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During an interventional study in a nephrology department, we investigated the effect of an electronic hand hygiene monitoring system on the hand hygiene compliance of healthcare workers (N = 99) and hospital-acquired bloodstream infections. The hand hygiene compliance of the doctors and nurses improved significantly during the intervention phase when they received group and individual feedback based on actionable insights from the electronic hand hygiene monitoring system. The improvements in hand hygiene compliance were associated with a significant reduction in the number of hospital-acquired bloodstream infections., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: We hypothesized that the amount of antigen produced in the body during a COVID-19 infection might differ between patients, and that maximum concentrations would predict the degree of both inflammation and outcome for patients., Methods: Eighty-four hospitalized and SARS-CoV-2 PCR swab-positive patients, were followed with blood sampling every day until discharge or death. A total of 444 serial EDTA plasma samples were analyzed for a range of biomarkers: SARS-CoV-2 nuclear antigen and RNA concentration, complement activation as well as several inflammatory markers, and KL-6 as a lung marker. The patients were divided into outcome groups depending on need of respiratory support and death/survival., Results: Circulating SARS-CoV-2 nuclear antigen levels were above the detection limit in blood in 65 out of 84 COVID-19 PCR swab-positive patients on day one of hospitalization, as was viral RNA in plasma in 30 out of 84. In all patients, complete antigen clearance was observed within 24 days. There were definite statistically significant differences between the groups depending on their biomarkers, showing that the concentrations of virus RNA and antigen were correlated to the inflammatory biomarker levels, respiratory treatment and death., Conclusions: Viral antigen is cleared in parallel with the virus RNA levels. The levels of antigens and SARS-CoV-2 RNA in the blood correlates with the level of IL-6, inflammation, respiratory failure and death. We propose that the antigens levels together with RNA in blood can be used to predict the severity of disease, outcome, and the clearance of the virus from the body., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Stratification by clinical scores of patients suspected of infection can be used to support decisions on treatment and diagnostic workup. Seven clinical scores, SepsisFinder (SF), National Early Warning Score (NEWS), Sequential Orgen Failure Assessment (SOFA), Mortality in Emergency Department Sepsis (MEDS), quick SOFA (qSOFA), Shapiro Decision Rule (SDR) and Systemic Inflammatory Response Syndrome (SIRS), were evaluated for their ability to predict 30-day mortality and bacteraemia and for their ability to identify a low risk group, where blood culture may not be cost-effective and a high risk group where direct-from-blood PCR (dfbPCR) may be cost effective., Methods: Retrospective data from two Danish and an Israeli hospital with a total of 1816 patients were used to calculate the seven scores., Results: SF had higher Area Under the Receiver Operating curve than the clinical scores for prediction of mortality and bacteraemia, significantly so for MEDS, qSOFA and SIRS. For mortality predictions SF also had significantly higher area under the curve than SDR. In a low risk group identified by SF, consisting of 33% of the patients only 1.7% had bacteraemia and mortality was 4.2%, giving a cost of € 1976 for one positive result by blood culture. This was higher than the cost of € 502 of one positive dfbPCR from a high risk group consisting of 10% of the patients, where 25.3% had bacteraemia and mortality was 24.2%., Conclusion: This may motivate a health economic study of whether resources spent on low risk blood cultures might be better spent on high risk dfbPCR., (© 2021. The Author(s).)

As part of a national surveillance programme initiated in 2004, fungal blood isolates from 2016-2018 underwent species identification and EUCAST susceptibility testing. The epidemiology was described and compared to data from previous years. In 2016-2018, 1454 unique isolates were included. The fungaemia rate was 8.13/100,000 inhabitants compared to 8.64, 9.03, and 8.38 in 2004-2007, 2008-2011, and 2012-2015, respectively. Half of the cases (52.8%) involved patients 60-79 years old and the incidence was highest in males ≥70 years old. Candida albicans accounted for 42.1% of all isolates and Candida glabrata for 32.1%. C. albicans was more frequent in males ( p = 0.03) and C. glabrata in females ( p = 0.03). During the four periods, the proportion of C. albicans decreased ( p < 0.001), and C. glabrata increased ( p < 0.001). Consequently, fluconazole susceptibility gradually decreased from 68.5% to 59.0% ( p < 0.001). Acquired fluconazole resistance was found in 4.6% Candida isolates in 2016-2018. Acquired echinocandin resistance increased during the four periods 0.0%, 0.6%, 1.7% to 1.5% ( p < 0.0001). Sixteen echinocandin-resistant isolates from 2016-2018 harboured well-known FKS resistance-mutations and one echinocandin-resistant C. albicans had an FKS mutation outside the hotspot (P1354P/S) of unknown importance. In C. glabrata specifically, echinocandin resistance was detected in 12/460 (2.6%) in 2016-2018 whereas multidrug-class resistance was rare (1/460 isolates (0.2%)). Since the increase in incidence during 2004-2011, the incidence has stabilised. In contrast, the species distribution has changed gradually over the 15 years, with increased C. glabrata at the expense of C. albicans . The consequent decreased fluconazole susceptibility and the emergence of acquired echinocandin resistance complicates the management of fungaemia and calls for antifungal drug development.

This study presents a general model predictive control (MPC) algorithm for optimizing wastewater aeration in Water Resource Recovery Facilities (WRRF) under different management objectives. The flexibility of the MPC is demonstrated by controlling a WRRF under four management objectives, aiming at minimizing: (A) effluent concentrations, (B) electricity consumption, (C) total operations costs (sum electricity costs and discharge effluent tax) or (D) global warming potential (direct and indirect nitrous oxide emissions, and indirect from electricity production) . The MPC is tested with data from the alternating WRRF in Nørre Snede (Denmark) and from the Danish electricity grid. Results showed how the four control objectives resulted in important differences in aeration patterns and in the concentration dynamics over a day. Controls B and C showed similarities when looking at total costs, while similarities in global warming potential for controls A and D suggest that improving effluent quality also reduced greenhouse gasses emissions. The MPC flexibility in handling different objectives is shown by using a combined objective function, optimizing both cost and greenhouse emissions. This shows the trade-off between the two objectives, enabling the calculation of marginal costs and thus allowing WRRF operators to carefully evaluate prioritization of management objectives. The long-term MPC performance is evaluated over 51 days covering seasonal and inter-weekly variations. On a daily basis, control A was 9-30% cheaper on average compared to controls A, D and to the current rule-based control. Similarly, control D resulted on average in 35-43% lower greenhouse gasses daily emission compared to the other controls. Difference between control performance increased for days with greater inter-diurnal variations in electricity price or greenhouse emissions from electricity production, i.e. when MPC has greater possibilities for exploiting input variations. The flexibility of the proposed MPC can easily accommodate for additional control objectives, allowing WRRF operators to quickly adapt the plant operation to new management objectives and to face new performance requirements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Healthcare associated infections (HAI) are a major burden for the healthcare system and associated with prolonged hospital stay, increased morbidity, mortality and costs. Healthcare associated urinary tract infections (HA-UTI) accounts for about 20-30% of all HAI's, and with the emergence of multi-resistant urinary tract pathogens, the total burden of HA-UTI will most likely increase., Objective: The aim of the current study was to develop two predictive models, using data from the index admission as well as historic data on a patient, to predict the development of UTI at the time of entry to the hospital and after 48 hours of admission (HA-UTI). The ultimate goal is to predict the individual patient risk of acquiring HA-UTI before it occurs so that health care professionals may take proper actions to prevent it., Methods: Retrospective cohort analysis of approx. 300 000 adult admissions in a Danish region was performed. We developed models for UTI prediction with five machine-learning algorithms using demographic information, laboratory results, data on antibiotic treatment, past medical history (ICD10 codes), and clinical data by transformation of unstructured narrative text in Electronic Medical Records to structured data by Natural Language Processing., Results: The five machine-learning algorithms have been evaluated by the performance measures average squared error, cumulative lift, and area under the curve (ROC-index). The algorithms had an area under the curve (ROC-index) ranging from 0.82 to 0.84 for the entry model (T = 0 hours after admission) and from 0.71 to 0.77 for the HA-UTI model (T = 48 hours after admission)., Conclusion: The study is proof of concept that it is possible to create machine-learning models that can serve as early warning systems to predict patients at risk of acquiring urinary tract infections during admission. The entry model and the HA-UTI models perform with a high ROC-index indicating a sufficient sensitivity and specificity, which may make both models instrumental in individualized prevention of UTI in hospitalized patients. The favored machine-learning methodology is Decision Trees to ensure the most transparent results and to increase clinical understanding and implementation of the models., Competing Interests: The authors have declared that no competing interests exist.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate., Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort., Design, Setting, and Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020., Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi., Main Outcomes and Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort., Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort., Conclusions and Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.

