Risk of acute kidney injury in critically-ill patients with COVID-19 compared with seasonal influenza: a retrospective cohort study.

Background: The SARS-CoV-2 virus can bind to angiotensin-converting enzyme 2 receptors on host renal cells and may cause acute kidney injury (AKI). The comparative risks of AKI in patients severely ill with COVID-19 and influenza A have not been examined. Methods: This is a retrospective cohort study including patients with positive PCR results for SARS-CoV-2 or influenza A virus admitted to the intensive care units (ICUs) of 15 public hospitals in Hong Kong between 1st January 2013 and 30th April 2023. Patients who were already on chronic dialysis or had missing values in the confounder model were excluded. Data were retrieved from Hong Kong Hospital Authority's electronic healthcare records. The primary outcome was incident AKI during ICU stay. Secondary outcomes included acute kidney disease (AKD) and hospital mortality. All analyses were examined in multivariable regression adjusting for potential confounders (age, sex, baseline eGFR, PaO2/FiO2 ratio, baseline comorbidities, APACHE IV predicted risk of death, Charlson Comorbidity Index, emergent hospital admission, admission from elderly home, reason for ICU admission, presence of bacterial co-infections, use of medications [including vasopressors, antiviral medications, steroids and nephrotoxic antibiotics], as well as anaemia and leucocytosis). Patients were matched in a 1:1 ratio using a propensity score generated based on the full confounder model. The analyses were repeated using inverse probability weighting and in propensity-score matched cohorts. Findings: A total of 5495 ICU patients were identified. After excluding 1093 (19.9%) patients who met the exclusion criteria and 74 (1.3%) patients who had one or more missing values in the logistic regression model, a total of 4328 patients were included in the final analysis, with 2787 (64.4%) patients who tested positive for SARS-CoV-2 reverse transcription (RT)-PCR and 1541 (35.6%) patients who tested positive for influenza A virus RT-PCR. The comorbidity burden was greater in patients with COVID-19 (Charlson Comorbidity Index 3 [2-4] vs. 3 [1-4]), but the median APACHE IV predicted risk of death was significantly lower (0.19 [0.08-0.38] vs. 0.25 [0.11-0.52]). A total of 1053 (37.8%) patients with COVID-19 and 828 (53.7%) patients with influenza A developed AKI of any stage during ICU stay. In adjusted analysis, the risk of AKI was significantly lower in patients with COVID-19 compared with influenza A (adjusted odds ratio 0.51, 95% confidence interval 0.42-0.61, P < 0.0001]. The risk of stage 3 AKI and AKD were also significantly lower in patients with COVID-19. These results remained robust in multiple pre-planned sensitivity analyses including inverse probability weighting and propensity score matching. Interpretation: Our results suggest that the risk of AKI in patients severely ill with COVID-19 was lower than in patients with influenza A. The burden of concurrent organ failure complicating respiratory viral infections, such as the higher disease-attributable risk of AKI associated with influenza, should be clarified. Funding: An unrestricted philanthropic donation from Mr and Mrs Laurence Tse, The Wai Im Charitable Foundation, Chan Sui Kau Family Benefits and Charitable Foundation, So Ka Wing and Lee Sau Ying Charitable Foundation, Mr & Mrs Tam Wing Fun Edmund Renal Research Fund, the Theme-Based Research Scheme of the Research Grants Council, Hong Kong Special Administrative Region, The Government of the Hong Kong Special Administrative Region; Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government; Emergency COVID-19 Project, Major Projects on Public Security, National Key Research and Development Program; Emergency Collaborative Project of Guangzhou Laboratory; the National Key Research and Development Program of China; Sanming Project of Medicine in Shenzhen China; and the High Level-Hospital Program, Health Commission of Guangdong Province, China.

A retrospective cohort study on the clinical outcomes of patients admitted to intensive care units with dysnatremia.

