Research Infrastructure Network Research Articles

Traffic-Related Air Pollution and Childhood Asthma—Are the Risks Appropriately Mitigated in Australia?

Childhood asthma is a major health issue in Australia, and traffic emissions play a causative role. Two urban planning policies that impact children’s exposure to traffic emissions are considered in terms of the potential health risks to children in a Melbourne suburb with high truck volumes and hospital attendances for childhood asthma. Firstly, the health impact assessment component of the state planning approval of a major road project, and secondly, local government placement of childcare centres and schools in relation to freight routes. Three sources of air quality monitoring data were examined: (i) a Victorian EPA reference site; (ii) a site with planning approval for development into a childcare centre; and (iii) five sites within the boundary of the West Gate Tunnel Project, an AUD 10 billion road and tunnel project. The Australian Urban Research Infrastructure Network data was utilised to assess distances of childcare centres and schools from major truck routes. A range of cconcentration–response functions for childhood asthma (0–18 years) from international systematic meta-analyses and a smaller Australian cross-sectional study were applied to comparative elevations in fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations between the EPA reference monitor (used for project risk assessment) and local roadside data. It was found that comparative elevations in NO2 concentrations were associated with the following risk increases: developing asthma 13%, active asthma 12%, and lifetime asthma 9%. Overall, 41% of childcare centres (n = 51) and 36% of schools (n = 22) were ≤150 m to a high-density truck route. Truck emissions likely make a substantial contribution to childhood asthma outcomes in the project area. This study exemplifies how current practices may not be commensurate with guiding policy objectives of harm minimisation and equitable protection.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial

Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

521 Bringing UCSF Research Resources to Community Health Systems: CTSI Research Infrastructure Network (RIN)

OBJECTIVES/GOALS: The CTSI Research Infrastructure Network (RIN) expands CTSI’s reach into the regional health systems to provide our services to a broad and diverse translational science community. We create and support research collaborations that span multiple geographies and patient populations and serve as a bridge between the affiliate sites and CTSI programs. METHODS/STUDY POPULATION: We conducted needs assessments at each site (n=6) via in-depth, semi-structured interviews with key stakeholders. Informants (n=40) included investigators, study personnel, and research administrators. Investigators were selected across a variety of departments and career stages. Interview transcripts and notes were analyzed using matrix-based qualitative methods to identify both the common and unique research infrastructure needs of each site. Individualized support plans were shared with each site and a comprehensive summary report was presented to CTSI leadership. RIN met with UCSF’s Comprehensive Cancer Center, which conducts clinical trials at 2 sites, to coordinator our effort and services. When possible, RIN addressed service requests in real time that arose during interviews. RESULTS/ANTICIPATED RESULTS: We identified heterogeneous needs across multiple sites. However, among the community health systems with non-academic clinicians, there were common needs for research training, consultations in biostatistics/study design, and finding academic collaborators. The needs of sites with UCSF academic faculty differed from those of community sites and mainly included improved awareness and access to CTSI programs, ease of use of data extraction services, training programs, and assistance with regulatory approvals. Site needs are best addressed with individual plans created with CTSI Program leaders. A developing governance structure will include representation on a CTSI advisory committee and an annual conference to facilitate the sharing of best practices and foster collaboration across member sites. DISCUSSION/SIGNIFICANCE: Providing an individualized, site-specific approach to expanding CTSI services to regional health systems, will increase research collaborations across Northern California through building relationships, addressing unique infrastructure needs and sharing best practices throughout the network.

Lessons from a research partnership in southwest England to understand community palliative care needs in rural, coastal and low-income communities.

