PubMed Health⌕ Search

Biomedical subjects

Michael B Bracken

Publications and source records attributed to Michael B Bracken.

At least 19 recordsLinked to original sources
PubMed2006

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma.

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A4/1A5haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted.

Alleles↗
PubMed2006

E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis.

PURPOSE: Multiple studies examining the relationship between loss of E-cadherin expression, a pivotal event for evolving metastatic behavior among epithelially derived cancers, and 5-year survival in infiltrating ductal breast carcinoma have yielded inconclusive and contradictory results. EXPERIMENTAL DESIGN: We conducted a systematic review of the PubMed database through August 2005 with no language restrictions to identify cohort studies that evaluated E-cadherin immunohistochemical expression as a prognostic marker for ductal breast carcinoma. 5-year all-cause mortality or 5-year breast cancer-specific mortality were the primary study outcomes. Meta-analysis was conducted using the REVMAN software and summary hazard ratios assuming both fixed effect and random effect models were calculated. RESULTS: Ten retrospective cohort studies were identified. Reduced or absent E-cadherin expression significantly increased the risk of all-cause mortality [combined HR = 1.55; 95% CI = 1.08-2.23] whereas a non-significant association was observed for breast cancer-specific mortality [combined HR = 0.70; 95% CI = 0.39-1.27]. We documented substantial inter-study heterogeneity with respect to all aspects of clinical data collection, immunohistochemical staining and interpretation as well as statistical modeling. These factors could not be formally analyzed but they challenge the robustness of our calculated summary estimates. CONCLUSIONS: Loss of E-cadherin expression may be an independent negative prognostic indicator for infiltrating ductal breast carcinoma and randomized, controlled studies evaluating this finding are justified. We encourage standardization of immunohistochemical techniques, data interpretation algorithms across laboratories and use of all-cause mortality to increase data compatibility and facilitate future efforts summarizing the utility of alternate prognostic markers in cancer.

Breast Neoplasms↗
PubMed2006

Caffeine metabolites in umbilical cord blood, cytochrome P-450 1A2 activity, and intrauterine growth restriction.

Studies investigating antenatal caffeine consumption and reproductive outcomes show conflicting results, and most studies have used maternal self-reported caffeine consumption to estimate fetal exposure. This study (n=1,606) was specifically designed to test the association of caffeine and its primary metabolites in umbilical cord blood with intrauterine growth restriction (IUGR). Pregnant women were recruited from 56 obstetric practices and 15 clinics affiliated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000. In an adjusted model including caffeine only, levels in all quartiles were associated with reduced risk of IUGR. In adjusted analyses including paraxanthine and caffeine, serum paraxanthine levels in the highest quartile were associated with increased risk of IUGR (adjusted odds ratio=3.29, 95% confidence interval: 1.17, 9.22); caffeine remained protective. These conflicting findings suggest that cytochrome P-450 1A2 (CYP1A2) metabolic activity may be associated with IUGR, so the ratio of paraxanthine to caffeine was then modeled. The likelihood of IUGR increased 21% for every one standard deviation change in the ratio (adjusted odds ratio=1.21, 95% confidence interval: 1.07, 1.37), suggesting that CYP1A2 activity, and not the absolute levels of paraxanthine, influences fetal growth. No associations were observed between caffeine or any metabolites and preterm delivery.

Adult↗
PubMed2006

Renal impairment and outcomes in heart failure: systematic review and meta-analysis.

