Total hip arthroplasty performed in summer is not associated with increased risk of revision due to prosthetic joint infection: a cohort study on 58 449 patients with osteoarthritis from the Danish Hip Arthroplasty Register.

Aims: Danish surveillance data indicated a higher risk of revision due to prosthetic joint infection (PJI) following total hip arthroplasty (THA) performed during the summer season. We investigated the association between summer and revision risk following primary THA. Methods: This study identified 58 449 patients from the Danish Hip Arthroplasty Register (DHR) with unilateral primary THA due to osteoarthritis from 2010-2018. From Danish Health Registries, we retrieved information on Charlson Comorbidity Index (CCI), immigration, and death and microbiological data on intraoperative biopsies and cohabitation status. Meteorological data were received from the Danish Meteorological Institute. Summer was defined as June-September, and THAs performed during October-May were used as controls. The primary outcome was revision due to PJI: the composite of revision with ≥2 culture-positive biopsies or reported PJI to the DHR. The secondary outcome was any revision. The cumulative incidences of revision and the corresponding adjusted relative risk (RR) with 95 % confidence intervals (CI) were calculated by season of the primary THA. Results: A total of 1507 patients were revised, and 536 were due to PJI. The cumulative incidence for THAs performed during summer and the rest of the year was 1.1 % (CI 1.0-1.3) and 1.1 % (CI 1.0-1.2) for PJI revision and 2.7 % (CI 2.5-3.0) and 2.5 % (CI 2.4-2.7) for any revision, respectively. The adjusted RR for THAs performed during summer vs. the rest of the year for PJI revision and any revision was 1.1 (CI 0.9-1.3) and 1.1 (CI 1.0-1.2), respectively. Conclusion: We found no association between summer and the risk of PJI revision or any revision in a northern European climate.

No Association Between Previous General Infection and Prosthetic Joint Infection After Total Hip Arthroplasty-A National Register-Based Cohort Study on 58,449 Patients Who Have Osteoarthritis.

BACKGROUND: Prosthetic joint infection (PJI) following total hip arthroplasty (THA) is a complication associated with increased risk of death. There is limited knowledge about the association between infection before THA, and risk of revision due to PJI. We investigated the association between any previous hospital-diagnosed or community-treated infection 0 to 6 months before primary THA and the risk of revision. METHODS: We obtained data on 58,449 patients who were operated with primary unilateral THA between 2010 and 2018 from the Danish Hip Arthroplasty Register. Information on previous infection diagnoses, redeemed antibiotic prescriptions up to 1 year before primary THA, intraoperative biopsies, and cohabitations was retrieved from Danish health registers. All patients had a 1-year follow-up. Primary outcome was revision due to PJI. Secondary outcome was any revision. We calculated the adjusted relative risk with 95% confidence intervals (CI), treating death as competing risk. RESULTS: Among 1,507 revisions identified, 536 were due to PJI with a cumulative incidence of 1.0% ([CI] 0.9 to 1.2) and 0.9% ([CI] 0.8 to 1.0) for patients who did and did not have previous infection. For any revision, the cumulative incidence was 3.1% ([CI] 2.9 to 3.4) and 2.4% ([CI] 2.3 to 2.6) for patients who did and did not have previous infection. The adjusted relative risk for PJI revision was 1.1 ([CI] 0.9 to 1.4) and for any revision 1.3 ([CI] 1.1 to 1.4) for patients who did have previous infection compared to those who did not. CONCLUSION: Previous hospital-diagnosed or community-treated infection 0 to 6 months before primary THA does not increase the risk of PJI revision. It may be associated with increased risk of any revision.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

Observed protection against SARS-CoV-2 reinfection following a primary infection: A Danish cohort study among unvaccinated using two years of nationwide PCR-test data.

