Incidence, risk factors, and fracture healing of atypical femoral fractures: a multicenter case-control study.

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment. INTRODUCTION: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing. METHODS: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing. RESULTS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment. CONCLUSIONS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.

The effect of malnutrition on the risk of diarrheal and respiratory mortality in children < 2 y of age in Cebu, Philippines.

The effects of nutritional status on diarrheal and acute lower respiratory infection (ALRI) mortality in children < 2 y of age were examined by using data from a 1988-1991 longitudinal study of 9942 children in Metro Cebu, Philippines. Cox regression methods were used to study the strengths of the associations, possible interactions with birth weight and breast-feeding status, and the effect of additional confounding factors. Nutritional status as measured by weight-for-age was a significant risk factor for both ALRI and diarrheal mortality in the first 2 y of life. Poor nutritional status resulted in a 1.6-fold increased risk of diarrheal mortality for each one-unit decrease in weight-for-age Z score. For ALRI mortality, a one-unit decrease in weight-for-age Z score resulted in a 1.7-fold increase in risk, and for mortality associated with ALRI and diarrhea combined, the relative risk was 2.0. This study provides further evidence that malnutrition is a major determinant of mortality in very young children and it is one of the first longitudinal studies to estimate the magnitude of the effect on cause-specific mortality associated with nutritional status.

Contribution of birth defects and genetic diseases to pediatric hospitalizations. A population-based study.

OBJECTIVE: To estimate the contribution of birth defects and genetic diseases to pediatric hospitalizations by use of population-based data. DESIGN: Hospital discharges were categorized according to the diagnostic codes of The International Classification of Diseases, Ninth Revision, Clinical Modification. Hospitalizations that were related to birth defects and genetic diseases were compared with hospitalizations for other reasons, with respect to age, race/ethnicity, sex, length of stay, charges, source of payment, and mortality rate. Hospitalization rates and per capita charges were computed with the use of population estimates from 1990 census data. MATERIALS: The 1991 population-based hospital discharge data from California and South Carolina. RESULTS: Nearly 12% of pediatric hospitalizations in the 2 states combined were related to birth defects and genetic diseases. These children were, on average, about 3 years younger, stayed 3 days longer in a hospital, incurred 184% higher charges, and had a 4 1/2 times greater in-hospital mortality rate than children who were hospitalized for other reasons. The rate of hospitalizations that were related to birth defects and genetic diseases was 4 per 1000 children in both states, but these rates varied by age and race. CONCLUSION: These population-based data are the first contemporary findings to show the substantial morbidity rate and hospitalization charges associated with birth defects and genetic diseases in the pediatric population. IMPLICATIONS: This information is important for planning effective health care strategies, especially as the causes, treatments, and prevention of these disorders are being further elucidated by findings from human genome research and epidemiologic studies.

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7,470 cases and 3,821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nation's leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Multiple congenital brachymetatarsia. A one-stage combined shortening and lengthening procedure without iliac bone graft.

We performed nine metatarsal and three proximal phalangeal lengthenings in five patients with congenital brachymetatarsia of the first and one or two other metatarsal bones, by a one-stage combined shortening and lengthening procedure using intercalcary autogenous bone grafts from adjacent shortened metatarsal bones. Instead of the isolated lengthening of the first and the other metatarsal bones, we shortened the adjacent normal metatarsal and used the excised bone to lengthen the short toes, except for the great toe, to restore the normal parabola. One skin incision was used. All the operations were performed bilaterally and the patients were followed up for a mean period of 69.5 months (29 to 107). They all regained a nearly normal parabola and were satisfied with the cosmetic results. Our technique is straightforward and produces good cosmetic results. Satisfactory, bony union is achieved, morbidity is low, and no additional surgery is required for the removal of metal implants.

Resource contribution by Canadian faculties of medicine to the discipline of emergency medicine.