The South West Peninsula (Cornwall, Devon, Somerset) has the highest proportion of over 65s (24.2%) and is the only English rural population with greater economic deprivation than in urban areas. Coastal populations have the worst health outcomes in England. Despite innovation among communities to support those with health and care needs in later life, recruitment to palliative care research in the region is low and there has been no evaluation of public health palliative care interventions. A new South West Peninsula Palliative Care Research Partnership was funded for 15 months, bringing together four universities, the voluntary and community sector (including hospices) and local National Institute for Health and Care Research networks. The aim was to establish a sustainable multisectoral partnership that would identify community-based support needs for underserved rural and coastal populations by: • conducting a literature scoping review on interventions to enable community members to support the dying; • delivering a research capacity-building programme; • co-creating public and patient involvement capacity; • determining the resources and needs for communities to support dying well; • integrating findings to develop a framework of community-based support and identify future research questions; • establishing a sustainable research network infrastructure for the long-term design and delivery of palliative care research. We convened partners to identify research needs and co-designed activities to meet our objectives. These included a scoping review; a capacity-building programme of training, seminars and a journal club; forming a patient and public involvement group; a multistranded community engagement programme using different creative approaches; four focus groups with members of the public and one with community workers; and producing three 'storytelling' audio recordings. Findings were presented to the partnership at a regional workshop. The scoping review showed that community-engaged palliative care interventions can improve outcomes for individuals but provided little evidence about which approaches work for different communities. Five online seminars and a quarterly journal club to develop research capacity were regularly attended by 15 to 25 participants from across the partnership. While evaluating our engagement methods was beyond the partnership's scope, levels of participation suggested that creative methods of engagement show potential to help researchers and practitioners better understand the needs and priorities of underserved populations. Data showed that rural, coastal and low-income communities face challenges in accessing end-of-life care and support due to issues such as transport to and distance from services, erosion of neighbourhood networks, isolation from family and friends, 'patchiness' of palliative care services and a lack of care providers. Community organisations are well-placed to co-produce and facilitate methodologies for involving communities in palliative care research. Although activities took place in diverse areas, it was not possible within the available resources to cover the entire large geographical region, particularly the most isolated rural areas. Partnerships bringing together voluntary and community sector organisations, palliative care providers, health and social care providers, individuals with experience and academics have potential to design future research and public health interventions that better understand local context, involving and supporting communities to address their needs at end of life. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR135312.

Polar research infrastructure network: the Ukrainian input

Polar research infrastructure network: the Ukrainian input

Research infrastructure as a tool for scientific integration: some aspects of the EU experience for Ukraine

Research infrastructure as a tool for scientific integration: some aspects of the EU experience for Ukraine

Regional access to a centralized extracorporeal membrane oxygenation (ECMO) service in Victoria, Australia

IntroductionVictoria, Australia provides a centralised state ECMO service, supported by ambulance retrieval. Equity of access to this service has not been previously described. ObjectiveDescribe the characteristics of ECMO recipients and quantify geographical and socioeconomic influence on access. DesignRetrospective observational study with spatial mapping. Participants and settingAdult (≥18 years) ECMO recipients from July 2016–June 2022. Data from administrative Victorian Admissions Episodes Database analysed in conjunction with Australian Urban Research Infrastructure Network population data and choropleth mapping. Presumed ECMO modes were inferred from cardiopulmonary bypass and pre-hospital cardiac arrest codes. Spatial autoregressive models including Moran's test used for spatial lag testing. OutcomesDemographics and outcomes of ECMO recipients; ECMO incidence by patient residence (Statistical-Area Level 2, SA-2) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD); and ECMO utilisation adjusted for patient factors and linear distance from the central ECMO referral site. Results631 adults received ECMO over 6 years, after exclusion of paediatric (n = 242), duplicate (n = 135), and interstate or incomplete (n = 72) records. Mean age was 51.8 years, and 68.8 % were male. Overall ECMO incidence was 3.00 ± 3.95 per 105 population. 135 (21.4 %) were presumed VA-ECMO, 59 (9.3 %) presumed ECPR, and 437 (69.3 %) presumed VV-ECMO. Spatial lag was non-significant after adjusting for patient characteristics. Distance from the central referral site (dy/dx = 0.19, 95% CI −0.41–0.04, p = 0.105) and IRSAD score (dy/dx = 0.17, 95% CI −0.19–0.53, p = 0.359) did not predict ECMO utilisation. ConclusionVictorian ECMO incidence rates were low. We did not find evidence of inequity of access to ECMO irrespective of regional area or socioeconomic status.

