Plasma immune signatures can predict rejection-free survival in the first year after pediatric liver transplantation.

BACKGROUND & AIMS: After pediatric liver transplantation (pLT), children undergo life-long immunosuppression since reliable biomarkers for the assessment of rejection probability are scarce. In the multicenter (n = 7) prospective clinical cohort "ChilSFree" study, we aimed to characterize longitudinal dynamics of soluble and cellular immune mediators during the first year after pLT and identify early biomarkers associated with outcome. METHODS: Using a Luminex-based multiplex technique paired with flow cytometry, we characterized longitudinal dynamics of soluble immune mediators (SIMs, n = 50) and immune cells in the blood of 244 patients at eight visits over 1 year: before, and 7/14/21/28 days and 3/6/12 months after pLT. RESULTS: The unsupervised clustering of patients based on SIM profiles revealed six unique SIM signatures associated with clinical outcome. From three signatures linked to improved outcome, one was associated with 1-year-long rejection-free survival and stable graft function and was characterized by low levels of pro-inflammatory SIMs (CXCL8/9/10/12, CCL7, SCGF-ß, sICAM-1), and high levels of regenerative (SCF, TNF-ß) and pro-apoptotic (TRAIL) SIMs (all, p <0.001, fold change >100). Of note, this SIM signature appeared 2 weeks after pLT and remained stable over the entire year, pointing towards its potential as a novel early biomarker for minimizing or weaning immunosuppression. In the blood of these patients, a higher frequency of CD56bright natural killer cells (p <0.01), a known hallmark also associated with operationally tolerant pLT patients, was detected. The concordance of the model for prediction of rejection based on identified SIM signatures was 0.715, and 0.795, in combination with living-related transplantation as a covariate, respectively. CONCLUSIONS: SIM blood signatures may enable the non-invasive and early assessment of rejection risks in the first year after pLT, paving the way for improved clinical management. IMPACT AND IMPLICATIONS: ChilSFree represents the largest pediatric liver transplant (pLT) cohort with paired longitudinal data on soluble immune mediators (SIMs) and immune phenotyping in the first year after pLT. SIM signatures allow for the selection of rejection-free patients 2 weeks after pLT independently of patient diagnosis, sex, or age. The SIM signatures may enable the non-invasive and early assessment of rejection risks, paving the way for minimization or withdrawal of immunosuppression after pLT.

Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study.

The aim of this study is to analyze patient movement patterns between hospital departments to derive the underlying intra-hospital movement network, and to assess if movement patterns differ between patients at high or low risk of colonization. For that purpose, we analyzed patient electronic medical record data from five hospitals to extract information on risk stratification and patient intra-hospital movements. Movement patterns were visualized as networks, and network centrality measures were calculated. Next, using an agent-based model where agents represent patients and intra-hospital patient movements were explicitly modeled, we simulated the spread of multidrug resistant enterobacteriacae (MDR-E) inside a hospital. Risk stratification of patients according to certain ICD-10 codes revealed that length of stay, patient age, and mean number of movements per admission were higher in the high-risk groups. Movement networks in all hospitals displayed a high variability among departments concerning their network centrality and connectedness with a few highly connected departments and many weakly connected peripheral departments. Simulating the spread of a pathogen in one hospital network showed positive correlation between department prevalence and network centrality measures. This study highlights the importance of intra-hospital patient movements and their possible impact on pathogen spread. Targeting interventions to departments of higher (weighted) degree may help to control the spread of MDR-E. Moreover, when the colonization status of patients coming from different departments is unknown, a ranking system based on department centralities may be used to design more effective interventions that mitigate pathogen spread.

Presentation, patterns of care, and outcomes of patients with prostate cancer in sub-Saharan Africa: A population-based registry study.

BACKGROUND: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA. METHODS: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs). RESULTS: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy. CONCLUSIONS: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.

Modelling pathogen spread in a healthcare network: Indirect patient movements.