With evolving patient characteristics and patterns of ICU utilization, the impact of dysnatremias on patient outcomes and healthcare costs in the present era have not been well studied. Patients ≥ 18 years admitted to the ICUs in public hospitals in Hong Kong between January 2010 and June 2022 and had at least one serum sodium measurement obtained within 24 h prior to or following ICU admission were stratified into normonatremic (135-145 mmol/L), hyponatremic (< 135 mmol/L) and hypernatremic (> 145 mmol/L) groups. A total of 162,026 patients were included-9098 (5.6%), 40,533 (25.0%) and 112,395 (69.4%) patients were hypernatremic, hyponatremic and normonatremic at the time of ICU admission, respectively. The odds of patients with hypernatremia and hyponatremia dying in the ICU were 27% and 14% higher (aOR 1.27, 95% CI 1.19-1.36 and aOR 1.14, 95% CI 1.08-1.19, respectively; P < 0.001 for both), and 52% and 21% higher for dying in the hospital (aOR 1.52, 95% CI 1.43-1.62 and aOR 1.21, 95% CI 1.17-1.26, respectively; P < 0.001 for both] compared with those with normonatremia. Patients with dysnatremia also had longer ICU length of stay (LOS), hospital LOS, and higher healthcare costs than the normonatremic group. Dysnatremias at ICU admission were associated with increased ICU and in-hospital mortality and overall healthcare burden.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Clinical Outcomes of Left Atrial Appendage Occlusion Versus Switch of Direct Oral Antcoagulant in Atrial Fibrillation: A Territory-Wide Retrospective Analysis.

Background Left atrial appendage occlusion (LAAO) has emerged as an alternative to oral anticoagulation therapy for stroke prevention in atrial fibrillation, but data comparing LAAO with direct oral anticoagulant (DOAC) are sparse. Methods and Results This cohort study compared LAAO (with or without prior anticoagulation) with a switch of one DOAC to another DOAC by 1:2 propensity score matching. The primary outcome was a composite of all-cause mortality, ischemic stroke, and major bleeding. A total of 2350 patients (874 in the LAAO group and 1476 in the DOAC switch group) were included. After a mean follow-up of 1052±694 days, the primary outcome developed in 215 (24.6%) patients in the LAAO group and in 335 (22.7%) patients in the DOAC switch group (hazard ratio [HR], 0.94 [95% CI, 0.80-1.12]; P=0.516). The LAAO group had a lower all-cause mortality (HR, 0.49 [95% CI, 0.39-0.60]; P<0.001) and cardiovascular mortality (HR, 0.49 [95% CI, 0.32-0.73]; P<0.001) but similar risk of ischemic stroke (HR, 0.83 [95% CI, 0.63-1.10]; P=0.194). The major bleeding risk was similar overall (HR, 1.18 [95% CI, 0.94-1.48], P=0.150) but was lower in the LAAO group after 6 months (HR, 0.71 [95% CI, 0.51-0.97]; P=0.032). Conclusions LAAO conferred a similar risk of composite outcome of all-cause mortality, ischemic stroke, and major bleeding, as compared with DOAC switch. The risks of all-cause mortality and cardiovascular mortality were lower with LAAO.

Population sepsis incidence, mortality, and trends in Hong Kong between 2009-2018 using clinical and administrative data.

BACKGROUND: Sepsis surveillance using electronic health record (EHR)-based data may provide more accurate epidemiologic estimates than administrative data, but experience with this approach to estimate population-level sepsis burden is lacking. METHODS: This was a retrospective cohort study including all adults admitted to publicly-funded hospitals in Hong Kong between 2009-2018. Sepsis was defined as clinical evidence of presumed infection (clinical cultures and treatment with antibiotics) and concurrent acute organ dysfunction (≥2 point increase in baseline SOFA score). Trends in incidence, mortality, and case fatality risk (CFR) were modelled by exponential regression. Performance of the EHR-based definition was compared with 4 administrative definitions using 500 medical record reviews. RESULTS: Among 13,550,168 hospital episodes during the study period, 485,057 (3.6%) had sepsis by EHR-based criteria with 21.5% CFR. In 2018, age- and sex-adjusted standardized sepsis incidence was 759 per 100,000 (relative +2.9%/year [95%CI 2.0, 3.8%] between 2009-2018) and standardized sepsis mortality was 156 per 100,000 (relative +1.9%/year [95%CI 0.9,2.9%]). Despite decreasing CFR (relative -0.5%/year [95%CI -1.0, -0.1%]), sepsis accounted for an increasing proportion of all deaths (relative +3.9%/year [95%CI 2.9, 4.9%]). Medical record reviews demonstrated that the EHR-based definition more accurately identified sepsis than administrative definitions (AUC 0.91 vs 0.52-0.55, p < 0.001). CONCLUSIONS: An objective EHR-based surveillance definition demonstrated an increase in population-level standardized sepsis incidence and mortality in Hong Kong between 2009-2018 and was much more accurate than administrative definitions. These findings demonstrate the feasibility and advantages of an EHR-based approach for widescale sepsis surveillance.