Corticosteroids versus clobazam for treatment of children with epileptic encephalopathy with spike-wave activation in sleep (RESCUE ESES): a multicentre randomised controlled trial

Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) is a rare syndrome associated with cognitive and behavioural regression. On the basis of mostly small observational and retrospective studies, corticosteroids and clobazam are often considered the most effective treatments for this syndrome. We aimed to compare cognitive outcomes of children with EE-SWAS 6 months after starting treatment with either corticosteroids or clobazam. We did a multicentre, randomised controlled trial at eight tertiary referral centres for rare epilepsies in seven European countries. Children were eligible to participate if they were aged 2-12 years, were diagnosed with EE-SWAS within 6 months before inclusion, and had not been treated with corticosteroids or clobazam previously. Participants were randomly assigned (1:1) to treatment with corticosteroids (either continuous treatment with 1-2 mg/kg per day of prednisolone orally or pulse treatment with 20 mg/kg per day of methylprednisolone intravenously for 3 days every 4 weeks) or clobazam (0·5-1·2 mg/kg per day orally). The primary outcome was cognitive functioning after 6 months of treatment, which was assessed by either the intelligence quotient (IQ) responder rate (defined as improvement of ≥11·25 IQ points) or the cognitive sum score responder rate (defined as improvement of ≥0·75 points). Safety was assessed by number of adverse events and serious adverse events. Data were analysed in the intention-to-treat population, which included all children as randomised who had primary outcome data available at 6 months. The trial is registered with the Dutch Trial Register, Toetsingonline, NL43510.041.13, and the ISRCTN registry, ISRCTN42686094. The trial was terminated prematurely because enrolment of the predefined number of 130 participants was deemed not feasible. Between July 22, 2014, and Sept 3, 2022, 45 children were randomly assigned to either corticosteroids (n=22) or clobazam (n=23); two children assigned clobazam dropped out before 6 months and were excluded from the intention-to-treat analysis. At the 6-month assessment, an improvement of 11·25 IQ points or greater was reported for five (25%) of 20 children assigned corticosteroids versus zero (0%) of 18 assigned clobazam (risk ratio [RR] 10·0, 95% CI 1·2-1310·4; p=0·025). An improvement of 0·75 points or more in the cognitive sum score was recorded for one (5%) of 22 children assigned corticosteroids versus one (5%) of 21 children assigned clobazam (RR 1·0, 95% CI 0·1-11·7, p=0·97). Adverse events occurred in ten (45%) of 22 children who received corticosteroids, most frequently weight gain, and in 11 (52%) of 21 children who received clobazam, most often fatigue and behavioural disturbances. Occurrence of adverse events did not differ between groups (RR 0·8, 95% CI 0·4-1·4; p=0·65). Serious adverse events occurred in one child in the corticosteroid group (hospitalisation due to laryngitis) and in two children in the clobazam group (hospitalisation due to seizure aggravation, and respiratory tract infection). No deaths were reported. The trial was terminated prematurely, and the target sample size was not met, so our findings must be interpreted with caution. Our data indicated an improvement in IQ outcomes with corticosteroids compared with clobazam treatment, but no difference was seen in cognitive sum score. Our findings strengthen those from previous uncontrolled studies that support the early use of corticosteroids for children with EE-SWAS. EpilepsieNL, WKZ fund, European Clinical Research Infrastructure Network, and Ming fund.

ECRIN - CESSDA strategies for cross metadata mappings in selected areas between life sciences and social sciences and humanities.