Inter-hospital patient transfers (direct transfers) between healthcare facilities have been shown to contribute to the spread of pathogens in a healthcare network. However, the impact of indirect transfers (patients re-admitted from the community to the same or different hospital) is not well studied. This work aims to study the contribution of indirect transfers to the spread of pathogens in a healthcare network. To address this aim, a hybrid network-deterministic model to simulate the spread of multiresistant pathogens in a healthcare system was developed for the region of Lower Saxony (Germany). The model accounts for both, direct and indirect transfers of patients. Intra-hospital pathogen transmission is governed by a SIS model expressed by a system of ordinary differential equations. Our results show that the proposed model reproduces the basic properties of healthcare-associated pathogen spread. They also show the importance of indirect transfers: restricting the pathogen spread to direct transfers only leads to 4.2% system wide prevalence. However, adding indirect transfers leads to an increase in the overall prevalence by a factor of 4 (18%). In addition, we demonstrated that the final prevalence in the individual healthcare facilities depends on average length of stay in a way described by a non-linear concave function. Moreover, we demonstrate that the network parameters of the model may be derived from administrative admission/discharge records. In particular, they are sufficient to obtain inter-hospital transfer probabilities, and to express the patients' transfers as a Markov process. Using the proposed model, we show that indirect transfers of patients are equally or even more important as direct transfers for the spread of pathogens in a healthcare network.

Bacterial community structure and effects of picornavirus infection on the anterior nares microbiome in early childhood.

BACKGROUND: Little is known regarding the nasal microbiome in early childhood and the impact of respiratory infection on the infants' nasal microbial composition. Here we investigated the temporal dynamics and diversity of the bacterial composition in the anterior nares in children attending daycare centers. RESULTS: For our investigation, we considered 76 parental-taken nasal swabs of 26 children (aged 13 to 36 months) collected over a study period of 3 months. Overall, there was no significant age-specific effect or seasonal shift in the nasal bacterial community structure. In a sub-sample of 14 healthy children the relative abundance of individual taxa as well as the overall diversity did not reveal relevant changes, indicating a stable community structure over the entire study period. Moreover, the nasal bacterial profiles clustered subject-specific with Bray-Curtis similarities being elevated in intra-subject calculations compared to between-subject calculations. The remaining subset of 12 children provided samples taken during picornavirus infection (PVI) and either before or after a PVI. We detected an association between the relative abundance of members of the genus Streptococcus and PV when comparing both (i) samples taken during PVI with samples out of 14 healthy children and (ii) samples taken during PVI with samples taken after PVI within the same individual. In addition, the diversity was higher during PVI than after infection. CONCLUSIONS: Our findings suggest that a personalized structure of the nasal bacterial community is established already in early childhood and could be detected over a timeframe of 3 months. Studies following infants over a longer time with frequent swab sampling would allow investigating whether certain parameter of the bacterial community, such as the temporal variability, could be related to viral infection.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study.

BACKGROUND: Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years. METHODS: We used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population. RESULTS: Projected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios. CONCLUSION: Demographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.

Predictive Factors for Survival in Children Receiving Liver Transplants for Wilson's Disease: A Cohort Study Using European Liver Transplant Registry Data.

Liver transplantation (LT) is a rescue therapy for life-threatening complications of Wilson's disease (WD). However, data on the outcome of WD patients after LT are scarce. The aim of our study was to analyze a large pediatric WD cohort with the aim of investigating the longterm outcome of pediatric WD patients after LT and to identify predictive factors for patient and transplant survival. This is a retrospective cohort study using data of all children (<18 years) transplanted for WD enrolled in the European Liver Transplant Registry from January 1968 until December 2013. In total, 338 patients (57.6% female) transplanted at 80 different European centers (1-26 patients per center) were included in this study. The median age at transplantation was 14.0 years (interquartile range [IQR], 11.2-16.1 years); patients were followed up for a median of 5.4 years (IQR, 1.0-10.9 years) after LT. Overall patient survival rates were high with 87% (1-year survival), 84% (5-year survival), and 81% (10-year survival); survival rates increased considerably with the calendar year (P < 0.001). Early age at LT, living donation, and histidine tryptophan ketoglutarate preservation liquid were identified as risk factors for poor patient survival in the multivariate analysis. LT is an excellent treatment option for pediatric patients with WD and associated end-stage liver disease. Longterm outcome in these patients is similar to other pediatric causes for LT. Overall patient and graft survival rates improved considerably over the last decades. To improve future research in the field, the vast variability of allocation strategies should be harmonized and a generally accepted definition or discrimination of acute versus chronic WD needs to be found.