OBJECTIVES: We estimated the prevalence of renal impairment in heart failure (HF) patients and the magnitude of associated mortality risk using a systematic review of published studies. BACKGROUND: Renal impairment in HF patients is associated with excess mortality, although precise risk estimates are unclear. METHODS: A systematic search of MEDLINE (through May 2005) identified 16 studies characterizing the association between renal impairment and mortality in 80,098 hospitalized and non-hospitalized HF patients. All-cause mortality risks associated with any renal impairment (creatinine >1.0 mg/dl, creatinine clearance [CrCl] or estimated glomerular filtration rate [eGFR] <90 ml/min, or cystatin-C >1.03 mg/dl) and moderate to severe impairment (creatinine > or =1.5, CrCl or eGFR <53, or cystatin-C > or =1.56) were estimated using fixed-effects meta-analysis. RESULTS: A total of 63% of patients had any renal impairment, and 29% had moderate to severe impairment. After follow-up > or =1 year, 38% of patients with any renal impairment and 51% with moderate to severe impairment died versus 24% without impairment. Adjusted all-cause mortality was increased for patients with any impairment (hazard ratio [HR] = 1.56; 95% confidence interval [CI] 1.53 to 1.60, p < 0.001) and moderate to severe impairment (HR = 2.31; 95% CI 2.18 to 2.44, p < 0.001). Mortality worsened incrementally across the range of renal function, with 15% (95% CI 14% to 17%) increased risk for every 0.5 mg/dl increase in creatinine and 7% (95% CI 4% to 10%) increased risk for every 10 ml/min decrease in eGFR. CONCLUSIONS: Renal impairment is common among HF patients and confers excess mortality. Renal function should be considered in risk stratification and evaluation of therapeutic strategies for HF patients.

Creatinine↗
PubMed2006

Safety of medications prescribed before and during early pregnancy in a cohort of 81,975 mothers from the UK General Practice Research Database.

PURPOSE: To demonstrate a linkage methodology for mother and baby automated medical records, and describe frequency, type, and pregnancy risk level of medications prescribed during pregnancy in a GPRD cohort, 1991-1999. METHODS: We linked records using a two-stage algorithm and selected pairs with > or = 7 months prenatal records and > or = 2 records in baby's first year of life. Periods of interest were: 90 days prior to a woman's earliest identified pregnancy record (Period I), and this record plus 70 days (Period II, approximate early pregnancy). Medications were classified using the British National Formulary and US Food and Drug Administration Pregnancy Risk Categories. RESULTS: We achieved over 80% record linkage and defined a cohort of 81,975. Sixty-five per cent of mothers had > or = 1 prescription during both periods combined. Most frequent medications in Period I were anti-bacterial, contraceptive, topical steroid, and bronchodilator. In Period II, they were folic acid, anti-bacterial, antacid, and gynecological anti-infective. In Period I, 4% were FDA category A (considered safest), 34% B, and 49% C and D combined. By Period II, prescription of category A medications increased (folic acid, iron) while other categories declined. Category X medications, with potential teratogenic risk that outweighs maternal benefit, were prescribed to 5714 (7%) women in Period I, and 501 (0.6%) women in Period II (46% progesterone). CONCLUSIONS: One in every 164 women received a category X prescription in early pregnancy. The visit when pregnancy is first medically recognized represents an opportunity to review prescribed medications in light of contraindication and/or fetal risk.

Adult↗
PubMed2006

The epidemiology of asthma during pregnancy: prevalence, diagnosis, and symptoms.

We demonstrated that asthma remains a common condition among pregnant women and that the prevalence of self-reported asthma in the United States is between 8.4% and 8.8%. In addition, approximately 4.1% of all pregnant women experienced an asthma attack in the previous year. Prevalence rates in other countries seem to be higher or substantially lower; however, further characterization of international trends using nationally representative data is needed. Data from a large prospective cohort study in the northeastern United States and national data demonstrate continued opportunities for population-level improvement in well-managed asthma during pregnancy. Finally, asthma diagnosis and asthma control seem to differ by population characteristics (eg, age, race/ethnicity, socio-economic status), and further research and clinical involvement are needed to ad-dress potentially systematic variation in reporting and management of the disease.

Asthma↗
PubMed2006

Duration of intrapartum prophylaxis for neonatal group B streptococcal disease: a systematic review.