Background: Most cancer treatments today take place in outpatient clinics; however, it might be necessary for some patients to be admitted to hospital departments due to severe side effects or complications. In such situations, support from family and social relations can be crucial for the patients' emotional well-being. Many young adolescents and children whose parents have cancer describe how they are not seen, heard, or listened to as the worried relatives they are. Within the intensive care unit, it has been recommended that early supportive interventions are tailored to include children of the intensive care patient; a similar approach might be relevant in the oncological setting. To our knowledge, no studies have explored how to involve young relatives who are visiting their parent at an oncological department. Recently, a framework for developing theory-driven, evidence-based serious games for health has been suggested. Such a process would include stakeholders from various disciplines, who only work toward one specific solution. However, it is possible that bringing together different disciplines, such as design, art, and health care, would allow a broader perspective, resulting in improved solutions., Objective: This study aims to develop tools to enhance the social interaction between a parent with cancer and their child when the child visits the parent in the hospital., Methods: In total, 4 groups of design students within the Visual Design program were tasked with developing games addressing the objective of strengthening relations in situ during treatment. To support their work, the applied methods included professional lectures, user studies, and visual communication (phase I); interviews with the relevant clinicians at the hospital (phase II), co-creative workshops with feedback (phase III), and evaluation sessions with selected populations (phase IV). The activities in the 4 phases were predefined. This modified user design had the child (aged 4-18 years) of a parent with cancer as its primary user., Results: Overall, 4 different games were designed based on the same information. All games had the ability to make adults with cancer and their children interact on a common electronic platform with a joint goal. However, the interaction, theme, and graphical expression differed between the games, suggesting that this is a wide and fertile field to explore., Conclusions: Playing a game can be an efficient way to create social interaction between a parent with cancer and a child or an adolescent, potentially improving the difficult social and psychological relations between them. The study showed that the development of serious games can be highly dependent on the designers involved and the processes used. This must be considered when a hospital aims to develop multiple games for different purposes., (©Karin Piil, Helle Holm Gyldenvang, Jeppe Kilberg Møller, Tine Kjoelsen, Jesper Juul, Helle Pappot. Originally published in JMIR Serious Games (http://games.jmir.org), 21.01.2021.)

Lyme neuroborreliosis (LNB) has recently been added to the list of diseases under the European Union epidemiological surveillance in order to obtain updated information on incidence. The goal of this study was to identify temporal (yearly) variation, high risk geographical regions and risk groups, and seasonal variation for LNB in Denmark. This cohort-study investigated Danish patients (n = 2791) diagnosed with LNB (defined as a positive Borrelia burgdorferi sensu lato (s.l.) intrathecal antibody test) between 1996-2015. We calculated incidence and incidence ratios of LNB by comparing 4-yr groups of calendar-years, area of residency, sex and age, income and education groups, and the number of new LNB cases per month. The incidence of LNB was 2.2 per 100,000 individuals and year in 1996-1999, 2.7 in 2004-2007 and 1.1 per 100,000 individuals in 2012-2015. Yearly variations in LNB incidence were similar for most calendar-year groups. LNB incidence was highest in Eastern Denmark and among males and individuals who were 0-14 yrs old, who had a yearly income of >449,000 DKK, and who had a Master's degree or higher education. The number of LNB cases was highest from July to November (p < 0.001). In conclusion, based on Danish nationwide data of patients with positive B. burgdorferi s.l. intrathecal antibody index (1996-2015) the incidence of LNB was found to increase until 2004-2007 but thereafter to decline. European surveillance studies of Lyme borreliosis should be encouraged to monitor the incidence trend., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction: This study investigated the feasibility of a risk-based screening approach combined with testing of Group B streptococcus (GBS) by polymerase chain reaction (PCR), the effect on use of intrapartum antibiotic prophylaxis (IAP) and the impact on the incidence of early-onset GBS infection (EOGBS)., Methods: During one year, 551 women giving birth at Lillebaelt Hospital, Denmark, having one or more risk factors for EOGBS (previous birth of infant with EOGBS, GBS bacteriuria during current pregnancy, gestational age less than 37 weeks, rupture of membranes greater than 18 hours, and temperature ≥ 38 °C) were tested by a GBS PCR assay intrapartum. IAP was administered when the woman tested positive., Results: Among 2,889 women in labour, 19.1% (n = 551) had one or more risk factors for EOGBS, and 5.1% (n = 146) had both risk factors for EOGBS and a positive intrapartum GBS PCR test. In total, 185 women with risk factors for EOGBS received IAP. If the former risk-based approach had been applied, 551 women giving birth would have received IAP. Implementing IAP based on the GBS PCR results produced a two-thirds reduction of IAP. No children were diagnosed with EOGBS., Conclusions: The GBS PCR assay was easy to perform and provided test results within 50 minutes. Implementation of risk-based screening combined with intrapartum GBS PCR testing reduces the use of IAP by two thirds compared with risk-based screening alone, thus minimising antibiotic resistance. The study material was too small to evaluate the effect on the incidence of EOGBS. Since EOGBS is a rare disease, more studies are required., Funding: The study was supported by Forskningsraadet Lillebaelt Hospital, Udviklingsraadet Lillebaelt Hospital, Johs. M. Klein og Hustrus Mindelegat, the Region of Southern Denmark, Farusa Emballage A/S., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

