Coping with interoperability in the development of a federated research infrastructure: achievements, challenges and recommendations from the JA-InfAct.

BACKGROUND: Information for Action! is a Joint Action (JA-InfAct) on Health Information promoted by the EU Member States and funded by the European Commission within the Third EU Health Programme (2014-2020) to create and develop solid sustainable infrastructure on EU health information. The main objective of this the JA-InfAct is to build an EU health information system infrastructure and strengthen its core elements by a) establishing a sustainable research infrastructure to support population health and health system performance assessment, b) enhancing the European health information and knowledge bases, as well as health information research capacities to reduce health information inequalities, and c) supporting health information interoperability and innovative health information tools and data sources. METHODS: Following a federated analysis approach, JA-InfAct developed an ad hoc federated infrastructure based on distributing a well-defined process-mining analysis methodology to be deployed at each participating partners' systems to reproduce the analysis and pool the aggregated results from the analyses. To overcome the legal interoperability issues on international data sharing, data linkage and management, partners (EU regions) participating in the case studies worked coordinately to query their real-world healthcare data sources complying with a common data model, executed the process-mining analysis pipeline on their premises, and shared the results enabling international comparison and the identification of best practices on stroke care. RESULTS: The ad hoc federated infrastructure was designed and built upon open source technologies, providing partners with the capacity to exploit their data and generate dashboards exploring the stroke care pathways. These dashboards can be shared among the participating partners or to a coordination hub without legal issues, enabling the comparative evaluation of the caregiving activities for acute stroke across regions. Nonetheless, the approach is not free of a number of challenges that have been solved, and new challenges that should be addressed in the eventual case of scaling up. For that eventual case, 12 recommendations considering the different layers of interoperability have been provided. CONCLUSION: The proposed approach, when successfully deployed as a federated analysis infrastructure, such as the one developed within the JA-InfAct, can concisely tackle all levels of the interoperability requirements from organisational to technical interoperability, supported by the close collaboration of the partners participating in the study. Any proposal for extension, should require further thinking on how to deal with new challenges on interoperability.

International versus national growth charts for identifying small and large-for-gestational age newborns: A population-based study in 15 European countries.

BACKGROUND: To inform the on-going debate about the use of universal prescriptive versus national intrauterine growth charts, we compared perinatal mortality for small and large-for-gestational-age (SGA/LGA) infants according to international and national charts in Europe. METHODS: We classified singleton births from 33 to 42 weeks of gestation in 2010 and 2014 from 15 countries (N = 1,475,457) as SGA (birthweight <10th percentile) and LGA (>90th percentile) using the international Intergrowth-21st newborn standards and national charts based on the customised charts methodology. We computed sex-adjusted odds ratios (aOR) for stillbirth, neonatal and extended perinatal mortality by this classification using multilevel models. FINDINGS: SGA and LGA prevalence using national charts were near 10% in all countries, but varied according to international charts with a north to south gradient (3.0% to 10.1% and 24.9% to 8.0%, respectively). Compared with appropriate for gestational age (AGA) infants by both charts, risk of perinatal mortality was increased for SGA by both charts (aOR[95% confidence interval (CI)]=6.1 [5.6-6.7]) and infants reclassified by international charts from SGA to AGA (2.7 [2.3-3.1]), but decreased for those reclassified from AGA to LGA (0.6 [0.4-0.7]). Results were similar for stillbirth and neonatal death. INTERPRETATION: Using international instead of national charts in Europe could lead to growth restricted infants being reclassified as having normal growth, while infants with low risks of mortality could be reclassified as having excessive growth. FUNDING: InfAct Joint Action, CHAFEA Grant n°801,553 and EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking ConcePTION grant n°821,520. AH received a PhD grant from EHESP.

Does Family History of Cancer Influence Undergoing Screening and Gastrointestinal Investigations?

