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P M Farrell

Publications and source records attributed to P M Farrell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of growth status of patients with cystic fibrosis between the United States and Canada.

BACKGROUND: Differences in growth status of patients with cystic fibrosis (CF) between the United States and Canada were reported in the 1980s based on analysis of data from 2 regional CF centers. OBJECTIVE: We evaluated the current growth status of the entire CF population in the United States and Canada in view of recent advances in the treatment of CF. DESIGN: Growth data from the 1992-1994 CF Patient Registries were analyzed. RESULTS: Mean height and weight were at approximately the 30th percentile for children with CF in the United States. Mean height and weight were 4-5 percentiles higher in children with CF in Canada than in those in the United States (P < 0.01), but percentages of ideal weight (104%) were similar in both populations. In adults with CF, mean height was similar at the 37th percentile; however, weight (26th compared with the 21st percentiles) and percentage of ideal weight (93% compared with 90%) were significantly higher in Canada than in the United States. Differences related to sex and age were similar in both countries for all indexes, which showed a high prevalence of underweight in infants and in older patients, but little sex discrepancy. CONCLUSION: We observed substantially smaller differences in the growth indexes of CF patients between the United States and Canada compared with results from the 1980s. These findings reflect significant improvements in the nutritional status of US patients in recent years. However, caution is required in the direct comparison of mean percentiles from reports using different growth standards because there are systematic differences in growth standards, which affect, in particular, the comparison of growth in males and females.

Adolescent↗
PubMed1998

Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis.

The objective of this study was to identify risk factors of significance for acquisition of Pseudomonas aeruginosa by children with cystic fibrosis (CF). Our working hypothesis is that exposure of infants and young children with CF to older, infected patients increases their risk for acquiring this organism. A special opportunity arose to study this question in detail, as we have been performing a randomized clinical trial of neonatal screening for CF throughout the state of Wisconsin during the period of 1985-1994. Patients were selected for this study based on either early identification through screening or diagnosis by standard methods. A longitudinal protocol employed at Wisconsin's two CF Centers includes routine cultures of respiratory secretions and collection of clinical, demographic, and activity information on patients and their families. Previous observations in our trial revealed that one center at an old hospital in an urban location showed a significantly shorter time to acquisition of P. aeruginosa for CF patients followed there. To study the center effect further, we performed statistical analyses using survival curves and stepwise regression analysis of all life history covariates available. The results of these analyses showed that the statistically significant correlations involve the following risk factors: 1) center and old hospital (r=0.42); 2) center and original physician (r=0.61); 3) center and exposure to pseudomonas-positive patients (r=0.29); and 4) population density and urban location (r=0.49). The final statistical model demonstrated that increased risk due to aerosol use (odds ratio=3.45, P=0.014) and a protective effect associated with education of the mother (odds ratio=0.81, P=0.024) were the most significant factors for acquisition of P. aeruginosa. The previously observed center effect was confined to the 1985-1990 interval at the old hospital (odds ratio=4.43, P < 0.001). We conclude that multiple factors are involved in increasing the risk of young children with CF to acquire P. aeruginosa, and that the observed center effect can best be explained by a combination of factors. These results suggest that facilities and methods used to care for young children with CF can significantly influence their likelihood of acquiring pseudomonas in the respiratory tract.

Age Factors↗
PubMed1998

Growth status in children with cystic fibrosis based on the National Cystic Fibrosis Patient Registry data: evaluation of various criteria used to identify malnutrition.

OBJECTIVES: The objectives of this study were to determine growth status and to identify malnutrition with various anthropometric indicators in children with cystic fibrosis (CF) based on cross-sectional analysis of the 1993 National CF Patient Registry data. METHODS: Heights and weights of 13,116 children with CF were evaluated with percentile, percent of reference median, Z-score, and percent ideal weight-for-height based on National Center for Health Statistics/Centers for Disease Control growth references. Malnutrition was defined by four criteria: (1) height-for-age <5th percentile ("stunting") or weight-for-age <5th percentile ("wasting") (2) height-for-age <90% of reference median or weight-for-age <80% of reference median, (3) height-for-age <5th percentile or percent ideal weight-for-height <85%, and (4) height-for-age <90% of reference median or weight-for-height <85% of reference median. RESULTS: Mean and median height- and weight-for-age were found to be at the 30th and 20th percentiles in children with CF. Malnutrition (height- or weight-for-age <5th percentile) was particularly pronounced in infants (47%) and adolescents (34%) and patients with newly diagnosed CF (44%). A significant sex difference (p < 0.01) in the occurrence of stunting (height-for-age <5th percentile) was observed during adolescence: boys 11 to 14 years of age showed lower occurrence of stunting (19%) compared with girls (29%), whereas the opposite trend was observed at 15 to 18 years (34% in male patients vs 28% in female patients). CONCLUSION: Twenty percent of all children in the 1993 National CF Patient Registry were <5th percentile for height- or weight-for-age. A significant discrepancy was found when different criteria were used to distinguish "stunting" versus "wasting" in malnourished children with CF.

