Joint analysis of vaccination effectiveness and antiviral drug effectiveness for COVID-19: a causal inference approach.

OBJECTIVES: This study aims to estimate the causal effects of oral antivirals and vaccinations in the prevention of all-cause mortality and progression to severe COVID-19 in an integrative setting with both antivirals and vaccinations considered as interventions. METHODS: We identified hospitalized adult patients (i.e. aged 18 or above) in Hong Kong with confirmed SARS-CoV-2 infection between March 16, 2022, and December 31, 2022. An inverse probability-weighted (IPW) Andersen-Gill model with time-dependent predictors was used to address immortal time bias and produce causal estimates for the protection effects of oral antivirals and vaccinations against severe COVID-19. RESULTS: Given prescription is made within 5 days of confirmed infection, nirmatrelvir-ritonavir is more effective in providing protection against all-cause mortality and development into severe COVID-19 than molnupiravir. There was no significant difference between CoronaVac and Comirnaty in the effectiveness of reducing all-cause mortality and progression to severe COVID-19. CONCLUSIONS: The use of oral antivirals and vaccinations causes lower risks of all-cause mortality and progression to severe COVID-19 for hospitalized SARS-CoV-2 patients.

Early sepsis care with the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the emergency department: hybrid type 1 effectiveness-implementation pilot stepped wedge randomised controlled trial (NEWS-1 TRIPS) protocol.

INTRODUCTION: Early sepsis treatment in the emergency department (ED) is crucial to improve patient survival. Despite international promulgation, the uptake of the Surviving Sepsis Campaign (SSC) Hour-1 Bundle (lactate measurement, blood culture, broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension/lactate ≥4 mmol/L and vasopressors for hypotension during/after fluid resuscitation within 1 hour of sepsis recognition) is low across healthcare settings. Delays in sepsis recognition and a lack of high-quality evidence hinder its implementation. We propose a novel sepsis care model (National Early Warning Score, NEWS-1 care), in which the SSC Hour-1 Bundle is triggered objectively by a high NEWS-2 (≥5). This study aims to determine the feasibility of a full-scale type 1 hybrid effectiveness-implementation trial on the NEWS-1 care in multiple EDs. METHODS AND ANALYSIS: We will conduct a pilot type 1 hybrid trial and prospectively recruit 200 patients from 4 public EDs in Hong Kong cluster randomised in a stepped wedge design over 10 months. All study sites will start with an initial period of standard care and switch in random order at 2-month intervals to the NEWS-1 care unidirectionally. The implementation evaluation will employ mixed methods guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, which includes qualitative and quantitative data from focus group interviews, staff survey and clinical record reviews. We will analyse the 14 feasibility outcomes as progression criteria to a full-scale trial, including trial acceptability to patients and staff, patient and staff recruitment rates, accuracy of sepsis screening, protocol adherence, accessibility to follow-up data, safety and preliminary clinical impacts of the NEWS1 care, using descriptive statistics. ETHICS AND DISSEMINATION: The institutional review boards of all study sites approved this study. This study will establish the feasibility of a full-scale hybrid trial. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. TRIAL REGISTRATION NUMBER: NCT05731349.

Effectiveness of Vaccines and Antiviral Drugs in Preventing Severe and Fatal COVID-19, Hong Kong.

We compared the effectiveness and interactions of molnupiravir and nirmatrelvir/ritonavir and 2 vaccines, CoronaVac and Comirnaty, in a large population of inpatients with COVID-19 in Hong Kong. Both the oral antiviral drugs and vaccines were associated with lower risks for all-cause mortality and progression to serious/critical/fatal conditions (study outcomes). No significant interaction effects were observed between the antiviral drugs and vaccinations; their joint effects were additive. If antiviral drugs were prescribed within 5 days of confirmed COVID-19 diagnosis, usage was associated with lower risks for the target outcomes for patients >60, but not <60, years of age; no significant clinical benefit was found if prescribed beyond 5 days. Among patients >80 years of age, 3-4 doses of Comirnaty vaccine were associated with significantly lower risks for target outcomes. Policies should encourage COVID-19 vaccination, and oral antivirals should be made accessible to infected persons within 5 days of confirmed diagnosis.

Risk of acute liver injury following the nirmatrelvir/ritonavir use.

