Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison.

Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0-21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3-4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn's, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.

Clinical epidemiology and outcomes of emergency department-acute kidney injury: A systematic review.

Background: Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI) is poorly characterised, poorly understood with no systematic review, often under-recognized and under-managed. Objective: To review the incidence, risk factors, and outcomes of ED-AKI, and risk factors of post-ED-AKI mortality globally. Methods: We included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 h of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to August 14, 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a Forest plot to present pooled ED-AKI incidence rates and I2 statistics. Other parameters were summarized narratively. Results: Using 24 h from ED admission as the definition for ED-AKI we identified six articles from 2005 to 2018 in high-income settings and one article with a 48-h timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. Crude, all-cause 24-h mortality rate was 4.56 % and the one-year mortality rate was 35.04 %. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates. Conclusion: The review reveals a paucity of relevant literature which calls for further research, increased vigilance, red flag identification, and standardized management protocols for ED-AKI.

The impact of anxiety on gait impairments in Parkinson's disease: insights from sensor-based gait analysis.

BACKGROUND: Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson's disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD. METHODS: We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments. RESULTS: During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)). CONCLUSION: Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.

The Effect of the COVID-19 Pandemic on Non-COVID-19 Deaths: Population-Wide Retrospective Cohort Study.

BACKGROUND: Health care avoidance in the COVID-19 pandemic has been widely reported. Yet few studies have investigated the dynamics of hospital avoidance behavior during pandemic waves and inferred its impact on excess non-COVID-19 deaths. OBJECTIVE: This study aimed to measure the impact of hospital avoidance on excess non-COVID-19 deaths in public hospitals in Hong Kong. METHODS: This was a retrospective cohort study involving 11,966,786 patients examined between January 1, 2016, and December 31, 2021, in Hong Kong. All data were linked to service, treatment, and outcomes. To estimate excess mortality, the 2-stage least squares method was used with daily tallies of emergency department (ED) visits and 28-day mortality. Records for older people were categorized by long-term care (LTC) home status, and comorbidities were used to explain the demographic and clinical attributes of excess 28-day mortality. The primary outcome was actual excess death in 2020 and 2021. The 2-stage least squares method was used to estimate the daily excess 28-day mortality by daily reduced visits. RESULTS: Compared with the prepandemic (2016-2019) average, there was a reduction in total ED visits in 2020 of 25.4% (548,116/2,142,609). During the same period, the 28-day mortality of non-COVID-19 ED deaths increased by 7.82% (2689/34,370) compared with 2016-2019. The actual excess deaths in 2020 and 2021 were 3143 and 4013, respectively. The estimated total excess non-COVID-19 28-day deaths among older people in 2020 to 2021 were 1958 (95% CI 1100-2820; no time lag). Deaths on arrival (DOAs) or deaths before arrival (DBAs) increased by 33.6% (1457/4336) in 2020, while non-DOA/DBAs increased only by a moderate 4.97% (1202/24,204). In both types of deaths, the increases were higher during wave periods than in nonwave periods. Moreover, non-LTC patients saw a greater reduction in ED visits than LTC patients across all waves, by more than 10% (non-LTC: 93,896/363,879, 25.8%; LTC: 7,956/67,090, 11.9%). Most of the comorbidity subsets demonstrated an annualized reduction in visits in 2020. Renal diseases and severe liver diseases saw notable increases in deaths. CONCLUSIONS: We demonstrated a statistical method to estimate hospital avoidance behavior during a pandemic and quantified the consequent excess 28-day mortality with a focus on older people, who had high frequencies of ED visits and deaths. This study serves as an informed alert and possible investigational guideline for health care professionals for hospital avoidance behavior and its consequences.

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.

Applying artificial neural network in predicting sepsis mortality in the emergency department based on clinical features and complete blood count parameters.

