Diagnostic accuracy of a prehospital electrocardiogram rule-based algorithm for ST-elevation myocardial infarction: results from a population-wide project.

INTRODUCTION: This study reviewed the diagnostic accuracy of the prehospital electrocardiogram (PHECG) rule-based algorithm for ST-elevation myocardial infarction (STEMI) universally utilised in Hong Kong. METHODS: This prospective observational study was linked to a population-wide project. We analysed 2210 PHECGs performed on patients who presented to the emergency medical service (EMS) with chest pain from 1 October to 31 December 2021. The diagnostic accuracy of the adopted rulebased algorithm, the Hannover Electrocardiogram System, was evaluated using the adjudicated blinded rating by two investigators as the primary reference standard. Diagnostic accuracy was also evaluated using the attending emergency physician's diagnosis and the diagnosis on hospital discharge as secondary reference standards. RESULTS: The prevalence of STEMI was 5.1% (95% confidence interval [CI]=4.2%-6.1%). Using the adjudicated blinded rating by investigators as the reference standard, the rule-based PHECG algorithm had a sensitivity of 94.6% (95% CI=88.2%-97.8%), specificity of 87.9% (95% CI=86.4%-89.2%), positive predictive value of 29.4% (95% CI=24.8%-34.4%), and negative predictive value of 99.7% (95% CI=99.3%-99.9%) [all P<0.05]. CONCLUSION: The rule-based PHECG algorithm that is widely used in Hong Kong demonstrated high sensitivity and fair specificity for the diagnosis of STEMI.

Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer.

Dysregulated Notch signaling has a critical role in the tumorigenesis. Jagged1, a Notch ligand, is overexpressed in various human cancers. Recent studies revealed the involvement of Jagged1 in colorectal cancer (CRC) development. These basic studies provide a promising potential for inhibition of the Notch pathway for the treatment of CRC. Herein, we aimed to investigate the consequences of targeting Jagged1 using shRNA on CRC both in vitro and in vivo to test their potential to inhibit this key element for CRC treatment. We found that downregulation of Jagged1 with lentiviral Jagged1-shRNA resulted in decreased colon cancer cell viability in vitro, most likely mediated through reduced cell proliferation. Importantly, Jagged1 knockdown induced G0/G1 phase cell cycle arrest, with reduced Cyclin D1, Cyclin E and c-Myc expression. Silencing of Jagged1 reduced the migration and invasive capacity of the colon cancer cells in vitro. Furthermore, colon cancer cells with knockdown of Jagged1 had much slower growth rate than control cells in a xenograft mouse model in vivo, with a marked downregulation of cell proliferation markers (PCNA, Ki-67, and c-Myc) and metastasis markers (MMP-2 and MMP-9). These findings rationalize a mechanistic approach to CRC treatment based on Jagged1-targeted therapeutic development.

A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections.

BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.

Interferon gamma release assay for differentiating tuberculosis among pneumonia cases in acute healthcare setting.

OBJECTIVES: Early diagnosis of smear-negative tuberculosis remains challenging. The role of an interferon-gamma release assay (IGRA) in discriminating active pulmonary tuberculosis (PTB) among cases of 'pneumonia' was investigated. METHODS: Consecutive patients admitted to an acute hospital in Hong Kong (intermediate TB burden) during 2006-2008 because of pneumonia and suspected PTB were recruited for IGRA (Quantiferon-TB Gold, QFN-G) study. Diagnosis of tuberculosis was confirmed by mycobacterial culture or histology. RESULTS: Altogether 179 patients were recruited (median (IQR) age 59 (44-75), 68.7% male); active PTB was confirmed in 63 (35.2%). Among the AFB-smear-negative 'pneumonias' (n = 152), age>50 (OR 0.27, 95% CI 0.09-0.84), absence of weight loss (OR 0.30, 95% CI 0.10-0.88), and negative IGRA (OR 0.08, 95% CI 0.03-0.25) were independently associated with lower risks of PTB. The overall sensitivity, specificity, positive and negative predictive values for the IGRA in diagnosing active PTB were 60%, 87%, 72% and 80% respectively. Among smear-negative 'pneumonias' (n = 152), the performance values of IGRA were 64%, 87%, 62% and 88% respectively; in the absence of characteristic clinical or radiographic features of PTB, the negative predictive value (NPV) improved to 90-95%. CONCLUSIONS: The high NPV of QFN-G among smear-negative 'pneumonias' can be useful for risk stratification in hospitalized patients suspected of PTB. Further investigation on the role of these assays in patient management is warranted.

Cautionary note: linewidth effect in dynamic NMR.

In using NMR spectroscopy to evaluate the effects of kinetic processes taking place in the solute molecules being studied, one must estimate the inherent width w of each line, which is hidden from view throughout the kinetic thermal region due to the line-width broadening effected by the processes. We have herein built a self-consistent model function w(T) to attempt to evaluate the variation in the Arrhenius activation energy obtained with the model parameters present in w(T). As it turns out, a sizable number of such line-width parameters yields excellent spectral fits, and these lead to a considerable range of possible activation energies.

Outcomes of adults hospitalised with severe influenza.

BACKGROUND: The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza. METHODS: A prospective, observational cohort study was conducted over 24 months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates. RESULTS: 754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation. CONCLUSIONS: Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.