Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases.

PURPOSE: A prompt and effective immune response is required for clearance of pathogens but exaggerated states of inflammation can cause extensive collateral damage to the host. We have previously used a rapid near-patient assay that measures the functional capacity of neutrophils to produce reactive oxygen species (ROS) to show that values are elevated in patients with severe COVID-19 or sepsis. Here, we assess the utility of longitudinal ROS measurements to monitor and predict mortality outcome for patients with COVID-19 infection being treated in an ICU setting. METHODS: We used the Leukocyte ImmunoTest™ (LIT™) to quantify neutrophil ROS release using a small volume (10 µL) of capillary blood in a portable, rapid (10-min) format. RESULTS: ROS values (LIT score) and ROS levels assessed in relation to neutrophil count (LIT/N) were both markedly elevated in the patient group. Furthermore, these correlated strongly with peripheral neutrophil count and CRP value. Serial measurement of neutrophil or CRP values were not able to reliably predict mortality within the study. In contrast, LIT and LIT/N values started to decline at 7 and 5 days, respectively, in patients who survived ICU admission and this increment increased further thereafter. CONCLUSIONS: This study raises the possibility of LIT and LIT/N to be used as a predictive clinical tool for patients with severe COVID-19 and argues for its assessment to inform on prognosis, and potentially guide treatment pathways, in other disorders associated with neutrophil activation. TAKE-HOME MESSAGE: A longitudinal study of 44 severe COVID-19 patients in the ICU of a leading teaching hospital has demonstrated the prognostic potential of a rapid bedside assay of neutrophil-derived reactive oxygen species (ROS). Assessment of changes in ROS production, as measured using the Leukocyte ImmunoTest™, shows that ROS production generally declined back to normal levels for patients who survived, but remained elevated for those patients who did not survive.

Vaccination status of COVID-19 patients followed up in the ICU in a country with heterologous vaccination policy: A multicenter national study in Turkey.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-2) prevents the development of serious diseases has been shown in many studies. However, the effect of vaccination on outcomes in COVID-19 patients requiring intensive care is not clear. METHODS: This is a retrospective multicenter study conducted in 17 intensive care unit (ICU) in Turkey between January 1, 2021, and December 31, 2021. Patients aged 18 years and older who were diagnosed with COVID-19 and followed in ICU were included in the study. Patients who have never been vaccinated and patients who have been vaccinated with a single dose were considered unvaccinated. Logistic regression models were fit for the two outcomes (28-day mortality and in-hospital mortality). RESULTS: A total of 2968 patients were included final analysis. The most of patients followed in the ICU during the study period were unvaccinated (58.5%). Vaccinated patients were older, had higher Charlson comorbidity index (CCI), and had higher APACHE-2 scores than unvaccinated patients. Risk for 28-day mortality and in-hospital mortality was similar in across the year both vaccinated and unvaccinated patients. However, risk for in-hospital mortality and 28-day mortality was higher in the unvaccinated patients in quarter 4 adjusted for gender and CCI (OR: 1.45, 95% CI: 1.06-1.99 and OR: 1.42, 95% CI: 1.03-1.96, respectively) compared to the vaccinated group. CONCLUSION: Despite effective vaccination, fully vaccinated patients may be admitted to ICU because of disease severity. Unvaccinated patients were younger and had fewer comorbid conditions. Unvaccinated patients have an increased risk of 28-day mortality when adjusted for gender and CCI.

Erratum: Evaluation of prevalence and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2021.254.].

Evaluation of prevalance and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients.

