Paper 1: The EUROCAT network--organization and processes

The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population-based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening. This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring. The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates-an example of information useful to clinicians, public health service managers, and patients.     

Congenital malformations in offspring of Vietnamese women in California, 1985-97

BACKGROUND: Little is known about reproductive outcome risks for Vietnamese women delivering infants and fetuses in the U.S. METHODS: Using data from a large population-based registry, we explored risks of selected congenital malformation phenotypes in offspring of Vietnamese women in California. Data were derived from the California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with congenital malformations using multiple source ascertainment. Approximately 3.4 million births (liveborn and stillborn) occurred during the ascertainment period, 1985-97. Information on maternal race/ethnic background was obtained from California birth certificate and fetal death files. Vietnamese women delivered 45,453 births and 1,257,853 births were delivered to non-Hispanic white women. RESULTS: The overall prevalence of structural congenital malformations was 1.92 among Vietnamese and 2.63 among non-Hispanic whites per 100 births and fetal deaths. Grouping by 20 3-digit malformation codes of the International Classification of Diseases-Ninth Revision revealed relative risks of 0.8 or less for spina bifida, eye, upper alimentary, genital, urinary, musculoskeletal, "other" limb, and "other" musculoskeletal anomalies, and relative risks of 1.3 or more for anencephaly and chromosomal anomalies. Grouping by the more specific 4-digit malformation codes revealed 50, among 178, malformation groupings with associated relative risks of >or=1.3 or 相似文献   

Ascertainment of pregnancies terminated because of birth defects: effect on completeness of adding a new source of data

BACKGROUND: When evaluating preventive programs such as folate promotion and rubella vaccination, it is critically important to include terminations of pregnancy for neural tube defects and congenital rubella syndrome. Data from birth defects registries are often used for this purpose. The Western Australian Birth Defects Registry ascertains cases of birth defects in livebirths, stillbirths, and terminations of pregnancy for fetal abnormality, using multiple sources of ascertainment. METHODS: Data on terminations of pregnancy for fetal abnormality from the Western Australian Hospital Morbidity Data System 1980-1997 (not previously available to the Registry) were used to estimate the completeness of ascertainment of such cases by the Registry. Ascertainment-adjusted prevalences were calculated using capture-recapture methods. RESULTS: A total of 702 terminations with birth defects were identified among hospital discharges, most of which were already known to the Registry (87.9%). Of the 85 new cases, seven had a neural tube defect, 23 had a chromosomal defect, and 12 had confirmed maternal rubella infection during pregnancy. The ascertainment-adjusted prevalence was not importantly [corrected] different for birth defects overall or for these individual conditions, although the 95% confidence intervals for all birth defects, and for all chromosomal defects, did not include the prevalence based on registered cases only. CONCLUSIONS: The Western Australian Birth Defects Registry ascertains a high proportion of pregnancies terminated for fetal abnormality, and should therefore be a reliable source of data with which to assist in monitoring the effectiveness of preventive programs.     

Polish Registry of Congenital Malformations - aims and organization of the registry monitoring 300 000 births a year

In 1997, the Polish Registry of Congenital Malformations (PRCM) was established, to fulfil epidemiological, prophylactic, socioeconomic and scientific functions. The PRCM is a population-based registry monitoring currently about 300 000 births a year in 13 provinces. Such a large area and population require a special organizational structure of the Registry. The PRCM Central Working Group and the computer database are located in the Department of Medical Genetics, University of Medical Sciences, Poznań. Here the data are collected, validated, encoded according to the ICD-10, and analysed. Provincial Working Groups are responsible for supervision of data collection in the given province. The PRCM staff has grown from about 250 members in 1997 to more than 400 members today. The PRCM collects information on structural defects diagnosed before the end of the second year of life. Minor anomalies are excluded from the registry. The main source of information is a registration form filled up by the physician diagnosing the anomaly. Since 2004 also electronic reporting has been possible. On 28 September 2005 there were 54 020 entries in the database concerning 33 729 children with at least one congenital malformation and 1261 control entries concerning children without malformations. The PRCM is also an important source of identification of families at genetic risk. Education of physicians and the community in the field of genetic counselling is also an important aim of the PRCM. Since 2001, the PRCM has been a member of the Eurocat. Detailed information on PRCM organization, electronic reporting, and results are available at the PRCM website (www.rejestrwad.pl).     

