·0012).
In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.
ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.
Background
Sexually transmitted infections (STIs) can have serious consequences, and the global STI incidence remains high. However, there is little information on the frequency of STIs with multiple ...pathogens according to age. Accordingly, we conducted a study to determine the trends of coinfection with sexually transmitted pathogens according to age in the Republic of Korea from 2018 to 2020.
Methods
From January 2018 to December 2020, 65,191 samples of swab, urine, and other types submitted for STI screening were obtained from U2Bio Co. Ltd. (Seoul, Republic of Korea). Multiplex polymerase chain reaction, a sensitive and rapid method for simultaneous detection of STIs caused by multiple different pathogens, was performed using an AccuPower STI4C‐Plex Real‐Time PCR kit, AccuPower STI8A‐Plex Real‐Time PCR kit, and AccuPower STI8B‐Plex Real‐Time PCR kit with an Exicycler 96 Real‐Time Quantitative Thermal Block.
Results
Of the 65,191 samples tested, 35,366 (54.3%) tested positive for one or more sexually transmitted pathogens. The prevalence of coinfections with two or more sexually transmitted pathogens was inversely proportional to age. Furthermore, the rates of coinfection with sexually transmitted pathogens and age distribution differed according to sex and the sexually transmitted pathogen type.
Conclusion
This study confirmed that a significant proportion of patients with STIs are coinfected with multiple pathogens. Public health managers could use these results to recognize and prevent STIs according to age.
Differences in sexually transmitted infections according to the pathogen. Black, light gray, and dark gray represent single, two types, and more than two types of infection, respectively. Candida, Candida albicans; CT, Chlamydia trachomatis, GV, Gardnerella vaginalis; HSV1, Herpes simplex virus 1; HSV2, Herpes simplex virus 2; MG, Mycoplasma genitalium; MH, Mycoplasma hominis; NG, Neisseria gonorrhoeae; TP, Treponema pallidum; TV, Trichomonas vaginalis; UP, Ureaplasma parvum; UU, Ureaplasma urealyticum.
The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established.
In two trials, we ...randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis.
The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval CI, 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06).
The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)
ABSTRACT
Introduction: Recently, some authors have claimed that the Awaji criteria (AC) are not always more sensitive than the revised El Escorial criteria (rEEC) in amyotrophic lateral sclerosis ...(ALS). Methods: A meta‐analysis examined 2 prospective and 7 retrospective studies, which included 1,121 ALS patients, to compare AC and rEEC for early diagnosis of ALS. Results: AC led to an 11% greater likelihood of being classified into the categories “clinically definite” or “clinically probable”, while if confined to the “clinically probable – laboratory supported (LS)” category, this effect was 40% higher with the rEEC (95% cnfidence interval, 3–82%; I2 = 98%). Specifically, AC downgraded 20% of the rEEC “clinically probable – LS” category to the AC “clinically possible”. Conclusions: Despite overall superiority of AC, this meta‐analysis shows that it is not always more sensitive than rEEC. These results are related to the requirement for 2 upper motor neuron signs in the AC “clinically probable” category. Muscle Nerve 51: 822–829, 2015
Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian ...populations remain uncertain.
In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months.
At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% 45/400 vs 5.3% 21/400; hazard ratio HR, 2.26; 95% confidence interval CI, 1.34 to 3.79;
=0.002). The incidences of major bleeding (7.5% 29/400 vs 4.1% 16/400,
=0.04) and fatal bleeding (1% 4/400 vs 0%,
=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% 36/400 vs 5.8% 23/400; HR, 1.62; 95% CI, 0.96 to 2.74;
=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups.
In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.
The risks and benefits of long-term dual antiplatelet therapy remain unclear.
This prospective, multicenter, open-label, randomized comparison trial was conducted in 24 clinical centers in Korea. In ...total, 5045 patients who received drug-eluting stents and were free of major adverse cardiovascular events and major bleeding for at least 12 months after stent placement were enrolled between July 2007 and July 2011. Patients were randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin (n=2531). The primary end point was a composite of death resulting from cardiac causes, myocardial infarction, or stroke 24 months after randomization. At 24 months, the primary end point occurred in 57 aspirin-alone group patients (2.4%) and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence interval, 0.66-1.35; P=0.75). The 2 groups did not differ significantly in terms of the individual risks of death resulting from any cause, myocardial infarction, stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%) of the aspirin-alone group and dual-therapy group patients, respectively (hazard ratio, 0.71; 95% confidence interval, 0.42-1.20; P=0.20).
Among patients who were on 12-month dual antiplatelet therapy without complications, an additional 24 months of dual antiplatelet therapy versus aspirin alone did not reduce the risk of the composite end point of death from cardiac causes, myocardial infarction, or stroke.
http://www.clinicaltrials.gov. Unique identifier: NCT01186146.
The use of big data may facilitate the recognition and interpretation of causal relationships between disease occurrence and climatic variables. This study examined the effects of various climatic ...variables on the seasonal epidemiology of respiratory syncytial virus (RSV) infections in the temperate climate of Korea. Trends in RSV detection were analyzed using 9010 samples tested between January 1, 2012, and December 31, 2018, at Dankook University Hospital in Cheonan, Korea. Seasonal patterns in RSV detection frequency were compared with local climatic variables during the same period. RSV detection rate of 12.8% (
n
= 1150/9010) was observed, which was higher for RSV-A (7.1%) than RSV-B (5.8%) and RSV-A and RSV-B alternated each year. Children < 1 year exhibited high infection rates with RSV-A (68.5%) and RSV-B (58.7%). RSV-A and RSV-B infection rates in children under 9 years old were 96.2% and 92.1%, respectively. RSV had a significant relationship with several climatic factors. Air temperature, wind chill temperature, and particulate matter concentration were lower on days with a higher frequency of RSV detection. In contrast, atmospheric pressure was higher on days with lower RSV detection. Although the detection rates for RSV-A and RSV-B increased on days with lower air temperatures, those for RSV-B also increased on days with lower wind chill temperatures. Our findings suggest that climatic variables affect the RSV detection rate among children under 10 years of age. The present data may help predict the time when prevention strategies may be the most effective.
Rhizoma Polygonati falcatum (RPF) has been used as a traditional herbal medicine in Asia, because of its anti-hyperglycemic, anti-triglycemic, and anti-tumor activity. In this study, we determined ...the anti-adipogenic potential of RPF extract and its component kaempferol in 3T3-L1 adipocytes, and the underlying molecular mechanism(s) using microarray analysis. Adipocyte differentiation of 3T3-L1 cells was significantly impaired by RPF extract and kaempferol as monitored by Oil Red O staining and quantitative measurement of lipid accumulation. Additionally, the mRNA expression of adipogenesis genes decreased on treatment with kaempferol. The role of kaempferol at the genome-wide level was further assessed by a microarray approach. Our analysis indicated that kaempferol decreased the expression of adipogenic transcription factors (Pparγ, Cebpβ, Srebp1, Rxrβ, Lxrβ, Rorα) and genes involved in triglyceride biosynthesis (Gpd1, Agpat2, Dgat2), while increasing lipolysis-related genes, such as Tnfα, Lsr, and Cel. Finally, co-transfection assays using luciferase reporter gene and reverse transcription-polymerase chain reaction (RT-PCR) analysis using peroxisome proliferator-activated receptor-γ (PPARγ) target genes indicated that kaempferol significantly repressed rosiglitazone-induced PPARγ transcriptional activity. Overall, our data suggests that kaempferol, a major component of RPF, may be beneficial in obesity, by reducing adipogenesis and balancing lipid homeostasis partly through the down-regulation of PPARγ.
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