BACKGROUND: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reported as adverse events of nirmatrelvir/ritonavir users in the EPIC-HR trial. AIM: To quantify the risk and severity of acute liver injury (ALI) associated with nirmatrelvir/ritonavir use. METHODS: This self-controlled case-series study was conducted using electronic medical records of patients with confirmed diagnosis of SARS-CoV-2 infection between 26th February 2022 and 12th February 2023 in Hong Kong. RESULTS: Among 2 409 848 patients with SARS-CoV-2 infection during the study period, 153 853 were prescribed with nirmatrelvir/ritonavir, of whom 834 (.5%) had incident ALI (moderate: 30.5%; moderate to severe: 18.9%; severe or fatal: 5.8%). Compared with the non-exposure period, risk of ALI increased significantly during the pre-exposure period (IRR = 38.13, 95% CI = 29.29-49.62) and remained elevated during the five-day nirmatrelvir/ritonavir treatment (IRR = 20.75, 95% CI = 17.06-25.25) and during wash-out period (IRR = 16.27, 95% CI = 13.23-20.01). Compared to the pre-exposure period, risk of ALI was not increased during the five-day nirmatrelvir/ritonavir treatment period (IRR = .54, 95% CI = .43-.70). Compared to 5469 non-nirmatrelvir/ritonavir users with incident ALI, nirmatrelvir/ritonavir users had less severe ALI by the severity index (p < .001) and peak INR (1.7 vs. 2.3; p < .001). ALI cases with nirmatrelvir/ritonavir use had lower risk of all-cause death (29.1% vs. 39.1%; OR = .64; p < .001) and no increase in risk of liver decompensation (1.0% vs. 1.3%; OR = .62; p = .230) compared to non-users. CONCLUSION: The risk of ALI associated with nirmatrelvir/ritonavir treatment for COVID-19 was elevated in the pre-exposure period, but not following nirmatrelvir/ritonavir initiation. ALI following nirmatrelvir/ritonavir treatment were mostly mild and less severe than ALI events in non-nirmatrelvir/ritonavir users.

Derivation and internal validation of a clinical prediction score to predict major effect or death in acute metamfetamine toxicity.

OBJECTIVE: Metamfetamine use can cause serious complications or death. We aimed to derive and internally validate a clinical prediction score to predict major effect or death in acute metamfetamine toxicity. METHODS: We performed secondary analysis of 1,225 consecutive cases reported from all local public emergency departments to the Hong Kong Poison Information Centre between 1 January 2010 and 31 December 2019. We split the entire dataset chronologically into derivation (first 70% of cases) and validation (the remaining 30% of cases) cohorts. Univariate analysis was conducted, followed by multivariable logistic regression in the derivation cohort to identify independent predictors of major effect or death. We developed a clinical prediction score based on the regression coefficients of the independent predictors in the regression model and compared its discriminatory performance with five existing early warning scores in the validation cohort. RESULTS: The MASCOT (Male, Age, Shock, Consciousness, Oxygen, Tachycardia) score was derived based on the six independent predictors: male gender (1 point), age (≥35 years, 1 point), shock (mean arterial pressure <65 mmHg, 3 points), consciousness (Glasgow Coma Scale <13, 2 points), need for supplemental oxygen (1 point), and tachycardia (pulse rate >120 beats/min, 1 point). The score ranges from 0-9, with a higher score indicating higher risk. The area under the receiver operating characteristic curve of the MASCOT score was 0.87 (95% CI 0.81-0.93) in the derivation cohort and 0.91 (95% CI 0.81-1.00) in the validation cohort, with a discriminatory performance comparable with existing scores. CONCLUSIONS: The MASCOT score enables quick risk stratification in acute metamfetamine toxicity. Further external validation is warranted before wider adoption.

The limited value of triage vital signs in predicting influenza infection in children aged 5 years and under in the emergency department: A single-center retrospective cross-sectional study.

ABSTRACT: Diagnosing influenza in children aged 5 years and under can be challenging because of their difficulty in verbalizing symptoms. This study aimed to explore the value of the triage heart rate (HR), respiratory rate (RR), and temperature, either alone or when combined with individual symptoms and signs, in predicting influenza infection in this age group.This was a retrospective study covering 4 influenza seasons from 2017 to 2019 in an emergency department (ED) in Hong Kong. We recruited patients ≤5 years of age who had an reverse transcription polymerase chain reaction influenza test within 48 hours of ED presentation. The diagnostic performance of the triage HR, RR, and temperature was evaluated as dichotomized or categorized values with diagnostic odds ratios (DORs) calculated based on different age-appropriate thresholds. Linear discriminant analysis was performed to assess the combined discriminatory effect of age, HR, RR, and temperature as continuous variables.Of 322 patients (median age 26 months), 99 had influenza A and 13 had influenza B infection. For HR and RR dichotomized based on age-appropriate thresholds, the DORs ranged from 1.16 to 1.54 and 0.78 to 1.53, respectively. A triage temperature ≥39.0 °C had the highest DOR (3.32) among different degrees of elevation of temperature. The diagnostic criteria that were based on the presence of fever and cough and/or rhinitis symptoms had a higher DOR compared with the Centers for Disease Control and Prevention influenza-like illness criteria (4.42 vs 2.41). However, combining HR, RR, or temperature with such diagnostic criteria added very little to the diagnostic performance. The linear discriminant analysis model had a high specificity of 92.5%, but the sensitivity (18.3%) was too low for clinical use.Triage HR, RR, and temperature had limited value in the diagnosis of influenza in children ≤5 years of age in the ED. Fever and cough and/or rhinitis symptoms had a better diagnostic performance than the Centers for Disease Control and Prevention influenza-like illness criteria in predicting influenza in this age group.