BACKGROUND AND AIMS: Although a family history of cancer (FHC) can modify the lifestyle and attitudes towards participation in cancer screening programs, studies on this relationship show mixed results and vary across populations. The objectives of the study were to compare sociodemographic characteristics, history of gastrointestinal (GI) investigations and Helicobacter pylori eradication, and modifiable cancer risk factors between those with FHC and those with no FHC (NFHC), and to investigate the association between FHC and a history of GI investigations. METHODS: A total of 3,455 questionnaires from the pilot study of the "Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia were analysed. We compared sociodemographic characteristics and history of GI investigations between participants with self- reported FHC and NFHC. Binary logistic regression models adjusted for socio-demographic characteristics and modifiable cancer risk factors were built for a FHC and each GI investigation. RESULTS: Participants with a FHC were more likely to be women, have a higher education and less likely to have harmful habits (smoking, alcohol consumption) than those with NFHC. Participants with a FHC were approximately twice as likely to report recent colorectal investigations specifically for screening, than those with NFHC. In fully adjusted logistic regression models, FHC was significantly associated with a recent history of faecal occult blood tests (FOBTs), colonoscopies, and colorectal investigations (FOBT or colonoscopy) specifically for screening as part of the national organized screening programme. CONCLUSION: Our results indicate that those with a FHC have different patterns of health-related behaviour than those with NFHC.

Maternal Risk Factors for Stillbirth: A Registry-Based Study.

Background and Objectives: The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. Placental pathologies and infection associated with preterm birth are linked to a substantial proportion of stillbirths. Appropriate preconception care and quality antenatal care that is accessible to all women has the potential to reduce stillbirth rates. The aim of the present study was to assess potential risk factors associated with stillbirth within maternal medical diseases and obstetric complications. Materials and Methods: Retrospective cohort study (2001-2014) was used to analyse data from the Medical Birth Register on stillbirth and live births as controls. Adjusted Odds ratios (aOR) with 95% confidence intervals (CI) were estimated. Multiple regression model adjusted for maternal age, parity and gestational age. Results: The stillbirth rate was 6.2 per 1000 live and stillbirths. The presence of maternal medical diseases greatly increased the risk of stillbirth including diabetes mellitus (aOR = 2.5; p < 0.001), chronic hypertension 3.1 (aOR = 3.1; p < 0.001) and oligohydromnios/polyhydromnios (aOR = 2.4; p < 0.001). Pregnancy complications such as intrauterine growth restriction (aOR = 2.2; p < 0.001) was important risk factor for stillbirth. Abruption was associated with a 2.8 odds of stillbirth. Conclusions: Risk factors most significantly associated with stillbirth include maternal history of chronic hypertension and abruptio placenta which is a common cause of death in stillbirth. Early identification of potential risk factors and appropriate perinatal management are important issues in the prevention of adverse fetal outcomes and preventive strategies need to focus on improving antenatal detection of fetal growth restriction.

Maternal and Neonatal Characteristics for Late Foetal Death in Latvia between 2001 and 2014: Population-Based Study.

INTRODUCTION: Stillbirth is one of the most common adverse pregnancy outcomes worldwide. Late foetal death (LFD) rates are mostly used for international comparisons because of the large variations in stillbirth rates between countries. OBJECTIVE: To examine trends in LFD (including antepartum and intrapartum) by multiple births, birth weight, and maternal age in two time periods. METHODS: A retrospective cohort study was used to analyse data from the Medical Birth Register (2001-2014), divided into 2 periods of 7 years each. In total, data on 1,340 singletons were analysed. This study calculated LFD rates and rate ratios (RR). RESULTS: The overall LFD rate showed a slight statistically significant reduction (p < 0.001) of 18% between 2001-2007 and 2008-2014. There was a slight increase in the mortality rate from multiple pregnancies (RR 1.1/1000; 95% CI 0.6-1.9). There were no major differences in the LFD rate by maternal age during the time periods. CONCLUSIONS: LFD decreased (RR 0.8/1000 births), as well as intrapartum LFD (RR 0.6/1000 births). Older maternal age influenced pregnancy outcomes, and higher LFD rates were observed in the age group ≥35 years. Substantial intrapartum stillbirths rates indicate problems with quality of intrapartum care and emergency obstetric care. Further research is needed to evaluate the strategies necessary to substantially reduce the number of stillbirths in the country.

Can the Apgar Score be Used for International Comparisons of Newborn Health?