OBJECTIVE: To examine published evidence regarding duration of intrapartum antibiotic prophylaxis administered to pregnant women colonized with group B Streptococcus (GBS) to reduce infant colonization with GBS and to prevent early-onset GBS sepsis. DATA SOURCES: A search was conducted in The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to January 2006), and in protocols and guidelines of the Centers for Disease Control and Prevention, American Academy of Pediatrics, and American College of Obstetrics and Gynecology. METHODS OF STUDY SELECTION: All randomized controlled trials and observational studies in which duration of intrapartum antibiotic prophylaxis is reported relative to subsequent neonatal GBS colonization or sepsis were considered. Case series and study designs using historical cohorts or controls for comparison were excluded. TABULATION, INTEGRATION, AND RESULTS: Three prospective cohort studies and one case-control study met inclusion criteria. Heterogeneity of study design and assembly of cohorts precluded meta-analysis. A systematic review of the individual studies was performed. All studies were rated as fair or poor validity with regard to their ability to evaluate duration of intrapartum prophylaxis and transmission of GBS to the newborn. All 4 studies were largely composed of women with existing risk factors for GBS disease of the newborn. One study supported more than 1 hour of prophylaxis, two studies supported more than 2 hours of prophylaxis, and one was inconclusive. CONCLUSION: Despite unequivocal clinical guidelines recommending at least 4 hours of intrapartum antibiotic prophylaxis, there are no well-designed studies examining duration of intrapartum antibiotic prophylaxis for prevention of early-onset GBS disease of the newborn. We recommend continuing to initiate intrapartum prophylaxis according to the American College of Obstetricians and Gynecologists guidelines; however, the transmission of GBS to neonates exposed to less than 4 hours of intrapartum prophylaxis and their subsequent management require further study.

Antibiotic Prophylaxis↗
PubMed2006

Low-level ozone exposure and respiratory symptoms in infants.

OBJECTIVE: Recent studies indicate that the U.S. Environmental Protection Agency (EPA) ozone standards may not protect sensitive individuals. In this study we examined respiratory effects of ozone in infants who may be vulnerable, particularly if they are children of asthmatic mothers. DESIGN: Women delivering babies at one of five hospitals in southwestern Virginia between 1994 and 1996 were invited to participate in a cohort study; 780 women enrolled. Ambient air quality data (ozone and particulate matter) were collected at a central monitoring site. PARTICIPANTS: This analysis is of 691 infants followed for approximately 83 days between 10 June and 31 August 1995 and/or 1996 ; they contributed a total of 52,421 infant-days of follow-up. Mothers were interviewed at enrollment and approximately biweekly to report infants' daily symptoms. Repeated measures logistic regression models were run separately for wheeze, difficulty breathing, and cough. Ozone metrics included 24-hr average, peak 1-hr, and maximum 8-hr average. Analyses were repeated for the 61 infants whose mothers had asthma. RESULTS: For every interquartile-range increase in same-day 24-hr average ozone, likelihood of wheeze increased 37% [95% confidence interval (CI), 2-84%]. Among infants of asthmatic mothers, same-day 24-hr average ozone increased likelihood of wheeze 59% (95% CI, 1-154%) and of difficulty breathing 83% (95% CI, 42-136%). Maximum 8-hr ozone and peak 1-hr ozone were associated with difficulty breathing, but not wheeze, in infants of asthmatic mothers. Ozone was not associated with cough. CONCLUSIONS: At levels of ozone exposure near or below current U.S. EPA standards, infants are at increased risk of respiratory symptoms, particularly infants whose mothers have physician-diagnosed asthma.

Cohort Studies↗
PubMed2005

Effect of fetal sex on airway lability in pregnant women with asthma.

The authors investigated the association between sex of the fetus and maternal airway lability among pregnant women with asthma. Data were prospectively collected among 702 pregnant women with a diagnosis of asthma who were recruited in southern New England between 1997 and 2000 and followed through pregnancy. Peak expiratory flow lability, defined as percent daily maximum minus the minimum divided by the mean, was assessed at enrollment and at 21, 29, and 37 weeks' gestation. There was a -9.9 percent (95 percent confidence interval: -19.4, -0.4) difference in airway lability observed between women carrying female fetuses and those carrying male fetuses. This difference persisted throughout pregnancy. Among pregnant asthmatic women, carrying a female fetus is associated with worse maternal asthma, as assessed by greater airway lability, than is carrying a male fetus.