A complete blood count (CBC) is routinely ordered for emergency department (ED) patients with infections. Certain parameters, such as the neutrophil-to-lymphocyte ratio (NLR), might have prognostic value. We aimed to evaluate the prognostic value of the presenting CBC parameters combined with clinical variables in predicting 30-day mortality in adult ED patients with infections using an artificial neural network (ANN). We conducted a retrospective study of ED patients with infections between 17 December 2021 and 16 February 2022. Clinical variables and CBC parameters were collected from patient records, with NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) calculated. We determined the discriminatory performance using the area under the receiver operating characteristic curve (AUROC) and performed a 70/30 random data split and supervised ANN machine learning. We analyzed 558 patients, of whom 144 (25.8%) had sepsis and 60 (10.8%) died at 30 days. The AUROCs of NLR, MLR, PLR, and their sum were 0.644 (95% CI 0.573-0.716), 0.555 (95% CI 0.482-0.628), 0.606 (95% CI 0.529-0.682), and 0.610 (95% CI 0.534-0.686), respectively. The ANN model based on twelve variables including clinical variables, hemoglobin, red cell distribution width, NLR, and PLR achieved an AUROC of 0.811 in the testing dataset.

Multi-Level Biomarkers for Early Diagnosis of Ischaemic Stroke: A Systematic Review and Meta-Analysis.

Blood biomarkers hold potential for the early diagnosis of ischaemic stroke (IS). We aimed to evaluate the current weight of evidence and identify potential biomarkers and biological pathways for further investigation. We searched PubMed, EMBASE, the Cochrane Library and Web of Science, used R package meta4diag for diagnostic meta-analysis and applied Gene Ontology (GO) analysis to identify vital biological processes (BPs). Among 8544 studies, we included 182 articles with a total of 30,446 participants: 15675 IS, 2317 haemorrhagic stroke (HS), 1798 stroke mimics, 846 transient ischaemic attack and 9810 control subjects. There were 518 pooled biomarkers including 203 proteins, 114 genes, 108 metabolites and 88 transcripts. Our study generated two shortlists of biomarkers for future research: one with optimal diagnostic performance and another with low selection bias. Glial fibrillary acidic protein was eligible for diagnostic meta-analysis, with summary sensitivities and specificities for differentiating HS from IS between 3 h and 24 h after stroke onset ranging from 73% to 80% and 77% to 97%, respectively. GO analysis revealed the top five BPs associated with IS. This study provides a holistic view of early diagnostic biomarkers in IS. Two shortlists of biomarkers and five BPs warrant future investigation.

An appraisal of studies using mouse models to assist the biomarker discovery for sepsis prognosis.

Introduction: Clinicians need reliable outcome predictors to improve the prognosis of septic patients. Mouse models are widely used in sepsis research. We aimed to review how mouse models were used to search for novel prognostic biomarkers of sepsis in order to optimize their use for future biomarker discovery. Methods: We searched PubMed from 2012 to July 2022 using "((sepsis) AND (mice)) AND ((prognosis) OR (prognostic biomarker))". Results: A total of 412 publications were retrieved. We selected those studies in which mouse sepsis was used to demonstrate prognostic potential of biomarker candidates and/or assist the subsequent evaluation in human sepsis for further appraisal. The most frequent models were lipopolysaccharide (LPS) injection and caecal ligation and puncture (CLP) using young male mice. Discovery technologies applied on mice include setting survival and nonsurvivable groups, detecting changes of biomarker levels and measuring physiological parameters during sepsis. None of the biomarkers achieved sufficient clinical performance for clinical use. Conclusions: The number of studies and strategies using mouse models to discover prognostic biomarkers of sepsis are limited. Current mouse models need to be further optimized to better conform to human sepsis. Current biomarker platforms do not achieve predictive performance for clinical use.

Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis.

