Detailed and up-to-date data on the epidemiology and healthcare costs of Influenza are fundamental for public health decision-making. We analyzed inpatient data on Influenza-associated ...hospitalizations (IAH), selected complications and risk factors, and their related direct costs for Germany during ten consecutive years.
We conducted a retrospective cost-of-illness study on patients with laboratory-confirmed IAH (ICD-10-GM code J09/J10 as primary diagnosis) by ICD-10-GM-based remote data query using the Hospital Statistics database of the German Federal Statistical Office. Clinical data and associated direct costs of hospital treatment are presented stratified by demographic and clinical variables.
Between January 2010 to December 2019, 156,097 persons were hospitalized due to laboratory-confirmed Influenza (J09/J10 primary diagnosis). The annual cumulative incidence was low in 2010, 2012 and 2014 (1.3 to 3.1 hospitalizations per 100,000 persons) and high in 2013 and 2015-2019 (12.6 to 60.3). Overall direct per patient hospitalization costs were mean (SD) 3521 EUR (± 8896) and median (IQR) 1805 EUR (1502; 2694), with the highest mean costs in 2010 (mean 8965 EUR ± 26,538) and the lowest costs in 2012 (mean 2588 EUR ± 6153). Mean costs were highest in 60-69 year olds, and in 50-59, 70-79 and 40-49 year olds; they were lowest in 10-19 year olds. Increased costs were associated with conditions such as diabetes (frequency 15.0%; 3.45-fold increase compared to those without diabetes), adiposity (3.3%; 2.09-fold increase) or immune disorders (5.6%; 1.88-fold increase) and with Influenza-associated complications such as Influenza pneumonia (24.3%; 1.95-fold), bacterial pneumonia (6.3%; 3.86-fold), ARDS (1.2%; 10.90-fold increase) or sepsis (2.3%; 8.30-fold). Estimated overall costs reported for the 10-year period were 549.6 Million euros (95% CI 542.7-556.4 million euros).
We found that the economic burden of IAH in Germany is substantial, even when considering solely laboratory-confirmed IAH reported as primary diagnosis. The highest costs were found in the elderly, patients with certain underlying risk factors and patients who required advanced life support treatment, and median and mean costs showed considerable variations between single years. Furthermore, there was a relevant burden of disease in middle-aged adults, who are not covered by the current vaccination recommendations in Germany.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigated empiric antibiotic treatment (EAT), guideline adherence, antibiotic streamlining and clinical outcomes in 1402 hospitalized children with pediatric parapneumonic ...effusion/pleural empyema (PPE/PE).
A nationwide surveillance study collected data on EAT, clinical course/outcome, pathogens, susceptibility testing and antibiotic streamlining of children with PPE/PE in Germany between 2010 and 2018. Subgroups were compared using χ2 test/Fisher exact test, Mann-Whitney U test and linear regression analysis adjusting for patient age where appropriate.
Complete data on EAT were available for 1402 children. In children with monotherapy (n = 567) and in children with combination therapy of 2 antibiotics (n = 589), the most commonly used antibiotics were aminopenicillin/beta-lactamase inhibitor 138/567 (24.3%) and 102/589 (17.3%) and cefuroxime 291/567 (51.3%) and 294/589 (49.9%). The most common combinations with these beta-lactams were macrolides, aminoglycosides and clindamycin. We observed no difference in clinical severity/outcome between EAT with aminopenicillin/beta-lactamase inhibitor and cefuroxime, neither when used in monotherapy nor when used in combination therapy of 2 antibiotics. Species diagnosis of Streptococcus pneumoniae (n = 192), Streptococcus pyogenes (n = 111) or Staphylococcus aureus (n = 38) in polymerase chain reaction or culture from pleural fluid or blood resulted in a switch to an appropriate narrow-spectrum beta-lactam therapy in 9.4%, 18.9 % and 5.2% of children. In a subset of children with reported bacterial susceptibility testing, penicillin resistance was reported in 3/63 (4.8%) of S. pneumoniae and methicillin resistance in S. aureus was reported in 10/32 (31.3%) of children.
This study points to antibiotic overtreatment in children with PPE/PE, particularly the frequent use of combinations of antibiotics. Children receiving combinations of antibiotics did not show differences in clinical outcomes. The low rate of children with streamlined antibiotic therapy even upon pathogen detection indicates a necessity for antibiotic stewardship measures in PPE/PE and the need of investigating other potential therapeutic strategies as anti-inflammatory therapy.