Changes in risk perceptions during the 2014 Ebola virus disease epidemic: results of two consecutive surveys among the general population in Lower Saxony, Germany.

BACKGROUND: The Ebola virus disease (EVD) outbreak 2014 received extensive news media coverage, which faded out before the outbreak ended. News media coverage impacts risk perception; it is, however, unclear if the components of risk perception (affective and cognitive responses) change differently over time. METHODS: In an online panel, we asked participants (n = 1376) about EVD risk perceptions at the epidemic's peak (November 2014) and after news media coverage faded out (August 2015). We investigated worry (affective response), perceived likelihood of infection, perceived personal impact, and coping efficacy (dimensions of cognitive response), and knowledge about transmission. Differences between the surveys with respect to manifestations of affective and cognitive dimensions were tested using the Wilcoxon signed-rank test. The association between individual change in knowledge and worries about EVD in the first survey was investigated using linear regression. RESULTS: In November 2014, the survey was filled in by 974 participants. Ten months later, 662 of them were still members of the online panel and were invited to the follow-up survey. Among the 620 respondents, affective response decreased between the surveys. Knowledge about EVD also decreased; however, participants worried about EVD in 2014 had increased knowledge in 2015. Perceived likelihood of infection decreased over time, while perceived personal impact and coping efficacy did not. CONCLUSIONS: Risk communication appealing to cognitive reactions by informing clearly on the risk of infection in unaffected countries may decrease inappropriate behaviors.

Perceptions of Zika virus risk in Germany in 2016.

Background: Risks associated with Zika virus (ZIKV) transmission in the Americas have been discussed widely in the media as several European athletes declined to participate in the 2016 Summer Olympic Games. Since risk perceptions of individuals in unaffected areas are unknown, we assessed the risk perceptions of ZIKV and related behaviour in Lower Saxony, Germany, with a specific focus on pregnant women and their partners. Methods: In May 2016, we surveyed 1,037 participants aged 15-69 years of an online panel (addressing hygiene and preventive behaviour regarding infections) in Lower Saxony with respect to their risk perceptions related to ZIKV. We additionally included 26 expectant parents who were recruited at antenatal preparation courses in Braunschweig and Hannover between May and July 2016. Results: Six hundred fifty-five (69.1%) of the panel participants had ever heard about ZIKV. About 8% of the study participants reported to be concerned about ZIKV. Pregnant women had the highest odds of reporting concern about ZIKV (OR: 6.24; 95% CI: 2.94-13.26, reference: non-pregnant women). The vast majority of participants (79%) would travel to the Olympics if they won a free trip; this proportion was lower in currently pregnant women (46%). Risk perceptions towards ZIKV were considerably lower than those towards Ebola during the 2014 epidemic. Conclusion: This study showed that fear of contracting ZIKV is not a major deterrent for travelling to high-risk areas. Pregnant women are appropriately concerned about the risk of ZIKV. Studies modelling the further spread of ZIKV need to account for these results.

Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children - a data-driven approach using machine-learning algorithms.

BACKGROUND: Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). METHODS: This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. RESULTS: A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70-0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52-0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87-100%), 28% (95% CI: 20-38%) of non-infectious SIRS cases were assorted correctly. CONCLUSIONS: Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005.

Time trends of chronic HBV infection over prior decades - A global analysis.