The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK. We conducted a retrospective cohort study including all ED visits and inpatient (IP) ward admissions from January 1st to March 31st, 2022. Vector Autoregression model evaluated the effects of a single variable on the targeted hospital boarding variables. Admissions from elderly homes with 6 lag days held the highest positive value of statistical significance (t-stat = 2.827, P < .05) caused prolonged admission waiting time, while medical patients with 4 lag days had the highest statistical significance (t-stat = 2.530, P < .05) caused an increased number of boarding patients. Within one week after impulses, medical occupancy's influence on the waiting time varied from 0.289 on the 1st day to -0.315 on the 7th day. While occupancy of medical wards always positively affected blocked number of patients, and its response was maximized at 0.309 on the 2nd day. Number of confirmed COVID-19 cases was not the sole significant contributor, while occupancy of medical wards was still a critical factor associated with patient boarding. Increasing ward capacity and controlling occupancy were suggested during the outbreak. Moreover, streamlining elderly patients in ED could be an approach to relieve pressure on the healthcare system.

Association of Molnupiravir and Nirmatrelvir-Ritonavir with reduced mortality and sepsis in hospitalized omicron patients: a territory-wide study.

This study evaluates the association between antivirals (Molnupiravir and Nirmatrelvir-Ritonavir) and all-cause and respiratory mortality and organ dysfunction among high-risk COVID-19 patients during an Omicron outbreak. Two cohorts, Nirmatrelvir-Ritonavir versus control and Molnupiravir versus control, were constructed with inverse probability treatment weighting to balance baseline characteristics. Cox proportional hazards models evaluated the association of their use with all-cause mortality, respiratory mortality, and all-cause sepsis (a composite of circulatory shock, respiratory failure, acute liver injury, coagulopathy, and acute liver impairment). Patients recruited were hospitalized and diagnosed with the COVID-19 Omicron variant between February 22, 2022 and April 15, 2022, and followed up until May 15, 2022. The study included 17,704 patients. There were 4.67 and 22.7 total mortalities per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio, - 18.1 [95% CI - 23.0 to - 13.2]; hazard ratio, 0.18 [95% CI, 0.11-0.29]). There were 6.64 and 25.9 total mortalities per 1000 person-days in the Molnupiravir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 19.3 [95% CI - 22.6 to - 15.9]; hazard ratio, 0.23 [95% CI 0.18-0.30]). In all-cause sepsis, there were 13.7 and 35.4 organ dysfunction events per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, - 21.7 [95% CI - 26.3 to - 17.1]; hazard ratio, 0.44 [95% CI 0.38-0.52]). There were 23.7 and 40.8 organ dysfunction events in the Molnupiravir and control groups respectively before adjustment (weighted incidence ratio per 1000 person-days, - 17.1 [95% CI, - 20.6 to - 13.6]; hazard ratio, 0.63 [95% CI 0.58-0.69]). Among COVID-19 hospitalized patients, use of either Nirmatrelvir-Ritonavir or Molnupiravir compared with no antiviral use was associated with a significantly lower incidence of 28-days all-cause and respiratory mortality and sepsis.

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.

Association of Molnupiravir and Nirmatrelvir-Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19.

Background: Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effectiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population. Methods: This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22-March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the primary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re-attendance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated. Findings: In the outpatient cohort (N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritonavir, while in the inpatient cohort (N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039; Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P<0.0001). Among hospitalised patients, both antiviral prescriptions were associated with significant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P=0.031; Nirmatrelvir-Ritonavir: OR=0.47 (0.24-0.93), P=0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care. Interpretation: In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrelvir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings. Funding: Centre for Health Systems & Policy Research is funded by The Tung's Foundation; and The Laboratory of Data Discovery for Health Limited(D24H) is funded the AIR@InnoHK platform administered by the Innovation and Technology Commission of Hong Kong. Funders did not have any role in study design, data collection, data analysis, interpretation and writing of this manuscript.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

BACKGROUND: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. METHODS: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. RESULTS: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. CONCLUSIONS: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Seizure as the clinical presentation of massive pulmonary embolism: Case report and literature review.

