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Biomedical subjects

Roger L Holder

Publications and source records attributed to Roger L Holder.

9 recordsLinked to original sources

The design of simulation studies in medical statistics.

Simulation studies use computer intensive procedures to assess the performance of a variety of statistical methods in relation to a known truth. Such evaluation cannot be achieved with studies of real data alone. Designing high-quality simulations that reflect the complex situations seen in practice, such as in prognostic factors studies, is not a simple process. Unfortunately, very few published simulation studies provide sufficient details to allow readers to understand fully all the processes required to design a simulation study. When planning a simulation study, it is recommended that a detailed protocol be produced, giving full details of how the study will be performed, analysed and reported. This paper details the important considerations necessary when designing any simulation study, including defining specific objectives of the study, determining the procedures for generating the data sets and the number of simulations to perform. A checklist highlighting the important considerations when designing a simulation study is provided. A small review of the literature identifies the current practices within published simulation studies.

Biomedical Research↗

Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study.

OBJECTIVES: This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy. BACKGROUND: Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality. METHODS: A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. RESULTS: A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months. CONCLUSIONS: Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.

Adolescent↗

Cluster analysis as a method for determining size ranges for spinal implants: disc lumbar replacement prosthesis dimensions from magnetic resonance images.

STUDY DESIGN: Statistical analysis of clinical radiologic data. OBJECTIVE: To develop an objective method for finding the number of sizes for a lumbar disc replacement. SUMMARY OF BACKGROUND DATA: Cluster analysis is a well-established technique for sorting observations into clusters so that the "similarity level" is maximal if they belong to the same cluster and minimal otherwise. METHODS: Magnetic resonance scans from 69 patients, with no abnormal discs, yielded 206 sagittal and transverse images of 206 discs (levels L3-L4-L5-S1). Anteroposterior and lateral dimensions were measured from vertebral margins on transverse images; disc heights were measured from sagittal images. Hierarchical cluster analysis was performed to determine the number of clusters followed by nonhierarchical (K-means) cluster analysis. Discriminant analysis was used to determine how well the clusters could be used to classify an observation. RESULTS: The most successful method of clustering the data involved the following parameters: anteroposterior dimension; lateral dimension (both were the mean of results from the superior and inferior margins of a vertebral body, measured on transverse images); and maximum disc height (from a midsagittal image). These were grouped into 7 clusters so that a discriminant analysis was capable of correctly classifying 97.1% of the observations. The mean and standard deviations for the parameter values in each cluster were determined. CONCLUSIONS: Cluster analysis has been successfully used to find the dimensions of the minimum number of prosthesis sizes required to replace L3-L4 to L5-S1 discs; the range of sizes would enable them to be used at higher lumbar levels in some patients.

Adult↗

Modeling physiological and anthropometric variables known to vary with body size and other confounding variables.

This review explores the most appropriate methods of identifying population differences in physiological and anthropometric variables known to differ with body size and other confounding variables. We shall provide an overview of such problems from a historical point of view. We shall then give some guidelines as to the choice of body-size covariates as well as other confounding variables, and show how these might be incorporated into the model, depending on the physiological dependent variable and the nature of the population being studied. We shall also recommend appropriate goodness-of-fit statistics that will enable researchers to confirm the most appropriate choice of model, including, for example, how to compare proportional allometric models with the equivalent linear or additive polynomial models. We shall also discuss alternative body-size scaling variables (height, fat-free mass, body surface area, and projected area of skeletal bone), and whether empirical vs. theoretical scaling methodologies should be reported. We shall offer some cautionary advice (limitations) when interpreting the parameters obtained when fitting proportional power function or allometric models, due to the fact that human physiques are not geometrically similar to each other. In conclusion, a variety of different models will be identified to describe physiological and anthropometric variables known to vary with body size and other confounding variables. These include simple ratio standards (e.g., per body mass ratios), linear and additive polynomial models, and proportional allometric or power function models. Proportional allometric models are shown to be superior to either simple ratio standards or linear and additive polynomial models for a variety of different reasons. These include: 1) providing biologically interpretable models that yield sensible estimates within and beyond the range of data; and 2) providing a superior fit based on the Akaike information criterion (AIC), Bayes information criterion (BIC), or maximum log-likelihood criteria (resulting in a smaller error variance). As such, these models will also: 3) naturally lead to a more powerful analysis-of-covariance test of significance, which will 4) subsequently lead to more correct conclusions when investigating population (epidemiological) or experimental differences in physiological and anthropometric variables known to vary with body size.