Objectives: In this study, we sought to determine the prevalence of bloodstream infection (BSI) in severe coronavirus disease 2019 (COVID-19) patients and to determine the risk factors of BSI in critical COVID-19 patients. Design: Retrospective, descriptive study between March 2020 and January 2021. Setting: An 1,007-bed university hospital. Participants: Patients who were hospitalized due to severe COVID-19 disease and had an aerobic blood culture taken at least once during hospitalization. Methods: Case definitions were made according to National Institutes of Health clinical definitions. According to the blood culture results, the patients were grouped as with and without BSIs, and compared for BSIs risk factors. Results: In total, 195 patients were included in the study. Blood culture positivity was detected in 76 (39.0%) of 196 patients. Excluding blood culture positivity considered as contamination, the prevalence of BSI in all severe COVID-19 cases was 18.5% (n = 36). In intensive care unit patients the prevalence of BSI was 30.6% (n = 26). In multivariate analyses, central venous catheter (odds ratio [OR], 8.17; 95% confidence interval [CI], 2.46-27.1; P < .01) and hospitalization in the multibed intensive care unit (OR, 4.28; 95% CI, 1.28-14.3; P < .01) were risk factors associated with the acquisition of BSI. Conclusion: The prevalence of BSI in COVID-19 patients is particularly high in critically ill patients. The central venous catheter and multibed intensive care follow-up are risk factors for BSI. BSIs can be reduced by increasing compliance to infection control measures and central venous catheter insertion-care procedures. The use of single-bed intensive care units where compliance can be achieved more effectively is important for the prevention of BSIs.

Socio-cultural Correlates of the COVID-19 Outcomes.

While basically all countries have been hit by the COVID-19 pandemic, the impact has varied in large degrees among countries. In the present study, national differences in six COVID-19 indicators (COVID-19 deaths per capita, excess mortality, change in GDP per capita, vaccination rate, stringency index, and overall impact of the pandemic) were studied in relation to socio-economic and Hofstede's cultural dimensions by using the latest data available. The results differed to some degree from the studies conducted in the earlier stage of the pandemic. COVID-19 deaths per capita were predicted by Uncertainty Avoidance (UA) and Indulgence (IVR); excess mortality by UA; the impact of pandemics by Power Distance (PDI), Long-term Orientation (LTOWS) and IVR; change in GDP per capita by PDI; vaccination rate by Individualism and UA; and Stringency Index by LTOWS. In addition to further clarifying the role of cultural dimensions in the pandemic, three conclusions can be drawn. First, the pandemic reached different countries at different times, which is reflected in the results. The conclusion about the role of socio-economic and cultural factors can be drawn only after the pandemic. Second, cultural dimensions were related to COVID-19 measures only when socio-economic indicators were not considered but lost their significance when socio-economic variables were entered into the models. Cultural dimensions influence the outcome variables via socio-economic factors. Third, earlier studies have focused mainly on COVID-19 deaths. The impact of the COVID-19 pandemic is a complex phenomenon and cannot be reduced to the death rate.

Community Use of Antibiotics in Turkey: The Role of Knowledge, Beliefs, Attitudes, and Health Anxiety.

Turkey has been among the leading countries in antibiotic consumption. As a result of the 4-year National Action Plan for Rational Drug Use, antibiotic prescriptions had declined from 34.9% in 2011 to 24.6% in 2018. However, self-medication with antibiotics without prescription is common, which is not reflected in official statistics. The present study aims at investigating antibiotic use in the community and the factors related to it. A web-based survey was conducted among 945 Turkish-speaking respondents (61.3% female). The questionnaire included questions about antibiotic use for different illnesses, ways to obtain and handle leftover antibiotics, knowledge, beliefs of the antibiotic effectiveness, attitudes, health anxiety, and background factors. According to the results, 34.2% of the sample had self-medicated themselves with antibiotics without a valid prescription. The most common way to self-medicate was to use leftover antibiotics. While 80.4% knew that antibiotics are used to treat bacterial infections, 51.4% thought that antibiotics are effective for viral diseases. The most important predictor of antibiotic use frequency was the belief in their efficiency for various illnesses and symptoms, followed by negative attitudes to antibiotics, health anxiety, knowledge level, positive attitudes, and health status. The results underline the importance of targeting misbeliefs about antibiotics in future campaigns.