Massive pulmonary embolism (MPE) is a high-risk medical emergency. Seizure as the clinical presentation of MPE is extremely rare, and to our knowledge, there have been no reports on successful percutaneous, catheter-based treatment of MPE presenting with new-onset seizures and cardiac arrest. In this report, we discuss the case of a 64-year-old woman who presented with an episode of seizure that lasted 5 h. Seizure occurred four times within 12 h after arrival at the hospital, and in the end, she sustained a cardiac arrest. The patient had no past history of seizure or cardiopulmonary disease. Bilateral MPE was detected by a computed tomography pulmonary angiogram, and she was successfully treated with percutaneous, catheter-directed anticoagulant therapy. Pulmonary embolism-related seizures are more difficult to diagnose and have higher mortality rates than seizures. MPE should be suspected in patients presenting with new-onset seizures and hemodynamic instability.

Comparison of the prognostic performance of the CURB-65 and a modified version of the pneumonia severity index designed to identify high-risk patients using the International Community-Acquired Pneumonia Collaboration Cohort.

BACKGROUND: Although the PSI and CURB-65 represent well-validated prediction rules for pneumonia prognosis, PSI was designed to identify patients at low risk and CURB- 65 patients at high risk of mortality. We compared the prognostic performance of a modified version of the PSI designed to identify high-risk patients (i.e., PSI-HR) to CURB-65 in predicting short-term mortality. METHODS: Using data from 6 pneumonia cohorts, we designed PSI-HR as a 6-class prediction rule using the original prognostic weights of all PSI variables and modifying the risk score thresholds to define risk classes. We calculated the proportion of low-risk and high-risk patients using CURB-65 and PSI-HR and 30-day mortality in these subgroups. We compared the rules' sensitivity, specificity, positive and negative predictive values for mortality at all risk class thresholds and assessed discriminatory power using areas under their receiver operating characteristic curves (AUROCs). RESULTS: Among 13,874 patients with pneumonia, 1,036 (7.5%) died. For PSI-HR versus CURB-65, aggregate mortality was lower in low-risk patients (1.6% vs. 2.2%, p = 0.005) and higher in high-risk patients (36.5% vs. 32.2%, p = 0.27). PSI-HR had higher sensitivities than CURB-65 at all thresholds; PSI-HR also had higher specificities at the 3 lowest thresholds and specificities within 0.5% points of CURB-65 at the 2 highest thresholds. The AUROC was larger for PSI-HR than CURB- 65 (0.82 vs. 0.77, p < 0.0001). CONCLUSIONS: PSI-HR demonstrated superior prognostic accuracy to CURB-65 at the lower end of the severity spectrum and identified high-risk patients with nonsignificant higher short-term mortality at the higher end.

Impact of varying wave periods of COVID-19 on in-hospital mortality and length of stay for admission through emergency department: A territory-wide observational cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with excess mortality and reduced emergency department attendance. However, the effect of varying wave periods of COVID-19 on in-hospital mortality and length of stay (LOS) for non-COVID disease for non-COVID diseases remains unexplored. METHODS: We examined a territory-wide observational cohort of 563,680 emergency admissions between January 1 and November 30, 2020, and 709,583 emergency admissions during the same 2019 period in Hong Kong, China. Differences in 28-day in-hospital mortality risk and LOS due to COVID-19 were evaluated. RESULTS: The cumulative incidence of 28-day in-hospital mortality increased overall from 2.9% in 2019 to 3.6% in 2020 (adjusted hazard ratio [aHR] = 1.22, 95% CI 1.20 to 1.25). The aHR was higher among patients with lower respiratory tract infection (aHR: 1.30 95% CI 1.26 to 1.34), airway disease (aHR: 1.35 95% CI 1.22 to 1.49), and mental disorders (aHR: 1.26 95% CI 1.15 to 1.37). Mortality risk in the first- and third-wave periods was significantly greater than that in the inter-wave period (p-interaction < 0.001). The overall average LOS in the pandemic year was significantly shorter than that in 2019 (Mean difference = -0.40 days; 95% CI -0.43 to -0.36). Patients with mental disorders and cerebrovascular disease in 2020 had a 3.91-day and 2.78-day shorter LOS than those in 2019, respectively. CONCLUSIONS: Increased risk of in-hospital deaths was observed overall and by all major subgroups of disease during the pandemic period. Together with significantly reduced LOS for patients with mental disorders and cerebrovascular disease, this study shows the spillover effect of the COVID-19 pandemic.

