Biomedical subjects

Martin L Hazelton

Publications and source records attributed to Martin L Hazelton.

6 recordsLinked to original sources

PubMed2006

Value of retinal vein pulsation characteristics in predicting increased optic disc excavation.

BACKGROUND: Retinal vein pulsation is often absent in glaucoma, but can be induced by applying a graded ophthalmodynamometric force (ODF) to the eye, which is elevated in glaucoma. AIM: To assess whether ODF has a predictive value in determining glaucoma progression. METHODS: 75 patients with glaucoma and suspected glaucoma were examined prospectively in 1996, and then re-examined at a mean of 82 months later. All subjects had intraocular pressure, visual fields, stereo optic disc photography and ODF measured on their initial visit. When venous pulsation was spontaneous, the ODF was said to be 0 g. At re-examination, central corneal thickness and blood pressure were also measured. Initial and subsequent optic disc photographs were compared and graded into those that had increased excavation and those that had remained stable. The relationship between increased excavation (recorded as a binary response) and the measured variables was modelled using a multiple mixed effects logistic regression. RESULTS: ODF at the initial visit was strongly predictive of increased excavation (p = 0.004, odds ratio 1.16/g, range 0-60 g), with greater predictive value in women than in men (p = 0.004). Visual field mean deviation was predictive of increased excavation (p = 0.044), as was optic nerve haemorrhage in association with older age (p = 0.038). Central corneal thickness was not significantly predictive of increased excavation (p = 0.074) after having adjusted for other variables. CONCLUSION: ODF measurement seems to be strongly predictive of the patient's risk for increased optic disc excavation. This suggests that ODF measurement may have predictive value in assessing the likelihood of glaucoma progression.

Aged↗

PubMed2005

Tutorial in biostatistics: spline smoothing with linear mixed models.

The semi-parametric regression achieved via penalized spline smoothing can be expressed in a linear mixed models framework. This allows such models to be fitted using standard mixed models software routines with which many biostatisticians are familiar. Moreover, the analysis of complex correlated data structures that are a hallmark of biostatistics, and which are typically analysed using mixed models, can now incorporate directly smoothing of the relationship between an outcome and covariates. In this paper we provide an introduction to both linear mixed models and penalized spline smoothing, and describe the connection between the two. This is illustrated with three examples, the first using birth data from the U.K., the second relating mammographic density to age in a study of female twin-pairs and the third modelling the relationship between age and bronchial hyperresponsiveness in families. The models are fitted in R (a clone of S-plus) and using Markov chain Monte Carlo (MCMC) implemented in the package WinBUGS.

Adolescent↗

PubMed2005

The force required to induce hemivein pulsation is associated with the site of maximum field loss in glaucoma.

PURPOSE: To determine the factors associated with central retinal vein pulsation changes in glaucoma and identify any hemiretinal vein pulsation changes and their association with sectoral visual field loss. METHODS: One hundred twenty-six patients with glaucoma and 40 normal subjects had automated perimetry, blood pressure, and intraocular pressure measured. A hemifield sensitivity loss was calculated from the upper and lower halves of each field. Those without spontaneous venous pulsation on the optic disc had an ophthalmodynamometer applied, to measure the minimum ophthalmodynamometric force (ODF) necessary to induce venous pulsation. When ODF was restricted to the hemiveins, the force needed to induce pulsation in each hemivein was measured. RESULTS: Eighty-three patients with glaucoma had no spontaneous venous pulsation. The minimum ODF was strongly correlated with mean deviation (Spearman rank r = -0.475, P < 0.0001). Mixed linear regression analysis showed that mean deviation (P < 0.0001) and pulse blood pressure (P < 0.0001) were significantly associated with minimum ODF. There was a strong association between differences in hemifield sensitivity loss and in hemivein ODF (rank r = 0.369, P < 0.0001, n = 80). Multiple linear regression modeling demonstrated that lower hemivein ODF was independently associated with upper field loss (P = 0.003) and upper hemivein ODF with lower field loss (P < 0.0001). CONCLUSIONS: These venous pulsation findings in glaucoma are independent of blood pressure. The hemifield and hemivein association suggests that the major hemivein change is adjacent to the site of major disc damage.

Aged↗

PubMed2004

Retinal venous pulsation in glaucoma and glaucoma suspects.