The recent COVID-19 (Corona Virus Disease 2019) pandemic dramatically underlined the multi-faceted nature of health research, requiring input from basic biological sciences, pharmaceutical technologies, clinical research), social sciences and public health and social engineering. Systems that could work across different disciplines would therefore seem to be a useful idea to explore. In this study we investigated whether metadata schemas and vocabularies used for discovering scientific studies and resources in the social sciences and in clinical research are similar enough to allow information from different source disciplines to be easily retrieved and presented together. As a first step a literature search was performed, exemplarily identifying studies and resources, in which data from social sciences have been usefully employed or integrated with that from clinical research and clinical trials. In a second step a comparison of metadata schemas and related resource catalogues in ECRIN (European Clinical Research Infrastructure Network) and CESSDA (Consortium of European Social Science Data Archives) was performed. The focus was on discovery metadata, here defined as the metadata elements used to identify and locate scientific resources. A close view at the metadata schemas of CESSDA and ECRIN and the basic discovery metadata as well as a crosswalk between ECRIN and CESSDA metadata schemas have shown that there is considerable resemblance between them. The resemblance could serve as a promising starting point to implement a common search mechanism for ECRIN and CESSDA metadata. In the paper four different options for how to proceed with implementation issues are presented.

The met and unmet health needs for HIV, hypertension, and diabetes in rural KwaZulu-Natal, South Africa: analysis of a cross-sectional multimorbidity survey

The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. For the isiZulu translation of the abstract see Supplementary Materials section.

Patient and public involvement in health research in Norway: a survey among researchers and patient organisations

BackgroundPatient and public involvement (PPI) in health research may improve both the relevance and quality of the research. There is however a lack of research investigating the experiences, attitudes and barriers towards PPI in clinical research in Norway. The Norwegian Clinical Research Infrastructure Network therefore conducted a survey among researchers and PPI contributors aiming to investigate experiences with PPI and identify current challenges for successful involvement.MethodsTwo survey questionnaires were developed and distributed in October and November 2021. The survey targeting 1185 researchers was distributed from the research administrative system in the Regional Health Trusts. The survey targeting PPI contributors was distributed through Norwegian patient organisations, regional and national competence centers.ResultsThe response rate was 30% among researchers and was unobtainable from PPI contributors due to the survey distribution strategy. PPI was most frequently used in the planning and conduct of the studies, and less utilized in dissemination and implementation of results. Both researchers and user representatives were generally positive to PPI, and agreed that PPI might be more useful in clinical research than in underpinning research. Researchers and PPI contributors who reported that roles and expectations were clarified in advance, were more likely to experience a common understanding of roles and responsibilities in the research project. Both groups pointed to the importance of earmarked funding for PPI activities. There was a demand for a closer collaboration between researchers and patient organisations to develop accessible tools and effective models for PPI in health research.ConclusionsSurveys among clinical researchers and PPI contributors indicate overall positive attitudes towards PPI in clinical research. However, more resources, such as budget, time, and accessible tools, are needed. Clarifying roles and expectations, and creating new PPI models under resource constraints can enhance its effectiveness. PPI is underutilized in disseminating and implementing research results, presenting an opportunity for improving healthcare outcomes.

Surveying volcanic crises exercises: From open-question questionnaires to a prototype checklist

Volcanic crisis exercises are usually run to test response capabilities, communication protocols, and decision-making procedures by agencies with responsibilities to cope with scenarios of volcanic unrest with inherent uncertainty, such as volcano observatories and/or civil protection authorities. During the last decades, the use of questionnaires has been increased to evaluate people's knowledge on volcanic hazards and their perception of risk, to better understand their preparedness to respond to emergency measures plans.In this paper, we present a study carried out within the European Network of Observatories and Research Infrastructures for Volcanology project (EUROVOLC) focused on extracting information on the experience gained during volcanic-crisis exercises by the project's participants and beyond. An open-ended question questionnaire was firstly distributed for a survey within the project community. Through the results obtained, we developed a user-friendly online multi-choice questionnaire that was submitted to the volcanological communities within and outside EUROVOLC. Analyzing the answers to the online questionnaire, we extracted a prototype checklist for guiding the design of such exercises in the future. Our results confirm this type of survey as a very useful tool for gathering information on participants' experience and knowledge, able to understand which data and information may be useful when designing exercises for scientists, emergency managers and decision makers. In particular, the main lessons learnt regard the need i) to increase training activities involving people exposed to volcanic hazards and media, ii) to improve external communication tools (between players and public/media), equipment and protocols and iii) to better define decision-makers' needs.