BACKGROUND: The Apgar score has been shown to be predictive of neonatal mortality in clinical and population studies, but has not been used for international comparisons. We examined population-level distributions in Apgar scores and associations with neonatal mortality in Europe. METHODS: Aggregate data on the 5 minute Apgar score for live births and neonatal mortality rates from countries participating in the Euro-Peristat project in 2004 and 2010 were analysed. Country level associations between the Apgar score and neonatal mortality were assessed using the Spearman rank correlation coefficient. RESULTS: Twenty-three countries or regions provided data on Apgar at 5 minutes, covering 2 183 472 live births. Scores <7 ranged from 0.3% to 2.4% across countries in 2004 and 2010 and were correlated over time (ρ = 0.88, P < 0.01). There were large differences in healthy baby scores: scores of 10 ranged from 8.8% to 92.7% whereas scores of 9 or 10 ranged from 72.9% to 96.8%. Countries more likely to score 10 s, as opposed to 9 s, for healthy babies had lower proportions of Apgar <7 (ρ = -0.43, P = 0.04). Neonatal mortality rates were weakly correlated with Apgar score <7 (ρ = -0.06, P = 0.61), but differences over time in these two indicators were correlated (ρ =0.56, P = 0.02). CONCLUSIONS: Large variations in the distribution of Apgar scores likely due to national scoring practices make the Apgar score an unsuitable indicator for benchmarking newborn health across countries. However, country-level trends over time in the Apgar score may reflect real changes and merit further investigation.

Role of serum cytokines in acute appendicitis and acute mesenteric lymphadenitis among children.

BACKGROUND AND OBJECTIVE: The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). The aim of this study was to evaluate differences in cytokine levels between AA and AML. MATERIALS AND METHODS: Data of 7- to 18-year-old children were collected prospectively from October 2010 to October 2013. There were 31 patients with AA (AA group), 26 with AML (AML group), and 17 with elective non-inflammatory surgical disease (control group). Serum levels of IL-10, IL-12(p70), IL-1ß, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α and white blood count (WBC) were measured three times consecutively in each group. RESULTS: The level of IL-6 and IL-10 was significantly higher in the AA group than the AML group at the first measurement (8pg/mL vs. 3.2pg/mL, P=0.000; 6.1pg/mL vs. 3.2pg/mL, P=0.005, respectively). There was a significant difference observed in time dynamics of concentration of IL-6 and MCP-1 for AA and AML. The area under the curve (AUC) was 0.77 (95% CI 0.64-0.89; P=0.001) for IL-6 with a cut-off value of 4.3pg/mL (67.7% sensitivity and 76.9% specificity) for AA 1h before surgery. The AUC for WBC was 0.72 (95% CI 0.58.4-0.85; P=0.005) with a cut-off value of 10.7×103/µL (sensitivity 71.0% and specificity 46.2%). CONCLUSIONS: Serum IL-6 with a cut-off value of 4.3pg/mL and WBC with a cut-off value of 10.7×103/µL assessed together will yield more sensitivity for AA.

Territorial differences in infant mortality in Latvia in the first decade of the third millennium.

OBJECTIVE: Infant and child mortality are some of the most substantial indicators of country welfare. Infant mortality (IM) in Latvia is constantly the highest among 25 Member States of the European Union. Since the regaining of independence in 1991, IM has decreased by almost 50%, however, it is still high enough to cause concern that the country will not be able to meet the UN Millennium Development Goals to decrease IM in Latvia by 2015. The Medical Faculty at the University of Latvia has conducted several studies identifying correlations between IM and GDP, total expenditure on health, unemployment and GINI coefficient. It is necessary to identify all IM causes and relationships which have not been studied, including the effect of social factors causing inequality between inhabitants of urban and rural areas: - The aim of the study was to determine the IM rate and the main death causes and their differences between rural and urban areas in Latvia (2000-2010). MATERIALS: This is a register-based study. The data of 1994 deceased infants was analyzed over the time period from 2000-2010. The studied population was divided into two groups - urban and rural areas by mothers' area of residence. Descriptive and analytical methods were used for analysis - frequency distribution, correlation and regression analysis. RESULTS: IM by maternal residence as well as IM indicators in the most common diagnostic subgroups have been higher in rural areas in the entire studied period (2000-2010). The decrease proportion of IM was more rapid in rural regions with a period average of 6.2% in comparison to urban regions - 2.6%. Annual decrease of IM from perinatal period conditions was 50% lower in rural than urban areas; annual decrease of IM from congenital malformations, deformations and chromosomal abnormalities was 20% lower in urban than rural areas; annual decrease in other diagnostic groups was 40% lower in urban than rural areas. During the study period, differences in infant mortality based on maternal socio- demographic factors, maternal health as well as pregnancy and obstetric history have been found, but the results of statistical analysis cannot be used to define these relationships as statistically significant in either areas. CONCLUSIONS: infant mortality in Latvia due to various conditions prevailing during perinatal period, external causes and sudden infant death syndrome can be substantially decreased - by improving the theoretical and technical capacity of obstetric departments in rural areas as well as educating society on preventable causes of death.