This study was designed to compare the performance of GeneXpert® and GenomEra® group B streptococcus (GBS) PCR assays, held up against standard culture of GBS performed with and without broth pre-enrichment. In Denmark, the strategy for preventing early onset GBS infection (EOGBS) is risk factor based. Three hundred and sixty six women fulfilling one or more of the criteria for presence of risk factors for EOGBS were prospectively included. Rectovaginal swab samples were taken intrapartum and tested bed-site by the GenomEra® and the GeneXpert® GBS PCR assays and cultured at the microbiology laboratory using Granada agar plates with and without prior growth of sampling material in selective enrichment broth. Among 366 participants tested intrapartum, 99 were GBS-positive by culture, 95 by GenomEra, and 95 by GeneXpert. Compared with culture, the GenomEra and the GeneXpert performed with a sensitivity of 91.8% and 91.7% and a specificity of 98.1% and 97.3%, respectively. A combined reference standard was established by defining true positives as either culture-positive samples or culture-negative samples where both the GeneXpert and the GenomEra GBS PCR assays were positive. Using this, the sensitivity increased to 92.2% and the specificity to 99.6% for GenomEra and to 92.0% and 96.8% for GeneXpert. The use of selective broth enrichment found only three additional GBS culture-positive samples. The performance of the two PCR methods examined was very similar and close to the findings by culture, and both PCR assays are thus applicable as rapid intrapartum bed-site tests.

Objective: To evaluate whether systematic antepartum screening for Group B Streptococci (GBS) by urine culture improves the risk factor-based selection of pregnant women for intrapartum GBS screening with a rapid polymerase chain reaction (PCR) assay., Methods: A prospective observational study was conducted between April 2013 and June 2014. GBS colonization judged by urine culture at 35-37 weeks of gestation was compared with the result of a vaginal GBS PCR test at labor as outcome. The results of urine culture were used as exposure variable. The PCR test was performed on intrapartum vaginal samples., Results: Screening for urine GBS in 902 unselected pregnant Danish women at 35-37 weeks of gestation predicted intrapartum PCR GBS status with a sensitivity of 33.6%. A positive predictive value of 41.2% was seen among women with low GBS counts (<104 CFU/mL) and 83.3% among women with high GBS counts (≥104 CFU/mL). Systematic GBS screening of urine at 35-37 weeks of gestation added 30.9% extra women for intrapartum GBS PCR screening in the study group., Conclusion: Systematic antepartum GBS screening of urine should be implemented in order to improve risk stratification for early onset GBS by offering laboring women an intrapartum GBS PCR test., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Lyme neuroborreliosis (LNB), caused by the tick-borne spirochetes of the Borrelia burgdorferi sensu lato species complex, has been suggested to be associated with a range of neurological disorders. In a nationwide, population-based cohort study, we examined the associations between LNB and dementia, Alzheimer's disease, Parkinson's disease, motor neuron disease, epilepsy, and Guillain-Barré syndrome., Methods: We used national registers to identify all Danish residents diagnosed during 1986-2016 with LNB (n = 2067), created a gender- and age-matched comparison cohort from the general population (n = 20 670), and calculated risk estimates and hazard ratios., Results: We observed no long-term increased risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, or epilepsy. However, within the first year, 8 (0.4%) of the LNB patients developed epilepsy, compared with 20 (0.1%) of the comparison cohort (difference, 0.3%; 95% confidence interval, .02-.6%). In the LNB group, 11 (0.5%) patients were diagnosed with Guillain-Barré syndrome within the first year after LNB diagnosis, compared with 0 (0.0%) in the comparison cohort. After the first year, the risk of Guillain-Barré was not increased., Conclusions: LNB patients did not have increased long-term risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, epilepsy, or Guillain-Barré. Although the absolute risk is low, LNB patients might have an increased short-term risk of epilepsy and Guillain-Barré syndrome., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Head and neck cancer survivors frequently experience nutritional challenges, and proper rehabilitation should be offered. The trial objective was to test the effect of a multidisciplinary residential nutritional rehabilitation programme addressing physical, psychological, and social aspects of eating problems after treatment. In a randomized controlled trial, 71 head and neck cancer survivors recruited through a nationwide survey were randomized to the program or a wait-list control group. Inclusion was based on self-reported interest in participation. The primary outcome was change in body weight. Secondary outcomes included physical function, quality of life, and symptoms of anxiety and depression. Differences between groups at the 3-month follow-up were tested. No significant differences were seen in body weight change, but there were overall trends towards greater improvements in physical function (hand grip strength: p = 0.042; maximal mouth opening: p = 0.072) and quality of life ("Role functioning": p = 0.041; "Speech problems": p = 0.040; "Pain": p = 0.048) in the intervention group. To conclude, a multidisciplinary residential nutritional rehabilitation program had no effect on body weight in head and neck cancer survivors with self-reported interest in participation, but it may have effect on physical function and quality of life. Further research on relevant outcomes, inclusion criteria, and the program's effect in different subgroups is needed.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial, and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development., (© 2020 APMIS. Published by John Wiley & Sons Ltd.)

Background: Hand hygiene compliance (HHC) among health care workers remains suboptimal, and good monitoring systems are lacking. We aimed to evaluate HHC using an automated monitoring system., Methods: A prospective, observational study was conducted at 2 Danish university hospitals employing a new monitoring system (Sani nudge). Sensors were located on alcohol-based sanitizers, health care worker name tags, and patient beds measuring hand hygiene opportunities and sanitations., Results: In total, 42 nurses were included with an average HHC of 52% and 36% in hospitals A and B, respectively. HHC was lowest in patient rooms (hospital A: 45%; hospital B: 29%) and highest in staff toilets (hospital A: 72%; hospital B: 91%). Nurses sanitized after patient contact more often than before, and sanitizers located closest to room exits and in hallways were used most frequently. There was no association found between HHC level and the number of beds in patient rooms. The HHC level of each nurse was consistent over time, and showed a positive correlation between the number of sanitations and HHC levels (hospital A: r = 0.69; hospital B: r = 0.58)., Conclusions: The Sani nudge system can be used to monitor HHC at individual and group levels, which increases the understanding of compliance behavior., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML)., Methods: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days)., Results: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event., Conclusions: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Background: Eating problems frequently affect quality of life and physical, psychological and social function in patients treated for head and neck cancer (HNC). Residential rehabilitation programmes may ameliorate these adverse effects but are not indicated for all individuals. Systematic assessment of rehabilitation needs may optimise the use of resources while ensuring referral to rehabilitation for those in need. Yet, evidence lacks on which nutrition screening and assessment tools to use. The trial objectives are: 1) To test the effect of a multidisciplinary residential nutritional rehabilitation programme compared to standard care on the primary outcome body weight and secondary outcomes health-related quality of life, physical function and symptoms of anxiety and depression in patients curatively treated for HNC and 2) To test for correlations between participants' development in outcome scores during their participation in the programme and their baseline scores in Nutritional Risk Screening 2002 (NRS 2002), the Scored Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), and M. D. Anderson Dysphagia Inventory (MDADI) and to assess sensitivity, specificity and predictive values of the three tools in relation to a clinically relevant improvement in outcome scores., Methods: In a randomised controlled trial, 72 patients treated for HNC recruited through a nationwide survey will be randomised to a multidisciplinary residential nutritional rehabilitation programme or to a wait-list control group. Data are collected at baseline, three and six months. Primary outcome is change in body weight, and secondary outcomes include changes in quality of life, physical function and symptoms of anxiety and depression. Potential correlations between intervention effect and baseline scores in NRS 2002, PG-SGA-SF and MDADI will be tested, and sensitivity, specificity and predictive values of the three tools in relation to a clinically relevant improvement in outcome scores will be assessed., Discussion: This is the first randomised controlled trial to test the effect of a multidisciplinary residential nutritional rehabilitation programme in patients treated for HNC. Recruitment through a nationwide survey gives a unique possibility to describe the trial population and to identify potential selection bias. As the trial will explore the potential of different nutrition screening and assessment tools in the assessment of rehabilitation needs in patients treated for HNC, the trial will create knowledge about how selection and prioritisation of nutritional rehabilitation aimed at patients treated for HNC should be offered. The results may contribute to a better organisation and use of existing resources in benefit of patients treated for HNC., Trial Registration: The trial is registered by The Danish Data Protection Agency (registration 2012-58-0018, approval number 18/14847) and the Regional Committees on Health Research Ethics for Southern Denmark (journal number 20182000-165). ClinicalTrials.gov Identifier: NCT03909256. Registered April 9, 2019.