BACKGROUND & AIMS: Information on trends in chronic hepatitis B virus (HBV) prevalence across countries is lacking. We studied changes in chronic HBV infection over previous decades by country, and assessed patterns of change between and within WHO-defined regions. METHODS: Based on data from a published systematic review on chronic HBV, we applied a linear model on the logit scale to assess time trends in country-specific prevalence. Estimated HBsAg prevalence in 2000 and relative changes in prevalence over time were evaluated by country and region. RESULTS: Sufficient data were available for 50 countries, mostly showing reductions in prevalence over time. Various degrees of heterogeneity were observed within regions, with a relatively homogenous pattern in the Eastern Mediterranean region with strong decreases in HBsAg prevalence. Europe showed a mixed pattern: higher and stable chronic HBsAg prevalence in Eastern, and constantly low prevalence in Western Europe. In Africa, some countries demonstrated no change in prevalence; increases were seen in Uganda (odds ratio 1.05 per year; 95% confidence interval 1.04-1.06), Nigeria (1.02; 1.02-1.02), Senegal (1.01; 1.01-1.02), and South Africa (1.02; 1.01-1.02). With some exceptions, country-patterns overlapped among countries of South East Asian and Western Pacific regions, characterized by low-medium HBsAg decreases, most prominent in China and Malaysia. CONCLUSIONS: Most countries experienced decreases in HBsAg prevalence. Dynamics varied, even within regions; decreases occurred mostly before the direct effects of childhood vaccination may have manifested. These findings together with stable and increasing HBsAg prevalence in some countries of Africa and Eastern Europe indicate the need for further tailored country-specific prevention. LAY SUMMARY: This study investigated time trends in prevalence of chronic HBV infection in 50 countries worldwide over the last decade, by estimating relative changes in prevalence. Results show decreases in chronic HBV infection in most countries; no changes or increases in prevalence are noted in some African countries. Reasons for time changes need to be investigated further; based on the results, various prevention measures have contributed to reductions, and further tailored HBV prevention is required to combat the disease on a global level.

Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.

BACKGROUND: Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice). METHODS: We used data from a longitudinal panel, the Hygiene and Behaviour Infectious Diseases Study (HaBIDS), conducted in 2014/2015 in four regions in Lower Saxony, Germany. Individuals were recruited using address-based probability sampling. In two regions, individuals could choose between paper-and-pencil and online questionnaires. In the other two regions, individuals were offered online-only participation. We compared sociodemographic characteristics of respondents who filled in all panel questionnaires between the mixed-mode group (n = 1110) and the online-only group (n = 482). Using 134 items, we performed multinomial logistic regression to compare responses between survey designs in terms of type (missing, "do not know" or valid response) and ordinal regression to compare responses in terms of content. We applied the false discovery rates (FDR) to control for multiple testing and investigated effects of adjusting for sociodemographic characteristic. For validation of the differential response patterns between mixed-mode and online-only, we compared the response patterns between paper and online mode among the respondents in the mixed-mode group in one region (n = 786). RESULTS: Respondents in the online-only group were older than those in the mixed-mode group, but both groups did not differ regarding sex or education. Type of response did not differ between the online-only and the mixed-mode group. Survey design was associated with different content of response in 18 of the 134 investigated items; which decreased to 11 after adjusting for sociodemographic variables. In the validation within the mixed-mode, only two of those were among the 11 significantly different items. The probability of observing by chance the same two or more significant differences in this setting was 22%. CONCLUSIONS: We found similar response patterns in both survey designs with only few items being answered differently, likely attributable to chance. Our study supports the equivalence of the compared survey designs and suggests that, in the studied setting, using online-only design does not cause strong distortion of the results.

Factors associated with attrition in a longitudinal online study: results from the HaBIDS panel.