The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children ...recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections.
Abstract
Background
Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age.
Methods
This single-center ...retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed RSV infection (2015–2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days.
Results
Three hundred twelve patients had RSV infection (ages 0 to <6 months 35%, 6 to <12 months 15%, 1 to <2 years 25%, and 2–5 years 25%); 16.3% had predefined comorbidities (excludes preterm infants). Median hospital LOS was 5.0 days and similar across age; 5.1% (16/312) were admitted to ICU (ICU LOS, 5.0 days), with those aged 0 to <6 months admitted most frequently (10/108 9.3%). Supplemental oxygen was administered in 57.7% of patients, with similar need across ages. Antibiotics were administered frequently during hospitalization (43.6%). Predictors of prolonged LOS included pneumonia (odds ratio OR, 2.33), supplemental oxygen need (OR, 5.09), and preterm births (OR, 3.37). High viral load (RT-PCR RSV cycle threshold value <25) was associated with greater need for supplemental oxygen.
Conclusions
RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged <6 months.
In 2004, routine varicella vaccination was recommended in Germany for children 11-14 months of age with one dose, and since 2009, with a second dose at 15-23 months of age. The effects on varicella ...epidemiology were investigated.
Data on varicella vaccinations, cases and complications were collected from annual parent surveys (2006-2011), monthly paediatric practice surveillance (Oct 2006 - Sep 2011; five varicella seasons) and paediatric hospital databases (2005-2009) in the area of Munich (about 238,000 paediatric inhabitants); annual incidences of cases and hospitalisations were estimated.
Varicella vaccination coverage (1st dose) in children 18-36 months of age increased in two steps (38%, 51%, 53%, 53%, 66% and 68%); second-dose coverage reached 59% in the 2011 survey. A monthly mean of 82 (62%) practices participated; they applied a total of 50,059 first-dose and 40,541 second-dose varicella vaccinations, with preferential use of combined MMR-varicella vaccine after recommendation of two doses, and reported a total of 16,054 varicella cases <17 years of age. The mean number of cases decreased by 67% in two steps, from 6.6 (95%CI 6.1-7.0) per 1,000 patient contacts in season 2006/07 to 4.2 (95%CI 3.9-4.6) in 2007/08 and 4.0 (95%CI 3.6-4.3) in 2008/09, and further to 2.3 (95%CI 2.0-2.6) in 2009/10 and 2.2 (95%CI 1.9-2.5) in 2010/11. The decrease occurred in all paediatric age groups, indicating herd protection effects. Incidence of varicella was estimated as 78/1,000 children <17 years of age in 2006/07, and 19/1,000 in 2010/11. Vaccinated cases increased from 0.3 (95%0.2-0.3) per 1,000 patient contacts in 2006/07 to 0.4 (95%CI 0.3-0.5) until 2008/09 and decreased to 0.2 (95%CI 0.2-0.3) until 2010/11. The practices treated a total of 134 complicated cases, mainly with skin complications. The paediatric hospitals recorded a total of 178 varicella patients, including 40 (22.5%) with neurological complications and one (0.6%) fatality due to varicella pneumonia. Incidence of hospitalisations decreased from 7.6 per 100,000 children <17 years of age in 2005 to 4.3 in 2009, and from 21.0 to 4.7 in children <5 years of age.
Overall, the results show increasing acceptance and a strong impact of the varicella vaccination program, even with still suboptimal vaccination coverage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in ...different age and risk groups.
Assessment of RSV-coded hospitalizations (ICD-10-GM RSV-code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office.
Overall, 205,352 RSV-coded hospitalizations (198,139 children < 18 years, 1,313 adults, 5,900 seniors > 59 years) were reported (median age < 1 year, IQR 0; 1; 56% males, 32% with RSV pneumonia). Annual median RSV-coded hospitalization incidence was 24.8/100,000 persons (IQR 21.3; 27.5); children reported a median incidence of 145.8 (IQR 130.9; 168.3). Between 2010 and 2019, hospitalization incidence increased 1.7-fold/15.1-fold/103-fold in children/adults/seniors. Adults and seniors reported higher rates of underlying chronic conditions, complications, and intensive care treatment than children; of 612 in-hospital fatalities, 103/51/458 occurred in children/adults/seniors. Per-patient mean costs varied between 3286€ ± 4594 in 1-4-year-olds and 7215€ ± 13,564 among adults. Increased costs were associated with immune disorders (2.55-fold increase compared to those without), nervous system disorders (2.66-fold), sepsis (7.27-fold), ARDS (12.85-fold), intensive care (4.60-fold) and ECMO treatment (16.88-fold).