PURPOSE: To determine whether changes in central retinal vein pulsation characteristics occur in glaucoma, and how these are related to indices of glaucoma severity. DESIGN: A large, consecutive, prospective, case-controlled study. PARTICIPANTS: Ninety-four consecutive glaucoma patients and 105 glaucoma suspects seen in a tertiary referral clinic were examined. Forty-one age-matched normal subjects also were examined. METHODS: The presence or absence of spontaneous venous pulsation was observed in these 3 groups. The ophthalmodynamometric force (ODF) required to induce venous pulsation at the optic disc was measured in those without spontaneous pulsation. Optic disc photographs were obtained and visual field testing was performed for all subjects. MAIN OUTCOME MEASURES: The prevalence of spontaneous venous pulsation between these 3 groups was compared. The relationship between ODF and visual field mean deviation, neuroretinal rim area, age, intraocular pressure (IOP), gender, and diagnosis of glaucoma was investigated using linear mixed models fitted by Gibb's sampling. RESULTS: Significantly fewer (chi-square, 27.7; P<0.001) glaucoma patients (54%) were observed to have spontaneous venous pulsation than suspects (75%) or normals (98%). A worse visual field mean deviation was shown to be the most significant predictor of a higher ODF (P<0.000), with younger age (P<0.000) also predictive of a higher ODF. A strong relationship between ODF and mean deviation was found in the glaucoma patients (r = 0.59; n = 52; P<0.001). CONCLUSIONS: Spontaneous venous pulsation is less common in glaucoma. The ODF required to induce venous pulsation is increased in glaucoma, and this ODF is greater in those with more severe field loss.

Aged↗

PubMed2003

A note on genetic variance components in mixed models.

Burton et al. ([1999] Genet. Epidemiol. 17:118-140) proposed a series of generalized linear mixed models for pedigree data that account for residual correlation between related individuals. These models may be fitted using Markov chain Monte Carlo methods, but the posterior mean for small variance components can exhibit marked positive bias. Burton et al. ([1999] Genet. Epidemiol. 17:118-140) suggested that this problem could be overcome by allowing the variance components to take negative values. We examine this idea in depth, and show that it can be interpreted as a computational device for locating the posterior mode without necessarily implying that the original random effects structure is incorrect. We illustrate the application of this technique to mixed models for familial data.

Data Interpretation, Statistical↗

PubMed2003

Uising WinBUGS to fit nonlinear mixed models with an application to pharmacokinetic modelling of insulin response to glucose challenge in sheep exposed antenatally to glucocorticoids.

Many chronic diseases of adulthood, such as hypertension and diabetes, are now believed to have at least some of their origins before birth. Extensive studies in animal models have identified antenatal exposure to excess glucocorticoids as a leading candidate for the physiological cause of fetal compromise. The resulting adverse intra-uterine environment appears to "program" the individual for higher risk of subsequent disease. We present an analysis of blood glucose and insulin concentrations collected during glucose tolerance tests at 6 and 12 months postnatal age in a cohort of sheep that were treated antenatally with injections of betamethasone (a synthetic glucocorticoid) which, when injected into the mother, cross the placenta to the fetus. A simple pharmacokinetic model, essentially a modification of the single compartment model with first-order absorption and elimination, is developed to describe the time course of glucose concentration and the associated insulin response. The resulting nonlinear mixed model is implemented in a Bayesian framework using the Markov chain Monte Carlo technique Gibbs Sampling via the software package BUGS. This sampling process allows inferences to be made directly about derived quantities with an immediate physical interpretation, such as the maximum insulin concentration in response to glucose challenge. At 6 months postnatal age, sheep treated with antenatal injections of synthetic glucocorticoids had raised insulin concentration in comparison to controls after bolus administration of glucose. This effect persisted to 12 months postnatal age only in the sheep that received multiple doses of glucocorticoids. Moreover, the raised insulin concentration in sheep that received direct injections of synthetic glucocorticoid as fetuses is accompanied by better glucose clearance than in those sheep that received only saline injections, a phenomenon that is not observed in the animals that received maternal injections. It is argued that the fitting of an appropriate statistical model to complex physiological data does not necessarily proclude a result that has a clear interpretation for clinical scientists.

Animals↗