Purpose: Caregivers to cancer patients often experience information needs. This study investigates the associations between perceived information needs and anxiety/depressive symptoms among caregivers to cancer patients. Design: Cross-sectional study using self-completed questionnaires. Sample: A total of 128 caregivers to cancer patients who participated in a rehabilitation stay at REHPA, The Danish Knowledge Center for Rehabilitation and Palliative Care, from April 2016 to March 2017. Methods: The caregivers completed a questionnaire assessing both information needs and anxiety/depressive symptoms. We used ordinal logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between seven information needs and anxiety/depressive symptoms. The reference group was caregivers with no perceived information needs. Findings: The combined score of perceived information needs was associated with higher odds of anxiety (OR = 3.86 per unit increase, 95% CI 1.85-8.03) and depressive symptoms (OR = 3.83 per unit increase, 95% CI 1.15-12.75). For the individual items, our results showed higher odds of anxiety symptoms for caregivers with perceived information needs regarding (1) the disease and its course, for both little need for information (OR = 3.62, 95% CI 1.39-9.43) and substantial need for information (OR = 4.57, 95% CI 1.40-14.93); however, for substantial information needs, an interaction with gender was found showing higher odds for men (OR = 28.90, 95% CI 4.46-187.41), but no significant association for women. Also, substantial need for information regarding the disease and its course were associated with higher odds of depressive symptoms (OR = 11.43, 95% CI 1.18-111.21). Furthermore, we found higher odds of anxiety symptoms for caregivers who perceived information needs regarding (2) which symptoms and adverse effects to be aware of; (3) how to help and support a cancer patient; (4) expected mental responses in a person with cancer; (5) how to find information on the internet, and (6) where to direct caregiver questions and/or concerns after patient discharge. Conclusions: Among caregivers to cancer patients, perceived needs regarding the disease and its course were associated with higher odds of anxiety and depressive symptoms. Furthermore, several other information needs were associated with anxiety symptoms. Implications for Psychosocial Providers or Policy: To prevent unnecessary anxiety and depressive symptoms among cancer caregivers, health care professionals should be aware of the importance of informing caregivers regarding the disease and its course. Other issues to address concerning anxiety symptoms are information regarding which symptoms and adverse effects to be aware of; how to help and support a cancer patient; expected mental responses in a person with cancer; how to find information on the internet; and where to direct caregiver questions and/or concerns after patient discharge.

Introduction: In pregnant women, bacteriuria with group B streptococci (GBS) may be associated with a high degree of recto-vaginal GBS colonisation and therefore an increased risk of early-onset GBS disease. The aim of this study was to assess the performance of routine use of dipstick urine analysis during pregnancy for prediction of recto-vaginal GBS colonisation at the time of labour., Methods: Among 902 unselected Danish pregnant women, we obtained results from 1) dipstick urine analysis, 2) urine culture carried out during pregnancy, if indicated, and 3) recto-vaginal culture at labour. The inclusion criteria were age > 18 years and gestational age ≥ 37 weeks., Results: Intrapartum recto-vaginal GBS colonisation was predicted by a positive urine dipstick with 5% sensitivity only., Conclusion: Dipstick urine analysis had a low sensitivity for predicting intrapartum recto-vaginal colonisation with GBS., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Systemic inflammation following curative surgery for colorectal cancer may be associated with increased risk of recurrence. [Correction added on 29 November 2019, after first online publication: text amended for accuracy.] This study investigated whether a clinically suspected infection, for which blood cultures were sent within 30 days after surgery for colorectal cancer, was associated with long-term oncological outcomes., Methods: This register-based national cohort study included all Danish residents undergoing surgery with curative intent for colorectal cancer between January 2003 and December 2013. Patients who developed recurrence or died within 180 days after surgery were not included. Associations between blood cultures taken within 30 days after primary surgery and overall survival, disease-free survival and recurrence-free survival were analysed using Cox regression models adjusted for relevant clinical confounders, including demographic data, cancer stage, co-morbidity, blood transfusion, postoperative complications and adjuvant chemotherapy., Results: The study included 21 349 patients, of whom 3390 (15·9 per cent) had blood cultures taken within 30 days after surgery. Median follow-up was 5·6 years. Patients who had blood cultures taken had an increased risk of all-cause mortality (hazard ratio (HR) 1·27, 95 per cent c.i. 1·20 to 1·35; P < 0·001), poorer disease-free survival (HR 1·22, 1·16 to 1·29; P < 0·001) and higher risk of recurrence (HR 1·15, 1·07 to 1·23; P < 0·001) than patients who did not have blood cultures taken., Conclusion: A clinically suspected infection requiring blood cultures within 30 days of surgery for colorectal cancer was associated with poorer oncological outcomes., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

The objective of this study was to examine the clinical presentation of community-acquired beta-haemolytic streptococcal (BHS) meningitis in adults. This is a nationwide population-based cohort study of adults (≥ 16 years) with BHS meningitis verified by culture or polymerase chain reaction of the cerebrospinal fluid (CSF) from 1993 to 2005. We retrospectively evaluated clinical and laboratory features and assessed outcome by Glasgow Outcome Scale (GOS). We identified 54 adults (58% female) with a median age of 65 years (IQR 55-73). Mean incidence rate was 0.7 cases per 1,000,000 person-years. Alcohol abuse was noted among 11 (20%) patients. Group A streptococci (GAS) were found in 17 (32%) patients, group B (GBS) in 18 (34%), group C (GCS) in four (8%) and group G (GGS) in 14 (26%). Patients with GAS meningitis often had concomitant otitis media (47%) and mastoiditis (30%). Among patients with GBS, GCS or GGS meningitis, the most frequent concomitant focal infections were bone and soft tissue infections (19%) and endocarditis (16%). In-hospital mortality was 31% (95% CI 19-45), and 63% (95% CI 49-76) had an unfavourable outcome at discharge (GOS < 5). BHS meningitis in adults is primarily observed among the elderly and has a poor prognosis. GAS meningitis is primarily associated with concomitant ear-nose-throat infection.