The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey

Background/aim: Pneumonia is the most serious clinical presentation of COVID-19. This study aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. Materials and methods: This study was conducted in the Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020 and 30 April 2020 were analyzed retrospectively. COVID-19 patients were separated into two groups, pneumonia and nonpneumonia, and then compared to determine predicting factors for COVID-19 pneumonia. Variables that had a P-value of less than 0.20 and were not correlated with each other were included in the logistic regression model. Results: Of the 247 patients included in the study 58% were female, and the median age was 40. COVID-19 was confirmed in 70.9% of these patients. Among the confirmed COVID-19 cases, 21.4% had pneumonia. In the multivariate analysis male sex (P = 0.028), hypertension (P = 0.022), and shortness of breath on hospital admission (P = 0.025) were significant factors predicting COVID-19 pneumonia. Conclusion: Shortness of breath, male sex, and hypertension were significant for predicting COVID-19 pneumonia on admission. Patients with these factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.

Socio-economic factors, cultural values, national personality and antibiotics use: A cross-cultural study among European countries.

There are considerable cross-national differences in public attitudes towards antibiotics use, use of prescribed antibiotics, and self-medication with antibiotics even within Europe. This study was aimed at investigating the relationships between socio-economic factors, cultural values, national personality characteristics and the antibiotic use in Europe. Data included scores from 27 European countries (14 countries for personality analysis). Correlations between socio-economic variables (Gross National Income per capita, governance quality, life expectancy, mean years of schooling, number of physicians), Hofstede's cultural value dimensions (power distance, individualism, masculinity, uncertainty avoidance, long-term orientation, indulgence), national personality characteristic (extraversion, neuroticism, social desirability) and antibiotic use were calculated and three regression models were constructed. Governance quality (r=-.51), mean years of schooling (r=-.61), power distance (r=.59), masculinity (r=.53), and neuroticism (r=.73) correlated with antibiotic use. The highest amount of variance in antibiotic use was accounted by the cultural values (65%) followed by socio-economic factors (63%) and personality factors (55%). Results show that socio-economic factors, cultural values and national personality characteristics explain cross-national differences in antibiotic use in Europe. In particular, governance quality, uncertainty avoidance, masculinity and neuroticism were important factors explaining antibiotics use. The findings underline the importance of socio-economic and cultural context in health care and in planning public health interventions.

Evaluation of nephrotoxicity and prognosis in patients treated with colistin due to hospital-acquired pneumonia.

INTRODUCTION: Colistimethate sodium (CMS) is frequently used in the treatment of nosocomial multidrug-resistant gram-negative infections. Nephrotoxicity is the most important side effect. The aim of this study is to evaluate the effect of colistin on nephrotoxicity and to assess prognosis in patients treated with CMS due to hospital-acquired pneumonia (HAP). MATERIALS AND METHODS: Patients treated with CMS for HAP due to multidrug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii were included in this cohort study. RESULT: We evaluated 281 patients treated with two different brands of CMS whose administration dose is different: imported (n= 58, low dose/kg) and domestic (n= 223, high dose/kg). Nephrotoxicity developed in 175 patients (62.3%). The median age (73 vs. 66 years, p= 0.004) and mortality rates were higher (66.9% vs. 52.8%, p= 0.022) in patients having nephrotoxicity. The patients receiving high dose/kg had higher nephrotoxicity rate (67.7% vs. 41.4%, p< 0.001). The clinical, bacteriological response and mortality rates of the whole group were 52.0%, 61.0%, 61.6%, respectively. The clinical and bacteriological response rates were similar in the different dose groups. Multivariate analysis showed that nephrotoxicity was associated with domestic brand depending on use of high dose (OR= 3.97), advanced age (ß= 0.29, p= 0.008), male gender (OR= 2.60), hypertension (OR= 2.50), red blood cells transfusion (OR= 2.54), absence of acute kidney injury (OR= 10.19), risk stage of RIFLE (OR= 11.9). CONCLUSIONS: Nephrotoxicity is associated with the use of high dose colistin, age, gender, hypertension, red blood cells replacement and RIFLE stage. The mortality rate is higher in patients developing nephrotoxicity.

Can admission serum cystatin C level be an early marker subclinical acute kidney injury in critical care patients?

