Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?

Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Changes in antimicrobial resistance and outcomes of health care-associated infections.

To describe the change in the epidemiology of health care-associated infections (HAI), resistance and predictors of fatality we conducted a nationwide study in 24 hospitals between 2015 and 2018. The 30-day fatality rate was 22% in 2015 and increased to 25% in 2018. In BSI, a significant increasing trend was observed for Candida and Enterococcus. The highest rate of 30-day fatality was detected among the patients with pneumonia (32%). In pneumonia, Pseudomonas infections increased in 2018. Colistin resistance increased and significantly associated with 30-day fatality in Pseudomonas infections. Among S. aureus methicillin, resistance increased from 31 to 41%.

A novel id-iri score: development and internal validation of the multivariable community acquired sepsis clinical risk prediction model.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Improvement of hand hygiene compliance in a private hospital using the Plan-Do-Check-Act (PDCA) method.

OBJECTIVE: Improving the compliance to hand hygiene in healthcare providers is important to reduce healthcare-associated infections. This study aimed to compare the compliance rate before and after the improvement of compliance to hand hygiene. METHODS: In this study 270 of the 348 medical staff working in a 61-bed private hospital was observed. The informed observation was performed by the infection control committee in the entire hospital using "Five Moments for Hand Hygiene" for a period of one year. After the first six months, an improvement study was conducted together with the hospital's quality department using the plan-do-check-act cycle. The study was conducted in a private hospital in Istanbul/Turkey; Kadikoy Florence Nightingale Hospital in 2014. RESULTS: In the first six months of the year, 153 actions were observed at 316 proper situations. The compliance rate was 35%, 54% and 64% for the physicians, nurses and, other healthcare staff, respectively. The overall compliance rate was 48%. One hundred eighty-three actions were observed for 306 situations after the improvement and education studies. The compliance rate was 29%, 72% and 86%. The overall mean compliance rate was 60%. CONCLUSION: The promotion of hand hygiene requires the cooperation of the hospital administrators, infection control committee, and quality departments for better hand hygiene practices among the healthcare providers.

Development and validation of a modified quick SOFA scale for risk assessment in sepsis syndrome.

Sepsis is a severe clinical syndrome owing to its high mortality. Quick Sequential Organ Failure Assessment (qSOFA) score has been proposed for the prediction of fatal outcomes in sepsis syndrome in emergency departments. Due to the low predictive performance of the qSOFA score, we propose a modification to the score by adding age. We conducted a multicenter, retrospective cohort study among regional referral centers from various regions of the country. Participants recruited data of patients admitted to emergency departments and obtained a diagnosis of sepsis syndrome. Crude in-hospital mortality was the primary endpoint. A generalized mixed-effects model with random intercepts produced estimates for adverse outcomes. Model-based recursive partitioning demonstrated the effects and thresholds of significant covariates. Scores were internally validated. The H measure compared performances of scores. A total of 580 patients from 22 centers were included for further analysis. Stages of sepsis, age, time to antibiotics, and administration of carbapenem for empirical treatment were entered the final model. Among these, severe sepsis (OR, 4.40; CIs, 2.35-8.21), septic shock (OR, 8.78; CIs, 4.37-17.66), age (OR, 1.03; CIs, 1.02-1.05) and time to antibiotics (OR, 1.05; CIs, 1.01-1.10) were significantly associated with fatal outcomes. A decision tree demonstrated the thresholds for age. We modified the quick Sequential Organ Failure Assessment (mod-qSOFA) score by adding age (> 50 years old = one point) and compared this to the conventional score. H-measures for qSOFA and mod-qSOFA were found to be 0.11 and 0.14, respectively, whereas AUCs of both scores were 0.64. We propose the use of the modified qSOFA score for early risk assessment among sepsis patients for improved triage and management of this fatal syndrome.

Secondary Infections in Febrile Neutropenia in Hematological Malignancies: More Than Another Febrile Neutropenic Episode.

INTRODUCTION: Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients. METHODS: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006. RESULTS: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related with gram positive bacteria (p=0.04) and fungi (p<0.001) and 30-day mortality rate (p<0.001) were significantly higher in secondary infections (p<0.001). DISCUSSION AND CONCLUSION: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.

A case of nocardiasis complicated with meningitis in a patient with immune thrombocytopenic purpura.

Nocardia infection is a well recognized complication of the immunocompromised hosts. It is mostly a primary pulmonary infection, which may disseminate to other organs. The central nervous system (CNS) involvement of nocardiosis is usually manifested as brain abscesses. We report a 25-year-old male patient who presented with nocardial pneumonia and meningitis without brain abscess. He was diagnosed as immune thrombocytopenic purpura and methyl prednisolone was started 5 weeks previously. Nocardia spp. was obtained from his cerebrospinal fluid culture, but he died at the 7th day of intensive care. Nocardia meningitis is a rare manifestation of systemic disease. Nocardia meningitis should be considered in the differential diagnosis of meningitis with the coexisting nodular pulmonary lesions in the immunocompromised patient and medications other than co-trimoxazole may be required.

Pneumopericardium due to invasive pulmonary aspergillosis.

We describe a 59-year-old female patient with leukemia who developed pneumopericardium as a complication of invasive pulmonary aspergillosis. Spiral computed tomography (CT) was very helpful for the detection of such complications.