Maternal age-associated congenital anomalies among newborns: a retrospective study in Latvia.

BACKGROUND AND OBJECTIVE: In Latvia, the mean age of women giving birth increased from 27.3 in 2000 to 29.0 years in 2010 during the last 11 years. The aim of this study was to report on major congenital anomalies of newborns at birth by the maternal age and to compare the mean maternal age by different diagnosis subgroups and maternal and neonatal characteristics. MATERIAL AND METHODS: A cross-sectional retrospective study with the data from the Medical Birth Register (2000-2010) was carried out. The live birth prevalence rate was calculated for the subgroups of major congenital anomalies per 10 000 live births by the maternal age. RESULTS: The live birth prevalence rate of major congenital anomalies during the period 2000-2010 was 211.4 per 10 000 live births. The prevalence rate increased depending on the maternal age. Congenital heart defects, limb defects, and urinary system anomalies were the most common anomalies. The study results showed an age-related risk of abdominal wall defects, orofacial clefts, and chromosomal anomalies. There were significantly higher proportions of preterm births, newborns with low birth weight, and complications during pregnancy among mothers aged 35 years and more. CONCLUSIONS: The data on congenital anomalies from the Latvian Medical Birth Register can be used for the assessment of epidemiology of congenital anomalies. The results of this retrospective study showed a decrease in the live birth prevalence rate of major congenital anomalies despite an increase in the mean age of mothers in Latvia.

Infant mortality gap in the Baltic region - Latvia, Estonia, and Lithuania - in relation to macroeconomic factors in 1996-2010.

BACKGROUND AND OBJECTIVE. A constant gap has appeared in infant mortality among the 3 Baltic States - Latvia, Estonia, and Lithuania - since the restoration of independence in 1991. The aim of the study was to compare infant mortality rates in all the 3 Baltic countries and examine some of the macro- and socioeconomic factors associated with infant mortality. MATERIAL AND METHODS. The data were obtained from international databases, such as World Health Organization and EUROSTAT, and the national statistical databases of the Baltic States. The time series data sets (1996-2010) were used in the regression and correlation analysis. RESULTS. In all the 3 Baltic States, a strong and significant correlation was found: Latvia (r=-0.81, P<0.01), Lithuania (r=-0.93, P<0.01), and Estonia (r=-0.91, P<0.01). There was also a correlation between infant mortality and healthcare expenditure in local currency per capita: Latvia (r=-0.81, P<0.01); Lithuania (r=-0.90, P<0.01) and Estonia (r=-0.88, P<0.01). In Latvia (r=0.87, P<0.01) and Estonia (r=0.70; P<0.01), a significant correlation between infant mortality and unemployment levels was observed from 1996 to 2008, whereas the statistical significance disappeared in the period from 1996 to 2010. In Lithuania, the relationship was not significant. CONCLUSIONS. Higher infant mortality rates and a less stable decreasing tendency in Latvia are apparently explained by less successful adaptation to a new political and economic situation and limited skills in adjusting the healthcare system to the reality of life.

Mortality of children under five and prevalence of newborn congenital anomalies in relation to macroeconomic and socioeconomic factors in Latvia.

BACKGROUND: Mortality of infants and children younger than 5 years is a globally recognized and broad national welfare indicator. Scientific literature has data on the correlation of mortality indicators with macroeconomic indicators. It is important to study the associations between prevalence and mortality indicators and socioeconomic factors, since deaths from congenital anomalies account for approximately 25%-30% of all deaths in infancy. The aim of the study was to analyze the overall trend in mortality of infants and young children aged 0 to 4 years in relation to macroeconomic factors in Latvia and prevalence of congenital anomalies in newborns in relation to socioeconomic factors. MATERIAL AND METHODS: The Newborns' Register and Causes of Death Register were used as data sources; data on specific socioeconomic factors were retrieved from the Central Statistics Office. RESULTS: The results of the study show a strong correlation between mortality in children younger than 5 years and gross domestic product, as well as health budget in LVL per capita and the national unemployment level. The average decrease in infant mortality from congenital anomalies in Latvia was found to be 6.8 cases per 100,000 live births. CONCLUSIONS: There is a strong correlation between child mortality and socioeconomic situation in the country. There is a need to analyze the data on child mortality in a transnational context on a regular basis and studying the correlations between child mortality indicators and socioeconomic indicators and health care management parameters.