Background: The level of protection after a SARS-CoV-2 infection against reinfection and COVID-19 disease remains important with much of the world still unvaccinated. Methods: Analysing nationwide, individually referable, Danish register data including RT-PCR-test results, we conducted a cohort study using Cox regression to compare SARS-CoV-2 infection rates before and after a primary infection among still unvaccinated individuals, adjusting for sex, age, comorbidity and residency region. Estimates of protection against infection were calculated as 1 minus the hazard ratio. Estimates of protection against symptomatic infections and infections leading to hospitalisation were also calculated. The prevalence of infections classified as symptomatic or asymptomatic was compared for primary infections and reinfections. The study also assessed protection against each of the main viral variants after a primary infection with an earlier variant by restricting follow-up time to distinct, mutually exclusive periods during which each variant dominated. Findings: Until 1 July 2021 the estimated protection against reinfection was 83.4% (95%CI: 82.2-84.6%); but lower for the 65+ year-olds (72.2%; 95%CI: 53.2-81.0%). Moderately higher estimates were found for protection against symptomatic disease, 88.3% overall (95%CI: 85.9-90.3%). First-time cases who reported no symptoms were more likely to experience a reinfection (odds ratio: 1.48; 95%CI: 1.35-1.62). By autumn 2021, when infections were almost exclusively caused by the Delta variant, the estimated protection following a recent first infection was 91.3% (95%CI: 89.7-92.7%) compared to 71.4% (95%CI: 66.9-75.3%) after a first infection over a year earlier. With Omicron, a first infection with an earlier variant in the past 3-6 months gave an estimated 51.0% (95%CI: 50.1-52.0%) protection, whereas a first infection longer than 12 months earlier provided only 19.0% (95%CI: 17.2-20.5%) protection. Protection by an earlier variant-infection against hospitalisation due to a new infection was estimated at: 86.6% (95%CI: 46.3-96.7%) for Alpha, 97.2% (95%CI: 89.0-99.3%) for Delta, and 69.8% (95%CI: 51.5-81.2%) for the Omicron variant. Interpretation: SARS-CoV-2 infection offered a high level of sustained protection against reinfection, comparable with that offered by vaccines, but decreased with the introduction of new main virus variants; dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections. The level of estimated protection against serious disease was somewhat higher than that against infection and possibly longer lasting. Decreases in protection against reinfection, seemed primarily to be driven by viral evolution. Funding: None.

Increased transmission of SARS-CoV-2 in Denmark during UEFA European championships.

Denmark hosted four games during the 2020 UEFA European championships (EC2020). After declining positive SARS-CoV-2 test rates in Denmark, a rise occurred during and after the tournament, concomitant with the replacement of the dominant Alpha lineage (B.1.1.7) by the Delta lineage (B.1.617.2), increasing vaccination rates and cessation of several restrictions. A cohort study including 33 227 cases was conducted from 30 May to 25 July 2021, 14 days before and after the EC2020. Included was a nested cohort with event information from big-screen events and matches at the Danish national stadium, Parken (DNSP) in Copenhagen, held from 12 June to 28 June 2021. Information from whole-genome sequencing, contact tracing and Danish registries was collected. Case-case connections were used to establish transmission trees. Cases infected on match days were compared to cases not infected on match days as a reference. The crude incidence rate ratio (IRR) of transmissions was 1.55, corresponding to 584 (1.76%) cases attributable to EC2020 celebrations. The IRR adjusted for covariates was lower (IRR 1.41) but still significant, and also pointed to a reduced number of transmissions from fully vaccinated cases (IRR 0.59). These data support the hypothesis that the EC2020 celebrations contributed to the rise of cases in Denmark in the early summer of 2021.

Information technology aspects of large-scale implementation of automated surveillance of healthcare-associated infections.

INTRODUCTION: Healthcare-associated infections (HAI) are a major public health concern. Monitoring of HAI rates, with feedback, is a core component of infection prevention and control programmes. Digitalization of healthcare data has created novel opportunities for automating the HAI surveillance process to varying degrees. However, methods are not standardized and vary widely between different healthcare facilities. Most current automated surveillance (AS) systems have been confined to local settings, and practical guidance on how to implement large-scale AS is needed. METHODS: This document was written by a task force formed in March 2019 within the PRAISE network (Providing a Roadmap for Automated Infection Surveillance in Europe), gathering experts in HAI surveillance from ten European countries. RESULTS: The document provides an overview of the key e-health aspects of implementing an AS system of HAI in a clinical environment to support both the infection prevention and control team and information technology (IT) departments. The focus is on understanding the basic principles of storage and structure of healthcare data, as well as the general organization of IT infrastructure in surveillance networks and participating healthcare facilities. The fundamentals of data standardization, interoperability and algorithms in relation to HAI surveillance are covered. Finally, technical aspects and practical examples of accessing, storing and sharing healthcare data within a HAI surveillance network, as well as maintenance and quality control of such a system, are discussed. CONCLUSIONS: With the guidance given in this document, along with the PRAISE roadmap and governance documents, readers will find comprehensive support to implement large-scale AS in a surveillance network.

