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Objectives : This study investigates the feasibility of implementing telescreening for retinopathy of prematurity (ROP) using the ICON GO ® widefield camera operated by a non-physician healthcare professional (NPHP). We hypothesized that images captured by an NPHP are adequate to evaluate ROP changes without further examinations. Secondly, the level of agreement between independent ROP graders were evaluated based on the fundus photographs. Methods : National ROP screening criteria were gestational age (GA) < 32 weeks or birthweight (BW) < 1500 g. Exclusion criteria were children hospitalized and born outside the Capital Region and examinations not performed by an NPHP. The screenings were performed using the ICON GO ® . The NPHP selected the best images for evaluation by an on -site ophthalmologist, regarding whether re-examination was necessary and if so, whether the re-examination was beneficial. Lastly, the images were re-evaluated by an independent off -site ophthalmologist. Results : A total of 415 screening sessions on 165 patients performed by an NPHP were included. Re-examination was necessary in three screening sessions and beneficial in two. The level of agreement between the on -site and off -site ophthalmologists regarding ROP screening outcome was k = 0.82, ROP stage k = 0.69, plus disease k = 0.69, and lastly ROP zone k = 0.37. Of the screened children, ninety-seven (58.8%) had no ROP at any time points, sixty-two (37.6%) had some stage of ROP not requiring treatment, and six (3.6%) received ROP treatment. Conclusions : Telemedicine screening for ROP with the ICON GO ® camera performed by an NPHP was feasible with an almost-perfect agreement and negligible need for re-examinations. The approach effectively identified children needing treatment, supporting the use of telescreening in ROP management.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice., (© 2024. The Author(s).)

Introduction: Simulation-based training (SBT) aids healthcare providers in acquiring the technical skills necessary to improve patient outcomes and safety. However, since SBT may require significant resources, training all skills to a comparable extent is impractical. Hence, a strategic prioritization of technical skills is necessary. While the European Training Requirements in Neonatology provide guidance on necessary skills, they lack prioritization. We aimed to identify and prioritize technical skills for a SBT curriculum in neonatology., Methods: A three-round modified Delphi process of expert neonatologists and neonatal trainees was performed. In round one, the participants listed all the technical skills newly trained neonatologists should master. The content analysis excluded duplicates and non-technical skills. In round two, the Copenhagen Academy for Medical Education and Simulation Needs Assessment Formula (CAMES-NAF) was used to preliminarily prioritize the technical skills according to frequency, importance of competency, SBT impact on patient safety, and feasibility for SBT. In round three, the participants further refined and reprioritized the technical skills. Items achieving consensus (agreement of ≥75%) were included., Results: We included 168 participants from 10 European countries. The response rates in rounds two and three were 80% (135/168) and 87% (117/135), respectively. In round one, the participants suggested 1964 different items. Content analysis revealed 81 unique technical skills prioritized in round two. In round three, 39 technical skills achieved consensus and were included., Conclusion: We reached a European consensus on a prioritized list of 39 technical skills to be included in a SBT curriculum in neonatology., (© 2024 S. Karger AG, Basel.)

Objective: To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization in neonatal patients during an MRSA outbreak to minimize future outbreaks., Design: Retrospective case-control study., Setting: Level-IV neonatal intensive care unit (NICU) at Copenhagen University Hospital, Rigshospitalet, Denmark., Patients: Neonates with either MRSA or methicillin-susceptible Staphylococcus aureus (MSSA)., Methods: Methicillin-resistant Staphylococcus aureus -positive neonates were matched with those colonized or infected with MSSA in a 1:1 ratio. The control group was selected from clinical samples, whereas MRSA-positive neonates were identified from clinical samples or from screening. A total of 140 characteristics were investigated to identify risk factors associated with MRSA acquisition. The characteristics were categorized into three categories: patient, unit, and microbiological characteristics., Results: Out of 1,102 neonates screened for MRSA, between December 2019 and January 2022, 33 were MRSA positive. They were all colonized with an MRSA outbreak clone ( spa type t127) and were included in this study. Four patients (12%) had severe infection. Admission due to respiratory diseases, need for intubation, need for peripheral venous catheters, admission to shared rooms with shared toilets and bath facilities in the aisles, and need for readmission were all correlated with later MRSA colonization ( P < 0.05)., Conclusion: We identified clinically relevant diseases, procedures, and facilities that predispose patients to potentially life-threatening MRSA infections. A specific MRSA reservoir remains unidentified; however, these findings have contributed to crucial changes in our NICU to reduce the number of MRSA infections and future outbreaks., Competing Interests: There was no conflict of interest., (© The Author(s) 2023.)