Comparison of COVID-19 with influenza A in the ICU: a territory-wide, retrospective, propensity matched cohort on mortality and length of stay.

OBJECTIVES: Direct comparisons between COVID-19 and influenza A in the critical care setting are limited. The objective of this study was to compare their outcomes and identify risk factors for hospital mortality. DESIGN AND SETTING: This was a territory-wide, retrospective study on all adult (≥18 years old) patients admitted to public hospital intensive care units in Hong Kong. We compared COVID-19 patients admitted between 27 January 2020 and 26 January 2021 with a propensity-matched historical cohort of influenza A patients admitted between 27 January 2015 and 26 January 2020. We reported outcomes of hospital mortality and time to death or discharge. Multivariate analysis using Poisson regression and relative risk (RR) was used to identify risk factors for hospital mortality. RESULTS: After propensity matching, 373 COVID-19 and 373 influenza A patients were evenly matched for baseline characteristics. COVID-19 patients had higher unadjusted hospital mortality than influenza A patients (17.5% vs 7.5%, p<0.001). The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) adjusted standardised mortality ratio was also higher for COVID-19 than influenza A patients ((0.79 (95% CI 0.61 to 1.00) vs 0.42 (95% CI 0.28 to 0.60)), p<0.001). Adjusting for age, PaO2/FiO2, Charlson Comorbidity Index and APACHE IV, COVID-19 (adjusted RR 2.26 (95% CI 1.52 to 3.36)) and early bacterial-viral coinfection (adjusted RR 1.66 (95% CI 1.17 to 2.37)) were directly associated with hospital mortality. CONCLUSIONS: Critically ill patients with COVID-19 had substantially higher hospital mortality when compared with propensity-matched patients with influenza A.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

Effects of varying blood flow rate during peripheral veno-arterial extracorporeal membrane oxygen (V-A ECMO) on left ventricular function measured by two-dimensional strain.

Background: We evaluated the effects of varying blood flow rate during peripheral veno-arterial extracorporeal membrane oxygen (V-A ECMO) on left ventricular function measured by two-dimensional strain. Methods: Adult patients who were supported by peripheral V-A ECMO were recruited. Serial hemodynamic and cardiac performance parameters were measured by transthoracic echocardiogram within the first 48 h after implementation of V-A ECMO. Measurements at 100%, 120%, and 50% of target blood flow (TBF) were compared. Results: A total of 54 patients were included and the main indications for V-A ECMO were myocardial infarction [32 (59.3%)] and myocarditis [6 (11.1%)]. With extracorporeal blood flow at 50% compared with 100% TBF, the mean arterial pressure was lower [66 ± 19 vs. 75 ± 18 mmHg, p < 0.001], stroke volume was greater [23 (12-34) vs. 15 (8-26) ml, p < 0.001], and cardiac index was higher [1.2 (0.7-1.7) vs. 0.8 (0.5-1.3) L/min/m2, p < 0.001]. Left ventricular contractile function measured by global longitudinal strain improved at 50% compared with 100% TBF [-2.8 (-7.6- -0.1) vs. -1.2 (-5.2-0) %, p < 0.001]. Similarly, left ventricular ejection fraction increased [24.4 (15.8-35.5) vs. 16.7 (10.0-28.5) %, p < 0.001] and left ventricular outflow tract velocity time integral increased [7.7 (3.8-11.4) vs. 4.8 (2.5-8.5) cm, p < 0.001]. Adding echocardiographic parameters of left ventricular systolic function to the Survival After Veno-arterial ECMO (SAVE) score had better discriminatory value in predicting eventual hospital mortality (AUROC 0.69, 95% CI 0.55-0.84, p = 0.008) and successful weaning from V-A ECMO (AUROC 0.68, 95% CI 0.53-0.83, p = 0.017). Conclusion: In the initial period of V-A ECMO support, measures of left ventricular function including left ventricular ejection fraction and global longitudinal strain were inversely related to ECMO blood flow rate. Understanding the heart-ECMO interaction is vital to interpretation of echocardiographic measures of the left ventricle while on ECMO.