BACKGROUND: In critical care patients, the diagnosis of subclinical acute kidney injury (AKI) might be difficult with measurements of serum creatinine and estimated glomerular filtration rate (eGFR). Their 'sensitive kidneys' can easily be affected from sepsis, underlying diseases, medications and volume status and if they can be detected earlier, some preventive measures might be taken. In this study we aimed to determine whether admission serum cystatin C (sCys-C) and other clinical parameters can identify subclinical AKI in medical intensive care unit (ICU) patients with normal creatinine-based eGFR at admission. METHODS: A prospective cohort study, performed in an adult ICU of a university hospital between January 2008 and March 2013. The blood samples were obtained within the first 24-48 hours of admission and sCys-C levels were analyzed with particle-enhanced immunonephelometric assay. AKI development was assessed according to RIFLE criteria. The cutoff value of sCys-C for the prediction of AKI was determined with receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 72 patients were included in the study and 19 (26%) of them developed AKI. Among the patients with AKI admission sCys-C levels were significantly higher when compared with non-AKI patients (1.06 ± 0.29 vs. 0.89 ± 0.28 respectively, p = 0.026). With ROC curve analysis, the threshold level for sCys-C was 0.94 mg/L with 63% sensitivity and 66% specificity [AUC: 0.67, p = 0.026]. With logistic regression analysis 'high sCys-C levels at admission' (OR = 4.73; 95%CI 1.03-21.5, p = 0.044) was found as one of the independent variables for the prediction of AKI development, in addition to 'being intubated before ICU admission' (OR = 10.2; 95%CI 1.72-60.4, p = 0.01) and 'hypotension during ICU follow-up' (OR = 12.3; 95%CI 2.5-60.1, p = 0.002). CONCLUSION: In this cohort of patients, a high sCys-C level at admission was found to be a predictor of subclinical AKI arising during their ICU stay. If supported with further studies, it might be used to provide more accurate and earlier knowledge about renal dysfunction and to take appropriate preventive measures.

Individual differences in behavioral reactions to H1N1 during a later stage of the epidemic.

Previous studies regarding individuals' behavioral reactions to the H1N1 epidemic have been conducted nearly exclusively on the pre-pandemic phase of the epidemic or when the vaccine was not available. The prevalence and correlates of behavioral reactions to the H1N1 epidemic in Turkey were investigated by surveying 1045 respondents. The results indicate that behavioral responses can be divided into three classifications: recommended protective behaviors, avoidance behaviors, and ineffective behaviors. The frequency of recommended behaviors was higher than other behaviors, and respondents perceived these behaviors to be more effective. Recommended behaviors were predicted by the following factors: age, being female and married, the individual's beliefs in the effectiveness of the behavior, the perception that one's own behavior influences the infection risk, and the personality factors "Activity" and "Impulsive Sensation Seeking." Avoidance behaviors were predicted by the following factors: marital status, having small children, beliefs in the effectiveness of the behavior, mistrust of the government's ability to manage the epidemic, State Anxiety, and "Impulsive Sensation Seeking." Ineffective behaviors were predicted by the following factors: lower socio-economic status, marital status, the presence of chronic illness, the perceived effectiveness of the behavior, and State Anxiety. This study demonstrates that different types of behavioral reactions to the epidemic have different contributing factors and that these differences should be taken into account in public health interventions.

Why were Turks unwilling to accept the A/H1N1 influenza-pandemic vaccination? People's beliefs and perceptions about the swine flu outbreak and vaccine in the later stage of the epidemic.

This study investigated the acceptability of the A/H1N1 influenza vaccination and related factors among 1137 adults in the later stage of the A/H1N1 outbreak in Turkey. Having already been vaccinated or intending to get vaccinated were related to trust in the vaccine effectiveness, perceived risk of the side effects, and benefits of getting vaccinated. Perceived long term consequences of the A/H1N1 infection, perceptions of the A/H1N1 information in media, and barriers for getting vaccinated were related to intention whereas anticipated epidemic situation in Turkey, being chronically ill, and being not married were related to having already been vaccinated.

Crimean-Congo hemorrhagic fever treated with ribavirin in a pregnant woman.

We report a case of Crimean-Congo Hemorrhagic Fever (CCHF) infection in a 36-week pregnant woman. She was treated with ribavirin. She did not transmit the disease to her baby. Her baby was the first known to survive being delivered by a woman with CCHF. The initialization of ribavirin treatment probably resulted in the survival of the mother and her baby.