Adult↗
PubMed2005

Association of indoor nitrogen dioxide exposure with respiratory symptoms in children with asthma.

RATIONALE: Chronic exposure to indoor nitrogen dioxide (NO2) is a public health concern. Over half of U.S. households have a source of NO2, and experimental data suggest potential for adverse respiratory effects. OBJECTIVE: To examine associations of indoor NO2 exposure with respiratory symptoms among children with asthma. METHODS: NO2 was measured using Palmes tubes, and respiratory symptoms in the month before sampling were collected during home interviews of mothers of 728 children with active asthma. All were younger than 12 yr, lived at the sampled home for at least 2 mo, and had asthma symptoms or used maintenance medication within the previous year. MEASUREMENTS: Respiratory symptoms (wheeze, persistent cough, shortness of breath, chest tightness). RESULTS: Mean (SD) NO2 was 8.6 (9.1) ppb in homes with electric ranges and 25.9 (18.1) ppb in homes with gas stoves. In models stratified by housing type (a factor associated with socioeconomic status), gas stove presence and elevated NO2 were each significantly associated with respiratory symptoms, controlling for age, ethnicity, medication, mold/mildew, water leaks, and season of sampling. Among children in multifamily housing, exposure to gas stoves increased likelihood of wheeze (odds ratio [OR], 2.27; 95% confidence interval [95% CI], 1.15, 4.47), shortness of breath (OR, 2.33; 95% CI, 1.12, 5.06), and chest tightness (OR, 4.34; 95% CI, 1.76, 10.69), whereas each 20-ppb increase in NO2 increased both likelihood of any wheeze (OR, 1.52; 95% CI, 1.04, 2.21) or chest tightness (OR, 1.61; 95% CI, 1.04, 2.49), and days of wheeze (rate ratio (RR), 1.33; 95% CI, 1.05, 1.68) or chest tightness (RR, 1.51; 95% CI, 1.18, 1.91). CONCLUSION: Exposure to indoor NO2 at levels well below the Environmental Protection Agency outdoor standard (53 ppb) is associated with respiratory symptoms among children with asthma in multifamily housing.

Air Pollution, Indoor↗
PubMed2005

Genomic epidemiology of complex disease: the need for an electronic evidence-based approach to research synthesis.

Modern microarray genotyping now permits simultaneous analysis of tens of thousands of polymorphisms, and this technology is being widely used to associate the role of genes with the etiology of complex disease. Genome-wide hypothesis-free mapping will also increasingly generate candidate genes that require further testing in association studies. At the same time, genetic effects are increasingly observed to be buffered by a wide array of biologic mechanisms that evolved to protect the genome from environmental insult and that serve to obscure observation of direct effects of polymorphisms on a disease phenotype. These two forces combine to make replication of genomic epidemiology extraordinarily difficult. Traditional research synthesis of emerging bodies of genomic epidemiology is problematic and often quickly outdated. The author proposes that electronic evidence-based methodology, perhaps modeled after that used by the Cochrane Collaboration in clinical medicine, would facilitate the systematic preparation and frequent updating of systematic reviews, which is essential for identifying valid and replicable gene-disease associations.

Chromosome Mapping↗
PubMed2005

Complement factor H polymorphism in age-related macular degeneration.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

Aged↗
PubMed2005

Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy.

PURPOSE: To review the methodologic issues complicating caffeine exposure assessment during pregnancy; to discuss maternal and fetal caffeine metabolism, including genetic polymorphisms affecting caffeine metabolism; and to discuss the endogenous and exogenous risk factors known to influence caffeine metabolism. METHODS: A review of the relevant literature. RESULTS: There is wide inter-individual variation in caffeine metabolism, primarily due to variations in CYP1A2 enzyme activity. Some variability in CYP1A2 activity is due to genetic polymorphisms in the CYP1A2 gene which can cause increased or decreased inducibility of the enzyme. Considerable evidence exists that maternal caffeine metabolism is influenced by a variety of endogenous and exogenous factors and studying the genetic polymorphisms may improve understanding of the potential effects of caffeine and its metabolites on perinatal outcomes. There is substantial evidence that measurement of maternal, fetal, and neonatal caffeine metabolites may allow for a more precise measure of fetal caffeine exposure. CONCLUSIONS: Research on the genetic polymorphisms affecting caffeine metabolism may further explain the potential effects of caffeine and its metabolites on perinatal outcomes.