Improving case ascertainment of a population-based birth defects registry in New York State using hospital discharge data

BACKGROUND: The assessment of the data quality of population-based registration systems is essential to understanding the reliability and usefulness of disease surveillance and research findings resulting from the use of registry data. Since the New York State Congenital Malformations Registry (CMR) uses passive case ascertainment, the completeness of the registry data is an important aspect of the quality of information. This paper presents the results of hospital audits, which were conducted to capture the unreported cases using hospital discharge files, and evaluates the effectiveness of the audits. METHODS: Children age 2 years or younger and diagnosed with reportable birth defects for the birth years 1998-2000 were selected from hospital discharge files of all reporting hospitals in the New York Statewide Planning and Research Cooperative System (SPARCS) and matched to the CMR database for the same birth year period.The unmatched reports from the SPARCS hospital discharge files that the CMR possibly missed were sent to hospitals, requesting submission of the missed reports. Two audits on all reporting hospitals in New York State were conducted: 1) 1998 and 1999 birth cohorts audited from June 2000 to March 2002, and 2) 2000 birth cohort audited from November 2001 to November 2002. RESULTS: Hospital audits using SPARCS hospital discharge data identified 5,460 reports that the CMR missed for the selected 66 hospitals analyzed. About 86% of these reports had reportable conditions and were added to the CMR, which comprised 21.4% of all reports from the 66 hospitals for the birth years 1998-2000. The number of reports that would have been missed without audits decreased from the 1998 and 1999 birth cohort (25.1%) to the 2000 birth cohort (13.9%). Low reporting rates and, thus, a high percent of added reports, were found for hospitals with a relatively small number of annual reports and for some specific birth defects such as chromosomal anomalies, anencephalus and congenital anomalies of the urinary system. CONCLUSION: The current study demonstrates that using hospital discharge data to improve case ascertainment is a valuable and effective method of enhancing birth defect surveillance, particularly for those hospitals with low reporting rates.     

An epidemiologic study of congenital malformations of the anterior abdominal wall in more than half a million consecutive live births.

The records of an ongoing health surveillance registry that utilizes multiple sources of ascertainment were used to study the incidence rate of congenital malformations of the anterior abdominal wall in live-born children in British Columbia during the period 1964--1978 inclusive. No overall increase in incidence rate of these anomalies was detected during the study period. The estimated live-born incidence rates were: one in 4,175 live births for omphalocoele, one in 12,328 live births for gastroschisis, and one in 29,231 live births for prune belly. The data were analyzed with regard to sex and associated anomalies. Some practical implications regarding assessment of these infants are discussed.     

Second generation registry framework

Background

Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage.

Results

This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised.

Conclusions

We introduce the second generation RDRF that enables the user-driven dynamic creation of patient registries. We believe this second generation RDRF is a novel approach to patient registry design, implementation and deployment and a significant advance on existing registry systems.

     

Staging practices and breast cancer stage among population-based registries in the MENA region

