The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Experiences of Pediatric Palliative Care Among Bereaved Parents Who Lost a Child With Leukemia in South Korea.

Pediatric palliative care was introduced in South Korea in 2018, with an increased need for care of children with life-limiting conditions, such as leukemia. However, the perspective of parents, who are the primary caregivers, regarding pediatric palliative care has not been explored. This study aimed to describe the pediatric palliative care-related experiences of parents who had lost a child to leukemia to better understand their needs and care outcomes. Ten mothers of children who received pediatric palliative care were recruited. Individual in-depth interviews were conducted. Phenomenology was applied to elucidate parents' experiences during their children's illness and after bereavement. From 179 main statements and 46 meaningful units, 22 themes were derived and grouped into 11 theme clusters and 4 categories. The participants described that the pediatric palliative care team had an indispensable role in providing emotional support to them and their children; this support continued even after the child's death. In addition, the participants were satisfied with their choice to receive pediatric palliative care and hoped that more regions could benefit from the services. The study findings could contribute to advances and the popularization of pediatric palliative care in South Korea.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Development and validation of a prognostic model for early triage of patients diagnosed with COVID-19.

We developed a tool to guide decision-making for early triage of COVID-19 patients based on a predicted prognosis, using a Korean national cohort of 5,596 patients, and validated the developed tool with an external cohort of 445 patients treated in a single institution. Predictors chosen for our model were older age, male sex, subjective fever, dyspnea, altered consciousness, temperature ≥ 37.5 °C, heart rate ≥ 100 bpm, systolic blood pressure ≥ 160 mmHg, diabetes mellitus, heart disease, chronic kidney disease, cancer, dementia, anemia, leukocytosis, lymphocytopenia, and thrombocytopenia. In the external validation, when age, sex, symptoms, and underlying disease were used as predictors, the AUC used as an evaluation metric for our model's performance was 0.850 in predicting whether a patient will require at least oxygen therapy and 0.833 in predicting whether a patient will need critical care or die from COVID-19. The AUCs improved to 0.871 and 0.864, respectively, when additional information on vital signs and blood test results were also used. In contrast, the protocols currently recommended in Korea showed AUCs less than 0.75. An application for calculating the prognostic score in COVID-19 patients based on the results of this study is presented on our website ( https://nhimc.shinyapps.io/ih-psc/ ), where the results of the validation ongoing in our institution are periodically updated.

Consensus Decision-Making for the Management of Antiplatelet Therapy before Non-Cardiac Surgery in Patients Who Underwent Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents: A Cohort Study.

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic-bleeding risks, it has been left to an individualized decision-making based on physicians' perspectives before non-cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug-eluting stents. Methods and Results A total of 3582 adult patients undergoing non-cardiac surgery after percutaneous coronary intervention with second-generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non-cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98-3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31-7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45-3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.

Patterns of Antiplatelet Therapy During Noncardiac Surgery in Patients With Second-Generation Drug-Eluting Stents.

Background Continuing antiplatelet therapy (APT) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second-generation drug-eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second-generation drug-eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all-cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P=0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69-1.44; P=0.995). In subgroup analysis, patients undergoing intra-abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI, 0.08-0.91; P=0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36-8.38; P=0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second-generation drug-eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra-abdominal surgery. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03908463.

Frequency of Vascular Inflammation and Impact on Neointimal Proliferation of Drug Eluting Stents in Porcine Coronary Arteries.