Dataset: A consolidated and harmonised Verbal Autopsy dataset from Health and Demographic Surveillance Sites in South Africa.

This data note provides details of the development of a Verbal Autopsy (VA) dataset produced with the South African Population Research Infrastructure Network (SAPRIN) drawing on datasets from health and socio-demographic surveillance sites' (HDSS) ' covering a population of over 250,000 in two rural provinces in South Africa for the period 2012-2019. The purpose of the data set was to refine an analytical tool within VA, which provides unique information on care seeking and utilisation at and around the time of death complementary to that of medical cause of death. On an individual basis, the dataset includes demographic data, probable cause of death data, and data on care seeking and utilisation at or around the time of death drawn from longitudinal population cohorts. The purpose of this publication is to describe both the dataset and methods in formatting and processing the data for other researchers who may be interested in similar data. The data described in this paper are available to be requested from the respective HDSS repositories.

PedCRIN tool for the biosamples management in pediatric clinical trials.

In pediatric clinical research, it is essential to implement ethical and regulatory requirements, training, and facilities to grant the proper management of specimens, considering that blood sampling may be difficult, the number of specimens is usually limited, and all efforts should be made to minimize sample volumes. In the context of the Pediatric Clinical Research Infrastructure Network (PedCRIN) project, an easy-to-use tool has been developed to guide investigators and sponsors in managing specimens and associated data in compliance with the applicable European rules in the context of pediatric clinical trials. Key topics and research questions to properly manage biosamples and related data in the context of pediatric trials were identified by PedCRIN partners; the current European regulatory/ethical and legal resources were searched for and analyzed; the items/measures/procedures to ensure regulatory compliance of a pediatric trial with regards to biosamples were defined. A checklist of the key items to be considered for the management of biological samples in pediatric clinical trials in compliance with the European applicable rules and legislation, was prepared. It is publicly available on the PedCRIN website https://ecrin.org/projects/pedcrin. Five different topics were covered: consent and assent; minimizing harm and maximizing welfare; sampling volume; skills, training and facilities required for sampling; and long-term storage of biological material. This exercise addressed a specific need in the field of pediatric research to implement ad hoc procedures for specimen handling. In fact, specific guidance on the management of biosamples in pediatrics is not available.

OLGA, plateforme numérique d’aide au pilotage de réseaux nationaux de recherche en santé : un modèle pour les organisations complexes ?

OLGA (which stands for "Activity Management Tool" in French) is a digital management platform developed by F-CRIN, the French Clinical Research Infrastructure Network, which was set up in 2012 to improve the performance and attractiveness of clinical research in France. F-CRIN currently represents a community made up of 21 different components-thematic research, investigation and research networks with a national scope-bringing together the equivalent of 1,500 clinical researchers and 400 research centres all around the country and belonging to many different organizations. Faced with the difficulty of gathering uniform collective data that meet the requirements of F-CRIN's supervisory authorities, in 2015 the F-CRIN community decided to develop a specific monitoring and management tool. Designed with input from its future users, OLGA currently has two modules: one for the components' research activity and the other for their financial operations, resources and expenses. These are able to take account of the activity of the components in all their diversity and produce various sets of indicators. Other features, including a space for sharing documents, are currently being developed. Today, OLGA is a reference tool for managing large-scale, complex organisations.

The CAPNET multi-center data set for child physical abuse: Rationale, methods and scope

BackgroundThe pediatric subspecialty of Child Abuse Pediatrics (CAP) was certified by the American Board of Medical Subspecialties in 2006. Relative to its impact on pediatric health, CAP-focused research has been relatively under-funded. Multi-center networks related to CAP-focused research have made important advances, but have been limited in scope and duration. CAPNET is multi-center network whose mission is to support CAP-focused research. ObjectiveTo describe the rationale, development, and scope of the CAPNET research network infrastructure, the CAPNET data registry and associated data resources. MethodsBased on existing priorities for CAP-focused research, we used consensus building and iterative testing to establish inclusion criteria, common data elements, data quality assurance, and data sharing processes for children with concerns of physical abuse. ResultsWe describe the rationale, methods and intended scope for the development of the CAPNET research network and data registry. CAPNET is currently abstracting data for children <10 years (120 months) old who undergo sub-specialty evaluation for physical abuse at 10 US pediatric centers (approximately 4000 evaluations/year total) using an online data capture form. Data domains include: demographics; visit timing and providers, medical/social history, presentation, examination findings, laboratory and radiographic testing, diagnoses, outcomes, and data for contact children. We describe the methods and criteria for collecting and validating data which are broadly available to CAP investigators. ConclusionsCAPNET represents a new data resource for the CAP research community and will increase the quantity and quality of CAP-focused research.