Students' interaction anxiety and social phobia in interprofessional education in Hong Kong: mapping a new research direction.

BACKGROUND: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. METHOD: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. RESULTS: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. CONCLUSIONS: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.

Feasibility of pump-controlled retrograde trial off in weaning from veno-arterial ECMO in adults: A single-center case series.

BACKGROUND: Various strategies of weaning V-A ECMO have been described. PCRTO is a weaning technique which involves serial decremental pump revolutions until a retrograde flow from the arterial to venous ECMO cannula is achieved. It has been reported as a feasible weaning strategy in the pediatric population, but its application in adults has not been widely reported. METHODS: This was a case series including all adult patients who underwent PCRTO during weaning from V-A ECMO at a tertiary ECMO center between January 2019 and July 2021. The primary end point was the successful weaning from V-A ECMO support. RESULTS: A total of 57 runs of PCRTO in 36 patients were analyzed-45 (78.9%) of the trials were concluded successfully. The median retrograde blood flow rate during PCRTO was 0.6 ± 0.2 L/min, and the median duration of each PCRTO was 180 (120-240) min. Of the 35 patients who had at least one session of successful PCRTO, 31 (88.6%) were ultimately weaned from ECMO. There were no major complications from PCRTO including systemic or circuit thrombosis. CONCLUSIONS: PCRTO is a feasible strategy for assessing readiness for weaning from V-A ECMO with a low risk of adverse events and high rate of predicting eventual successful ECMO decannulation. Further investigation including comparison with alternative weaning strategies in prospective studies is required to confirm the approach.

Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study.

OBJECTIVES: The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined. DESIGN: Retrospective observational study. SETTING: Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System). PATIENTS: All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69-0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38-0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively). CONCLUSIONS: In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.

A prospective study on serum citrate levels and clinical correlations in patients receiving regional citrate anticoagulation.

Background: Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods: A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results: Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81-1.16) versus 0.37 mmol/L (IQR 0.26-0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion: Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. CLINICAL TRIALS REGISTRATION: NCT04647695.

Restrictive and liberal transfusion strategies in extracorporeal membrane oxygenation: A retrospective observational study.

BACKGROUND: To compare the outcomes of patients requiring extracorporeal membrane oxygenation (ECMO) support who had a restrictive transfusion strategy with those who had a liberal strategy. STUDY DESIGN AND METHODS: We retrospectively reviewed all adult patients from 2010 to 2019 who received a minimum of one packed red blood cell (pRBC) during ECMO. Hemoglobin values before each transfusion were retrieved. Restrictive transfusion strategy was defined as a transfusion threshold ≤8.5 g/dl in all transfusion episodes for a single patient, while liberal transfusion strategy was defined as a transfusion threshold >8.5 g/dl in any transfusion episode. RESULTS: The analysis included 763 patients, with 138 (18.1%) patients in the restrictive and 625 (81.9%) in the liberal transfusion strategy group. The median hemoglobin level, taking into account all measured hemoglobin values, during ECMO support was 8.3 and 9.9 g/dl, and the average units of pRBC received per day were 0.7 (0.3-1.8) and 1.2 (0.6-2.3), respectively. There were no significant differences in intensive care unit (ICU) mortality (adjusted odds ratio (OR), 0.86; 95% CI 0.56-1.30; p = .47), hospital mortality (adjusted OR, 0.79; 95% CI 0.52-1.21; p = .28), and 90-day mortality (adjusted OR, 0.84; 95% CI 0.55-1.28; p = .42) between the two groups. Among subgroup analyses, a restrictive transfusion strategy was associated with decreased risk of ICU mortality in patients on veno-venous ECMO (adjusted OR, 0.36; 95% CI 0.17-0.73; p = .005). There was no heterogeneity on outcomes across patients stratified by age, APACHE IV score, or need for large volume transfusion. DISCUSSION: Our data suggested it may be safe to adopt a restrictive red cell transfusion threshold of 8.5 g/dl in patients on ECMO, and highlighted the need for prospective trials in this heavily-transfused population.