BACKGROUND: We aimed to describe the frequency of vascular inflammatory reactions with second generation drug eluting stents (DES) compared to first generation DES, and analyze the impact on inflammation and neointimal proliferation in a porcine coronary model. METHODS: A total of 26 stents (7 multi-link VISION, 6 CYPHER, 6 TAXUS and 7 XIENCE V) were deployed in the coronary arteries of 10 domestic swine for 28 days, after which each stent was harvested and processed (divided into 8 or 9 segments) for histomorphometric analysis. RESULTS: A total of 202 histological segments [146 DES and 56 bare metal stents (BMS)] were included in this study. The mean neointimal thickness was significantly reduced in the DES group compared to the BMS group. The DES group had higher injury scores (DES = 0.99 ± 0.79 versus BMS = 0.67 ± 0.44, p < 0.004), inflammatory scores (DES = 2.09 ± 1.54 versus BMS = 0.64 ± 0.98, p < 0.001) and presence of para-strut granulomas (DES = 35% versus BMS = 2%, p < 0.001). In logistic regression analysis, the presence of para-strut granulomas correlated with an area of stenosis > 50% (RR: 6.11, 95% CI: 2.97 to 12.59, p = 0.001). In the DES group, the second generation stents had a lower neointimal area (XIENCE V: 1.64 ± 0.90 mm2) compared to the first generation stents (TAXUS: 2.36 ± 1.56 mm2, p = 0.005; CYPHER 2.78 ± 1.82 mm2, p = 0.001). The XIENCE V stents had lower inflammatory scores and lower frequency of para-strut granulomas compared to the first generation stents. CONCLUSIONS: Second generation DES had a lower incidence of vascular inflammatory reactions compared to first generation DES. This biological phenomenon appears to influence the patterns of neointimal formation.

Creating Anti-icing Surfaces via the Direct Immobilization of Antifreeze Proteins on Aluminum.

Cryoprotectants such as antifreeze proteins (AFPs) and sugar molecules may provide a solution for icing problems. These anti-icing substances protect cells and tissues from freezing by inhibiting ice formation. In this study, we developed a method for coating an industrial metal material (aluminum, Al) with AFP from the Antarctic marine diatom, Chaetoceros neogracile (Cn-AFP), to prevent or delay ice formation. To coat Al with Cn-AFP, we used an Al-binding peptide (ABP) as a conjugator and fused it with Cn-AFP. The ABP bound well to the Al and did not considerably change the functional properties of AFP. Cn-AFP-coated Al (Cn-AFP-Al) showed a sufficiently low supercooling point. Additional trehalose coating of Cn-AFP-Al considerably delayed AFP denaturation on the Al without affecting its antifreeze activity. This metal surface-coating method using trehalose-fortified AFP can be applied to other metals important in the aircraft and cold storage fields where anti-icing materials are critical.

The effects of a smoking cessation programme on health-promoting lifestyles and smoking cessation in smokers who had undergone percutaneous coronary intervention.

Smoking is a major risk factor for not only the occurrence of myocardial ischaemia but also recurrences of vascular stenosis. This study aimed to evaluate health-promoting lifestyles and abstinence rate after a smoking cessation programme. Sixty-two smokers who had undergone percutaneous coronary intervention were randomly assigned to either the experimental or control group. The experimental group (n = 30) received 10 phone counselling sessions and 21 short message service messages for abstinence and coronary disease prevention, whereas the control group (n = 32) received only the standard education. After the intervention, 14 members of the experimental group had switched to a non-smoking status, confirmed biochemically; moreover, their physical activity and stress management scores increased significantly. However, self-efficacy of smoking cessation was not reflected in the cotinine levels. Thus, it is necessary not only to increase self-efficacy but also to determine the factors that affect the success of smoking cessation so that they can be included in the intervention. Our results suggest that phone counselling and short message service messaging might be important tools for the realization of smoking cessation and lifestyle changes among patients who have undergone percutaneous coronary intervention.

Production of bio-based phenolic resin and activated carbon from bio-oil and biochar derived from fast pyrolysis of palm kernel shells.

A fraction of palm kernel shells (PKS) was pyrolyzed in a fluidized bed reactor. The experiments were performed in a temperature range of 479-555 °C to produce bio-oil, biochar, and gas. All the bio-oils were analyzed quantitatively and qualitatively by GC-FID and GC-MS. The maximum content of phenolic compounds in the bio-oil was 24.8 wt.% at ∼500 °C. The maximum phenol content in the bio-oil, as determined by the external standard method, was 8.1 wt.%. A bio-oil derived from the pyrolysis of PKS was used in the synthesis of phenolic resin, showing that the bio-oil could substitute for fossil phenol up to 25 wt.%. The biochar was activated using CO2 at a final activation temperature of 900 °C with different activation time (1-3 h) to produce activated carbon. Activated carbons produced were microporous, and the maximum surface area of the activated carbons produced was 807 m(2)/g.