Executive Summary: Evaluations of improvements in long chronic-patient pathways must include both short- and long-term effects on patients; that is, effects on the full patient pathway. Otherwise, costs might be cut without considering the long-term effects and, consequently, the overall cost of the pathway could increase. Unfortunately, current methods of evaluation present several issues: (1) they do not provide valid insights regarding the effects of a given improvement effort until several years later, (2) they provide imprecise and biased results, and (3) the aggregated results are not useful for identifying and disseminating the best practices that lead to an improvement. In this article, the accelerated longitudinal design with decomposition of total costs (ALDD) method is applied to evaluate the effects of improvement efforts on inpatient utilization for long cardiac pathways at a Danish hospital. The results show that the ALDD method can deliver valid results much faster than traditional methods and can uncover hidden improvements in the local work processes of clinical teams. Application of the ALDD method at a hospital in Denmark identified a significant reduction (15.4%) in the mean total bed utilization per cardiac pathway and revealed that this reduction was caused by improvements in the work processes.

Objective: To investigate an association between Group B streptococci (GBS) in urine culture during pregnancy and preterm delivery. Methods: A population-based cohort consisted of all the pregnant women ( n  = 36,097) from the catchment area of Lillebaelt Hospital, Denmark, during the period January 2002 -December 2012. The cohort of 34,285 singleton pregnancies used in this study was divided into three groups. Group I ( N  = 249) included women whose urine culture was positive for GBS; group II ( N  = 5765) included women whose urine culture was negative for GBS; and group III ( N  = 28 271) included women whose urine had not been cultured during pregnancy. Primary outcome was preterm delivery before 37 weeks' gestation (PTD). Results: We did not find an association between PTD and GBS bacteriuria in the cultured groups (odds ratios (OR) = 0.89; 95% CI: 0.5-1.4) ( Table 1 ). After controlling for potential confounders, the PTD remained not associated with GBS bacteriuria (adjusted OR = 0.99; 95% CI: 0.6-1.6). Combined, the cultured groups (I and II) were associated with a statistically significant higher risk for PTD, when compared with the group with no urine specimens taken for culture (OR = 1.96; 95% CI: 1.8-2.2 and adjusted or 1.80; 95% CI 1.6-2.0). The cultured group of women differed considerably from the group of women with no urine specimens taken for culture on the vast majority of variables examined. Conclusions: No association between asymptomatic GBS bacteriuria and preterm delivery among women with singleton pregnancy and urine specimens cultured during pregnancy was found. Previous suggestions of such association may have been compromised by a selection problem for testing due to a high-risk profile of pregnancy complications in pregnant women selected for urine culture.

In May 2016, an unusual outbreak with the Panton-Valentine leukocidin-positive human variant of meticillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 occurred among mothers and infants in the maternity unit of a Danish hospital. MRSA sharing genotypic and phenotypic characteristics was confirmed in 36 cases, including 26 patients, nine household members and a healthcare worker (HCW) who had contact with all the patients. The national MRSA database contained 37 seemingly unlinked MRSA cases whose isolates shared the same genotypic and phenotypic characteristics as the outbreak strain. Whole genome sequencing showed that three of these isolates clustered together with the 36 outbreak isolates, suggesting spread outside the hospital. The HCW and 21 of 37 cases from the national MRSA database had links to south-eastern Asia, where the outbreak strain is endemic. These findings suggest that the HCW acquired the outbreak strain while travelling in south-eastern Asia and then introduced it into the hospital; from there, it spread within the patients' households and into the community. Screening of travellers returning from countries with high levels of MRSA could be an important intervention to prevent spread of these bacteria into hospitals via patients or HCWs.

Background: Testicular microlithiasis and its clinical significance are not fully understood. Testicular microlithiasis and risk factors have been associated with testicular cancer. The role of testicular microlithiasis is investigated., Purpose: To investigate the association between testicular microlithiasis and socioeconomic and other pre-diagnostic factors., Material and Methods: All men who had a scrotal ultrasound examination at the Department of Radiology, Vejle Hospital, during 2001-2013 were included. They were categorized as patients with and without testicular microlithiasis and compared with pre-diagnostic data from a nationwide registry. A total of 2404 men (283 [11.8%] with testicular microlithiasis and 2121 [88.2%] without testicular microlithiasis) were included. The association between testicular microlithiasis and pre-diagnostic conditions was investigated with logistic regression., Results: Overall, we found no statistically significant differences in demographics, socioeconomic characteristics, or testicular diseases in men with and without testicular microlithiasis. Men with testicular microlithiasis had more often been treated for infertility (odds ratio [OR] 2.09, 95% confidence interval [CI] 0.84-5.24) and testicular torsion (OR 1.58, 95% CI 0.34-7.36) compared to men without testicular microlithiasis. We found no association between sexually transmitted diseases and testicular microlithiasis., Conclusion: Treatment for infertility and torsion was non-significantly associated with testicular microlithiasis and no other association was found. These data do not suggest early exposure is related to testicular microlithiasis., (© The Foundation Acta Radiologica 2019.)

Objective: To compare a risk-based and culture-based screening approach for identification of group B streptococci (GBS) vaginal colonization using an intrapartum rectovaginal culture as the reference standard., Methods: Pregnant women attending the prenatal clinic at Lillebaelt Hospital, Kolding, Denmark, between April 1, 2013, and June 30, 2014, were invited to participate in a prospective observational study. For prepartum culture-based screening, vaginal and rectal culture samples were obtained and, for reference, standard, paired vaginal and rectal culture samples were collected during labor. Risk factors for risk-based screening were previous early-onset GBS, GBS bacteriuria during pregnancy, maternal temperature ≥38.0°C intrapartum, and rupture of membranes for more than 18 hours., Results: The intrapartum rectovaginal GBS colonization rate was 30% (32/108) among participants with risk factors and 15% (123/794) among participants without risk factors. Culture-based screening demonstrated a sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio in predicting intrapartum GBS carriage of 78% (95% confidence interval [CI] 71-84), 95% (94-97), 78% (70-84), 95% (94-97), and 17 (12-23), respectively; for risk-based screening, these values were 21% (15-28), 90% (87-92), 30% (22-38), 85% (83-86), and 2 (1-3), respectively., Conclusions: Culture-based screening performed considerably better than a risk-based approach in identifying intrapartum GBS colonization., (© 2018 International Federation of Gynecology and Obstetrics.)

