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Biomedical subjects

Larry Burd

Publications and source records attributed to Larry Burd.

At least 19 recordsLinked to original sources

A staged screening strategy for prenatal alcohol exposure and maternal risk stratification.

AIMS: To present an incremental process for a staged screening strategy to identify women at increased risk of having a child with fetal alcohol spectrum disorder (FASD) and to enhance the management of women using alcohol during pregnancy. We include an illustrative example of the development of a screening component using an existing data set. METHODS: We describe a seven-step protocol to screen for alcohol use during pregnancy. The screening process begins with a one-question initial screen, followed by exposure assessment, maternal risk stratification to estimate risk for FASD, and concludes with recommendations for intervention and monitoring of exposure for women drinking during pregnancy. CONCLUSIONS: This screening process has very modest time commitments in the early stages. Time commitments increase for women drinking during pregnancy and the process focuses on the population at highest risk of having a child with FASD. The process has the benefit of risk specificity, since the process refines risk estimates for an adverse outcome specific for FASD. The process concludes with a programme to facilitate intervention and to monitor changes in prenatal alcohol exposure during pregnancy. Prevention of FASD is an important public health priority. In addition to the ongoing study of clinical strategies to improve detection rates of alcohol exposure at all stages of pregnancy, additional research on the tools and the process used in screening efforts is urgently needed. The efforts should also include research on both the screening tools and the outcome of the screening process in routine prenatal care settings.

Alcohol Drinking↗

Tourette Syndrome and learning disabilities.

BACKGROUND: Tourette Syndrome (TS) is a neurodevelopmental disorder of childhood. Learning disabilities are frequently comorbid with TS. Using the largest sample of TS patients ever reported, we sought to identify differences between subjects with TS only and subjects with TS and a comorbid learning disability. METHODS: We used the Tourette Syndrome International Consortium database (TIC) to compare subjects with comorbid Tourette Syndrome and learning disabilities (TS + LD) to subjects who did not have a comorbid learning disability (TS-LD). The TIC database contained 5,500 subjects. We had usable data on 5,450 subjects. RESULTS: We found 1,235 subjects with TS + LD. Significant differences between the TS + LD group and the TS-LD group were found for gender (.001), age onset (.030), age first seen (.001), age at diagnosis (.001), prenatal problems (.001), sibling or other family member with tics (.024), two or more affected family members (.009), and severe tics (.046). We used logistic modeling to identify the optimal prediction model of group membership. This resulted in a five variable model with the epidemiologic performance characteristics of accuracy 65.2% (model correctly classified 4,406 of 5,450 subjects), sensitivity 66.1%, and specificity 62.2%. CONCLUSION: Subjects with TS have high prevalence rates of comorbid learning disabilities. We identified phenotype differences between the TS-LD group compared to TS + LD group. In the evaluation of subjects with TS, the presence of a learning disability should always be a consideration. ADHD may be an important comorbid condition in the diagnosis of LD or may also be a potential confounder. Further research on etiology, course and response to intervention for subjects with TS only and TS with learning disabilities is needed.

Attention Deficit Disorder with Hyperactivity↗

Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12.

AIMS: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy characterized by impaired ventricular contractility. This study was designed to examine the effect of group B vitamin supplementation on short-term exposure of the main alcohol metabolite acetaldehyde (ACA)-induced cardiac contractile dysfunction in rat ventricular myocytes. METHODS: Mechanical contractile properties were evaluated by an IonOptix SoftEdge system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays, respectively. RESULTS: Short-term (4-6 h) culture of myocytes with ACA (10 microM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, shortened duration of shortening but not the duration of relengthening. ACA exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The toxin-induced mechanical defects, protein damage and apoptosis were ablated by vitamin B1 (10 microM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 microM) attenuated ACA-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated ACA-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other ACA-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the ACA-induced carbonyl formation without affecting ACA-induced apoptosis. CONCLUSIONS: These data provide evidence that vitamin B1 supplementation may be protective for ACA-induced cytotoxicity through protection against protein damage and apoptotic cell death in ventricular myocytes.

Acetaldehyde↗

Cost of fetal alcohol spectrum disorders.