BackgroundAvailability of stage information by population-based cancer registries (PBCR) remains scarce for diverse reasons. Nevertheless, stage is critical cancer control information particularly for cancers amenable to early detection. In the framework of the Global Initiative for Cancer Registry Development (GICR), we present the status of stage data collection and dissemination among registries in the Middle East and Northern Africa (MENA) region as well as the stage distribution of breast cancer patients.MethodsA web-based survey exploring staging practices and breast cancer stage was developed and sent to 30 PBCR in 18 countries of the MENA region.ResultsAmong 23 respondent PBCR, 21 collected stage data, the majority (80%) for all cancers. Fourteen registries used a single classification (9 TNM and 5 SEER), 7 used both staging systems in parallel. Out of 12,888 breast cancer patients (seven registries) 27.7% had unknown TNM stage (11.1% in Oman, 46% in Annaba). When considering only cases with known stage, 65.3% were early cancers (TNM I+II), ranging from 57.9% in Oman to 83.3% in Batna (Algeria), and 9.9% were stage IV cancers. Among the nine registries providing SEER Summary stage for breast cancer cases, stage was unknown in 19% of the cases, (0 in Bahrain, 39% in Kuwait). Stage data were largely absent from the published registry reports.ConclusionDespite wide stage data collection by cancer registries, missing information and low dissemination clearly limit informing efforts on early detection. The use of two classification systems in parallel implies additional workload and might undermine completeness. The favourable results of early cancer (TNM I+II) in two thirds of breast cancer patients needs to be interpreted with caution and followed up in time. Although efforts to improve quality of stage data are needed, our findings are particularly relevant to the WHO Global Breast Cancer Initiative.     

Under-diagnosis and under-ascertainment of cases may be the reasons for low childhood cancer incidence in rural India

Cancer statistics from India revealed that childhood cancer incidence is lesser in rural than urban India. This might be due to under-diagnosis or under-ascertainment of cases or could even be true. With registries able to explicitly measure and appropriately streamline the ascertainment of cases to comply with acceptable standards, it is under-diagnosis that is variable and highly influenced by development of or accessibility to specialized centres in or around the registry area. This is reflected implicitly by marked variation in incidence between different populations in India: weighted age standardized rates of all childhood cancers together was the highest (108 per million) in metropolitan areas, followed by other urban (86) and rural (53) areas in that order. A childhood cancer registry focusing on pertinent data collection and specific epidemiological studies is desirable to explain the variations in incidence and outcome of childhood cancers in India.     

Active follow-up versus passive linkage with cancer registries for case ascertainment in a cohort

BackgroundAscertaining incident cancers is a critical component of cancer-focused epidemiologic cohorts and of cancer prevention trials. Potential methods: for cancer case ascertainment include active follow-up and passive linkage with state cancer registries. Here we compare the two approaches in a large cancer screening trial.MethodsThe Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial enrolled 154,955 subjects at ten U.S. centers and followed them for all-cancer incidence. Cancers were ascertained by an active follow-up process involving annual questionnaires, retrieval of records and medical record abstracting to ascertain and confirm cancers. For a subset of centers, linkage with state cancer registries was also performed. We assessed the agreement of the two methods in ascertaining incident cancers from 1993 to 2009 in 80,083 subjects from six PLCO centers where cancers were ascertained both by active follow-up and through linkages with 14 state registries.ResultsThe ratio (times 100) of confirmed cases ascertained by registry linkage compared to active follow-up was 96.4 (95% CI: 95.1–98.2). Of cancers ascertained by either method, 86.6% and 83.5% were identified by active follow-up and by registry linkage, respectively. Of cancers missed by active follow-up, 30% were after subjects were lost to follow-up and 16% were reported but could not be confirmed. Of cancers missed by the registries, 27% were not sent to the state registry of the subject’s current address at the time of linkage.ConclusionLinkage with state registries identified a similar number of cancers as active follow-up and can be a cost-effective method to ascertain incident cancers in a large cohort.     

Problems in using birth certificate files in the capture-recapture model to estimate the completeness of case ascertainment in a population-based birth defects registry in New York State