Online model predictive control (MPC) of water resource recovery facilities (WRRFs) requires simple and fast models to improve the operation of energy-demanding processes, such as aeration for nitrogen removal. Selected elements of the activated sludge model number 1 modelling framework for ammonium and nitrate removal were included in discretely observed stochastic differential equations in which online data are assimilated to update the model states. This allows us to produce model-based predictions including uncertainty in real time while it also reduces the number of parameters compared to many detailed models. It introduces only a small residual error when used to predict ammonium and nitrate concentrations in a small recirculating WRRF facility. The error when predicting 2 min ahead corresponds to the uncertainty from the sensors. When predicting 24 hours ahead the mean relative residual error increases to ∼10% and ∼20% for ammonium and nitrate concentrations respectively. Consequently this is considered a first step towards stochastic MPC of the aeration process. Ultimately this can reduce electricity demand and cost for water resource recovery, allowing the prioritization of aeration during periods of cheaper electricity.

Background: The buttonhole cannulation technique for arteriovenous fistulas is widely used, but has been associated with an increased rate of vascular access-related infections. We describe the frequency and type of bacterial colonization of the buttonhole tract over time and associated clinical infections., Study Design: A prospective observational cohort study with 9 months of follow-up., Setting & Participants: 84 in-center hemodialysis patients using the buttonhole cannulation technique at 2 Danish dialysis centers., Outcomes: Bacterial growth from the buttonhole tract and dialysis cannula tip and clinically important infections during follow-up., Measurements: On 3 occasions 1 month apart, cultures before dialysis (from the skin surrounding the buttonhole before disinfection and from the cannulation tract after disinfection and scab removal) and the cannula tip after dialysis. Patients with positive cultures from the buttonhole tract or cannula tip had repeat cultures within 1 week, along with blood cultures., Results: Growth from the cannulation tract and/or cannula tip at each of the 3 monthly sets of cultures was found in 18%, 20%, and 17% of patients, respectively. 38% of patients had at least 1 positive culture from the buttonhole tract. Sustained growth was detected in 11% of patients, whereas asymptomatic bacteremia was seen in 30% of those with positive buttonhole cultures. Staphylococci species were the most common pathogens (Staphylococcus aureus, 25%; and Staphylococcus epidermidis, 41%). Colonization-positive buttonholes had more localized redness and slightly more tenderness. During follow-up, significantly more access-related infections were diagnosed among those with positive buttonhole cultures (P<0.001)., Limitations: No comparison to area puncture cannulation technique. Blood cultures were obtained only from patients with positive buttonhole bacteriology., Conclusions: Transient or sustained colonization of the buttonhole tract by staphylococci and asymptomatic bacteremia is common in hemodialysis patients, implying a substantial risk for access-related infections among patients using a buttonhole cannulation technique. These findings suggest the possible value of surveillance of buttonhole colonization., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Outbreak investigations demand a fast and discriminative typing method. MALDI-TOF MS has been shown to be a rapid, easy and inexpensive method of subtyping MRSA.The aim of the present study is to explore whether it is possible to subdivide isolates of MRSA CC398, commonly livestock associated, using an enhanced version of the MALDI-TOF MS typing method that we previously described (Østergaard et al, 2015). We included MALDI-TOF spectra from 378 isolates of MRSA belonging to CC398, of which 322 were epidemiologically independent. We identified 17 peaks as discriminatorily useful and could therefore reliably subdivide the isolates into 23 subtypes, including a distinct type corresponding to a strain from an unusual and initially undiscovered hospital outbreak. Whole genome sequencing was carried out for 193 of the isolates and compared with both the spa type and an antibiogram of these strains. The proposed MALDI-TOF subdivision method for MRSA CC398 was found to be more discriminative than both spa typing and resistotyping, and had a high negative predictive value for ruling out a close genetic relationship between pairs of strains with different MALDI-TOF types. We conclude that the MALDI-TOF-based typing method can be used for rapid and inexpensive routine subdivision of MRSA belonging to CC398., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Objective: To evaluate GBS colony numbers in the urine at 35-37 weeks' gestation to predict the load of GBS-colonization of the vagina at birth., Study Design: In this prospective observational study, we included 902 unselected pregnant women. Exposure was GBS colony forming units (CFU) per mL urine at 35-37 weeks' gestation. Outcome was vaginal GBS colonization at birth as assessed by a semi-quantitative culture of a vaginal swab sample (negative, +1, +2, +3)., Results: Bacteriuria with GBS at 35-37 weeks' gestation performed with a sensitivity of 30% concerning any degree of vaginal GBS colonization at birth (31 of 104 cases); 19% for light (+1), 17% for medium (+2), and 52% for high load (+3) vaginal GBS colonization. The colony count in case of GBS bacteriuria at 35-37 weeks' gestation performed with positive predictive values of 35% for <10 4  CFU/mL, 70% for 10 4 CFU/mL, and 67% for >10 4  CFU/mL., Conclusion: Even though the urinary GBS CFU at 35-37 weeks' gestation is strongly associated with a high load of vaginal GBS colonization intrapartum, it may not perform satisfactorily as a standalone-screening marker for risk of early-onset GBS disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Diagnosing of influenza rapidly and accurately helps clinicians to initiate appropriate treatment options and isolation protocols. Unnecessary antimicrobial treatment and laboratory testing can also be reduced. Assess commercial alternatives to in-house assays that may not only reduce laboratory technician "hands on" time but also the laboratory turnaround time is of interest., Objectives: We evaluated the performance of the VIASURE Flu A, B & RSV Real Time RT-PCR Detection Kit (CerTest Biotec) for detecting Influenza A and B viruses., Study Design: During the 2016/17 influenza season 532 clinical samples were tested with the VIASURE assay on the BD MAX™ system versus an in-house real time RT-PCR assay with discrepant results resolved by a real time RT-PCR assay at a national reference laboratory., Results: The VIASURE assay on the BD MAX showed a sensitivity of 99.5% (95% CI: 97.3-100) and a specificity of 99.1% (95% CI: 97.4-99.8) for detection of Influenza A virus. The positive predictive and negative predictive values were 98.5% (95% CI: 95.8-99.7) and 99.7% (95% CI: 98.3-100) respectively. Influenza B virus detection could not be evaluated due to a low positivity rate. The BD MAX platform offered the flexibility of several daily runs, shorter hands-on-time and shorter turnaround time than the in-house assay., Conclusions: The VIASURE assay on the BD MAX performed well and is now implemented in our clinical laboratory., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Currently, no consensus exists on a model describing endogenous glucose production (EGP) as a function of glucagon concentrations. Reliable simulations to determine the glucagon dose preventing or treating hypoglycemia or to tune a dual-hormone artificial pancreas control algorithm need a validated glucoregulatory model including the effect of glucagon., Methods: Eight type 1 diabetes (T1D) patients each received a subcutaneous (SC) bolus of insulin on four study days to induce mild hypoglycemia followed by a SC bolus of saline or 100, 200, or 300 µg of glucagon. Blood samples were analyzed for concentrations of glucagon, insulin, and glucose. We fitted pharmacokinetic (PK) models to insulin and glucagon data using maximum likelihood and maximum a posteriori estimation methods. Similarly, we fitted a pharmacodynamic (PD) model to glucose data. The PD model included multiplicative effects of insulin and glucagon on EGP. Bias and precision of PD model test fits were assessed by mean predictive error (MPE) and mean absolute predictive error (MAPE)., Results: Assuming constant variables in a subject across nonoutlier visits and using thresholds of ±15% MPE and 20% MAPE, we accepted at least one and at most three PD model test fits in each of the seven subjects. Thus, we successfully validated the PD model by leave-one-out cross-validation in seven out of eight T1D patients., Conclusions: The PD model accurately simulates glucose excursions based on plasma insulin and glucagon concentrations. The reported PK/PD model including equations and fitted parameters allows for in silico experiments that may help improve diabetes treatment involving glucagon for prevention of hypoglycemia.