Fetal alcohol syndrome (FAS) is a common identifiable teratogenic cause of mental retardation, neurological deficit, mental disorders, and developmental disabilities. Accurate estimates of the cost of care for persons with FAS are essential for appropriate funding of health care, developmental disabilities services, special education, and other service systems, as well as prioritizing funding of public health prevention efforts. The cost of care for individuals with FAS can be conceptualized as the annual cost of care for one person or a population, or as the lifetime cost of care for an individual. Annual cost estimates for the United States range from $75 million in 1984 to $4.0 billion in 1998. Estimates of lifetime cost vary from $596,000 in 1980 to $1.4 million in 1988. After adjustments for changes in inflation and population, 2002 estimates of total annual cost and lifetime cost are higher. FAS is increasingly being recognized as a large public health problem with high potential for the prevention of future cases and for the prevention of excess disability and premature mortality in persons who are affected. Each day, from 6-22 infants with FAS are born in the United States, and as many as 87-103 more are born with other impairments resulting from prenatal alcohol exposure. Updated and improved cost data on FAS should be a research priority.

Alcohol Drinking↗

Fetal, infant, and child mortality in a context of alcohol use.

Alcohol is an important element in the causal chain of risk for fetal, infant, and childhood mortality. Mortality risk is influenced by interactions of alcohol with other environmental and genetic factors and temporal periods of susceptibility. In this paper we discuss four time periods (preconceptual, gestational, infancy, and childhood) where alcohol use may create a context of risk. Alcohol use in one period increases the risk of alcohol use in subsequent periods. Gestational alcohol use can influence risk of mortality from abuse of mother/fetus, can cause other adverse outcomes, and can result in fetal alcohol spectrum disorders (FASDs). In infancy alcohol use can increase risk from impairment of arousal in adults who use alcohol. Infants with gestational exposure can be behaviorally difficult with sleep disturbance, irritability, and colic. This can increase the risk of harm or death, especially during periods of caretakers' alcohol use. Caretakers' alcohol use and smoking are strongly correlated. The all-cause mortality rate in people diagnosed with fetal alcohol syndrome (FAS) is over 5%. All-cause mortality in siblings of diagnosed cases of FAS is increased 530% compared to siblings of matched controls. We recommend that a context of alcohol use be considered as a marker for multifactorial risk in all fetal, infant, and child deaths. A schema to collect data on alcohol use is provided to increase awareness of alcohol use as an environmental risk marker for mortality.

Alcohol Drinking↗

Fetal alcohol syndrome in the United States corrections system.

Prenatal alcohol exposure can result in fetal alcohol syndrome (FAS), which may increase the risk of confinement in the corrections system. In the United States each state and four major cities' corrections systems were asked to complete a questionnaire on the prevalence of FAS and alcohol-related neurodevelopmental disorder (ARND) in the offender population, the availability of screening and diagnostic services to identify offenders with FAS and staff training needs related to FAS. The total population in the 54 entities was 3,080,904 inmates. Completed questionnaires were obtained from 42 entities (78%). The mean rate of reported substance abuse in offenders was 60.1%. Specialized programs for persons with mental retardation were reported for 44.4% of corrections facilities and 25.9% of community corrections facilities. Programs for pregnant women were reported for 46.3% of corrections facilities and 29.6% of community facilities. One program (1.9%) reported having a screening program for FAS in the corrections system. Only four programs (7.4%) reported having access to diagnostic services for FAS in the corrections facilities. Of the 3,080,904 offenders, only one offender was reported to have a diagnosis of FAS. Reported staff training needs were very large. In conclusion, corrections systems have high unmet needs to screen, identify, and treat offenders with FAS and ARND. Staff training needs are substantial.

Female↗

Increased sibling mortality in children with fetal alcohol syndrome.