Pediatric Hospital Medicine Needs More Randomized Controlled Trials.

Pediatric Hospital Medicine Needs More Randomized Controlled Trials.

Statistical validation of Aeolus L2A particle backscatter coefficient retrievals over ACTRIS/EARLINET stations on the Iberian Peninsula

Abstract. The Global Observing System (GOS) has encountered some limitations due to a lack of worldwide real-time wind measurements. In this context, the European Space Agency (ESA) has developed the Aeolus satellite mission, based on the ALADIN (Atmospheric Laser Doppler Instrument) Doppler wind lidar; this mission aims to obtain near-real-time wind retrievals at the global scale. As spin-off products, the instrument retrieves aerosol optical properties such as particle backscatter and extinction coefficients. In this work, a validation of Aeolus reprocessed (baseline 10) co-polar backscatter coefficients (βAeoluspart) is presented through an intercomparison with analogous ground-based measurements taken at the ACTRIS (Aerosols, Clouds and Trace gases Research InfraStructure Network)/EARLINET (European Aerosol Research Lidar Network) stations of Granada (Spain), Évora (Portugal) and Barcelona (Spain) over the period from July 2019 until October 2020. Case studies are first presented, followed by a statistical analysis. The stations are located in a hot spot between Africa and the rest of Europe, which guarantees a variety of aerosol types, from mineral dust layers to continental/anthropogenic aerosol, and allows us to test Aeolus performance under different scenarios. The so called Aeolus-like profiles (βAeoluslike,355part) are obtained from total particle backscatter coefficient and linear particle depolarization ratio (δlinearpart) profiles at 355 and 532 nm measured from the surface, through a thorough bibliographic review of dual-polarization measurements for relevant aerosol types. Finally, the study proposes a relation for the spectral conversion of δlinearpart, which is implemented in the Aeolus-like profile calculation. The statistical results show the ability of the satellite to detect and characterize significant aerosol layers under cloud-free conditions, along with the surface effect on the lowermost measurements, which causes the satellite to largely overestimate co-polar backscatter coefficients. Finally, the Aeolus standard correct algorithm middle bin (SCAmb) shows a better agreement with ground-based measurements than the standard correct algorithm (SCA), which tends to retrieve negative and meaningless coefficients in the clear troposphere. The implementation of Aeolus quality flags entails a vast reduction in the number of measurements available for comparison, which affects the statistical significance of the results.