OBJECTIVE: Undergraduate and postgraduate emergency medicine (EM) education has developed rapidly over the last 20 years. Our objective was to establish a national educational inventory, cataloguing the human and financial resources provided to EM programs by Canadian faculties of medicine. METHODS: A 17-question survey was distributed to all 27 Canadian EM program directors, representing 11 Royal College of Physicians and Surgeons of Canada (RCPSC) programs and 16 College of Family Physicians of Canada (CFPC-EM) programs. The questionnaire addressed teaching responsibilities, teaching support and academic support in each program. RESULTS: All 27 program directors returned valid questionnaires. Annually, an estimated 3,049 students and residents participate in EM learning. This includes 1,369 undergraduates (45%), 1,621 postgraduates (53%) and 59 others (2%). Of the postgraduates, 173 are EM residents -- 92 (53%) in RCPSC programs and 81 (47%) in CFPC-EM programs. Overall, 587 EM faculty teach residents and students, but only 36 (6%) of these hold academic geographical full time positions. At the university level, all 16 CFPC-EM programs are administered by departments of family medicine. Of 11 RCPSC programs, 1 has full departmental status, 2 are free-standing divisions, 3 are administered through family medicine, 3 through medicine, 1 through surgery and 1 by other arrangements. Currently 8 programs (30%) have associate faculty, 14 (52%) have designated research directors and 10 (37%) describe other human resources. Sixteen (59%) programs receive direct financial and administrative support and 17 (63%) receive financial support for resident initiatives. Only 8 program directors (30%) perceive that they are receiving adequate support. CONCLUSIONS: Despite major teaching and clinical responsibilities within the faculties of medicine, Canadian EM programs are poorly supported. Further investment of human and financial and human resources is required.

A decade of public health genomics in the United States: centers for disease control and prevention 1997-2007.

Since 1997, the Centers for Disease Control and Prevention (CDC) has collaborated with numerous partners to develop and chart the course of the multidisciplinary field of public health genomics in the USA and globally. During this period, CDC has developed major initiatives for the appropriate integration of genomics into public health research, policy and programs. In this paper, we review briefly the progress in public health genomics made over the past decade in the USA, including population research, the human genome epidemiology network (HuGENet(TM)), the evaluation of genomic applications in practice and prevention (EGAPP), the family history public health initiative, and efforts in building the public health genomics capacity. We also outline a vision for public health genomics for the next decade.

Impact of prenatal diagnosis and elective termination on the prevalence of selected birth defects in Hawaii.

This study examined the effect of prenatal diagnosis and elective termination on the prevalence of neural tube defects, oral clefts, abdominal wall defects, and chromosomal anomalies in Hawaii by using actively ascertained surveillance data collected between 1987 and 1996 by the Hawaii Birth Defects Program. Because the Program has nearly universal access to prenatal diagnostic information and to follow-up data on elective terminations, Hawaii is an ideal setting in which to study their effects on prevalence rates of birth defects. Except for oral clefts, a large proportion of the defects studied were prenatally diagnosed: anencephaly (87%), spina bifida (62%), encephalocele (83%), cleft palate (0%), cleft lip with or without cleft palate (14%), omphalocele (60%), gastroschisis (76%), Down syndrome (43%), trisomy 18 (61 %), and trisomy 13 (40%). The effect of elective terminations on the birth prevalence rates for most of these birth defects was significant. Including electively terminated cases in the calculations of birth prevalence rates increased the rates by more than 50% for five of the 10 birth defects studied.

PIP: A surveillance study was conducted to examine the effects of prenatal diagnosis and elective terminations on the prevalence of neural tube defects (NTDs), oral clefts, abdominal wall defects, and chromosomal anomalies in Hawaii. The analysis involved 10 years of data collected through the Hawaii Birth Defects Program during 1987-96; the data comprised all reported cases of anencephaly, spina bifida, encephalocele, cleft palate, cleft lip with or without cleft palate, omphalocele, gastroschisis, Down syndrome, trisomy 18, and trisomy 13. Findings showed that there were 211 infants with NTDs (87% anencephaly, 62% spina bifida, and 83% encephalocele), 376 infants with oral cleft (14% cleft lip with or without cleft palate), 117 with abdominal wall defects (60% omphalocele and 76% gastroschisis), and 449 chromosomal anomalies (43% Down's syndrome, 61% trisomy 18, and 40% trisomy 13). Prenatal diagnosis and elective pregnancy terminations have a significant impact on the birth prevalence rates of NTDs and chromosomal anomalies. These finding have important implications for other birth defects surveillance programs.

Effect of not breastfeeding on the risk of diarrheal and respiratory mortality in children under 2 years of age in Metro Cebu, The Philippines.

The effects of not breastfeeding on mortality due to diarrhea and acute lower respiratory infection (ALRI) in children under 2 years of age were examined using data from a 1988-1991 longitudinal study of 9,942 children in Metro Cebu, The Philippines. Cox regression methods were used to study the magnitude of the risks, possible interactions with birth weight and nutritional status, and the effect of additional confounding factors. Not breastfeeding had a greater effect on diarrheal mortality than on ALRI mortality. In the first 6 months of life, failing to initiate breastfeeding or ceasing to breastfeed resulted in an 8- to 10-fold increase in the rate of diarrheal mortality. The rate of mortality associated with both ALRI and diarrhea was increased nearly six times by not breastfeeding, but the rate of ALRI mortality alone was not increased. The data also suggested that the risk of mortality associated with not breastfeeding was greater for low birth weight infants and infants whose mothers had little formal education. After age 6 months, the protective effects of breastfeeding dropped dramatically. These findings underscore the importance of promoting breastfeeding, especially during the first 6 months of life, and of targeting high risk groups such as low birth weight babies and those of low socioeconomic status.

