Comparing Coronavirus Disease 2019 (COVID-19) Pandemic Waves in Hospitalized Patients: A Retrospective, Multicenter, Cohort Study.

BACKGROUND: Coronavirus disease 2019 was first diagnosed in Israel at the end of February 2020. By the end of June 2021, there were 842 536 confirmed cases and 6428 deaths. Our aim in this multicenter, retrospective, cohort study is to describe the demographic and clinical characteristics of hospitalized patients and compare the pandemic waves before immunization. METHODS: Of 22 302 patients hospitalized in general medical centers, we randomly selected 6329 for the study. Of these, 3582 and 1106 were eligible for the study in the first period (first and second waves) and in the second period (third wave), respectively. RESULTS: Thirty-day mortality was higher in the second period than in the first period, 25.20% vs 13.68% (P < .001). Invasive mechanical ventilation supported 9.19% and 14.21% of patients in the first period and second period, respectively. Extracorporeal membrane oxygenation (ECMO) was used more than twice as often in the second period. CONCLUSIONS: Invasive ventilation, use of ECMO, and mortality rate were 1.5 to 2 times higher in the second period than in the first period. In the second period, patients had a more severe presentation and higher mortality than those in the first period.

Heparanase level and procoagulant activity are reduced in severe sepsis.

BACKGROUND: During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. AIM: To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. MATERIALS AND METHODS: Twenty-one patients with non-trauma, non-surgical sepsis admitted to the intensive care unit and 35 controls were recruited. Plasma samples were drawn from the study participants on days 1 and 7 following admission. RESULTS: Heparanase levels and procoagulant activity on day 1 were significantly reduced in patients compared to controls (P < .0001, P < .0001, respectively). Day 1 heparanase procoagulant activity ≥350 ng/mL yielded a negative predictive value for severe sepsis of 89%. Additionally, heparanase procoagulant activity on day 7 correlated with the change in the APACHE score between days 1 and 7 (r = .66, P = .007). CONCLUSIONS: Heparanase procoagulant activity decreases during sepsis and returns to normal levels as soon as the patient recovers. Hence, it can be potentially used to predict the risk of severe sepsis. These findings need to be further explored in large-scale studies.

[REDUCTION OF ANTIBIOTIC CONSUMPTION IN RAMBAM HEALTH CARE CAMPUS - THE ROLE OF AN ANTIBIOTIC STEWARDSHIP PROGRAM].

INTRODUCTION: Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs. AIMS: To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide. METHODS: Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards. RESULTS: Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments. CONCLUSIONS: Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Effect of infections on 30-day mortality among critically ill patients hospitalized in and out of the intensive care unit.

BACKGROUND: This analysis is part of a multicenter study conducted in Israel to evaluate survival of critically ill patients treated in and out of intensive care units (ICUs). OBJECTIVE: To assess the role of infection on 30-day survival among critically ill patients hospitalized in ICUs and regular wards. DESIGN: All adult inpatients were screened on four rounds for patients meeting ICU admission criteria. Retrospective chart review was used to detect presence and type of infection. Mortality was ascertained from day of meeting study criteria to 30 days thereafter. ANALYSIS: The effect of infection on mortality among patients, treated in and out of the ICU, was compared using Kaplan Meier survival curves. Multivariate Cox models were constructed to adjust interdepartmental comparisons for case-mix differences. RESULTS: Of 641 critically ill patients identified, 36.8% already had an infection on day 0. An additional 40.2% subsequently developed a new infection during the follow-up period, ranging from 64.6% in the ICU to 31.5% in regular wards (p < .001). Resistant infections were more prevalent in ICUs. Infection was independently associated with an increase in mortality, regardless of whether the patient was admitted to the ICU. There was no difference in the adjusted risk of mortality associated with an infection diagnosed on day 0 vs. an infection diagnosed later. Risk of dying was similar in resistant and nonresistant infections. Adjusting for infections, survival of ICU patients was better relative to patients in regular wards (adjusted hazard ratio = 0.7). Among the different types of infection, risk of mortality from pneumonia was significantly lower in ICUs relative to regular wards. There was a protective effect in ICUs among noninfected patients. CONCLUSION: The risk of acquiring a new infection is greater in the ICU. However, risk of mortality among ICU patients was lower for the most serious infections and for those without any infection.

Survival of critically ill patients hospitalized in and out of intensive care.

OBJECTIVE: A lack of intensive care units beds in Israel results in critically ill patients being treated outside of the intensive care unit. The survival of such patients is largely unknown. The present study's objective was to screen entire hospitals for newly deteriorated patients and compare their survival in and out of the intensive care unit. DESIGN: A priori developed intensive care unit admission criteria were used to screen, during 2 wks, the patient population for eligible incident patients. A screening team visited every hospital ward of five acute care hospitals daily. Eligible patients were identified among new admissions in the emergency department and among hospitalized patients who acutely deteriorated. Patients were followed for 30 days for mortality regardless of discharge. SETTING: Five acute care hospitals. PATIENTS: A total of 749 newly deteriorated patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Crude survival of patients in and out of the intensive care unit was compared by Kaplan-Meier curves, and Cox models were constructed to adjust the survival comparisons for residual case-mix differences. A total of 749 newly deteriorated patients were identified among 44,000 patients screened (1.7%). Of these, 13% were admitted to intensive care unit, 32% to special care units, and 55% to regular departments. Intensive care unit patients had better early survival (0-3 days) relative to regular departments (p=.0001) in a Cox multivariate model. Early advantage of intensive care was most pronounced among patients who acutely deteriorated while on hospital wards rather than among newly admitted patients. CONCLUSIONS: Only a small proportion of eligible patients reach the intensive care unit, and early admission is imperative for their survival advantage. As intensive care unit benefit was most pronounced among those deteriorating on hospital wards, intensive care unit triage decisions should be targeted at maximizing intensive care unit benefit by early admitting patients deteriorating on hospital wards.

Survival of critically ill patients hospitalized in and out of intensive care units under paucity of intensive care unit beds.

OBJECTIVE: The demand for intensive care beds far exceeds their availability in many European countries. Consequently, many critically ill patients occupy hospital beds outside intensive care units, throughout the hospital. The outcome of patients who fit intensive care unit admission criteria but are hospitalized in regular wards needs to be assessed for policy implications. The object was to screen entire hospital patient populations for critically ill patients and compare their 30-day survival in and out of the intensive care unit. DESIGN: Screening teams visited every hospital ward on four selected days in five acute care Israeli hospitals. The teams listed all patients fitting a priori developed study criteria. One-month data for each patient were abstracted from the medical records. SETTING: Five acute care Israeli hospitals. PATIENTS: All patients fitting a priori developed study criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survival in and out of the intensive care unit was compared for screened patients from the day a patient first met study criteria. Cox multivariate models were constructed to adjust survival comparisons for various confounding factors. The effect of intensive care unit vs. other departments was estimated separately for the first 3 days after deterioration and for the remaining follow-up time. Results showed that 5.5% of adult hospitalized patients were critically ill (736 of 13,415). Of these, 27% were admitted to intensive care units, 24% to specialized care units, and 49% to regular departments. Admission to an intensive care unit was associated with better survival during the first 3 days of deterioration, after we adjusted for age and severity of illness (p =.018). There was no additional survival advantage for intensive care unit patients (p =.9) during the remaining follow-up time. CONCLUSIONS: The early survival advantage in the intensive care unit suggests a window of critical opportunity for these patients. Under economic constraints and dearth of intensive care unit beds, increasing the turnover of patients in the intensive care unit, thus exposing more needy patients to the early benefit of treatment in the intensive care unit, may be advantageous.