Improving the quality of surveillance data on congenital heart defects in the metropolitan Atlanta congenital defects program

BACKGROUND: One of the challenges in epidemiologic studies of congenital heart defects (CHDs) has been the lack of a current, standard nomenclature and classification system. Recently such a standard nomenclature became available from the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. This study reports the classification of cases of CHDs in a birth defects surveillance database using modified STS nomenclature. METHODS: Records of infants and fetuses in the Metropolitan Atlanta Congenital Defects Program delivered during 1968-2003 with CHD diagnoses were reviewed by a team of pediatric cardiologists. The cases were assigned one or more STS codes and subsequently grouped into successively broader levels of aggregation. Aggregation was based on presumed morphogenetically similar developmental mechanisms. RESULTS: There were 12,639 cases reviewed, of which 89% had a single, primary STS code. Structural CHDs were found in 7,749 infants, while 4,890 were considered to have structurally normal hearts. Application of clinical CHD nomenclature improved the clinical accuracy of surveillance data by eliminating normal physiologic variants and obligatory shunt lesions. Classification also aggregated specific CHDs into groups appropriate for research and surveillance. CONCLUSIONS: Application of a current, standard CHD nomenclature and classification system to cases in a birth defects surveillance database improves the specificity of cardiac diagnoses and allows for the development of a flexible case aggregation system for monitoring of CHD prevalence.     

Wearable defibrillator use in heart failure (WIF): results of a prospective registry

Background

In patients with non-valvular atrial fibrillation (NVAF) at high risk for stroke guidelines consistently recommend long-term oral anticoagulation (OAC) with a vitamin K antagonist. However recommendations remain ambiguous in respect to the precise OAC initiation regimens. Based on the clinical observation, that the initiation of OAC for NVAF varies considerably in daily practice, we aimed to assess the current practice in Switzerland.

Methods

Cross-sectional survey of randomly selected general practitioners, internists and cardiologists from different health care settings in an urban Swiss region that covers 1.4 million inhabitants. The main outcome measures were the preferred antithrombotic initiation regimen and long-term treatment in patients with newly diagnosed NVAF at high risk for stroke.

Results

We received 226 out of 388 (58.2%) surveys. Compared to physicians working in a hospital setting (33.6% of respondents) physicians in ambulatory care reported more years of experience and claimed lower-use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long-term thromboembolic prophylaxis 93.7% of all responders followed current recommendation by choosing an OAC. When focussing on guideline-consistent correct OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC) adherence dropped to 60.6% with hospital physicians demonstrating a significantly higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality in non-hospital physicians was not related to correct guideline-use. Hospital setting remained independently associated with a guideline-conform OAC initiation regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians' characteristics and clinical experience. Problems when starting an anticoagulation treatment were seldom reported (never or seldom accounting for 94.1% of all responses).

Conclusions

The guideline adherence with respect to OAC initiation regimens in NVAF was significantly lower when compared to long-term treatment and health care setting rather than medical speciality explained guideline-conform OAC initiation. The majority of the physicians did not consider the initiation of anticoagulation to be a major obstacle in outpatient care.     

Patterns of first-year survival among infants with selected congenital anomalies in Texas, 1995-1997.

BACKGROUND: Few registry-based studies have investigated survival among infants with congenital anomalies. We conducted a registry-based study to examine patterns and probability of survival during the first year of life among infants with selected congenital anomalies. METHODS: Data from the Texas Birth Defects Monitoring Division were merged with linked birth-infant death files for 2,774 infants born January 1, 1995 to December 31, 1997, with at least 1 of 23 common anomalies. Deaths before the first birthday were assessed from infant death files. Kaplan-Meier was used to estimate first-year survival; first-year survival was assessed for specific anomalies and by the number of life-threatening anomalies. RESULTS: Overall, 80.8% of infants with these 23 anomalies survived the first year of life. We observed the highest survival rates for infants with gastroschisis (92.9%, 95% CI = 86.8, 96.3), trisomy 21 (92.3%, 95% CI = 89.5, 94.4) or cleft lip with or without cleft palate (87.6%, 95% CI = 84.0, 90.5). Infants with intermediate survival rates included those with microcephaly (79.7%; 95% CI = 73.6, 84.6), tetralogy of Fallot (75.0%; 95% CI = 65.5, 82.2), or with diaphragmatic hernia (72.8%; 95% CI = 61.8, 81.2). As expected, all infants with anencephaly and almost all infants with trisomy 13 or trisomy 18 died during the first year of life. First-year survival declined as the number of co-occurring life-threatening anomalies increased. CONCLUSIONS: Overall, first-year survival for infants with congenital anomalies was high. Additional population-based studies are needed to quantify improvements in first-year survival.     

Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans

Congenital heart defects (CHDs) are among the most common birth defects in humans (incidence 8-10 per 1,000 live births). Although their etiology is often poorly understood, most are considered to arise from multifactorial influences, including environmental and genetic components, as well as from less common syndromic forms. We hypothesized that disturbances in left-right patterning could contribute to the pathogenesis of selected cardiac defects by interfering with the extrinsic cues leading to the proper looping and vessel remodeling of the normally asymmetrically developed heart and vessels. Here, we show that heterozygous loss-of-function mutations in the human GDF1 gene contribute to cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries and that decreased TGF- beta signaling provides a framework for understanding their pathogenesis. These findings implicate perturbations of the TGF- beta signaling pathway in the causation of a major subclass of human CHDs.     

Cancer incidence in southern Iran, 1998-2002: results of population-based cancer registry

Purpose: The main aim of this study was to obtain population-based cancer incidence data for the entire population of Fars province in Iran, and to compare these rates with those obtained from a previous study in the same population ten years previously. Methods: Data were collected on all patients in major cities of Fars province who were diagnosed with cancer between 1998 and 2002. The data were computerized using SPSS (Chicago, IL) software, version 13.0, and MS EXCEL (Microsoft, Redmond, WA) software with Persian fonts. The results are presented as incidence rates of cases by site, sex, age, crude rates, and age-standardized rates per 100,000 person-years (ASRs), using the direct method of standardization to the world population. Results: During the 5-year study period, 8359 new cancer cases were registered. Diagnosis of cancer was based on histopathological criteria in 86.7%, clinical or radiological criteria in 9.4% and death certificate only in 3.9% of cases. According to the calculated ASRs, the 5 most frequent cancers in women were breast (13 per 100,000), stomach (4.4 per 100,000), lung and bronchus (2.9 per 100,000), uterus (2.7 per 100,000), and colon and rectum (2.6 per 100,000); and in men, the 5 most frequent types were stomach (9.2 per 100,000), bladder (6.8 per 100,000), lung and bronchus (6.3 per 100,000), lymphocytic leukemia (4.1 per 100,000), and skin melanoma (3.8 per 100,000). The ASR for all cancers in men was 64.5 per 100,000, and that for women was 55.5 per 100,000. Conclusion: Considering the limitations of this study, our results should be taken as the minimum incidence rates of cancers in Fars province, southern Iran. Significant differences were observed between the two study periods. However, we most likely have underestimated the frequencies of some tumors.     

Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics

BACKGROUND: Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. METHODS: A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. RESULTS: Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). CONCLUSIONS: Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.     

Testing association of a pathway with survival using gene expression data

MOTIVATION: A recent surge of interest in survival as the primary clinical endpoint of microarray studies has called for an extension of the Global Test methodology to survival. RESULTS: We present a score test for association of the expression profile of one or more groups of genes with a (possibly censored) survival time. Groups of genes may be pathways, areas of the genome, clusters from a cluster analysis or all genes on a chip. The test allows one to test hypotheses about the influence of these groups of genes on survival directly, without the intermediary of single gene testing. The test is based on the Cox proportional hazards model and is calculated using martingale residuals. It is possible to adjust the test for the presence of covariates. We also present a diagnostic graph to assist in the interpretation of the test result, visualizing the influence of genes. The test is applied to a tumor dataset, revealing pathways from the gene ontology database that are associated with survival of patients. AVAILABILITY: The Global Test for survival has been incorporated into the R-package globaltest (version 3.0), available at http://www.bioconductor.org     

The prevalence of cytogenetic anomalies in children with congenital developmental defects (CDD)

The analysis of the cytogenetic anomalies frequencies in children with inborn defects of development was carried out, and the comparative evaluation of involving in cytogenetic anomalies of the individual chromosomes was determined. Chromosomes 9, 13 and 18 were most frequently involved in chromosomal anomalies. There no direct relations were revealed between peculiarities of inborn defects of development and definite cytogenetic anomalies.     

Thymic medullary structures: Microscopical picture of the thymic medullary structures in children with congenital heart defects

The aim of this work is to describe the structure of the thymus, especially its medullary part, in children with congenital heart defects. It is known that development of the thymus and the heart is also influenced by neural crest cells. During the early development of the heart and the thymus cells proliferate and migrate to their primordia. It is known that inadequate cephalic neural crest contribution during development of pharyngeal pouch derivatives results in defective organogenesis of the face, the thymus, parathyroid glands and also the heart. We studied the structure of the thymus in children with congenital heart defects from 0 to 12 years of life at light microscopic and electron-microscopic levels. Thymuses of the patients were surgically removed in the Children’s Cardiocenter in Bratislava. The results of our study confirmed the differences in the medullary structures of thymuses with chosen diagnoses. Hassall’s corpuscles in the thymic medulla were various in size and also in structure and number. The special structures of the thymic medullary region in children with ventricular septal defects and defects of outflow of the heart were big cystic Hassall’s corpuscles. In comparison with a size of Hassall’s corpuscles in normal thymuses the size of Hassall’s corpuscles in studied thymuses suprisingly ranged between 100–250 μm.