Governance aspects of large-scale implementation of automated surveillance of healthcare-associated infections.

OBJECTIVES: Surveillance of healthcare-associated infections (HAI) is increasingly automated by applying algorithms to routine-care data stored in electronic health records. Hitherto, initiatives have mainly been confined to single healthcare facilities and research settings, leading to heterogeneity in design. The PRAISE network - Providing a Roadmap for Automated Infection Surveillance in Europe - designed a roadmap to provide guidance on how to move automated surveillance (AS) from the research setting to large-scale implementation. Supplementary to this roadmap, we here discuss the governance aspects of automated HAI surveillance within networks, aiming to support both the coordinating centres and participating healthcare facilities as they set up governance structures and to enhance involvement of legal specialists. METHODS: This article is based on PRAISE network discussions during two workshops. A taskforce was installed that further elaborated governance aspects for AS networks by reviewing documents and websites, consulting experts and organizing teleconferences. Finally, the article has been reviewed by an independent panel of international experts. RESULTS: Strict governance is indispensable in surveillance networks, especially when manual decisions are replaced by algorithms and electronically stored routine-care data are reused for the purpose of surveillance. For endorsement of AS networks, governance aspects specifically related to AS networks need to be addressed. Key considerations include enabling participation and inclusion, trust in the collection, use and quality of data (including data protection), accountability and transparency. CONCLUSIONS: This article on governance aspects can be used by coordinating centres and healthcare facilities participating in an AS network as a starting point to set up governance structures. Involvement of main stakeholders and legal specialists early in the development of an AS network is important for endorsement, inclusivity and compliance with the laws and regulations that apply.

PRAISE: providing a roadmap for automated infection surveillance in Europe.

INTRODUCTION: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. METHODS: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. RESULTS: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. CONCLUSIONS: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists.

Risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark: an observational cohort study.

BACKGROUND: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. METHODS: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. FINDINGS: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72-0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25-1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period-the two covariates with the largest contribution to confounding of the crude RR. INTERPRETATION: Infection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7. FUNDING: None.

Electronic reporting of diagnostic laboratory test results from all healthcare sectors is a cornerstone of national preparedness and control of COVID-19 in Denmark.

The COVID-19 pandemic has led to an unprecedented demand for real-time surveillance data in order to inform critical decision makers regarding the management of the pandemic. The aim of this review was to describe how the Danish national microbiology database, MiBa, served as a cornerstone for providing data to the real-time surveillance system by linkage to other nationwide health registries. The surveillance system was established on an existing IT health infrastructure and a close network between clinical microbiologists, information technology experts, and public health officials. In 2020, testing capacity for SARS-CoV-2 was ramped up from none to over 10,000 weekly PCR tests per 100,000 population. The crude incidence data mirrored this increase in testing. Real-time access to denominator data and patient registries enabled adjustments for fluctuations testing activity, providing robust data on crude SARS-CoV-2 incidence during the changing diagnostic and management strategies. The use of the same data for different purposes, for example, final laboratory reports, information to the public, contact tracing, public health, and science, has been a critical asset for the pandemic response. It has also raised issues concerning data protection and critical capacity of the underlying technical systems and key resources. However, even with these limitations, the setup has enabled decision makers to adopt timely interventions. The experiences from COVID-19 may motivate a transformation from traditional indicator-based public health surveillance to an all-encompassing information system based on access to a comprehensive set of data sources, including diagnostic and reference microbiology.

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study.