Anthropometry↗

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Adolescent↗

Does lower-body BMD develop at the expense of upper-body BMD in female runners?

PURPOSE: Evidence suggests that exercise plays an important role in stimulating site-specific bone mineral density (BMD). However, what is less well understood is how these benefits dissipate throughout the body. Hence, the purpose of the present study was to compare the levels of, and the correlation between, BMD recorded at 10 sites in female endurance runners, and to investigate possible determinants responsible for any inter-site differences observed. METHODS: Repeated measures ANOVA was used to compare the BMD between sites and factor analysis was used to describe the pattern of intersite correlations. Allometric ANCOVA was used to identify the primary determinants of bone mass and how these varied between sites. RESULTS: The ANOVA and factor analysis identified systematic differences in BMD between sites, with the greatest BMD being observed in the lower-body sites, in particular the legs. An investigation into the possible mechanisms responsible for these differences revealed "distances run" (km.wk-1) as a positive, and "years of training" as a negative determinant of bone mass (P < 0.001). However, the effect of a number of determinants varied between sites (P < 0.05). Specifically, the ANCOVA identified that running further distances resulted in higher bone mass in the arms and legs. In contrast, training for additional years appeared to result in lower bone mass in the arms and lumbar spine. Calcium intake was also found to be positively associated with bone mass in the legs but negatively associated at all other sites. CONCLUSIONS: A combination of running exercise and calcium intake would appear to stimulate the bone mass of women endurance runners at lower-body sites but at the expense of bone mass at upper-body sites.

Adult↗

Oxygen uptake during post dive recovery in a diving bird Aythya fuligula: implications for optimal foraging models.

The rate of oxygen uptake at the surface between dives was measured for four tufted ducks, Aythya fuligula, during bouts of foraging dives to a depth of 1.8 m. The ducks surfaced into a respirometer box after each dive so that the rate of oxygen uptake ((O(2))) could be measured. (O(2)) decreased over time at the surface and there was a particularly rapid phase of oxygen uptake for approximately the first 3s. The specific shape of the oxygen uptake curve is dependent upon the duration of the preceding dive. The uptake curve after longer dives was significantly steeper during the first 3s at the surface than after shorter dives, although (O(2)) after the first 3s was not significantly different between these two dive duration bins. Thus, the mean total oxygen uptake (V(O(2))) was higher after surface periods following longer dives. Due to the high (O(2)) during the initial part of the surface period, the curve associated with longer dives was statistically biphasic, with the point of inflection at 3.3s. The curve for shorter dives was not statistically biphasic. The birds may increase their respiratory frequency during the first 3s after longer dives, producing the increased (O(2)), which would enable the birds to resaturate their oxygen stores more rapidly in response to the increased oxygen depletion of the longer submergence time.

Animals↗

Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.

The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant.

Adolescent↗

A comparison of Bayesian and maximum likelihood methods to determine the performance of a point of care test for Helicobacter pylori in the office setting.

OBJECTIVE: Evaluations of point of care tests (PCT) are often hampered by a lack of appropriate gold standards. This study aimed to compare the results of a Bayesian statistical analysis and a maximum likelihood method to evaluate the performance of a PCT for Helicobacter pylori in primary care. METHODS: The Helisal Rapid Blood Test (Cortecs Diagnostics) was performed in 311 patients from 6 primary care centers, and a concurrent venous sample was taken for 2 enzyme-linked immunosorbent assays (ELISA) performed at the laboratory, blind to the PCT result. The Bayesian analysis was conducted using Markov Chain Monte Carlo methods (WinBUGS). The performance characteristics of the PCT and the 2 ELISA tests were estimated together with 95% credible intervals (95% CIs). RESULTS: The estimate of prevalence of H. pylori in this population was 64% (95% CI, 59% to 70%), the sensitivity and specificity of the PCT were 89% (84% to 94%) and 84% (77% to 91%), respectively (likelihood ratios positive 5.6, negative 0.13). The equivalent maximum likelihood results were prevalence, 65%; sensitivity, 90%; and specificity, 83%. CONCLUSIONS: The Helisal Rapid Blood Test performed as well as laboratory-based ELISA tests in this cohort of patients. The Bayesian analysis and the maximum likelihood method gave similar results, the Bayesian method also simultaneously estimating 95% CIs.

Aged↗