Limited onward transmission potential of reassortment genotypes from chickens co-infected with H9N2 and H7N9 avian influenza viruses.

The segmented genome of influenza A virus has conferred significant evolutionary advantages to this virus through genetic reassortment, a mechanism that facilitates the rapid expansion of viral genetic diversity upon influenza co-infections. Therefore, co-infection of genetically diverse avian influenza viruses in poultry may pose a significant public health risk in generating novel reassortants with increased zoonotic potential. This study investigated the reassortment patterns of a Pearl River Delta-lineage avian influenza A(H7N9) virus and four genetically divergent avian influenza A(H9N2) viruses upon co-infection in embryonated chicken eggs and chickens. To characterize "within-host" and "between-host" genetic diversity, we further monitored the viral genotypes that were subsequently transmitted to contact chickens in serial transmission experiments. We observed that co-infection with A(H7N9) and A(H9N2) viruses may lead to the emergence of novel reassortant viruses in ovo and in chickens, albeit with different reassortment patterns. Novel reassortants detected in donor chickens co-infected with different combinations of the same A(H7N9) virus and different A(H9N2) viruses showed distinct onward transmission potential to contact chickens. Sequential transmission of novel reassortant viruses was only observed in one out of four co-infection combinations. Our results demonstrated different patterns by which influenza viruses may acquire genetic diversity through co-infection in ovo, in vivo, and under sequential transmission conditions.

Clinical, laboratory, and radiological features indicative of novel coronavirus disease (COVID-19) in emergency departments: a multicenter case-control study in Hong Kong.

Objectives: Little is known about the value of routine clinical assessment in identifying patients with coronavirus disease 2019 (COVID-19) in the emergency department (ED). We aimed to compare the exposure history, signs and symptoms, laboratory, and radiographic features of ED patients who tested positive and negative for COVID-19. Methods: This was a case-control study in 7 EDs in Hong Kong from 20 January to 29 February 2020. Thirty-seven patients with laboratory-confirmed COVID-19 were age- and sex-matched to 111 controls. We compared the groups with univariate analysis and calculated the odds ratio (OR) of having COVID-19 for each characteristic that was significantly different between the groups with adjustment for age and presumed location of acquiring the infection. Results: There were no significant differences in patient characteristics and reported symptoms between the groups. A positive contact history within 14 days (adjusted OR 37.61, 95% CI: 10.86-130.19), bilateral chest radiograph shadow (adjusted OR 13.19, 95% CI: 4.66-37.35), having prior medical consultation (adjusted OR 7.43, 95% 2.89-19.09), a lower white blood cell count (adjusted OR 1.30, 95% CI: 1.11-1.51), and a lower platelet count (adjusted OR 1.07, 95% CI: 1.01-1.12) were associated with a higher odds of COVID-19 separately. A higher neutrophil count was associated with a lower odds of COVID-19 (adjusted OR 0.77, 95% CI: 0.65-0.91). Conclusion: This study highlights a number of clinical features that may be useful in identifying high-risk patients for early testing and isolation while waiting for the test result. Further studies are warranted to verify the findings.

Performance of a three-level triage scale in live triage encounters in an emergency department in Hong Kong.