We compared the rate of all-cause mortality in siblings of children diagnosed with fetal alcohol syndrome (FAS) with the siblings of matched controls. The siblings of children with FAS had increased mortality (11.4%) compared with matched controls (2.0%), a 530% increase in mortality. The age of death in case siblings deaths occurred later (between 1 day and 7 years) compared with the controls (1 day to 4 years) [odds ratio (OR)=2.4 (0.4-15.6)]. Siblings of children with FAS had increased risk of death due to infectious illness [OR=13.7 (1.2-361)] and sudden infant death syndrome compared with controls [OR=10.2 (1.2-75.1)]. A diagnosis of FAS is an important risk marker for mortality in the siblings of the proband even if they do not have FAS. Maternal alcoholism appears to be a useful risk marker for increased mortality risk in diagnosed cases and their siblings. This has important implications in the management of family members of children with FAS.

Child↗

Impact of smoking on cancer stage at diagnosis.

BACKGROUND: Studies evaluating the relationship between smoking and cancer spread are limited. METHODS: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied. RESULTS: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P <.001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P <.001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P <.001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P =.003). An increase in regional disease was most evident for head and neck (RR, 3.53; P <.001), prostate (RR, 1.83; P =.030), and breast cancer (RR, 1.22; P =.005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P =.004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P =.004). CONCLUSION: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.

Adolescent↗

Children and adolescents with attention deficit-hyperactivity disorder: 1. Prevalence and cost of care.

The objective of this study was to use population-based data to estimate the prevalence and cost of treatment for attention-deficit hyperactivity disorder (ADHD). The North Dakota Department of Health Claims Database was used to estimate the administrative prevalence, annual cost of care per case, and total annual cost of care for subjects with ADHD compared with controls. The case population was 7745, and the mean prevalence rate was 3.9%, with a peak prevalence at 10 years of age. For children with ADHD, the annual cost of care was 649 dollars compared with that of controls at 495 dollars. Cost of care attributable to ADHD was 649 dollars - 495 dollars = 54 dollars (31%). Utilization by children with ADHD with publicly funded payers was increased 25 to 175% over that of children with privately funded coverage. In North Dakota, the annual cost of care for children with ADHD was 5.1 million dollars, 5.6% of all health care costs for children. The annual attributable cost of care was 1.79 million dollars. Thus, 1.9% of total health expenditures for children was attributable to ADHD. In the United States, the cost of care attributable to children with ADHD would be 2.15 billion dollars annually.

Adolescent↗

The attention-deficit hyperactivity disorder paradox: 2. Phenotypic variability in prevalence and cost of comorbidity.

The objective of this study was to use population-based data to estimate the cost and phenotypic variation of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). The North Dakota Department of Health's Claims Database was used to estimate the administrative prevalence, rates of comorbidity, and cost of care for subjects with ADHD. The case population was 7745 children. We then examined the 10 most frequent comorbidities for a defined condition in the International Classification of Diseases-9th edition (ICD-9). The observed prevalence of general health conditions was 12 to 70% less than expected. The presence of a comorbid condition resulted in increases in costs of care of dollar 381 to dollar 731 per case per year. The observed prevalence of comorbid mental health conditions was 97 to 5286% higher than expected. The prevalence of conditions comorbid with ADHD varies widely, with rates of general medical conditions decreased and rates of most mental disorders increased. The costs for comorbidity with general health conditions were offset by large decreases in prevalence rates compared with controls. We identified an ADHD paradox: decreased rates of comorbid general health conditions and increased rates of comorbid mental disorders. Further research on comorbidity in ADHD is required.

Attention Deficit Disorder with Hyperactivity↗

Effects of maternal and paternal age on Caucasian and Native American preterm births and birth weights.

The purpose of this study was to compare the effects of maternal and paternal age on Native American and Caucasian infants. Data were abstracted from birth records compiled in North Dakota from 1978 to 1992. Native Americans had a 45% higher risk for preterm births, a 140% higher risk for low birth weight (LBW) (<2500 g), and a 131% higher risk for very LBW (<1500 g) compared with Caucasians. Maternal and paternal age both had a "U-shaped" effect on preterm birth. However, while the risk for preterm birth was increased for both teenage mothers and fathers, the risk was also significantly increased only for mothers between the ages of 36-40 and 41-45. There was also a "U-shaped" relationship between LBW and parental age, and again the risk was statistically significant for different age groups. For mothers, the risk was decreased significantly for those 26 to 30 years of age, whereas for fathers, it was increased significantly for those <20 years of age. There was also a significant interaction between paternal age and race, with teenage Native American fathers having a slight (4%), but statistically significant, increased risk for having LBW children compared with teenage Caucasian fathers. The relationship between parental age and very LBW was also "U-shaped," but while the odds ratios for each maternal age group were significant, none of the odds ratios for any of the paternal age groups was statistically significant. The influence of teenage fathers on preterm and LBWs has not been previously reported, and the finding that paternal age has a greater influence among Native Americans is especially intriguing and deserving of further investigation.