BACKGROUND: Knowing about predictors of attrition in a panel is important to initiate early measures against loss of participants. We investigated attrition in both early and late phase of an online panel with special focus on preferences regarding mode of participation. METHODS: We used data from the HaBIDS panel that was designed to investigate knowledge, attitudes, and practice regarding infections in the German general population. HaBIDS was divided into two phases: an initial phase when some participants could choose their preferred mode of participation (paper-and-pencil or online) and an extended phase when participants were asked to become members of an online panel that was not limited regarding its duration (i.e. participants initially preferring paper questionnaires switched to online participation). Using competing risks regression, we investigated two types of attrition (formal withdrawal and discontinuation without withdrawal) among online participants, separately for both phases. As potential predictors of attrition, we considered sociodemographic characteristics, physical and mental health as well as auxiliary information describing the survey process, and, in the extended phase, initial mode preference. RESULTS: In the initial phase, higher age and less frequent Internet usage predicted withdrawal, while younger age, higher stress levels, delay in returning the consent form, and need for receiving reminder emails predicted discontinuation. In the extended phase, only need for receiving reminder emails predicted discontinuation. Numbers of withdrawal in the extended phase were too small for analysis. Initial mode preference did not predict attrition in the extended phase. Besides age, there was no evidence of differential attrition by sociodemographic factors in any phase. CONCLUSIONS: Predictors of attrition were similar in both phases of the panel, but they differed by type of attrition (withdrawal vs. discontinuation). Sociodemographic characteristics only played a minor role for both types of attrition. Need for receiving a reminder was the strongest predictor of discontinuation in any phase, but no predictor of withdrawal. We found predictors of attrition, which can be identified already in the early phase of a panel so that countermeasures (e.g. special incentives) can be taken.

Cost-effectiveness of human papillomavirus vaccination in Germany.

BACKGROUND: The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. METHODS: Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys. RESULTS: From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls. CONCLUSIONS: Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.

Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013.

BACKGROUND: The quantification of the burden of disease attributable to hepatitis B virus (HBV) infection and the adaptation of prevention and control measures requires knowledge on its prevalence in the general population. For most countries such data are not routinely available. We estimated the national, regional, and global prevalence of chronic HBV infection. METHODS: For this systematic review and pooled analysis, we searched for data on prevalence of chronic HBV infection published between Jan 1, 1965, and Oct 23, 2013, in the databases Medline, Embase, CAB Abstracts (Global health), Popline, and Web of Science. We included studies reporting the hepatitis B surface antigen (HBsAg) serological marker of chronic HBV infection in non-high-risk groups and extracted data into a customised database. For each country, we calculated HBsAg prevalence estimates and 95% CIs weighted by study size. We extrapolated prevalence estimates to population sizes in 2010 to obtain the number of individuals with chronic HBV infection. FINDINGS: Of the 17,029 records screened, 1800 report on the prevalence of HBsAg covering 161 countries were included. HBsAg seroprevalence was 3·61% (95% CI 3·61-3·61) worldwide with highest endemicity in countries of the African region (total 8·83%, 8·82-8·83) and Western Pacific region (total 5·26%, 5·26-5·26). Within WHO regions, prevalence ranged from 0·20% (0·19-0·21; Mexico) to 13·55% (9·00-19·89; Haiti) in the Americas, to 0·48% (0·12-1·90; the Seychelles) to 22·38% (20·10-24·83; South Sudan) in the African region. We estimated that in 2010, globally, about 248 million individuals were HBsAg positive. INTERPRETATION: This first global assessment of country-level population prevalence of chronic HBV infection found a wide variation between countries and highlights the need for continued prevention and control strategies and the collection of reliable epidemiologic data using standardised methodology. FUNDING: World Health Organization.

Perception of High Alcohol Use of Peers Is Associated With High Personal Alcohol Use in First-Year University Students in Three Central and Eastern European Countries.