Vírusellenes terápiás lehetőségek COVID–19 fertőzés kezelésére

Összefoglaló. A COVID–19-járvány egyre növekvő számú fertőzött betegének ellátása érdekében rövid időn belül szükség mutatkozott vírusellenes terápiás lehetőségekre. A gyors reagálás szempontját figyelembe véve erre a célra elsősorban más vírusok ellen már kifejlesztett vírusellenes szerek jöhetnek szóba. A magyar betegek ellátásbiztonsága szempontjából különösen fontos a hatóanyagok és gyógyszerkészítmények hazai gyártása. Ezt a cél tűzte ki a favipiravir, egy széles spektrumú antivirális hatóanyag hazai fejlesztése, amely sikeresen befejeződött, a gyógyszerkészítmény klinikai vizsgálata folyamatban van. Summary. Increasing impact of COVID-19 on the healthcare system prompted the identification of potential antiviral therapies. Due to the immediate demand, known drugs were subjected to repositioning attempts. These drugs include agents inhibiting the viral entry into the host cells, drugs potentially blocking the release of the viral RNA from the endosomes, antivirals inhibiting the replication of the viral RNA and finally compounds that might prevent the assembly of the new virion. Since there is less experience with camostat and nafamostat, the entry inhibitors tested in Japan, and due to the ambiguous data collected with the endosome blocking chloroquine and hydroxyl-chloroquine, we focused on the actual antiviral treatment options for COVID-19 infections. In addition to favipiravir and remdesivir that were used early, at the onset of the pandemic, we discuss novel candidates including molnupiravir, a promising antiviral actually investigated in clinical trials. Considering the needs of Hungarian COVID patients and the security of supply as first priority, we selected favipiravir and developed a convenient process for the industry-scale production of the active pharmaceutical ingredient (API). At the end of this review we summarize the development and clinical investigation of favipiravir, a wide spectrum antiviral drug used for the treatment of mild and moderate COVID patients in Hungary in both ambulant and clinical settings. The Hungarian COVID Task Force set up two consortia, one for the development and the other for the clinical investigations of favipiravir. The objective of the favipiravir development consortium was to develop processes for the production of Favipiravir API and dosage forms. The consortium completed the pilot plant scale industrial production of the API and produced clinical samples for the upcoming trials. The selection and laboratory scale optimization of the synthesis route was performed at the Medicinal Chemistry Research Group of the Research Center for Natural Sciences. The laboratory scale synthesis was scaled up for pilot plant production at EVI plc and Gedeon Richter plc. GMP production was realized at the facilities of Gedeon Richter plc. Finished dosage forms were developed at Meditop Ltd who produced the clinical samples under GMP conditions. The clinical consortium is headed by the Hungarian section of the European Clinical Research Infrastructure Network (ECRIN) and organized two trials. One of these trials investigates favipiravir produced in Hungary while the other trial is performed with favipiravir produced in Japan. Both studies were approved by the Hungarian regulatory agency (OGYÉI) and are ongoing.

Anti-inflammatory Diet for Interstitial Cystitis (AID-IC): Study Protocol for a Randomized Controlled Cross-Over Trial

ObjectivesIC/BPS is characterized by pelvic pain, pressure, or discomfort in the bladder and pelvic area coupled with urinary frequency and urgency. The cause is unknown. Dietary intake appears to exacerbate IC/BPS symptoms for many patients; however, the association is not well understood. The potential role of saturated fat and other inflammatory dietary components in provoking IC/BPS symptoms will be explored. Animal studies associate high dietary intake of saturated fats with activation of toll-like receptor (TLR4) cell signaling and pro-inflammatory responses. Saturated free fatty acids were linked to changes in the bladder on a cellular level. The goal of the AID-IC study is to investigate the efficacy of an anti-inflammatory diet (limits lipid intake and increases antioxidant intake) on symptom severity. MethodsIn a 22-week, crossover study, women with IC/BPS will be randomized into two groups. Group one will receive 10 weeks of a therapeutic anti-inflammatory diet that eliminates foods commonly bothersome for those with this condition; 5 days/week prepared, home-delivered meals were provided. Group 2 will receive counseling from a dietitian on standard IC/BPS dietary recommendations (control diet). After a two-week washout period, dietary interventions for the two groups will be switched. Primary outcomes include changes in inflammatory biomarkers (TNF-alpha and IL-1) and scores on three validated symptom severity surveys. ResultsWe hypothesize that an anti-inflammatory diet that excludes foods commonly bothersome for individuals with IC/BPS will help manage symptomology for these patients. Furthermore, we hypothesize that the severity of symptoms will be mediated by the reduction of pro-inflammatory responses associated with the influence of a diet low in saturated fats and high in anti-inflammatory dietary components. ConclusionsThe feasibility of managing IC/BPS symptoms by influencing inflammatory activity via restricting lipid intake and increasing antioxidant-rich foods has not previously been investigated. The findings may offer preliminary data on a cost-effective, noninvasive therapy. Funding SourcesMountain West Clinical & Translational Research Infrastructure Network (National Institute of General Medical Sciences, NIH).