Biomedical subjects

Anthony P Fitzgerald

Publications and source records attributed to Anthony P Fitzgerald.

4 recordsLinked to original sources

PubMed2006

Adenocarcinoma of the oesophagus and gastric cardia: male preponderance in association with obesity.

Recent evidence links obesity with the rising incidence of oesophageal adenocarcinoma. In Ireland between 1995 and 2004 the incidence of oesophageal adenocarcinoma increased by 38%, and this coincided with a 67% increase in the prevalence of obesity. In this study, a prospective case-control study was undertaken in 760 patients presenting to a tertiary centre between 1994 and 2004 diagnosed with cancer of the oesophagus, gastric cardia or stomach. Data were compared with 893 healthy controls. Multivariate logistic regression models were used to calculate the odds ratio (OR) of developing either cancer type according to quartiles of body mass index (BMI). Based on pre-illness BMI, 82% of patients who developed adenocarcinoma of the oesophagus were either overweight or obese compared with 59% of the healthy control population (P<0.001). A dose-dependent relationship existed between BMI and oesophageal adenocarcinoma in males. The adjusted odds ratio was 4.3 (95% CI: 2.3-7.9) among males in the highest BMI quartile compared with males in the lowest quartile (P<0.001 for trend). Using common cut-off points for BMI, the OR of adenocarcinoma of the lower oesophagus was 11.3 times higher (95% CI: 3.5-36.4) for individuals with a BMI >30 kg/m2 versus individuals with a BMI <22 kg/m2 (P<0.001 for trend). For adenocarcinoma of the gastric cardia, males in the top quartile of BMI had an OR of 3.5 (95% CI: 1.3-9.4) compared with the lowest quartile (P=0.03 for trend). A significant (P<0.001) inverse relationship between BMI and oesophageal SCC was observed. The odds ratio for adenocarcinoma of the oesophagus, the oesophago-gastric junction and gastric cardia rose significantly with increasing BMI. For tumours of the lower oesophagus, obesity increased the risk 10.9-fold. The increased risk is significant in males only.

Adenocarcinoma↗

PubMed2006

Prediction of seizures in asphyxiated neonates: correlation with continuous video-electroencephalographic monitoring.

BACKGROUND: After perinatal asphyxia, predicting which infants will develop significant hypoxic-ischemic encephalopathy and neonatal seizures remains a difficult task. High-risk markers (Apgar score, acidosis, nucleated red blood cells, and resuscitation) have been used to predict neonatal seizures with varying success. The "3 strikes" of Apgar score of <5 at 5 minutes, pH <7.00, and need for intubation have been cited as having a positive predictive value of 80%. We examined whether the predictive values of these markers would be increased if early continuous electroencephalographic monitoring allowed us to accurately identify all neonatal seizures and to grade the encephalopathy. METHOD: We recruited term infants with perinatal asphyxia. Continuous video electroencephalography was commenced soon after birth and continued for 24 to 72 hours. The abilities of high-risk markers to predict electroencephalographic seizures, background electroencephalographic activity, and Sarnat grade were examined. RESULTS: Forty-nine infants were suitable for analysis. Electrographic seizures occurred in 11 of the 49 infants. Encephalopathy was scored by using Sarnat grade (6, severe; 18, moderate; 25, mild) and electroencephalographic findings (4 inactive, 4 major abnormalities, 16 moderate abnormalities, and 25 normal/mildly abnormal). Apgar score of <5 at 5 minutes, pH <7.0, and the need for intubation had positive predictive values for neonatal seizures of 18%, 16%, and 21%, respectively. Combining these markers gave a positive predictive value of 25% and a negative predictive value of 77%. Substituting base deficit or lactate for pH in the 3-strikes model did not improve its predictive value. Apgar score of <5 at 5 minutes, nucleated red blood cells, and a base deficit less than -15 mEq/L showed some association with Sarnat grade. Only 5-minute Apgar score was significantly associated with both Sarnat grade and electroencephalographic grade. CONCLUSION: After perinatal asphyxia, neither the condition at birth nor the degree of metabolic acidosis reliably predict neonatal seizures.

Apgar Score↗

PubMed2005

Overdispersion of allele frequency differences between populations: implications for meta-analyses of genotypic disease associations.

Methods correcting case-control studies of genetic polymorphisms for unmeasured genetic population substructure by modelling the variation at a number of variant loci provide no standard and easily implemented approach to meta-analysis, which is a key to understanding the effects of minor genotypic risks on complex diseases. A correction of the odds ratio estimate and its confidence interval is shown to be easy to implement using a mixed effects logistic regression. The method is shown to substantially reduce bias and to give accurate coverage even when there is substantial overdispersion of allele frequency differences between populations. Major sequence classes of single-nucleotide polymorphism (SNP) are likely to act as valid controls for each other, since CpG SNPs did not differ in the extent of population structure from other SNPs. Agreement among investigators and journals to provide these straightforward statistics in publications of polymorphism studies will enhance the ability of future investigators to perform meta-analyses of weak genetic effects across accumulated studies that allow for population structure.

Case-Control Studies↗

PubMed2002

Modelling HIV viral rebound using non-linear mixed effects models.

Individuals infected with the human immunodeficiency virus type 1 (HIV-1) who initiate antiretroviral therapy typically experience a marked decline in concentrations of HIV-1 RNA in plasma. Often, however, viral rebound occurs within the first year of treatment and this rebound may be associated with resistance to antiretroviral therapy. For this reason, it is important to study the patterns of virological response of HIV-1 RNA to treatment. In particular, there is interest in the relationship between the lowest level of plasma HIV-1 RNA attained after initiation of therapy (nadir value) and the time until rebound. To investigate this question, we implement a simple and flexible non-linear mixed effects model for the trajectory of the HIV-1 RNA until rebound. This model is also consistent with biological insights into the effects of treatment. We also show how the problem of censoring of HIV-1 RNA values at the lower limit of assay quantification can be addressed using a multiple imputation scheme. The algorithm is simple to implement and is based on accessible software. Our application makes use of data from clinical trial 315 conducted by the AIDS Clinical Trials Group (ACTG 315). We find a strong relationship between HIV-1 RNA nadir and time to rebound, with potentially important consequences for the management of HIV-infected individuals.

Adolescent↗