Adolescent↗
PubMed1998

Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling.

OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF) on the reproductive knowledge and behavior of CF families and to determine if heterozygote detection with the immunoreactive trypsinogen (IRT) method in conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal Screening Project investigated 650 340 infants from 1985 to 1994 in a comprehensive randomized controlled trial to study both benefits and risks of newborn screening and to determine if early diagnosis would improve the prognosis of children with CF. Assessments of reproductive knowledge, attitudes, and behaviors of 135 families of children diagnosed as having CF in both the early treatment group and control groups were made 3 months after diagnosis using a questionnaire which was completed by 100 families. The same questionnaire was administered 1 year later to evaluate retention of information. It was completed by 71 families. A follow-up assessment tool was also administered in 1994 and responses obtained from 73 families. Knowledge, attitudes, and behavior among false-positive families were also assessed at the time of the sweat test in 206 families who experienced IRT screening and 109 families tested with the IRT/DNA method. Follow-up assessments were completed 1 year later in 106 IRT families and 63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially understood that there was a 1 in 4 risk in subsequent pregnancies, and there was good retention of this information 1 year later. At the 1994 assessment, 52% of families had not yet conceived more children, but 74% of these already had children. In the couples in whom CF was diagnosed in the first child, 70% (95% confidence interval = 54% to 85%) conceived more children. There were 43 subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with CF detected, all of which were carried to term. In the false-positive groups, >95% of families initially understood that their child definitely did not have CF. There was no difference between false-positive IRT and IRT/DNA groups, and the information was retained at 1 year. Follow-up assessment 1 year after negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families still thought about the results often or constantly. When asked whether the experience of screening affected feelings about having more children, an affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA families. One year later, more than half of the false-positive IRT/DNA families did not understand that they were at increased risk of having a child with CF. CONCLUSIONS: We conclude that CF neonatal screening does not have a significant impact on the reproductive behavior of most families and that prenatal diagnosis is not used by the majority of CF families. IRT/DNA testing experiences seem to affect attitudes about having more children, and some parents are confused about the implications of the results, even with genetic counseling. However, persistent concerns about the sweat test result are limited. Questions raised by this study confirm the need for more research regarding the process of genetic counseling and its impact on reproductive attitudes and behavior in the newborn screening setting.

Cystic Fibrosis↗
PubMed1997

Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

BACKGROUND: Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known. METHODS: We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements. RESULTS: The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P=0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation. CONCLUSIONS: Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.

Body Height↗
PubMed1997

State-to-state variations in newborn screening policies.

BACKGROUND: Population-based newborn screening for genetic and metabolic disorders is standard practice in all states in the United States. Policies governing newborn screening are determined at the state level; however, and thus, a great degree of variability exists between states regarding many facets of such screening. OBJECTIVE: To gather information relating to the processes, content, and outcomes of policy making affecting newborn screening programs across the United States. METHODS: We surveyed the directors of newborn screening programs for each of the 50 states using a postal questionnaire. The questionnaire solicited information about the specific tests incorporated in each state's panel of screening tests and information pertaining to the policy-making processes by which decisions are reached regarding this testing. RESULTS: Substantial variation exists across states regarding both the processes of policy formulation and the outcomes of decisions made about newborn screening. All states currently screen for phenylketonuria and congenital hypothyroidism. Extensive variation exists across states in testing for other disorders. The processes by which state policy makers arrive at decisions in this area are extremely diverse. Almost three fourths of the states have standing expert advisory bodies who issue recommendations regarding screening program modifications, but the authority granted to these panels varies substantially. Some regional cooperation in this area exists. CONCLUSIONS: Further development of regional cooperation could offer some states greater efficiency in both laboratory testing and screening policy formulation. From the standpoint of an individual state. Wisconsin's approach to policy development in this area is described as a model worthy of consideration.

Health Policy↗
PubMed1997

Acquisition of Pseudomonas aeruginosa in children with cystic fibrosis.

OBJECTIVE: This study was pursued as an extension of a randomized clinical investigation of neonatal screening for cystic fibrosis (CF). The project included assessment of respiratory secretion cultures for pathogens associated with CF. The objective was to determine whether patients diagnosed through neonatal screening and treated in early infancy were more likely to become colonized with Pseudomonas aeruginosa compared with those identified by standard diagnostic methods. METHODOLOGY: The design involved prospective cultures of respiratory secretions obtained generally by oropharyngeal swabs at least every 6 months and more often if clinically indicated. Patients were managed with a standardized evaluation and treatment protocol at the two Wisconsin certified CF centers; however, there were community and environmental variations associated with the follow-up period as described below. RESULTS: Overall, there were no differences in acquisition of respiratory pathogens between the screened and the control (standard diagnosis) groups. Evaluation of the data between and within the two centers, however, revealed significant differences with earlier acquisition of P aeruginosa in the center with the following distinguishing characteristics: urban location; following patients with the standard US approach in which newly diagnosed, young children were interspersed with older CF patients; and where there were more opportunities for social interactions with other CF patients. The differences were confined to the screened group followed in the urban center in which the median pseudomonas-free survival period was 52 weeks contrasted with 289 weeks in the other center. In addition, assessment of data for the entire CF populations followed at the two centers revealed that the urban center showed a significantly higher prevalence of P aeruginosa colonization in patients between the ages of 3 and 9 years. CONCLUSIONS: These results present questions and generate hypotheses on risk factors for acquisition of P aeruginosa in CF and suggest that clinic exposures and/or social interactions may predispose such patients to pseudomonas infections.