BACKGROUND: The limitations and underlying assumptions of the capture-recapture methods have hindered their application in epidemiological settings, especially in evaluating the completeness of birth defects registries. This study explored the possibility of using birth certificates as the secondary data source in a simple two-source capture-recapture model to estimate the completeness of case ascertainment of the Congenital Malformations Registry (CMR) for selected major birth defects. METHODS: The CMR and the birth certificates were used as the primary and secondary sources, respectively. Children who were born in 1996-2001 and had selected major birth defects were identified from the two sources. The accuracy of the diagnoses was examined by comparing the individual birth defect categories of the children from the two sources. RESULTS: Discrepancies in birth defect categories in the two data sources and false positives in the birth certificates were the major problems encountered in estimating the completeness of the CMR using the simple two-source capture-recapture method. The estimated completeness for selected major birth defects was only about 71%. Stratified analyses resulted in relatively high estimated completeness for oral clefts (90%) and Down syndrome (88%). CONCLUSIONS Although the birth certificate data was not a good source for estimating the completeness of case ascertainment of the CMR using capture-recapture methods, the analyses provided reasonable estimates for some conditions that were relatively easy to identify and diagnose at birth, such as oral clefts and Down syndrome.     

Genetic disorders in children and young adults: a population study.

The data base of an ongoing population-based registry with multiple sources of ascertainment was used to estimate the present population load from genetic disease in more than 1 million consecutive live births. It was found that, before approximately age 25 years, greater than or equal to 53/1,000 live-born individuals can be expected to have diseases with an important genetic component. This total was composed of single-gene disorders (3.6/1,000), consisting of autosomal dominant (1.4/1,000), autosomal recessive (1.7/1,000), and X-linked recessive disorders (0.5/1,000). Chromosomal anomalies accounted for 1.8/1,000, multifactorial disorders (including those present at birth and those of onset before age 25 years) accounted for 46.4/1,000, and cases of genetic etiology in which the precise mechanism was not identified accounted for 1.2/1,000. Previous studies have usually considered all congenital anomalies (ICD 740-759) as part of the genetic load, but only those judged to fit into one of the above categories were included in the present study. Data for congenital anomalies are therefore also presented separately, to facilitate comparison with earlier studies. If all congenital anomalies are considered as part of the genetic load, then greater than or equal to 79/1,000 live-born individuals have been identified as having one or other genetic disorder before approximately age 25 years. These new data represent a better estimate of the genetic load in the population than do previous studies.     

The completeness and timeliness of cancer registration and the implications for measuring cancer burden

BackgroundPopulation based cancer registration provides a critical role in disease surveillance in terms of incidence, survival, cancer cluster investigations and prevalence trends, and therefore high levels of completeness and timeliness are required. This study estimates completeness and variation between early and late registrations in the N. Ireland Cancer Registry (NICR) and assesses the implications for reporting cancer incidence and for registry-based research.MethodsTwo main approaches assessed completeness. For the period 2010–2012, incidence reported in the first year of data publication was compared to incidence reported in subsequent years until 2015. Demographic characteristics and survival of incident cases ascertained before the first publication year were compared to those ascertained in subsequent years. The flow method approach was used to estimate completeness annually after the incident year.ResultsOverall incidence for all cancers increased between the first year of data publication and subsequent years up to 2015, irrespective of year of diagnosis. Late registrations had poorer survival. The flow method approach estimated the completeness of case ascertainment of NICR data to be 96% complete at five years for all cancers combined.ConclusionThe estimated completeness levels for the NICR are comparable to other high quality cancer registries internationally. While data timeliness has little impact on incidence estimates, delays in registration may have implications for specific research studies into incidence and survival. This means that improvements in the timeliness of reporting should be a target for all registries but not at the expense of completeness.     

Full Likelihood Analysis of Genetic Risk with Variable Age at Onset Disease—Combining Population-Based Registry Data and Demographic Information

Background

In genetic studies of rare complex diseases it is common to ascertain familial data from population based registries through all incident cases diagnosed during a pre-defined enrollment period. Such an ascertainment procedure is typically taken into account in the statistical analysis of the familial data by constructing either a retrospective or prospective likelihood expression, which conditions on the ascertainment event. Both of these approaches lead to a substantial loss of valuable data.