Population study on diagnosis, treatment and outcomes of critically ill patients with tuberculosis (2008-2018).

BACKGROUND: Tuberculosis (TB) is a preventable and curable disease, but mortality remains high among those who develop sepsis and critical illness from TB. METHODS: This was a population-based, multicentre retrospective cohort study of patients admitted to all 15 publicly funded Hong Kong adult intensive care units (ICUs) between 1 April 2008 and 31 March 2019. 940 adult critically ill patients with at least one positive Mycobacterium tuberculosis (MTB) culture were identified out of 133 858 ICU admissions. Generalised linear modelling was used to determine the impact of delay in TB treatment on hospital mortality. Trend of annual Acute Physiology and Chronic Health Evaluation (APACHE) IV-adjusted standardised mortality ratio (SMR) over the 11-year period was analysed by Mann-Kendall's trend test. RESULTS: ICU and hospital mortality were 24.7% (232/940) and 41.1% (386/940), respectively. Of those who died in the ICU, 22.8% (53/232) never received antituberculosis drugs. SMR for ICU patients with TB remained unchanged over the study period (Kendall's τb=0.37, p=0.876). After adjustment for age, Charlson comorbidity index, APACHE IV, albumin, vasopressors, mechanical ventilation and renal replacement therapy, delayed TB treatment was directly associated with hospital mortality. In 302/940 (32.1%) of patients, TB could only be established from MTB cultures alone as Ziehl-Neelsen staining or PCR was either not performed or negative. Among this group, only 31.1% (94/302) had concurrent MTB PCR performed. CONCLUSIONS: Survival of ICU patients with TB has not improved over the last decade and mortality remains high. Delay in TB treatment was associated with higher hospital mortality. Use of MTB PCR may improve diagnostic yield and facilitate early treatment.

Effects of ß-blockers therapy on the 28-day and 3-year survival rates of end-stage renal disease patients with cardiovascular disease: a retrospective cohort study.

Background: ß-blockers have been used in the treatment of end-stage renal disease (ESRD) patients and cardiovascular disease (CVD) patients, separately. However, the effects of ß-blockers on ESRD patients with CVD have not been fully investigated. This study sought to investigate the effects of ß-blockers therapy on the 28-day and 3-year survival rates of ESRD patients with pre-existing CVD who were admitted to the intensive care unit (ICU). Methods: After excluding patients without CVD, receiving a kidney transplant, not admitted to the ICU, and with missing baseline data, this cohort study included 1081 ESRD participants with CVD from the Medical Information Mark for Intensive Care III database. Baseline characteristics, including demographic data and clinical data, were collected. The outcomes were 28-day and 3-year survival rates of the patients. At the 28-day of ICU hospitalization, patients had a mean inpatient hospital stay of 24.7 days. At 3-year, the patients had a median survival time of 489.2 days. Univariate and multivariate Cox regression analyses were used to evaluate the effects of ß-blockers therapy on the 28-day and 3-year survival outcomes of ESRD patients with CVD. Results: The 28-day and 3-year survival rates were 82.8% and 37.9%, respectively. The mean age of the all patients was 68 years, and 642 were male. After adjusting for age, race, hyperlipidemia, dialysis, simplified acute physiological score (SAPS) II, sequential organ failure assessment (SOFA) score, glucocorticoid, hemoglobin, diabetes, hypertension, the 28-day survival rate of the ESRD patients with CVD requiring intensive care who received ß-blockers therapy was higher than that of the patients who did not receive the treatment. Similarly, after adjusting for age, race, hyperlipidemia, dialysis, SAPS II, SOFA score, glucocorticoid, hemoglobin, diabetes, hypertension, creatinine, the long-term survival rate of the patients who received ß-blockers therapy was also higher than that of those who did not. Conclusions: ß-blockers therapy was associated with increased 28-day and 3-year survival rates in ESRD patients with CVD requiring intensive care. Our findings may provide a theoretical basis for the prognostic impact of ß-blockers therapy among patients with ESRD and CVD who were admitted to the ICU.

