Methods: It was a cross-sectional study using online questionnaire, carried out in a public university in Sarawak, Malaysia. All medical and nursing students were invited to participate in this study. Data was entered and analysed using IBM SPSS version 22.
Result: A total of 304 respondents participated in the study, with 81.6% female and 69.4% medical students. Majority of the respondents were most willing to take a medical history, do a physical examination, throat swabbing, draw blood and perform IV drip insertion. There was a high commitment among respondents to treat COVID-19 patients regardless of personal risks. Majority of the respondents also agreed that medical staff who are involved in treating COVID-19 patients should be receiving a salary increase and compensation should be given to affected healthcare families, and all non-medical staff should be involved in treating COVID-19 patients. About 71% agreed about a law mandating medical staffs to treat patient.
Conclusion: The willingness and commitment of medical and nursing students to treat COVID-19 patients was high, indicating their potential work force as healthcare providers.
METHODS: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.
RESULTS: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.
CONCLUSIONS: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.
METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario).
RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences.
CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.
STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.
SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.
SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.
DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.
ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.
RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.
LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.
CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.
RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).
CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.
RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.
CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.
RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.
CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).
METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo.
RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD.
CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.
METHODS AND RESULTS: Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.
CONCLUSION: In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.
METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.
RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.
CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.
METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials.
CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.