Cystic Fibrosis↗
PubMed1997

Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.

OBJECTIVES: To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. METHODS: From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. RESULTS: Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. CONCLUSIONS: Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.

Apgar Score↗
PubMed1996

The incidence of cystic fibrosis.

We develop a statistical model for estimating cystic fibrosis (CF) incidence among infants born in the U.S.A. that accounts for under-diagnosis due to death prior to diagnosis and we apply it to the Cystic Fibrosis Foundation Patient Registry data for the years 1989 to 1991. The resulting estimate of incidence relative to live births among whites is 1:3419 while that among non-whites is 1:12,163. As a by-product of the modelling approach, estimates of the underlying average diagnosis age given survival to diagnosis are 4.09 years for whites and 4.55 years for non-whites, but this difference was not statistically significant and appears to demonstrate that diagnosis efforts may be approximately the same for whites and non-whites. Also, as another by-product of the modelling approach, CF mortality was estimated as more severe for females than males and marginally more severe for non-whites than whites. A variety of statistical methods underlie achievement of these results, including semi-parametric maximum likelihood, survival analysis, multiple imputation and bootstrap techniques.

Actuarial Analysis↗
PubMed1996

Effects of maternal dexamethasone therapy on fetal lung development in the rhesus monkey.

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.

Animals↗
PubMed1996

Effect of linoleic acid intake on growth of infants with cystic fibrosis.

Essential fatty acid deficiency as a result of inadequate linoleic acid impairs growth in healthy infants and is common in infants with malabsorption due to cystic fibrosis (CF). We investigated the effect of dietary linoleic acid intake on the growth of infants with CF. In this study, predigested formula preparations A and B, with linoleic acid contents of 12% and 7% of energy, respectively, were fed before and after 1989 to infants enrolled in the evaluation and treatment protocol of the Wisconsin CF Neonatal Screening Project. Outcome was assessed from height-for-age (HAZ) and weight-for-age (WAZ) Z scores on follow-up exams during the first year. Baseline characteristics did not differ significantly between groups A (n = 43) and B (n = 33). At diagnosis, 53% of the enrolled infants (n = 76) showed low plasma linoleic acid concentrations and 22% had a high ratio of triene to tetraene. After correcting for the effect of potentially confounding variables, we found that HAZ (by .27, P < 0.05) and WAZ (by 0.26, P = 0.081) were higher in group A than in group B. This occurred despite a significantly higher energy intake in group B. This difference was most pronounced between 6 and 9 mo of age. Our results suggest that a high linoleic acid content in formula benefits infants with CF because it optimizes nutrition, growth, and feeding efficiency.

Age Factors↗
PubMed1996

Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis.

OBJECTIVE: To determine whether an adequate volume of sweat could be obtained routinely from infants younger than 6 weeks old and to evaluate sweat chloride levels in infants with known genotype statuses, including heterozygote carriers for cystic fibrosis (CF). METHODOLOGY: Infants were evaluated using pilocarpine iontophoresis and measurement of sweat volume and chloride concentration. The majority of these infants were referred because of newborn screening test results positive for CF based on immunoreactive trypsinogen analysis. DNA analyses for the 3-base pair deletion at codon 508 of the CF transmembrane regulator gene (F508 mutation) were performed whenever possible, and patients with CF were categorized by genotype. RESULTS: Sweat tests were performed successfully (>/-50 mg of sweat) in 99.3% of the infants tested, and there was no difference in the proportion of unsuccessful tests in infants younger than or older than 6 weeks of age. The normal mean +/- SD sweat chloride was 10.6 +/- 5.2 mEq/L (95% confidence interval, 9.9-11.3). Patients with CF who are F508 homozygotes or F508 compound heterozygotes or who have two other non-F508 mutant alleles were shown to have similar sweat chloride levels, with mean values of 99.9, 98.8, and 96.6 mEq/L, respectively. The group of infants who were found to be CF (F508) heterozygote carriers, when compared with the healthy group, had mildly but significantly increased sweat chloride concentrations, with a mean +/- SD of 14.9 +/- 8.4 mEq/L (95% confidence interval, 13.4-16.4). CONCLUSIONS: Quantitative pilocarpine iontophoresis can be used successfully in infants younger than 6 weeks of age who are undergoing routine diagnostic evaluations to follow up newborn screening test results that are positive for CF. The upper limit of normal sweat chloride in infants should be revised to 40 mEq/L (mean + 3 SD of the CF heterozygote carrier group). CF heterozygote carrier infants with one F508 mutant allele show phenotypic manifestations of CF, including subclinical elevations of sweat chloride.

Age Factors↗