BACKGROUND: The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. METHODS: In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 - RR. FINDINGS: During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51-0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22-3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155-0·246]). Protection against repeat infection was 80·5% (95% CI 75·4-84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179-0·251], estimated protection 78·8% [74·9-82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7-62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1-83·2] vs female 79·1% [73·9-83·3]) or evidence of waning protection over time (3-6 months of follow-up 79·3% [74·4-83·3] vs ≥7 months of follow-up 77·7% [70·9-82·9]). INTERPRETATION: Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on. FUNDING: None.

Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: a nationwide cohort.

BACKGROUND: Population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) is urgently needed to inform targeted protection strategies in the general population. METHODS: We examined characteristics and predictors of hospitalization and death in a nationwide cohort of all Danish individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 27 February 2020 until 19 May 2020. RESULTS: We identified 11 122 SARS-CoV-2 polymerase chain reaction-positive cases of whom 80% were community-managed and 20% were hospitalized. Thirty-day all-cause mortality was 5.2%. Age was strongly associated with fatal disease {odds ratio [OR] 15 [95% confidence interval (CI): 9-26] for 70-79 years, increasing to OR 90 (95% CI: 50-162) for ≥90 years, when compared with cases aged 50-59 years and adjusted for sex and number of co-morbidities}. Similarly, the number of co-morbidities was associated with fatal disease [OR 5.2 (95% CI: 3.4-8.0), for cases with at least four co-morbidities vs no co-morbidities] and 79% of fatal cases had at least two co-morbidities. Most major chronic diseases were associated with hospitalization, with ORs ranging from 1.3-1.4 (e.g. stroke, ischaemic heart disease) to 2.6-3.4 (e.g. heart failure, hospital-diagnosed kidney disease, organ transplantation) and with mortality with ORs ranging from 1.1-1.3 (e.g. ischaemic heart disease, hypertension) to 2.5-3.2 (e.g. major psychiatric disorder, organ transplantation). In the absence of co-morbidities, mortality was <5% in persons aged ≤80 years. CONCLUSIONS: In this nationwide population-based COVID-19 study, increasing age and multimorbidity were strongly associated with hospitalization and death. In the absence of co-morbidities, the mortality was, however, <5% until the age of 80 years.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

National Automated Surveillance of Hospital-Acquired Bacteremia in Denmark Using a Computer Algorithm.

BACKGROUND In 2015, Denmark launched an automated surveillance system for hospital-acquired infections, the Hospital-Acquired Infections Database (HAIBA). OBJECTIVE To describe the algorithm used in HAIBA, to determine its concordance with point prevalence surveys (PPSs), and to present trends for hospital-acquired bacteremia SETTING Private and public hospitals in Denmark METHODS A hospital-acquired bacteremia case was defined as at least 1 positive blood culture with at least 1 pathogen (bacterium or fungus) taken between 48 hours after admission and 48 hours after discharge, using the Danish Microbiology Database and the Danish National Patient Registry. PPSs performed in 2012 and 2013 were used for comparison. RESULTS National trends showed an increase in HA bacteremia cases between 2010 and 2014. Incidence was higher for men than women (9.6 vs 5.4 per 10,000 risk days) and was highest for those aged 61-80 years (9.5 per 10,000 risk days). The median daily prevalence was 3.1% (range, 2.1%-4.7%). Regional incidence varied from 6.1 to 8.1 per 10,000 risk days. The microorganisms identified were typical for HA bacteremia. Comparison of HAIBA with PPS showed a sensitivity of 36% and a specificity of 99%. HAIBA was less sensitive for patients in hematology departments and intensive care units. Excluding these departments improved the sensitivity of HAIBA to 44%. CONCLUSIONS Although the estimated sensitivity of HAIBA compared with PPS is low, a PPS is not a gold standard. Given the many advantages of automated surveillance, HAIBA allows monitoring of HA bacteremia across the healthcare system, supports prioritizing preventive measures, and holds promise for evaluating interventions. Infect Control Hosp Epidemiol 2017;38:559-566.

The development and use of a new methodology to reconstruct courses of admission and ambulatory care based on the Danish National Patient Registry.