Objective: To assess the performance of a polymerase chain reaction - group B streptococci test (PCR-GBS test) - in deciding antibiotic prophylaxis in term laboring women., Study Design: In this observational study, we enrolled 902 unselected Danish term pregnant women. During labor, midwives obtained vaginal swabs that were used for both GBS cultures (reference standard) and for the PCR-GBS test. Furthermore, we recorded the presence of risk factors for EOGBS (Early Onset Group B Streptococcal disease): (1) Bacteriuria during current pregnancy, (2) Prior infant with EOGBS (3) Temperature above 38.0°C during labor, and (4) Rupture of membranes ≥18h., Results: The prevalence of GBS carriers was 12% (104 of 902), the sensitivity of the PCR-GBS test 83% (86 of 104), and the specificity 97% (774 of 798). Among the 108 with one or more EOGBS-risk factors, GBS was present in 23% (25 of 108), the sensitivity 92% (23 of 25), and the specificity 89% (74 of 83)., Conclusion: In programs that aim to treat all laboring women with vaginal GBS-colonization (12% in the present study) with penicillin, the PCR-GBS will perform well (sensitivity 83% and specificity 97%). In programs aiming to treat only GBS-carriers among those with risk factors of EOGBS, a reduction of penicillin usage by two-thirds from 12% to 4% may be possible., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to compare the performances of two strategies for predicting intrapartum vaginal carriage of group B streptococci (GBS). One strategy was based on an antepartum culture and the other on an intrapartum polymerase chain reaction (PCR). We conducted a prospective observational study enrolling 902 pregnant women offered GBS screening before delivery by two strategies. The Culture-strategy was based on vaginal and rectal cultures at 35-37 weeks' gestation, whereas the PCR-strategy was based on PCR assay on intrapartum vaginal swab samples. An intrapartum vaginal culture for GBS was used as the reference standard from which the performances of the 2 strategies were evaluated. The reference standard showed a GBS-prevalence of 12%. The culture-strategy performed with a sensitivity of 82%, specificity of 91%, positive predictive value (PPV) of 55%, negative predictive value (NPV) of 98%, and Likelihood ratio (LH+) of 9.2. The PCR-strategy showed corresponding values as sensitivity of 83%, specificity of 97%, PPV of 78%, NPV of 98%, and LH+ of 27.5. We conclude that in a Danish population with a low rate of early-onset neonatal infection with GBS, the intrapartum PCR assay performs better than the antepartum culture for identification of GBS vaginal carriers during labor.

Objective: To examine the trend of Prosthetic Joint Infections (PJI) following primary total hip arthroplasty (THA) and the antimicrobial resistance of the bacteria causing these infections., Materials and Methods: We identified a population-based cohort of patients in the Danish Hip Arthroplasty Register (DHR) who had primary THA and received their surgery in Jutland or Funen between 2005 and 2014. We followed the patients until revision, emigration, death, or up to 1-year of follow-up. Data from the DHR were combined with those from microbiology databases, the National Register of Patients, and the Civil Registration System. We estimated the cumulative 1-year incidence of PJI for two 5-year periods; 2005-2009 and 2010-2014. The hazard ratio of PJI as a measure of relative risk after adjusting for multiple risk factors was calculated., Results: Of 48,867 primary THAs identified, 1120 underwent revision within 1 year. Of these, 271 were due to PJI. The incidence of PJI was 0.53% (95% confidence interval (CI): 0.44; 0.63) during 2005-2009 and 0.57% (95% CI: 0.49; 0.67) during 2010-2014. The adjusted relative risk was 1.05 (95% CI: 0.82; 1.34) for the 2010-2014 period vs the 2005-2009 period. The most common micro-organisms identified in the 271 PJI were Staphylococcus aureus (36%) and coagulase-negative staphylococci (CoNS) (33%); others commonly identified included Enterobacteriaceae, enterococci, and streptococci. Antimicrobial resistance to beta-lactams and gentamicin did not change during the study period., Conclusion: The risk of PJI within 1-year after primary THA and the antimicrobial resistance of the most prevalent bacteria remained unchanged during the 2005-2014 study period., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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.