PIP: The effects of not breastfeeding upon mortality due to diarrhea and acute lower respiratory infection (ALRI) in children under age two years were examined using data from a 1988-91 longitudinal study of 9942 children in Metro Cebu, Philippines. Cox regression methods were used to study the magnitude of the risks, possible interactions with birth weight and nutritional status, and the effect of any additional confounding factors. Not breastfeeding was found to have a greater effect upon diarrheal mortality than upon ALRI mortality. Specifically, failing to initiate breastfeeding or ceasing to breastfeed during an infant's first six months of life resulted in an 8-10-fold increase in the rate of diarrheal mortality. The rate of mortality associated with both ALRI and diarrhea was increased almost six times by not breastfeeding, but the rate of ALRI mortality alone was not increased. The data also suggest that the risk of mortality associated with no breastfeeding was greater for low-birth-weight infants and infants whose mothers had little formal education. After age six months, the protective effects of breastfeeding dropped dramatically. The authors note how these findings highlight the importance of promoting breastfeeding, especially during the first six months of life, and of targeting high-risk groups such as low-birth-weight babies and those of low socioeconomic status.

Epidemiology of biliary atresia: a population-based study.

OBJECTIVE: Biliary atresia is the leading cause of extrahepatic obstructive jaundice in the newborn and is the single most frequent indication for liver transplantation in children. The cause of biliary atresia is unknown, although several mechanisms have been postulated to explain the inflammatory process that obliterates the bile ducts. Most interest has been directed toward viral infections. Information about the epidemiologic characteristics of biliary atresia in well-defined populations is lacking but is essential for developing and addressing hypotheses of causation for the disease. METHODS: Infants with biliary atresia were identified in metropolitan Atlanta from 1968 through 1993 by a population-based birth defects surveillance system that ascertains infants with serious birth defects in the first year of life using active case ascertainment. Birth prevalence rates were analyzed for spatial and temporal clustering and effects attributable to county of residence, sex, race, maternal age, parity, and birth weight. Logistic regression was used to study the independent effects of the risk factors and to look for interactions. RESULTS: Fifty-seven infants with biliary atresia were identified, for a rate of 0.73 per 10,000 live births. There was significant seasonal clustering of the disease, with rates three times higher from December through March compared with rates from April through July. Rates were significantly higher among nonwhite infants compared with white infants (0.96 vs 0.44 per 10,000 live births) and infants born at term with low birth weights (<2500 g) compared with infants born at term with normal birth weights (> or = 2500 g) (2.62 vs 0.75 per 10,000 live births). CONCLUSIONS: Our study is the first in the United States to describe the epidemiologic characteristics of biliary atresia using a population-based approach. The demonstration of significant seasonal clustering provides support for theories that biliary atresia may be caused by environmental exposure (consistent with a viral cause) during the perinatal period.

Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of chromosomal error: a population-based study.

The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women > or = 40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women > or = 40 years old were 4.2/1000 births for MMI errors and 1.9/1000 for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal-age related mechanism acting around the time of conception.

Public health impact of genetic tests at the end of the 20th century.

PURPOSE: To evaluate genetics tests available for clinical, research, and public health purposes in terms of their public health impact as measured by the number of people who could potentially be tested. METHODS: Genetic tests for the 751 inherited diseases or conditions listed in the GeneTests database as of November 2000, were classified on the basis of their use for population-based testing and the prevalence of the disease or condition being tested. The GeneTests database divides the tests into two groups: those offered for clinical use and those available for research only. RESULTS: Of the 423 clinical tests, 51 had potentially greater impact on public health because of their use in statewide newborn screening programs, other population screening programs, or testing for common diseases with a prevalence over 1 in 2,000 people. Among the 328 tests performed for research purposes only, 18 met the criteria for potentially greater public health impact. CONCLUSIONS: Our classification scheme indicated that fewer than 10% of the genetic tests listed in the GeneTests database at the end of 2000 are highly relevant to public health. The majority of genetic tests are used in diagnosis and/or genetic counseling for rare, single-gene disorders in a limited number of people. However, as more tests are being considered for newborn screening, and associations between genes and common diseases are being discovered, the impact of genetic testing on public health is likely to increase.