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PurposeSepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis.MethodsWe searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed.ResultsOf the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17–31.8%, range 16–36.4%). In the ICU, 24.4% (95% CI 16.7–34.2%, range 10.3–42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3–59.3%, range 18.7–69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3–11.9, range 2–20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35–90.2, range 9.2–254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4–61.1%, range 30.1–64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies.ConclusionHA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients.

Strengthening governance is an essential strategy to tackling antimicrobial resistance (AMR) at all levels: global, national, regional, and local. To date, no systematic approach to governance of national action plans on AMR exists. To address this issue, we aimed to develop the first governance framework to offer guidance for both the development and assessment of national action plans on AMR. We reviewed health system governance framework reviews to inform the basic structure of our framework, international guidance documents from WHO, the Food and Agriculture Organization, the World Organisation for Animal Health, and the European Commission, and sought the input of 25 experts from international organisations, government ministries, policy institutes, and academic institutions to develop and refine our framework. The framework consists of 18 domains with 52 indicators that are contained within three governance areas: policy design, implementation tools, and monitoring and evaluation. To consider the dynamic nature of AMR, the framework is conceptualised as a cyclical process, which is responsive to the context and allows for continuous improvement and adaptation of national action plans on AMR.

BackgroundNeonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide.MethodsWe performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979–May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level.ResultsThe search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009–2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias.ConclusionNeonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.

Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009-2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. We estimated the EU/EEA burden of HAIs in DALYs in 2011-2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.

Background The co-occurrence of two or more medical conditions in the same individual is not uncommon. If disability-adjusted life year (DALY) calculations are carried out for each condition separately, multimorbidity may lead to an overestimation of the morbidity component, the Years Lived with Disability (YLD). Adjusting for comorbidity may be straightforward if all symptoms have same onset and duration; however, when the comorbid health states occur at different time points, an analytical solution to the comorbidity problem becomes more complex. The aim of this study was to develop an individual-based modelling (IBM) approach to adjust incidence-based disease burden estimation for multimorbidity that allows simulating hypothetical individuals and tracking their disease history, including possible comorbidities, over time. Methods We demonstrated the IBM approach using an example of external comorbidity, i.e., colon cancer comorbid with healthcare-associated pneumonia (HAP) and by assuming an independent multiplicative model. First, each cumulative progression probabilities were converted to a daily transition probabilities. Second, disability weights for simultaneously experienced health states and duration in each health state were determined. Third, YLD, adjusted for comorbidity, was calculated at every time step. We simulated a cohort of 1000 colorectal cancer patients aged 65 years. Ninety-five percent uncertainty intervals around median YLD values were estimated by Monte Carlo methods. Results The median estimated YLD per 1000 cases (due to both cancer and HAP) adjusted for co-morbidity was 545 YLD/1000 (95% interval: 513–585). The impact of not adjusting disability weights for co-existent health states varied from minimal to small; YLD for colorectal cancer would be overestimated only slightly – by 1.6 YLD/1000 – by not adjusting for concurrent HAP. YLD for those HAP patients who have concurrent early-stage colorectal cancer would be overestimated by 2.3 YLD/1000. Conclusions The computation of disease burden in the presence of multimorbidity using the incidence-based DALY approach can be handled through IBM. Our approach can be extended to other, more complicated multimorbidity scenarios which are responsible for a high current global disease burden, such as tuberculosis and HIV infection.

SummaryThe high clinical burden of antimicrobial resistance (AMR) and the dwindling antibiotic pipeline demand standardised tools to monitor resistance development to new antibiotics. The Emerging Resistance Index (ERI) is a novel quantitative tool designed to track resistance to newly developed antibiotics. The ERI incorporates various parameters: AMR pooled proportions and trends, availability of AMR and antimicrobial consumption surveillance systems, time lag between antibiotic approval and resistance detection, and the average annual number of outbreaks caused by resistant strains. AMR and antimicrobial consumption data on 13 new antibiotics were extracted by reviewing the literature and the reports from 38 surveillance systems included in the European Clinical Research Alliance on Infectious Diseases–The Epidemiology Network central data repository, encompassing 27 EU countries, four European Free Trade Association countries, and the UK. Our analysis revealed rapid resistance development to all new Gram-negative-targeting antibiotics, with particularly high ERI values for imipenem–relebactam and cefiderocol. Combinations of old β-lactams with novel inhibitors were especially prone to rapid resistance development. The ERI could offer a quantitative and dynamic tool for monitoring resistance trends. Also, the ERI could support more timely surveillance efforts, inform antibiotic policy decisions, and aid in prioritising antibiotic research and development.