INTRODUCTION: The Danish National Patient Registry (DNPR) contains clinical and administrative data on all patients treated in Danish hospitals. The data model used for reporting is based on standardized coding of contacts rather than courses of admissions and ambulatory care. METHODS: To reconstruct a coherent picture of courses of admission and ambulatory care, we designed an algorithm with 28 rules that manages transfers between departments, between hospitals and inconsistencies in the data, e.g., missing time stamps, overlaps and gaps. We used data from patients admitted between 1 January 2010 and 31 December 2014. RESULTS: After application of the DNPR algorithm, we estimated an average of 1,149,616 courses of admission per year or 205 hospitalizations per 1000 inhabitants per year. The median length of stay decreased from 1.58days in 2010 to 1.29days in 2014. The number of transfers between departments within a hospital increased from 111,576 to 176,134 while the number of transfers between hospitals decreased from 68,522 to 61,203. CONCLUSIONS: We standardized a 28-rule algorithm to relate registrations in the DNPR to each other in a coherent way. With the algorithm, we estimated 1.15 million courses of admissions per year, which probably reflects a more accurate estimate than the estimates that have been published previously. Courses of admission became shorter between 2010 and 2014 and outpatient contacts longer. These figures are compatible with a cost-conscious secondary healthcare system undertaking specialized treatment within a hospital and limiting referral to advanced services at other hospitals.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

Respiratory virology and microbiology in intensive care units: a prospective cohort study.

Our aim was to determine the frequency of 12 common respiratory viruses in patients admitted to intensive care units with respiratory symptoms, evaluate the clinical characteristics and to compare the results to routine microbiological diagnostics. Throat swabs from 122 intensive care-patients >18 years with acute respiratory symptoms were collected upon admission and analysed with multiplex real-time polymerase chain reaction, for 12 community respiratory viruses. Blood and respiratory tract specimens were analysed for bacteria and fungi upon clinicians' request. Clinical and paraclinical data were collected. Viruses were detected in 19 (16%) of the 122 study patients. Five virus-positive patients (26%) had possible clinically relevant bacteria or fungi co-detected. Patients with exacerbation in COPD were associated with a viral infection (p = 0.02). Other comorbidities, clinical and paraclinical parameters, and death were independent of a viral infection or co-detection of bacteria/fungi. In conclusion, respiratory viruses were frequently detected in the patients. The investigated clinical and paraclinical parameters were not different in viral infections compared to other agents, thus respiratory viruses likely have similar impact on the clinical course as other agents. In 25% of the virus-positive patients, polymicrobial aetiology was identified. Comprehensive and sensitive diagnostic methods should be emphasized to enhance respiratory diagnostics.

A waterborne outbreak with a single clone of Campylobacter jejuni in the Danish town of Køge in May 2010.

BACKGROUND: In Denmark, large-scale waterborne outbreaks are rare. This report describes the investigation of an outbreak that occurred in the town of Køge in May 2010. METHODS: The epidemiological investigation consisted of hypothesis generating telephone interviews, followed by a cohort study among approximately 20,000 residents using an online questionnaire. Odds ratios were calculated for exposures including the number of glasses of tap water consumed. Geographical spreading was assessed using a geographical information system. The microbiological investigation included cultures of stool samples and flagellin-typing. In the environmental investigation, water samples were tested for Escherichia coli and coliform counts and for DNA of Campylobacter, Enterococcus, and Bacteroides. During the outbreak investigation a water boiling order was enforced, as tap water was considered a potential source. RESULTS: Of 45 patients with laboratory confirmed Campylobacter infection in the municipality of Køge in May, 43 lived in the area covered by the central water supply. Of 61 patients with laboratory confirmed Campylobacter jejuni by 8 June, 50 shared a common flagellin gene type--flaA type 36 (82%). The epidemic curve from the cohort study showed a wave of diarrhoea onset from 14 to 20 May (n = 176). Among these patients, the development of diarrhoea was associated with drinking tap water with a dose-response pattern (linear increase by 2 glasses: odds ratio 1.40, 95% confidence interval 1.16-1.70). No bacterial DNA was found in water samples. CONCLUSIONS: These findings indicated a point source contamination of tap water with a single clone of C. jejuni which likely occurred on 12-13 May. The water boiling order was lifted on 18 June.

Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5-14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5-5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.