Incidence, Prediction, and Outcomes of Major Bleeding After Percutaneous Coronary Intervention in Chinese Patients.

Background: The patterns of late major bleeding (MB) after percutaneous coronary intervention (PCI) remain unknown in Chinese patients. Objectives: This study sought to determine the incidence, prediction, and long-term outcomes of late MB in Chinese patients. Methods: This was a retrospective cohort study from 14 hospitals in Hong Kong. Participants were patients undergoing first-time PCI without MB within 30 days or death within 1 year. Patients were stratified by the presence of late MB, defined as MB between 30 and 365 days. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiac events (MACE). Results: A total of 32,057 patients were analyzed. After adjustment for baseline characteristics, periprocedural characteristics, and medications on discharge, the risks of all-cause mortality at 5 years were significantly higher with late MB (HR: 2.15; 95% CI: 1.92-2.41; P < 0.001). Late MB was also associated with a higher risk of MACE (HR: 1.57; 95% CI: 1.03-1.50; P < 0.001), myocardial infarction (HR: 1.25; 95% CI: 1.04-1.52; P = 0.02), and stroke (HR: 1.38; 95% CI: 1.09-1.73; P = 0.006). The CARDIAC (anti-Coagulation therapy, Age, Renal insufficiency, Drop In hemoglobin, baseline Anemia in Chinese patients) score had a good discriminating power for prediction of MB within 365 days (area under the receiver-operating characteristic curve: 0.76). Conclusions: Late MB was independently associated with a higher risk of mortality, MACE, myocardial infarction, and stroke in patients undergoing PCI. The CARDIAC score is a simple model that can predict MB after PCI. Prevention of MB represents an important strategy to optimize cardiovascular outcomes for patients undergoing PCI.

Sensitivity of ventricular systolic function to afterload during veno-arterial extracorporeal membrane oxygenation.

AIMS: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction. METHODS AND RESULTS: A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P < 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P < 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. CONCLUSIONS: We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

Effect of hospital case volume on clinical outcomes of patients requiring extracorporeal membrane oxygenation: a territory-wide longitudinal observational study.

Background: The utilization of extracorporeal membrane oxygenation (ECMO) has increased rapidly around the world. Being an overall low-volume high-cost form of therapy, the effectiveness of having care delivered in segregated units across a geographical locality is debatable. Methods: All adult extracorporeal membrane oxygenation cases admitted to public hospitals in Hong Kong between 2010 and 2019 were included. "High-volume" centers were defined as those with >20 extracorporeal membrane oxygenation cases in the respective calendar year, while "low-volume" centers were those with ≤20. Clinical outcomes of patients who received extracorporeal membrane oxygenation care in high-volume centers were compared with those in low-volume centers. Results: A total of 911 patients received extracorporeal membrane oxygenation-297 (32.6%) veno-arterial extracorporeal membrane oxygenation, 450 (49.4%) veno-venous extracorporeal membrane oxygenation, and 164 (18.0%) extracorporeal membrane oxygenation-cardiopulmonary resuscitation. The overall hospital mortality was 456 (50.1%). The annual number of extracorporeal membrane oxygenation cases in high- and low-volume centers were 29 and 11, respectively. Management in a high-volume center was not significantly associated with hospital mortality (adjusted odds ratio (OR) 0.86, 95% confidence interval (CI): 0.61-1.21, P=0.38), or with intensive care unit mortality (adjusted OR 0.76, 95% CI: 0.54-1.06, P=0.10) compared with a low-volume center. Over the 10-year period, the overall observed mortality was similar to the Acute Physiology And Chronic Health Evaluation IV-predicted mortality, with no significant difference in the standardized mortality ratios between high- and low-volume centers (P=0.46). Conclusions: In a territory-wide observational study, we observed that case volumes in extracorporeal membrane oxygenation centers were not associated with hospital mortality. Maintaining standards of care in low-volume centers is important and improves preparedness for surges in demand.