BACKGROUND: Despite its continued use in many low-volume emergency departments (EDs), 3-level triage systems have not been extensively studied, especially on live triage cases. We have modified from the Australasian Triage Scale and developed a 3-level triage scale, and sought to evaluate its validity, reliability, and over- and under-triage rates in real patient encounters in our setting. METHOD: This was a cross-sectional study in a single ED with 24,000 attendances per year. At triage, each patient was simultaneously assessed by a triage nurse, an adjudicator (the "criterion standard"), and a study nurse independently. Predictive validity was determined by comparing clinical outcomes, such as hospitalization, across triage levels. The discriminating performance of the triage tool in identifying patients requiring earlier medical attention was determined. Inter-observer reliability between the triage nurse and criterion standard, and across providers were determined using kappa statistics. RESULTS: In total, 453 triage ratings of 151 triage cases, involving 17 ED triage nurses and 57 nurse pairs, were analysed. The proportion of hospital admission significantly increased with a higher triage rating. The performance of the scale in identifying patients requiring earlier medical attention was as follows: sensitivity, 68.2% (95% CI 45.1-86.1%); specificity, 99.2% (95% CI 95.8-100%); positive predictive value, 93.8% (95% CI 67.6-99.1%); and negative predictive value, 94.8% (95% CI 90.8-97.1%). The over-triage and under-triage rates were 0.7% and 4.6%, respectively. Agreement between the triage nurse and criterion standard was substantial (quadratic-weighted kappa = 0.76, 95% CI, 0.60-0.92, p < 0.001), so was the agreement across nurses (quadratic-weighted kappa = 0.81, 95% CI 0.65-0.97, p < 0.001). CONCLUSIONS: The 3-level triage system appears to have good validity and reasonable reliability in a low-volume ED setting. Further studies comparing 3-level and prevailing 5-level triage scales in live triage encounters and different ED settings are warranted.

Injury patterns of mass casualty incidents involving high-speed passenger ferries presenting to accident and emergency departments in Hong Kong: a retrospective review.

BACKGROUND: Accidents involving high-speed passenger ferries have the potential to cause mass-casualty incidents (MCIs), yet there is a lack of relevant studies available to inform hospital disaster preparedness planning. OBJECTIVE: The objective was to study the injury patterns and outcomes of MCI victims involved in high-speed passenger ferry accidents in Hong Kong waters. METHODS: A retrospective study was conducted from 1 January 2005 to 31 December 2015. All MCIs involving high-speed passenger ferries were captured from the Marine Department of Hong Kong. Victims of all age who were sent to the accident and emergency departments (A&Es) of seven public hospitals around Victoria Harbour, including three trauma centres, were identified from electronic disaster registries of the study hospitals. Data on injury patterns and outcomes were extracted from medical records with the Injury Severity Score (ISS) calculated for each victim. The Kruskal-Wallis test was used to compare medians of the ISS across different mechanisms of injury. Multivariable logistic regression was performed to identify independent predictors for major trauma (ISS≥16). RESULTS: During the study period, eight MCIs involving high-speed passenger ferries were reported and 512 victims (median age: 44 years, age range: 2-85 years) were sent to the study hospitals. The A&E triage categories were Cat 1, 3.1%; Cat 2, 4.3%; Cat 3, 19.3%; Cat 4, 72.9%; and Cat 5, 0.4%, respectively. The median ISS was 1.0 (interquartile range: 1.0-2.0). Fourteen victims (2.7%) had an ISS≥16 and age was the only independent predictor for major trauma (OR 1.06, p = 0.025, 95% CI 1.01-1.11). Trauma call was activated at A&E for 11 victims. In total, 100 victims (19.5%) were admitted to the study hospitals, including 19 (3.5%) and 15 (2.9%) who required surgery and intensive care unit stay, respectively. Eleven victims (2.1%) died, mostly due to drowning. CONCLUSION: MCIs involving high-speed passenger ferries can result in a sudden surge in demand for both A&E and in-patient care, though the majority of victims may have minor injuries. Better access to lifejackets and mandatory seatbelt use may help to reduce injuries and deaths.

Age and Sex Differences in Rates of Influenza-Associated Hospitalizations in Hong Kong.

Few studies have explored age and sex differences in the disease burden of influenza, although men and women probably differ in their susceptibility to influenza infections. In this study, quasi-Poisson regression models were applied to weekly age- and sex-specific hospitalization numbers of pneumonia and influenza cases in the Hong Kong SAR, People's Republic of China, from 2004 to 2010. Age and sex differences were assessed by age- and sex-specific rates of excess hospitalization for influenza A subtypes A(H1N1), A(H3N2), and A(H1N1)pdm09 and influenza B, respectively. We found that, in children younger than 18 years, boys had a higher excess hospitalization rate than girls, with the male-to-female ratio of excess rate (MFR) ranging from 1.1 to 2.4. MFRs of hospitalization associated with different types/subtypes were less than 1.0 for adults younger than 40 years except for A(H3N2) (MFR = 1.6), while all the MFRs were equal to or higher than 1.0 in adults aged 40 years or more except for A(H1N1)pdm09 in elderly persons aged 65 years or more (MFR = 0.9). No MFR was found to be statistically significant (P < 0.05) for hospitalizations associated with influenza type/subtype. There is some limited evidence on age and sex differences in hospitalization associated with influenza in the subtropical city of Hong Kong.