Background: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data., Aim: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI) and to describe surveillance data from 2010 to 2014., Methods: The HA-UTI algorithm defined a laboratory-diagnosed UTI as a urine culture positive for no more than two micro-organisms with at least one at ≥10(4)cfu/mL, and a probable UTI as a negative urine culture and a relevant diagnosis code or antibiotic treatment. UTI was considered hospital-acquired if a urine sample was collected ≥48h after admission and <48h post discharge. Incidence of HA-UTI was calculated per 10,000 risk-days. For validation, prevalence was calculated for each day and compared to point prevalence survey (PPS) data., Findings: HAIBA detected a national incidence rate of 42.2 laboratory-diagnosed HA-UTI per 10,000 risk-days with an increasing trend. Compared to PPS the laboratory-diagnosed HA-UTI algorithm had a sensitivity of 50.0% (26/52) and a specificity of 94.2% (1842/1955). There were several reasons for discrepancies between HAIBA and PPS, including laboratory results being unavailable at the time of the survey, the results considered clinically irrelevant by the surveyor due to an indwelling urinary catheter or lack of clinical signs of infection, and UTIs being considered HA-UTI in PPS even though the first sample was taken within 48h of admission., Conclusion: The HAIBA algorithm was found to give valid and valuable information and has, among others, the advantages of covering the whole population and allowing continuous standardized monitoring of HA-UTI., (Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Urinary tract infections account for as much as one-third of all nosocomial infections. The aim of this study was to examine previously reported characteristics of patients with hospital-acquired urinary tract infections (HA-UTI) using an automated infection monitoring system (Hospital-Acquired Infection Registry: HAIR). A matched case-control study was conducted to investigate the association of risk factors with HA-UTI. Patients with HA-UTI more frequently had indwelling urinary catheters or a disease in the genitourinary or nervous system than the controls. Automated hospital-acquired infection monitoring enables documentation of key risk factors to better evaluate infection control interventions in general or for selected groups of patients., (Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Fast and reliable discrimination of methicillin-resistant Staphylococcus aureus (MRSA) isolates is essential in identifying an outbreak. Molecular typing methods, such as S. aureus protein A (spa) typing, multi locus sequence typing (MLST) and pulse field gel electrophoresis (PFGE) are generally used for this purpose. These methods are all relatively time-consuming and not performed routinely in all laboratories. The aim of this study is to examine whether MALDI-TOF MS can be used as a fast, simple and easily implemented method for first-line discrimination of MRSA isolates. Mass spectra from 600 clinical MRSA isolates were included in the study, representing 89 spa types, associated with 16 different known clonal complexes. All spectra were obtained directly from colony material obtained from overnight cultures without prior protein extraction. We identified 43 useful discriminatory m/z-values (peaks) and used a concept of arranging these peaks into pairs or small clusters within a small mass range, allowing for quality control of the spectra obtained. Using this concept we could reproducibly characterise and arrange the isolates into 26 MALDI-TOF groups, which strongly correlated with spa types and clonal complexes. The results of this study clearly show that MALDI-TOF MS can be used for first-line discrimination of MRSA isolates, using a simple and fast method that is easy to implement as part of routine testing., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Monitoring of hospital-acquired infection (HAI) by automated compilation of registry data may address the disadvantages of laborious, costly and potentially subjective and often random sampling of data by manual surveillance., Aim: To evaluate a system for automated monitoring of hospital-acquired urinary tract (HA-UTI) and bloodstream infections (HA-BSI) and to report incidence rates over a five-year period in a Danish hospital trust., Methods: Based primarily on electronically available data relating to microbiology results and antibiotic prescriptions, the automated monitoring of HA-UTIs and HA-BSIs was validated against data from six previous point-prevalence surveys (PPS) from 2010 to 2013 and data from a manual assessment (HA-UTI only) of one department of internal medicine from January 2010. Incidence rates (infections per 1000 bed-days) from 2010 to 2014 were calculated., Findings: Compared with the PPSs, the automated monitoring showed a sensitivity of 88% in detecting UTI in general, 78% in detecting HA-UTI, and 100% in detecting BSI in general. The monthly incidence rates varied between 4.14 and 6.61 per 1000 bed-days for HA-UTI and between 0.09 and 1.25 per 1000 bed-days for HA-BSI., Conclusion: Replacing PPSs with automated monitoring of HAIs may provide better and more objective data and constitute a promising foundation for individual patient risk analyses and epidemiological studies. Automated monitoring may be universally applicable in hospitals with electronic databases comprising microbiological findings, admission data, and antibiotic prescriptions., (Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Lyme neuroborreliosis (LNB) is a tick-borne infection of the nervous system caused by the spirochete Borrelia burgdorferi sensu lato. The primary symptoms are usually painful radiculitis, facial palsy and lymphocytic meningitis. The aim of this study was to provide data on the seasonal variation, anamnesis, symptoms, laboratory data and course of the disease in adults (≥ 16 years)., Methods: The medical records of 69 patients with confirmed LNB who attended the Department of Neurology, Lillebaelt Hospital, Vejle, Denmark, were analysed. The diagnosis was confirmed by the presence of leucocytosis in the cerebrospinal fluid and intrathecal production of immunoglobulin M and/or G anti-B. burgdorferi antibodies., Results: Onset of neurological symptoms in LNB occurred year round in the Region of Southern Denmark. Only half of the patients had a history of a tick bite or erythema migrans (EM). Half of the patients who observed a tick bite subsequently reported EM. The duration from the onset of neurological symptoms to referral to hospital was remarkably long for patients with radiculoneuritis, whereas the onset of facial palsy led to a swift referral. Patients who were ≥ 50 years old had a significantly lower age-related risk of facial palsy without radicular symptoms., Conclusion: In this study, winter as a low-risk season was not a reliable factor in ruling out LNB. This finding may be relevant when investigating the cause of facial palsy and radicular symptoms.

Background and Purpose: It has been suggested that the risk of prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA) may be underestimated if based only on arthroplasty registry data. We therefore wanted to estimate the "true" incidence of PJI in THA using several data sources., Patients and Methods: We searched the Danish Hip Arthroplasty Register (DHR) for primary THAs performed between 2005 and 2011. Using the DHR and the Danish National Register of Patients (NRP), we identified first revisions for any reason and those that were due to PJI. PJIs were also identified using an algorithm incorporating data from microbiological, prescription, and clinical biochemistry databases and clinical findings from the medical records. We calculated cumulative incidence with 95% confidence interval., Results: 32,896 primary THAs were identified. Of these, 1,546 had first-time revisions reported to the DHR and/or the NRP. For the DHR only, the 1- and 5-year cumulative incidences of PJI were 0.51% (0.44-0.59) and 0.64% (0.51-0.79). For the NRP only, the 1- and 5-year cumulative incidences of PJI were 0.48% (0.41-0.56) and 0.57% (0.45-0.71). The corresponding 1- and 5-year cumulative incidences estimated with the algorithm were 0.86% (0.77-0.97) and 1.03% (0.87-1.22). The incidences of PJI based on the DHR and the NRP were consistently 40% lower than those estimated using the algorithm covering several data sources., Interpretation: Using several available data sources, the "true" incidence of PJI following primary THA was estimated to be approximately 40% higher than previously reported by national registries alone.

This national population-based study was conducted as part of the development of a national automated surveillance system for hospital-acquired bacteraemia and ascertains the utilization of blood cultures (BCs). A primary objective was to understand how local differences may affect interpretation of nationwide surveillance for bacteraemia. From the Danish Microbiology Database, we retrieved all BCs taken between 2010 and 2013 and linked these to admission data from the National Patient Registry. In total, 4 587 295 admissions were registered, and in 11%, at least one BC was taken. Almost 50% of BCs were taken at admission. The chance of having a BC taken declined over the next days but increased after 4 days of admission. Data linkage identified 876 290 days on which at least one BC was taken; 6.4% yielded positive results. Ten species, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae and Klebsiella oxytoca, accounted for 74.7% of agents for this purpose classified as pathogenic. An increase in BCs and positive BCs was observed over time, particularly among older patients. BCs showed a seasonal pattern overall and for S. pneumoniae particularly. A predominance of male patients was seen for bacteraemias due to S. aureus, E. faecium and K. pneumoniae. Minor differences in BCs and positive BCs between departments of clinical microbiology underpin the rationale of a future automated surveillance for bacteraemia. The study also provides important knowledge for interpretation of surveillance of invasive infections more generally., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection., Design: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010., Setting: Nine multidisciplinary ICUs across Denmark., Patients: A total of 1,200 critically ill patients., Intervention: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596)., Measurements and Main Results: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006)., Conclusions: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.