The economic burden of RSV-related hospitalizations in Germany is substantial, even when only considering cases with RSV-coded as the primary discharge diagnosis. Children represented the vast majority of RSV-coded hospitalizations. However, adults and seniors hospitalized for RSV were at a higher risk of severe complications, required more costly treatments, and had higher fatality rates; although their RSV-coded hospitalization incidence showed a clear upward trend since 2017, their true hospitalization incidence is still likely to be underestimated due to lack of routine RSV testing in these age groups. Hence, new treatments and vaccines for RSV ideally should also target adults and seniors in addition to children.
Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies ...with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils use 2 distinct and independent phagolysosomal mechanisms to kill Candida albicans. The first mechanism for the killing of unopsonized C albicans was found to be dependent on complement receptor 3 (CR3) and the signaling proteins phosphatidylinositol-3-kinase and caspase recruitment domain-containing protein 9 (CARD9), but was independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The second mechanism for the killing of opsonized C albicans was strictly dependent on Fcγ receptors, protein kinase C (PKC), and reactive oxygen species production by the NADPH oxidase system. Each of the 2 pathways of Candida killing required Syk tyrosine kinase activity, but dectin-1 was dispensable for both of them. These data provide an explanation for the variable clinical presentation of fungal infection in patients suffering from different immune defects, including dectin-1 deficiency, CARD9 deficiency, or chronic granulomatous disease.
•Human neutrophils use 2 independent mechanisms for the killing of unopsonized and serum-opsonized C albicans.•Unopsonized Candida killing depends on CR3 and CARD9 but not dectin-1; opsonized Candida killing on FcγR, PKC, and NADPH oxidase activity.
Respiratory viruses were detected by multiplex-polymerase chain reaction from oropharyngeal swabs in 114/168 (67.9%) children with acute respiratory infection presenting to 5 pediatric practices in ...Germany between November 2020 and April 2021. In contrast to rhino- (48.8%), adeno- (14.3%) and endemic coronaviruses (14.9%), SARS-CoV-2 and influenza virus were detected only once; respiratory syncytial virus was not detected. This demonstrates differing impacts of pandemic infection control measures on the spread of respiratory viruses.
Parapneumonic pleural effusion and pleural empyema (PPE/PE) are complications of community-acquired pneumonia. The objective of this study was to analyze prehospital antibiotic therapy (PH-ABT) of ...children with PPE/PE and investigate its effects on clinical outcome and pathogen detection.
Prospective nationwide active surveillance in Germany between October 2010 and June 2018. Children and adolescents <18 years of age with pneumonia-associated PE or PPE requiring drainage or with persistence of PPE/PE >7 days were included.
A total of 1724 children with PPE/PE were reported, of whom 556 children (32.3% of 1719 with available data) received PH-ABT. Children with PH-ABT had a shorter median hospital length of stay (15 vs. 18 days, P < 0.001), a longer time from onset of symptoms until hospital discharge (25 vs. 23 days, P = 0.002), a lower rate of intensive care unit admission (58.3% vs. 64.4%, P = 0.015) and fewer infectious complications (5.9% vs. 10.0%; P = 0.005). Bacterial pathogens in blood or pleural fluid culture were detected in 597 (34.5%) of 1513 children. Positive culture results were less frequent in children with than without PH-ABT (81/466 17.4% vs. 299/1005 29.8%; P < 0.001), whereas detection rates in pleural fluid samples by polymerase chain reaction were similar (91/181 50.3% vs. 220/398 55.3%; P = 0.263).
In children with PPE/PE, PH-ABT significantly reduced the overall rate of bacterial pathogen detection by culture, but not by polymerase chain reaction. PH-ABT was associated with a lower rate of infectious complications but did not affect the overall duration of disease. We therefore speculate that the duration of PPE/PE is mainly a consequence of an infection-induced inflammatory process, which can only partially be influenced by antibiotic treatment.
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