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41., Competing Interests: Dr Breindahl has a patent (NeoHelp) with royalties paid. Dr Breindahl has nothing else to disclose. All other authors have nothing else to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 de Knegt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed., Competing Interests: Author PH held an unpaid position at Brazen Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Malange, Hedermann, Lausten-Thomsen, Hoffmann, Voldstedlund, Aabakke, Eltvedt, Jensen, Breindahl, Krebs, Christiansen and Hedley.)

Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune- and non-immune hydrops fetalis. Today, the non-immune form is the most common. Once born, the child is initially handled symptomatically and will often need intensive care and treatment. Even though approximately one in five cases is still idiopathic, genetic diagnostic tools have become increasingly important in the diagnostic process. The prognosis depends on the aetiology and the gestational age when diagnosed and at birth, as argued in this review.

Aim: Our aim was to investigate the rates of preterm births, live births and stillbirths in Denmark during the first year of the COVID-19 pandemic., Methods: This was a national, cross-sectional registry-based study that used the Danish Newborn Quality database, which covers all births in Denmark. The proportions of preterm births were compared between the COVID-19 pandemic period of 1 March 2020 to 28 February 2021 and the preceding 4-year pre-pandemic period., Results: We studied 60 323 and 244 481 newborn infants from the pandemic and pre-pandemic periods, respectively. The proportion of preterm live births and stillbirths declined slightly, from 6.29% during the pre-pandemic period to 6.02% during the pandemic period. This corresponded to a relative risk (RR) of 0.96, with a 95% confidence interval (CI) of 0.93-0.99 during the pandemic. The RRs for extremely preterm, very preterm and moderately preterm infants were 0.88 (95% CI 0.76-1.02), 0.91 (95% CI 0.82-1.02) and 0.97 (95% CI 0.93-1.01), respectively., Conclusion: This comparative study showed a small reduction in just over 4%, from 6.29 to 6.02% in the proportion of all preterm births during the pandemic period, compared with the previous four pandemic-free years. There were no differences between subcategories of preterm births., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12-April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27-September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known: • The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors. • The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New: • The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period. • The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions., (© 2021. The Author(s).)

Background: The 2020 novel coronavirus (SARS-Cov-2) pandemic necessitates tailored recommendations addressing specific procedures for neonatal and paediatric transport of suspected or positive COVID-19 patients. The aim of this consensus statement is to define guidelines for safe clinical care for children needing inter-facility transport while making sure that the clinical teams involved are sufficiently protected from SARS-CoV-2., Methods: A taskforce, composed of members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Transport section and the European Society for Paediatric Research (ESPR), reviewed the published literature and used a rapid, two-step modified Delphi process to formulate recommendations regarding safety and clinical management during transport of COVID-19 patients., Results: The joint taskforce consisted of a panel of 12 experts who reached an agreement on a set of 17 recommendations specifying pertinent aspects on neonatal and paediatric COVID-19 patient transport. These included: case definition, personal protective equipment, airway management, equipment and strategies for invasive and non-invasive ventilation, special considerations for incubator and open stretcher transports, parents on transport and decontamination of transport vehicles., Conclusions: Our consensus recommendations aim to define current best-practice and should help guide transport teams dealing with infants and children with COVID-19 to work safely and effectively., Impact: We present European consensus recommendations on pertinent measures for transporting infants and children in times of the coronavirus (SARS-Cov-2 /COVID-19) pandemic. A panel of experts reviewed the evidence around transporting infants and children with proven or suspected COVID-19. Specific guidance on aspects of personal protective equipment, airway management and considerations for incubator and open stretcher transports is presented. Based on scant evidence, best-practice recommendations for neonatal and paediatric transport teams are presented, aiming for the protection of teams and patients. We highlight gaps in knowledge and areas of future research.