Caffeine↗
PubMed2005

Polymorphisms in the 5' region of the CD14 gene are associated with eczema in young children.

BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene. OBJECTIVE: We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes. RESULTS: Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses. CONCLUSIONS: Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.

5' Flanking Region↗
PubMed2005

Indoor heating sources and respiratory symptoms in nonsmoking women.

BACKGROUND: Secondary heating appliances are important indoor sources of air pollution, including particulate matter, nitrogen dioxide (NO2), and sulfur dioxide (SO2). We hypothesized that the use of secondary heating sources increases respiratory symptoms in women living in nonsmoking households and specifically that concentrations of SO2 and NO2 emitted from heating sources are associated with respiratory symptoms. METHODS: Mothers who delivered babies at 12 hospitals in Connecticut and Virginia (1993-1996) were enrolled. There were 888 women who contributed symptom and exposure information during the winter heating season (15 October to 15 April), for a total of 9783 reporting periods (median = 12 reporting periods per woman, interquartile range 11-12). Adjusted rate ratios (RRs) of effects of source use and measured concentrations on rate of days with symptoms were obtained using generalized estimating equations for a log-linear Poisson model, controlling age, education, race, history of allergies, number of children, dwelling type, and residence state. RESULTS: In adjusted models, each hour-per-day increase in kerosene heater use is associated with an increase in wheezing (RR = 1.06; 95% confidence interval (CI) = 1.01-1.11). Each hour of fireplace use is associated with increased cough (1.05; 1.01-1.09), sore throat (1.04; 1.00-1.08), and marginally with chest tightness (1.05; 0.99-1.12). Each 10 ppb increase in SO2 (a proxy for sulfate aerosol) is associated with increased wheezing (1.57; 1.10-2.26) and chest tightness (1.32; 1.01-1.71). CONCLUSIONS: Emissions from fireplaces, gas space heaters, and kerosene heaters may contribute to respiratory symptoms in a population of nonsmoking women.

Air Pollution, Indoor↗
PubMed2004

Collaborative quality improvement to promote evidence based surfactant for preterm infants: a cluster randomised trial.

OBJECTIVE: To test a multifaceted collaborative quality improvement intervention designed to promote evidence based surfactant treatment for preterm infants of 23-29 weeks' gestation. DESIGN: Cluster randomised controlled trial. SETTING AND PARTICIPANTS: 114 neonatal intensive care units (which treated 6039 infants of 23-29 weeks gestation born in 2001). MAIN OUTCOME MEASURES: Process of care measures: proportion of infants receiving first surfactant in the delivery room, proportion receiving first surfactant more than two hours after birth, and median time from birth to first dose of surfactant. Clinical outcomes: death before discharge home, and pneumothorax. INTERVENTION: Multifaceted collaborative quality improvement advice including audit and feedback, evidence reviews, an interactive training workshop, and ongoing faculty support via conference calls and email. RESULTS: Compared with those in control hospitals, infants in intervention hospitals were more likely to receive surfactant in the delivery room (adjusted odds ratio 5.38 (95% confidence interval 2.84 to 10.20)), were less likely to receive the first dose more than two hours after birth (adjusted odds ratio 0.35 (0.24 to 0.53)), and received the first dose of surfactant sooner after birth (median of 21 minutes v 78 minutes, P < 0.001). The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth. There were no significant differences in mortality or pneumothorax. CONCLUSION: A multifaceted intervention including audit and feedback, evidence reviews, quality improvement training, and follow up support changed the behaviour of health professionals and promoted evidence based practice.

Cluster Analysis↗