Methodology and Findings

Here we consider instead the possibilities provided by a Bayesian approach to risk analysis, which also incorporates the ascertainment procedure and reference information concerning the genetic composition of the target population to the considered statistical model. Furthermore, the proposed Bayesian hierarchical survival model does not require the considered genotype or haplotype effects be expressed as functions of corresponding allelic effects. Our modeling strategy is illustrated by a risk analysis of type 1 diabetes mellitus (T1D) in the Finnish population-based on the HLA-A, HLA-B and DRB1 human leucocyte antigen (HLA) information available for both ascertained sibships and a large number of unrelated individuals from the Finnish bone marrow donor registry. The heterozygous genotype DR3/DR4 at the DRB1 locus was associated with the lowest predictive probability of T1D free survival to the age of 15, the estimate being 0.936 (0.926; 0.945 95% credible interval) compared to the average population T1D free survival probability of 0.995.

Significance

The proposed statistical method can be modified to other population-based family data ascertained from a disease registry provided that the ascertainment process is well documented, and that external information concerning the sizes of birth cohorts and a suitable reference sample are available. We confirm the earlier findings from the same data concerning the HLA-DR3/4 related risks for T1D, and also provide here estimated predictive probabilities of disease free survival as a function of age.     

Practice of ST-segment elevation myocardial infarction care in the Netherlands during four snapshot weeks with the National Cardiovascular Database Registry for Acute Coronary Syndrome

Background

Clinical registries provide information on the process of care and patient outcomes, with the potential to improve the quality of patient care. A large Dutch national acute coronary syndrome (ACS) registry is currently lacking. Recently, we initiated the National Cardiovascular Database Registry (NCDR) for ACS in the Netherlands. The purpose of this study was to assess the NCDR ACS registry on feasibility and data completeness during a pilot phase of four snapshot weeks.

Methods

Between 2013 and 2015, we invited all hospitals in the Netherlands to record a predefined dataset for every patient that was admitted to their hospital with ST-segment elevation myocardial infarction (STEMI). Data were entered in an online case report form. All patient-specific data were encrypted to ensure privacy.

Results

A total of 392 patients were registered in 35 centres. The mean age of the patients was 64 years (SD 13); 8% of patients presented with signs of cardiogenic shock and 11% with an out-of-hospital cardiac arrest. The median time from first medical contact to percutaneous coronary intervention (PCI) was 75 min (IQR 51–108) and this was significantly longer for patients who presented at a non-PCI centre or to a primary care physician. In-hospital and 30-day mortality rates were 5.2% and 7.8%, respectively. The amount of completeness varied, with improved completeness over time.

Conclusion

This report shows that a Dutch ACS registry is feasible with respect to STEMI patients. Data completeness, however, was suboptimal. Improved data completeness is warranted for the future.

     

Adjusting for reporting delay in cancer incidence when combining different sets of cancer registries

Cancer registries collect cancer incidence data that can be used to calculate incidence rates in a population and track changes over time. For incidence rates to be accurate, it is critical that diagnosed cases be reported in a timely manner. Registries typically allow a fixed amount of time (e.g. two years) for diagnosed cases to be reported before releasing the initial case counts for a particular diagnosis year. Inevitably, however, additional cases are reported after the initial counts are released; these extra cases are included in subsequent releases that become more complete over time, while incidence rates based on earlier releases will underestimate the true rates. Statistical methods have been developed to estimate the distribution of reporting delay (the amount of time until a diagnosed case is reported) and to correct incidence rates for underestimation due to reporting delay. Since the observed reporting delays must be less than the length of time the registry has been collecting data, most methods estimate a truncated delay distribution. These methods can be applied to a group of registries that began collecting data in the same diagnosis year. In this paper, we extend the methods to two groups of registries that began collecting data in two different diagnosis years (so that the delay distributions are truncated at different times). We apply the proposed method to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program, a consortium of U.S. cancer registries that includes nine registries with data collection beginning in 1981 and four registries with data collection beginning in 1992. We use the method to obtain delay‐adjusted incidence rates for melanoma, liver cancer, and Hodgkin lymphoma.     

Completeness and validity in a national clinical thyroid cancer database: DATHYRCA

BackgroundAlthough a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA.Study design and settingNational prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference.ResultThe database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement.ConclusionIn a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level.