To explore the impact of COVID-19 lockdown on premature birth rates in Denmark, a nationwide register-based prevalence proportion study was conducted on all 31 180 live singleton infants born in Denmark between 12 March and 14 April during 2015-2020.The distribution of gestational ages (GAs) was significantly different (p=0.004) during the lockdown period compared with the previous 5 years and was driven by a significantly lower rate of extremely premature children during the lockdown compared with the corresponding mean rate for the same dates in the previous years (OR 0.09, 95% CI 0.01 to 0.40, p<0.001). No significant difference between the lockdown and previous years was found for other GA categories.The reasons for this decrease are unclear. However, the lockdown has provided a unique opportunity to examine possible factors related to prematurity. Identification of possible causal mechanisms might stimulate changes in clinical practice., Competing Interests: Competing interests: MB has a patent (NeoHelp) with royalties paid., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: No national guidelines exist in Denmark regarding interhospital transport of critically ill children. The aim of this study was to disclose which physicians actually accompany critically ill children during interhospital transports nationwide and whether the physicians have adequate clinical skills to perform interhospital transfers., Methods: A questionnaire was sent to the youngest pediatrician on-call at every hospital in Denmark receiving pediatric emergencies except the tertiary Copenhagen University Hospital, Rigshospitalet., Results: Seventeen pediatric departments were contacted (response rate, 100%). All departments indicated that they perform interhospital transport of pediatric patients. When presented with 5 cases, great heterogeneity in the choice of transport physician and accompanying staff was seen. With increasing severity, fewer pediatricians were willing to transport the children (24% vs 6%). Irrespective of the degree of severity, more transports were delegated to anesthesiologists than performed by pediatricians. Pediatricians who agreed to transport the infant and neonate had adequate competencies. In cases with older children, 0 to 75% of physicians who would do the transport had adequate clinical skills and experience in emergency pediatric respiratory and cardiovascular management. Training in interhospital transport was offered by 1 department; 6 departments (35%) had local guidelines describing the management of pediatric transports., Conclusions: Great heterogeneity was found in the local transport strategies and practical skill sets of accompanying physicians. Overall, there is room for improvement in the management of interhospital transport of critically ill children in Denmark, perhaps by increasing the availability of specialized pediatric transport services for critically ill children nationwide.

Interhospital transport of sick newborn infants is dangerous, but the risk of adverse events can be reduced, when transport is being performed by trained neonatal retrieval teams. In this review, we describe the current organisation of neonatal retrieval service in Denmark. The services are based at the neonatal intensive care units of the four university hospitals. Improved cooperation and harmonisation of operations between the teams is needed, as this is a prerequisite for the development of a national clinical consensus guideline and national quality metrics enabling benchmarking both within Denmark and abroad.

There is a growing interest worldwide in using echocardiography in the neonatal unit to act as a complement to the clinical assessment of the hemodynamic status of premature and term infants. However, there is a wide variation in how this tool is implemented across many jurisdictions, the level of expertise, including the oversight of this practice. Over the last 5 years, three major expert consensus statements have been published to provide guidance to neonatologists performing echocardiography, with all recommending a structured training program and clinical governance system for quality assurance. Neonatal practice in Europe is very heterogeneous and the proximity of neonatal units to pediatric cardiology centers varies significantly. Currently, there is no overarching governance structure for training and accreditation in Europe. In this paper, we provide a brief description of the current training recommendations across several jurisdictions including Europe, North America, and Australia and describe the steps required to achieve a sustainable governance structure with the responsibility to provide accreditation to neonatologist performed echocardiography in Europe.