Changes in Emergency Department Visits, Diagnostic Groups, and 28-Day Mortality Associated With the COVID-19 Pandemic: A Territory-Wide, Retrospective, Cohort Study.

STUDY OBJECTIVE: We aimed to evaluate and characterize the scale and relationships of emergency department (ED) visits and excess mortality associated with the early phase of the COVID-19 pandemic in the territory of Hong Kong. METHODS: We conducted a territory-wide, retrospective cohort study to compare ED visits and the related impact of the COVID-19 pandemic on mortality. All ED visits at 18 public acute hospitals in Hong Kong between January 1 and August 31 of 2019 (n=1,426,259) and 2020 (n=1,035,562) were included. The primary outcome was all-cause mortality in the 28 days following an ED visit. The secondary outcomes were weekly number of ED visits and diagnosis-specific mortality. RESULTS: ED visits decreased by 27.4%, from 1,426,259 in 2019 to 1,035,562 in 2020. Overall period mortality increased from 28,686 (2.0%) in 2019 to 29,737 (2.9%) in 2020. The adjusted odds ratio for 28-day, all-cause mortality in the pandemic period of 2020 relative to 2019 was 1.26 (95% confidence interval 1.24 to 1.28). Both sexes, age more than 45 years, all triage categories, all social classes, all ED visit periods, epilepsy (odds ratio 1.58, 95% confidence interval 1.20 to 2.07), lower respiratory tract infection, and airway disease had higher adjusted ORs for all-cause mortality. CONCLUSION: A significant reduction in ED visits in the first 8 months of the COVID-19 pandemic was associated with an increase in deaths certified in the ED. The government must make provisions to encourage patients with alarming symptoms, mental health conditions, and comorbidities to seek timely emergency care, regardless of the pandemic.

Seven-year excess mortality, functional outcome and health status after trauma in Hong Kong.

PURPOSE: The purpose was to investigate long-term health impacts of trauma and the aim was to describe the functional outcome and health status up to 7 years after trauma. METHODS: We conducted a prospective, multi-centre cohort study of adult trauma patients admitted to three regional trauma centres with moderate or major trauma (ISS ≥ 9) in Hong Kong (HK). Patients were followed up at regular time points (1, 6 months and 1, 2, 3, 4, 5, 6, and 7 years) by telephone using extended Glasgow Outcome Scale (GOSE) and the Short-Form 36 (SF36). Observed annual mortality rate was compared with the expected mortality rate estimated using the HK population cohort. Linear mixed model (LMM) analyses examined the changes in SF36 with subgroups of age ≥ 65 years, ISS > 15, and GOSE ≥ 5 over time. RESULTS: At 7 years, 115 patients had died and 48% (138/285) of the survivors responded. The annual mortality rate (AMR) of the trauma cohort was consistently higher than the expected mortality rate from the general population. Forty-one percent of respondents had upper good recovery (GOSE = 8) at 7 years. Seven-year mean PCS and MCS were 45.06 and 52.06, respectively. LMM showed PCS improved over time in patients aged < 65 years and with baseline GOSE ≥ 5, and the MCS improved over time with baseline GOSE ≥ 5. Higher mortality rate, limited functional recovery and worse physical health status persisted up to 7 years post-injury. CONCLUSION: Long-term mortality and morbidity should be monitored for Asian trauma centre patients to understand the impact of trauma beyond hospital discharge.