Birth Weight↗

Prospective long-term follow-up of patients with pervasive developmental disorders.

We conducted a 12-year prospective study of children with pervasive developmental disorders from North Dakota. In a prospective longitudinal follow-up study, of 59 patients, we found 52 patients with pervasive developmental disorders (88%). Ten (17%) declined to participate. We collected data on 42 (71%) of the original cohort. Of the 42 subjects, 1 died (1.7%). The other 41 were followed up for 492 person-years. Severity scores for the Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) declined 20% and for DSM-IV 23%. Global Assessment of Functioning improved 19%, and the average number of comorbidities decreased 45%. Thirty-seven percent of patients improved in all four measures, whereas only 5% improved in only one measure. Pervasive developmental disorders are developmental disorders with a long-term course of limited improvement for most patients. Male subjects demonstrated substantially more variability in improvement but, overall, demonstrated more improvement than female subjects.

Adult↗

A school-based screening program for fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is a common cause of birth defects and neuropsychiatric impairment. Identification of affected people is crucial for early entry into intervention programs and for the development of prevalence estimates. The objective of this project was to determine if screening for FAS in a community elementary school-based setting was feasible, to estimate prevalence in the screened population, and to determine if a screening program for FAS can be implemented using available personnel from the community. The FAS Screen was used to screen kindergarten students enrolled in a school system. Students with scores on the FAS Screen above the cutoff for a positive screen (20) were referred to one of several diagnostic clinics for evaluation. Over a 9-year period, 1384 students were screened and 69 (5%) had a positive screen (20 or above). These 69 children were then seen in a genetics/dysmorphology diagnostic clinic and 7 (10%) were found to have FAS (n=6) or partial FAS (n=1). The prevalence of affected children (FAS and partial FAS) was 1 per 198 students or 4.3 per 1000. The FAS Screen was completed annually by school staff, teachers, social workers, and psychologists. The test has acceptable epidemiologic performance characteristics in a community setting. The screening takes about 8-10 min. The procedure was well accepted in the community. This screening strategy was inexpensive to implement (less than US8.00 dollars per student), and can be easily included with the other screens completed at kindergarten entry.

Child↗

Combined acetaldehyde and nicotine exposure depresses cardiac contraction in ventricular myocytes: prevention by folic acid.

Chronic alcoholism can progress to alcoholic cardiomyopathy characterized by ventricular dilation and impaired ventricular contractility. Nicotine abuse continues to remain a serious risk factor for cardiovascular diseases. However, little is know regarding the combined effects. This study was designed to examine the role of short-term combined exposure of the main alcohol metabolite acetaldehyde (ACA) and nicotine on cardiac contractile function in adult rat ventricular myocytes, and if folate exposure attenuates the effect of ACA/nicotine. Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge system. Short-term (4-6 h) culture of myocytes with ACA (10 microM), nicotine (100 microM), or combination of the two in sealed vials with silicone septa depressed maximal velocity of shortening/relengthening, without affecting duration of shortening/relengthening and intracellular Ca2+ handling. Interestingly, the toxin-induced defects on myocyte mechanical properties were ablated with cotreatment of folate (100 microM), an essential vitamin required for DNA synthesis and repair. Collectively, these data provided evidence that ACA and nicotine, either alone or in combination, directly depressed cardiomyocyte mechanical function possibly through mechanisms related to DNA damage.

Acetaldehyde↗

Fetal alcohol syndrome prevention: annual and cumulative cost savings.