IntroductionTo accelerate the response to the public health threat by antimicrobial resistance (AMR), the WHO is developing a Global Research Agenda for AMR in the human health sector that aims to provide a global and transparent assessment of priority knowledge gaps related to critical bacteria—including Mycobacterium tuberculosis—and fungi that inform control and response strategies to tackle AMR by 2030. A literature scoping review represents the first phase in a stepwise process, and we hereby outline the protocol to review current knowledge gaps and research questions on AMR in the human health sector.Methods and analysisThis literature scoping review will follow the Arksey and O’Malley (2005) methodology and will include: (1) a hand search to identify relevant WHO guidelines and documents suggested by the WHO Steering Group for the AMR Global Research Agenda; (2) a grey literature search through a stakeholder mapping process and google searches of organisational websites; (3) a systematic search of relevant systematic reviews through bibliographic databases (PubMed, Embase and Web of Science); (4) screening of the reference lists of included studies. We will include relevant publications from the last 10 years (January 2012 to December 2021). Two researchers separately will review the yielded citations to determine eligibility based on predefined criteria. Relevant research questions with attributes will be extracted using a tool developed through an iterative process by the research team. Each identified research question will be classified and aggregated according to a conceptual framework (ie, ‘knowledge matrix’), composed of three themes (ie, Prevention, Diagnosis and Care & Treatment) and four cross-cutting domains (ie, Descriptive, Discovery, Development, Delivery). We will present numerical and thematic summaries of the knowledge matrix. A qualitative content analysis is out of the scope of this protocol.Ethics and disseminationThe scoping review process will only involve identification, selection and analysis of documents available for use in the public domain, and will not include any personal information on individuals, therefore ethical approval is not required. The findings will be disseminated through a peer-reviewed publication and stakeholder meetings.

Background In calculations of burden of disease using disability-adjusted life years, disability weights are needed to quantify health losses relating to non-fatal outcomes, expressed as years lived with disability. In 2012 a new set of global disability weights was published for the Global Burden of Disease 2010 (GBD 2010) study. That study suggested that comparative assessments of different health outcomes are broadly similar across settings, but the significance of this conclusion has been debated. The aim of the present study was to estimate disability weights for Europe for a set of 255 health states, including 43 new health states, by replicating the GBD 2010 Disability Weights Measurement study among representative population samples from four European countries. Methods For the assessment of disability weights for Europe we applied the GBD 2010 disability weights measurement approach in web-based sample surveys in Hungary, Italy, Netherlands, and Sweden. The survey included paired comparisons (PC) and population health equivalence questions (PHE) formulated as discrete choices. Probit regression analysis was used to estimate cardinal values from PC responses. To locate results onto the 0-to-1 disability weight scale, we assessed the feasibility of using the GBD 2010 scaling approach based on PHE questions, as well as an alternative approach using non-parametric regression. Results In total, 30,660 respondents participated in the survey. Comparison of the probit regression results from the PC responses for each country indicated high linear correlations between countries. The PHE data had high levels of measurement error in these general population samples, which compromises the ability to infer ratio-scaled values from discrete choice responses. Using the non-parametric regression approach as an alternative rescaling procedure, the set of disability weights were bounded by distance vision mild impairment and anemia with the lowest weight (0.004) and severe multiple sclerosis with the highest weight (0.677). Conclusions PC assessments of health outcomes in this study resulted in estimates that were highly correlated across four European countries. Assessment of the feasibility of rescaling based on a discrete choice formulation of the PHE question indicated that this approach may not be suitable for use in a web-based survey of the general population.

Despite under-reporting, health workers (HWs) accounted for 2 to 30% of the reported COVID-19 cases worldwide. In line with data from other countries, Jordan recorded multiple case surges among HWs. Based on the standardized WHO UNITY case-control study protocol on assessing risk factors for SARS-CoV-2 infection in HWs, HWs with confirmed COVID-19 were recruited as cases from eight hospitals in Jordan. HWs exposed to COVID-19 patients in the same setting but without infection were recruited as controls. The study lasted approximately two months (from early January to early March 2021). Regression models were used to analyse exposure risk factors for SARS-CoV-2 infection in HWs; conditional logistic regressions were utilized to estimate odds ratios (ORs) adjusted for the confounding variables. A total of 358 (102 cases and 256 controls) participants were included in the analysis. The multivariate analysis showed that being exposed to COVID-19 patients within 1 metre for more than 15 minutes increased three-fold the odds of infection (OR 2.92, 95% CI 1.25-6.86). Following IPC standard precautions when in contact with patients was a significant protective factor. The multivariate analysis showed that suboptimal adherence to hand hygiene increased the odds of infection by three times (OR 3.18; 95% CI 1.25-8.08). Study findings confirmed the role of hand hygiene as one of the most cost-effective measures to combat the spreading of viral infections. Future studies based on the same protocol will enable additional interpretations and confirmation of the Jordan experience.

The burden of disease framework facilitates the assessment of the health impact of diseases through the use of summary measures of population health such as Disability-Adjusted Life Years (DALYs). However, calculating, interpreting and communicating the results of studies using this methodology poses a challenge. The aim of the Burden of Communicable Disease in Europe (BCoDE) project is to summarize the impact of communicable disease in the European Union and European Economic Area Member States (EU/EEA MS). To meet this goal, a user-friendly software tool (BCoDE toolkit), was developed. This stand-alone application, written in C++, is open-access and freely available for download from the website of the European Centre for Disease Prevention and Control (ECDC). With the BCoDE toolkit, one can calculate DALYs by simply entering the age group- and sex-specific number of cases for one or more of selected sets of 32 communicable diseases (CDs) and 6 healthcare associated infections (HAIs). Disease progression models (i.e., outcome trees) for these communicable diseases were created following a thorough literature review of their disease progression pathway. The BCoDE toolkit runs Monte Carlo simulations of the input parameters and provides disease-specific results, including 95% uncertainty intervals, and permits comparisons between the different disease models entered. Results can be displayed as mean and median overall DALYs, DALYs per 100,000 population, and DALYs related to mortality vs. disability. Visualization options summarize complex epidemiological data, with the goal of improving communication and knowledge transfer for decision-making.