Comparison of four different threshold values of shock index in predicting mortality of COVID-19 patients

Objective: The object of this study was to examine the accuracy in pre-hospital shock index (SI) for predicting intensive care unit (ICU) requirement and 30-day mortality among from COVID-19 patients transported to the hospital by ambulance. Method: All consecutive patients who were the age ≥18 years, transported to the emergency department (ED) by ambulance with a suspected or confirmed COVID-19 in the pre-hospital frame were included in the study. Four different cut-off points were compared (0.7, 0.8, 0.9, and 1.0) to examine the predictive performance of both the mortality and ICU requirement of the SI. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was employed to evaluate each cut-off value discriminatory for predicting 30-day mortality and ICU admission. Results: The total of 364 patients was included in this study. The median age in the study population was 69 (55-80), of which 196 were men and 168 were women. AUC values for 30-day mortality outcome were calculated as 0.672, 0.674, 0.755, and 0.626, respectively, for threshold values of 0.7, 0.8, 0.9 and 1.0. ICU admission was more likely for the patients with pre-hospital SI> 0.9. Similarly, the mortality rate was higher in patients with pre-hospital SI> 0.9. Conclusion: Early triage of COVID-19 patients will ensure efficient use of healthcare resources. The SI could be a helpful, fast and powerful tool for predicting mortality status and ICU requirements of adult COVID-19 patients. It was concluded that the most useful threshold value for the shock index in predicting the prognosis of COVID-19 patients is 0.9.

The association between the initial outcomes of COVID-19 and the human development index: An ecological study

BACKGROUND & OBJECTIVE: Outcomes of the pandemic COVID-19 varied from one country to another. We aimed to describe the association between the global recovery and mortality rates of COVID-19 cases in different countries and the Human Development Index (HDI) as a socioeconomic indicator. METHODS: A correlational (ecological) study design is used. The analysis used data from 173 countries. Poisson regression models were applied to study the relationship between HDI and pandemic recovery and mortality rates, adjusting for country median age and country male to female sex ratio. RESULTS: During the first three months, the global pooled recovery rate was 32.4%(95%CI 32.3%–32.5%), and the pooled mortality rate was 6.95%(95%CI 6.94%–6.99%). Regression models revealed that HDI was positively associated with recovery β= 1.37, p = 0.016. HDI was also positively associated with the mortality outcome β= 1.79, p = 0.016. CONCLUSIONS: Our findings imply that the positive association between the HDI and recovery rates is reflective of the pandemics’ preparedness. The positive association between the HDI and mortality rates points to vulnerabilities in approaches to tackle health crises. It is critical to better understand the connection between nations’ socioeconomic factors and their readiness for future pandemics in order to strengthen public health policies.

Reverse Bayesian Implications of p-Values Reported in Critical Care Randomized Trials

Background Misinterpretations of the p-value in null-hypothesis statistical testing are common. We aimed to determine the implications of observed p-values in critical care randomized controlled trials (RCTs). Methods We included three cohorts of published RCTs: Adult-RCTs reporting a mortality outcome, Pediatric-RCTs reporting a mortality outcome, and recent Consecutive-RCTs reporting p-value ≤.10 in six higher-impact journals. We recorded descriptive information from RCTs. Reverse Bayesian implications of obtained p-values were calculated, reported as percentages with inter-quartile ranges. Results Obtained p-value was ≤.005 in 11/216 (5.1%) Adult-RCTs, 2/120 (1.7%) Pediatric-RCTs, and 37/90 (41.1%) Consecutive-RCTs. An obtained p-value .05–.0051 had high False Positive Rates; in Adult-RCTs, minimum (assuming prior probability of the alternative hypothesis was 50%) and realistic (assuming prior probability of the alternative hypothesis was 10%) False Positive Rates were 16.7% [11.2, 21.8] and 64.3% [53.2, 71.4]. An obtained p-value ≤.005 had lower False Positive Rates; in Adult-RCTs the realistic False Positive Rate was 7.7% [7.7, 16.0]. The realistic probability of the alternative hypothesis for obtained p-value .05–.0051 (ie, Positive Predictive Value) was 28.0% [24.1, 34.8], 30.6% [27.7, 48.5], 29.3% [24.3, 41.0], and 32.7% [24.1, 43.5] for Adult-RCTs, Pediatric-RCTs, Consecutive-RCTs primary and secondary outcome, respectively. The maximum Positive Predictive Value for p-value category .05–.0051 was median 77.8%, 79.8%, 78.8%, and 81.4% respectively. To have maximum or realistic Positive Predictive Value >90% or >80%, RCTs needed to have obtained p-value ≤.005. The credibility of p-value .05–.0051 findings were easy to challenge, and the credibility to rule-out an effect with p-value >.05 to .10 was low. The probability that a replication study would obtain p-value ≤.05 did not approach 90% unless the obtained p-value was ≤.005. Conclusions Unless the obtained p-value was ≤.005, the False Positive Rate was high, and the Positive Predictive Value and probability of replication of “statistically significant” findings were low.

Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivor' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA we show that transport function of HSA maybe impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 mM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), logrank c2 = 12.1, p=4.9x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

The Role of Procalcitonin in Predicting Risk of Mechanical Ventilation and Mortality among moderate to Severe COVID-19 Patients

BackgroundSerum procalcitonin (PCT) has become an emerging prognostic biomarker of disease progression in patients with COVID-19. This study aims to determine the optimal cut-off value of PCT with regards to important clinical outcomes, especially for mechanical ventilation and all-cause mortality among moderate to severe COVID-19 patients in Malaysia.MethodsA total of 319 moderate to severe COVID-19 patients hospitalized at the National Referral Hospital in December 2020 were included in the study retrospectively. Demographics, comorbidities, the severity of COVID-19 infection, laboratory and imaging findings, and treatment given were collected from the hospital information system for analysis. The optimal cut-point values for PCT were estimated in two levels. The first level involved 276 patients who had their PCT measured within 5 days following their admission. The second level involved 237 patients who had their PCT measured within 3 days following their admission. Further, a propensity score matching analysis was performed to determine the adjusted relative risk of patients with regards to various clinical outcomes according to the selected cut-point among 237 patients who had their PCT measured within 3 days. ResultsThe results showed that a PCT level of 0.2 ng/mL was the optimal cut-point for prognosis especially for mortality outcome and the need for mechanical ventilation. Before matching, patients with PCT ≥ 0.2ng/mL were associated with significantly higher odds in all investigated outcomes. After matching, patients with PCT > 0.2 ng/mL were associated with higher odds in all-cause mortality (OR: 4.629, 95% CI: 1.387 – 15.449, p = 0.0127) and non-invasive ventilation (OR: 2.667, 95% CI: 1.039 – 6.847, p = 0.0415). Furthermore, patients with higher PCT were associated with significantly longer days of mechanical ventilation (p = 0.0213). There was however no association between higher PCT level and the need for mechanical ventilation (OR: 2.010, 95% CI: 0.828 - 4.878, p = 0.1229).ConclusionOur study indicates that a rise in PCT above 0.2ng/ml is associated with an elevated risk in all-cause mortality, the need for non-invasive ventilation, and a longer duration of mechanical ventilation. The study offers concrete evidence for PCT to be used as a prognostication marker among moderate to severe COVID-19 patients.

Ethnicity and outcomes in COVID-19 in the United Kingdom: a systematic review and meta-analysis

This systematic review and meta-analysis evaluated the clinical outcomes of COVID-19 disease in the ethnic minorities of the UK in comparison to the White ethnic group. Medline, Embase, Cochrane, MedRxiv, and Prospero were searched for articles published between May 2020 to April 2021. PROSPERO ID: CRD42021248117. Fourteen studies (767177 participants) were included in the review. In the adjusted analysis, the pooled Odds Ratio (OR) for the mortality outcome was higher for the Black (1.83, 95% CI: 1.21-2.76), Asian (1.16, 95% CI: 0.85-1.57), and Mixed and Other (MO) groups (1.12, 95% CI: 1.04-1.20) compared to the White group. The adjusted and unadjusted ORs of intensive care admission were more than double for all ethnicities (OR Black 2.32, 95% CI: 1.73-3.11, Asian 2.34, 95% CI: 1.89-2.90, MO group 2.26, 95% CI: 1.64-3.11). In the adjusted analysis of mechanical ventilation need the ORs were similarly significantly raised (Black group 2.03, 95% CI: 1.80-2.29, Asian group 1.84, 95% CI: 1.20-2.80, MO 2.09, 95% CI: 1.35-3.22). This review confirmed that all ethnic groups in the UK suffered from increased disease severity and mortality with regards to COVID-19. This has urgent public health and policy implications to reduce the health disparities.

Evaluation of antigen-detecting and antibody-detecting diagnostic test combinations for diagnosing melioidosis

Background Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in many tropical developing countries and has a high mortality. Here we evaluated combinations of a lateral flow immunoassay (LFI) detecting B. pseudomallei capsular polysaccharide (CPS) and enzyme-linked immunosorbent assays (ELISA) detecting antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS) for diagnosing melioidosis. Methodology/Principal findings We conducted a cohort-based case-control study. Both cases and controls were derived from a prospective observational study of patients presenting with community-acquired infections and sepsis in northeast Thailand (Ubon-sepsis). Cases included 192 patients with a clinical specimen culture positive for B. pseudomallei. Controls included 502 patients who were blood culture positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae or were polymerase chain reaction assay positive for malaria or dengue. Serum samples collected within 24 hours of admission were stored and tested using a CPS-LFI, Hcp1-ELISA and OPS-ELISA. When assessing diagnostic tests in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Using a positive cut-off OD of 2.912 for Hcp1-ELISA, the combination of the CPS-LFI and Hcp1-ELISA had a sensitivity of 67.7% (130/192 case patients) and a specificity of 95.0% (477/502 control patients). The sensitivity of the combination (67.7%) was higher than that of the CPS-LFI alone (31.3%, p<0.001) and that of Hcp1-ELISA alone (53.6%, p<0.001). A similar phenomenon was also observed for the combination of CPS-LFI and OPS-ELISA. In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, high modified Sequential (sepsis-related) Organ Failure Assessment (SOFA) score, bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a longer duration of symptoms, low modified SOFA score, non-bacteraemia and survival outcome. Conclusions/Significance A combination of antigen-antibody diagnostic tests increased the sensitivity of melioidosis diagnosis over individual tests while preserving high specificity. Point-of-care tests for melioidosis based on the use of combination assays should be further developed and evaluated.

Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.