Fetal alcohol syndrome (FAS) is a common developmental disability. FAS is thought to be 100% preventable. While this is a theoretical truth, a prevention rate of 100% appears unlikely in the near future. However, several prevention strategies are available. In this paper, we examine the potential cost savings from prevention of one case of FAS each year in the state of North Dakota. We utilized the North Dakota Health Claims Database to examine annual cost of health care for children birth through 21 years of age with FAS and controls. The mean annual cost of health care for children birth through 21 years of age with FAS was US2842 dollars (n=45). This is US2342 dollars per capita more than the annual average cost of care for children in North Dakota who do not have FAS (US$500 per year). Prevention of one case of FAS per year in North Dakota would result in a cost savings of US128,810 dollars in 10 years and US491,820 dollars after 20 years. After 10 years of prevention, the annual savings in health care costs alone for one case of FAS would be US23,420 dollars.

Adolescent↗

Fetal alcohol syndrome: neuropsychiatric phenomics.

Fetal alcohol syndrome (FAS) is a common developmental disorder with impairments in multiple neuropsychiatric spheres of varying severity. Few population-derived studies of the behavioral phenotype are available. The purpose of this study was to estimate the prevalence of neuropsychiatric disorders in three groups: subjects who met criteria for FAS (n=152); subjects who met criteria for partial FAS/ARND (n=150); and referred subjects who did not meet criteria for either FAS or partial FAS/ARND (n=86). Each subject had a standardized evaluation by a medical geneticist. All subjects were from North Dakota. We found increases in the prevalence rates of neuropsychiatric disorders in subjects with FAS compared to subjects with partial FAS/ARND and the lowest rates in the group that did not meet criteria for either FAS or partial FAS/ARND. Comorbid attention deficit hyperactivity disorder occurred in 73% of cases with FAS, in 72% cases with partial FAS/ARND, and in 36% subjects who did not meet criteria for either. For other neuropsychiatric disorders, a similar distribution of comorbidity was found. This study supports the concept of a continuum of impairment resulting from prenatal alcohol exposure. The presence of complex cognitive, behavioral, and physical symptomatology in the affected subjects with prenatal alcohol exposure would seem to fit well under the diagnostic rubric of fetal alcohol spectrum disorder (FASD). Diagnosis and long-term management will require increasing access to multidisciplinary child development teams including mental health professionals who treat children and adolescents. Adults will require care primarily from teams with expertise in mental health and developmental disabilities.

Adolescent↗

Diagnosis of FAS: a comparison of the Fetal Alcohol Syndrome Diagnostic Checklist and the Institute of Medicine Criteria for Fetal Alcohol Syndrome.

UNLABELLED: Fetal alcohol syndrome (FAS) is a common cause of neuropsychiatric disorders, growth impairment and craniofacial abnormalities. The syndrome may be more common than has been previously reported. Considerable controversy exists over the approaches for diagnosis of the syndrome. METHOD: In this study, we examined the rate of agreement for two diagnostic schema using 385 subjects that had been referred for assessment of possible FAS. Cases had initially been diagnosed using the Fetal Alcohol Syndrome Diagnostic Checklist (FASDC). We then reviewed the chart of each of the 385 subjects referred and assigned each subject to a category from the Institute of Medicine (IOM) Criteria or to a NOFAS category. We then compared the IOM categories with the FASDC. RESULTS: Rates of agreement with the IOM Criteria ranged from 59-71% using the FASDC. Poorest agreement was found in conjunction with partial FAS (PFAS)/alcohol-related neurodevelopmental disorder (ARND). Removal of exposure data from the scores greatly affected accuracy for the FASDC scores. DISCUSSION: The schema had only modest rates of agreement for classification of subjects with a diagnosis of FAS. This study does not determine if the diagnosis used in the development of the cohort was accurate. Further study utilizing multiple diagnostic schema in a single population will help examine the rates of diagnostic agreement between differing diagnostic schema. A valuable cohort to study would be the subjects in the CDC surveillance system. A perspective study utilizing a single cohort and applying multiple diagnostic criteria at the same time would be useful.

Diagnosis, Differential↗