OBJECTIVES: The objectives of this study were to assess discrepancies between estimated peer and personal drinking behavior and to determine associations between perceptions of peer and personal drinking behavior among university students from Hungary (HU), Lithuania (LT), and the Slovak Republic (SK). METHODS: 2,554 freshman university students completed an online questionnaire on the frequency of their personal alcohol use, the number of heavy drinking occasions and on their perception concerning the corresponding drinking behavior of a typical student. Associations between perceived peer and personal use were analyzed by means of logistic regression, adjusting for sex. RESULTS: The majority of students across all countries thought their peers drink more frequently and are more often involved in heavy drinking occasions than themselves. Students who perceived the frequency of peer alcohol use to be higher were more likely to drink alcohol twice a week or more often (SR: OR = 3.81, 95% CI = 2.51-5.79; LT: OR = 3.16, 95% CI = 2.11-4.75; HU: OR = 2.10, 95% CI = 1.53-2.87) compared with students who drink alcohol monthly or less. Those who perceived the number of peer heavy drinking occasions as high were more likely to report heavy drinking weekly or more often (SR: OR = 3.16, 95% CI = 1.92-5.20; LT:OR = 3.56, 95% CI = 2.14-5.94; HU:OR = 1.41, 95% CI = 0.79-2.51) compared with students who report heavy drinking less than monthly. CONCLUSIONS/IMPORTANCE: University students perceived peer alcohol use to be higher than their personal use. Given the association between perceptions and personal alcohol use, future research should investigate if targeting perceptions in the surveyed countries may have an impact on alcohol use.

Ebola risk perception in Germany, 2014.

Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.

Proposing an empirically justified reference threshold for blood culture sampling rates in intensive care units.

Early and appropriate blood culture sampling is recommended as a standard of care for patients with suspected bloodstream infections (BSI) but is rarely taken into account when quality indicators for BSI are evaluated. To date, sampling of about 100 to 200 blood culture sets per 1,000 patient-days is recommended as the target range for blood culture rates. However, the empirical basis of this recommendation is not clear. The aim of the current study was to analyze the association between blood culture rates and observed BSI rates and to derive a reference threshold for blood culture rates in intensive care units (ICUs). This study is based on data from 223 ICUs taking part in the German hospital infection surveillance system. We applied locally weighted regression and segmented Poisson regression to assess the association between blood culture rates and BSI rates. Below 80 to 90 blood culture sets per 1,000 patient-days, observed BSI rates increased with increasing blood culture rates, while there was no further increase above this threshold. Segmented Poisson regression located the threshold at 87 (95% confidence interval, 54 to 120) blood culture sets per 1,000 patient-days. Only one-third of the investigated ICUs displayed blood culture rates above this threshold. We provided empirical justification for a blood culture target threshold in ICUs. In the majority of the studied ICUs, blood culture sampling rates were below this threshold. This suggests that a substantial fraction of BSI cases might remain undetected; reporting observed BSI rates as a quality indicator without sufficiently high blood culture rates might be misleading.

Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials.

BACKGROUND: A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany. METHODS: Parents of 1- to 3-year-old children (n = 75) were recruited in nursery schools. They were asked to complete a symptom diary on a daily basis and to take monthly and symptom-triggered nasal swabs and stool samples from their child over the study period of three months. Feasibility was measured by means of the return proportions of symptom diaries and bio samples; acceptance was assessed by a questionnaire delivered to participants at the end of the study. RESULTS: The majority of the participants filled in the symptom diary during the three months study for 75 or more days (77.3%), and provided the monthly nasal swabs (62.7%) and stool samples (65.3%). The time needed for the tasks was acceptable for most participants (symptom diary: 92.3%, nasal swabs: 98.5%, stool samples: 100.0%). In 64.3% of the symptom-triggered nasal swabs, respiratory viruses were found compared to 55.5% in throat swabs taken by health-care professionals within the "ARE surveillance Lower Saxony", a special project by the Governmental Institute of Public Health of Lower Saxony to investigate causal pathogens for acute respiratory infections in children. CONCLUSIONS: The parental assessment of symptoms and collection of biomaterials in a birth cohort dedicated to studying infections appears feasible in a middle class German population. The success of the study will depend on the ability to maintain these activities over a long time period.

Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries.

BACKGROUND: A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies. METHODS: A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries. RESULTS: A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold. CONCLUSIONS: While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.