Background: Neonatal resuscitation (NR) combines a set of life-saving interventions in order to stabilize compromised newborns at birth or when critically ill. Médecins Sans Frontières/Doctors Without Borders (MSF), as an international medical-humanitarian organization working particularly in low-resource settings (LRS), assisted over 250,000 births in obstetric and newborn care aid projects in 2016 and provides thousands of newborn resuscitations annually. The Helping Babies Breathe (HBB) program has been used as formal guidance for basic resuscitation since 2012. However, in some MSF projects with the capacity to provide more advanced NR interventions but a lack of adapted guidance, staff have felt prompted to create their own advanced algorithms, which runs counter to the organization's aim for standardized protocols in all aspects of its care., Objectives: The aim is to close a significant gap in neonatal care provision in LRS by establishing consensus on a protocol that would guide MSF field teams in their practice of more advanced NR., Methods: An independent committee of international experts was formed and met regularly from June 2016 to agree on the content and design of a new NR algorithm., Results: Consensus was reached on a novel, mid-level NR algorithm in April 2017. The algorithm was accepted for use by MSF Operational Center Paris., Conclusion: This paper contributes to the literature on decision-making in the development of cognitive aids. The authors also highlight how critical gaps in healthcare delivery in LRS can be addressed, even when there is limited evidence to guide the process., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: The European Society for Neonatology (ESN) developed a curriculum for subspecialist training in Europe recommending standards for national neonatal training programmes. We speculate whether these official recommendations are widely accepted or used in practice., Objectives: To characterize the variation in national neonatal training programmes, to enhance transparency, and to compare them to the ESN Curriculum., Methods: We constructed a database based on the backbone of the ESN Curriculum: (1) training - knowledge, (2) training - skills, (3) key competencies, (4) personal development, and (5) recording of progress. National neonatal representatives from all 30 member states of the Union of European Medical Specialties (UEMS) provided data on national training programmes., Results: Although only one country (3%) based its neonatology training entirely on the ESN Curriculum, we found high levels of uniformity among the UEMS member countries regarding knowledge, skills, and key competencies needed to practice neonatology at a tertiary care level. Discrepancy was encountered on ethical and legal issues and on personal development of the trainees. Mentoring and professional evaluation was generally not implemented in the participating countries., Conclusions: There is an awareness and readiness to focus on educational demands for neonatal trainees. Further discussions about the overall educational goals of neonatal training and the essence of practicing neonatology in each country are needed. The ESN will undertake this process to provide an updated and effective syllabus aimed to harmonize care and outcomes for babies and their families across Europe., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone., Methods: Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7., Results: The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0-5,080.8] and 5,288.4 [4,713.3-5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0-4,038.4] and 5,646.5 [4,481.3-7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4-26,312.0] and 26,981.9 [23,909.5-30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7-9,826.6] and 11,182.7 [9,924.8-12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population., Conclusions: Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9-15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study sought to determine the incidence and the burden of severe diarrheal disease in Denmark with emphasis on rotavirus (RV) disease., Methods: This study was designed as a national prospective disease surveillance of children <5 years of age hospitalized for acute gastroenteritis in Denmark during March 2009 to April 2010, using rapid RV and adenovirus antigen detection., Results: A total of 3100 hospitalizations annually among Danish children <5 years of age can be attributed to acute gastroenteritis and 1210 (39%) of these to RV disease. The majority of RV-associated hospitalizations occur among children ≤ 24 months of age (RV-associated hospitalization rate: 7.7/1000 children ≤ 24 months of age and 3.8/1000 children <5 years of age). Although the well-known seasonal pattern of RV was evident with a peak during the spring months of March through April, our active surveillance demonstrated RV-associated hospitalizations throughout the year. Genotyping of a subset of RV-samples demonstrated high frequency of G1 (39%) and G4 (32%). Adenovirus was detected in 350 acute gastroenteritis-associated hospitalizations (11.2%)., Conclusion: In conclusion, we present national disease burden data on severe cases of gastroenteritis and specifically RV-associated disease and demonstrate that RV is indeed ubiquitous in the population and can be considered a major health burden among young Danish children.

Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of coagulation status after an operative procedure. This study compared uF1+2 levels in patients with symptomatic and non-symptomatic venous thromboembolism (VTE) after total knee replacement (TKR) and in event-free sex- and age-matched controls. Significantly higher median uF1+2 levels were seen in the VTE patients on days 1, 3, and the day of venography (mostly day 7) after TKR compared with controls. The uF1+2 levels tended to be high in some patients with symptomatic VTE; however, the discriminatory efficacy of the test could not be evaluated. In conclusion, this study showed that patients with VTE tend to have significantly higher uF1+2 levels compared with patients without events between days 1 and 7 after TKR surgery. Measurement of uF1+2 could provide a simple, non-invasive clinical test to identify patients at risk of VTE.

Purpose: Prothrombin fragment 1+2 measured in spot urine (uF1+2) is an indicator of thrombin generation. We examined whether measured levels of uF1+2 can be used to differentiate between patients who do and do not acquire sustained coagulation activation after total hip arthroplasty (THA)., Methods: We performed two separate studies in patients undergoing THA. Study 1 was a prospective pilot study aiming to roughly estimate the extent of pre- and postoperative fluctuations in the uF1+2 concentration. Study 2 was a larger prospective cohort study aiming to verify the findings of Study 1 and to examine the association between the uF1+2 concentrations and risk of vascular thrombotic complications (VTC) or death. Finally, we sought to define a cut-off concentration value that could be used to identify patients with a sustained uF1+2 elevation after the first postoperative week. The urine samples were analysed by ELISA. In both studies thromboprophylaxis was used for at least 7 days after the operation., Results: The operative trauma resulted in elevation of the uF1+2 level in all patients compared with the preoperative level and levels in the healthy volunteers. Ten out of 113 patients (8.8%) in the second study suffered VTC or death, assumed to be caused by a coagulation problem. Analysis of variance revealed the following statistically significant associations: pre- vs. postoperative log uF1+2 levels (P<0.0001), log uF1+2 levels comparing patients with and without events (P=0.004); and the individual log uF1+2 levels (P<0.0001). A cut-off value of uF1+2 concentration between 0.3 and 0.5 nmol/l had a sensitivity and a negative predictive value between100% and 90%, and specificity between 45% and 63% and overall accuracy between 50% and 65%. This value was obtained by the analysis of a receiver operating characteristic curve with the purpose of identifying patients with sustained coagulation activation on day 5 after operation., Conclusion: Our studies suggest that measured levels of uF1+2 can be potentially used to assess the individual risk of VTC after THA and to test for non-invasive detection of sustained coagulation activation.