The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.
The purpose of this study was to investigate whether the 'bystander effect' known to occur in emergency situations is effective in bullying situations through examination of the individual experiences of 467 middle-and high-school students. While the bystander effect was not found to be valid in bullying situations, there were significant differences in factors influencing a bystander's defending behavior in terms of the presence of other bystanders. In cases where bullying was witnessed in the presence of other bystanders, factors such as one's previous experience as a perpetrator, antisocial behavior, level of harm, relationship to the victim and popularity had an effect on the defending behavior of bystanders. On the other hand, in the absence of other bystanders, one's previous experience as a victim, level of empathy, and perceived control had an effect on the defending behavior of bystanders. The implications of these results for an effective intervention for school bullying in terms of bystanders are discussed.
The present study explored the relationship between the regional Cold-Heat sensation, the key indicator of the Cold-Heat patterns in traditional East Asian medicine (TEAM), and various biomarkers in Korean population. 734 apparently healthy volunteers aged 20 years and older were enrolled. Three scale self-report questions on the general thermal feel in hands, legs, and abdomen were examined. We found that 65% of women tended to perceive their body, particularly their hands and legs, to be cold, versus 25% of men. Energy expenditure and temperature load at resting state were lower in women, independently of body mass index (BMI). Those with warm hands and warm legs had a 0.74 and 0.52 kg/m2 higher BMI than those with cold hands and cold legs, respectively, regardless of age, gender, and body weight. Norepinephrine was higher, whereas the dynamic changes in glucose and insulin during an oral glucose tolerance test were lower in those with cold extremities, particularly hands. No consistent differences in biomarkers were found for the abdominal dimension. These results suggest that gender, BMI, the sympathetic nervous system, and glucose metabolism are potential determinants of the Cold-Heat sensation in the hands and legs, but not the abdomen.
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