Biomedical subjects

A Donner

Publications and source records attributed to A Donner.

At least 19 recordsLinked to original sources

PubMed2007

Methods for the statistical analysis of binary data in split-mouth designs with baseline measurements.

Many split-mouth trials are characterized by the pairing of site-specific outcome and baseline data within each segment of a subject's mouth. However when the response variable of interest is binary, methods of statistical analysis for this design are not well developed. In this paper we present several analytic approaches that may be taken to the resulting data, showing how the efficiency of statistical inferences can be improved by appropriately incorporating the baseline information. The advantages and disadvantages of the different approaches are discussed in the context of an example from the published literature. The results from a limited simulation study are also presented.

Clinical Trials as Topic↗

PubMed2007

Bivariate models for co-aggregation of dichotomous traits in twins.

The study of twins is widely used for research into genetic and environmental influences on human traits. Study designs in which independent samples of monozygotic and dizygotic twins are compared with respect to their similarity have focused on single binary trait. However, the risk of co-occurrence of more than one disease in twins is a parameter of interest to genetic epidemiologists and other investigators. For example, they may be interested in assessing the genetic and environmental etiologies of reading deficits (RD) and attention deficit hyperactivity disorder (ADHD) and their co-morbidity. In this paper, we present statistical methodology for the estimation of twin similarity with respect to two dichotomous traits measured on each member of the twin pair. For two sample problems, several test procedures that account for the correlation between twins and the correlation between traits are presented. An example based on the Australian population-based twin registry published data is given to illustrate the methodology.

Adult↗

PubMed2007

Developments in cluster randomized trials and Statistics in Medicine.

The design and analysis of cluster randomized trials has been a recurrent theme in Statistics in Medicine since the early volumes. In celebration of 25 years of Statistics in Medicine, this paper reviews recent developments, particularly those that featured in the journal. Issues in design such as sample size calculations, matched paired designs, cohort versus cross-sectional designs, and practical design problems are covered. Developments in analysis include modification of robust methods to cope with small numbers of clusters, generalized estimation equations, population averaged and cluster specific models. Finally, issues on presenting data, some other clustering issues and the general problem of evaluating complex interventions are briefly mentioned.

Bayes Theorem↗

PubMed2005

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers.

OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. METHODS: Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations. Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 microg/ml and 0.341 microg/ml. A CSF-plasma partition coefficient of 0.002 and a k(e0) value of 0.059 h(-1) were estimated by means of population modeling. CONCLUSION: In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations experimentally proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient.

Adult↗

PubMed2005

Synchronous occurrence of a follicular, papillary and medullary thyroid carcinoma in a recurrent goiter.

The simultaneous occurrence of different types of thyroid carcinoma in a single patient is an unusual event. We report the case of a 52-year-old man with the history of two previous thyroid operations for benign goiters, who developed a recurrent goiter. The patient was referred to our department for thyroidectomy. In the pathohistological examination the specimen showed a 5 cm follicular carcinoma and a 0.3 cm papillary microcarcinoma in the right lobe as well as a 1.5 cm medullary carcinoma in the left lobe. All tumors were clearly separated from each other, representing the pure entity of each type. Postoperatively, RET germline mutation was ruled out by sequence analysis of peripheral blood leucocytes. Postoperative I-131-radioiodine scan showed multiple lung and liver metastases, while calcitonin was negative. There is no known common cause of these three different tumor types and they developed most independently from each other. The personal history of our patient was interesting in two aspects: (1) he suffered a period of severe staphylococcal sepsis with temporal immunosuppression and (2) he worked for long years as a coremaker in a foundry. This work represented possible long term exposure to inhalative carcinogenous toxins like hydrazine, which caused thyroid parafollicular cell adenomas in an animal model.

Adenocarcinoma, Follicular↗

PubMed2004

[Behçet's disease with gastrointestinal involvement without evidence for chronic inflammatory bowel disease].

A case of a 32-year-old male patient with lower gastrointestinal bleeding is reported as an initial manifestation of Behçet's disease. The early diagnosis of this chronic-systemic disease is often very difficult, in particular with regard to the differentiation from chronic inflammatory bowel diseases. In addition, lower gastrointestinal bleeding is a rare manifestation of Behçet's disease. An immunosuppressive therapy was initiated and the course of the disease with recurrent oral ulcerations gave evidence for the diagnosis. Further bleeding episodes or other gastrointestinal symptoms have not been observed during a follow-up period of 36 months. The diagnostic problems and the therapeutic management of the disease are discussed in relation to neighbouring entities.

Adult↗

PubMed2003

Hydrocortisone improved haemodynamics and fluid requirement in surviving but not non-surviving of severely burned patients.

Recent studies have shown that administration of hydrocortisone may lead to a reduction of catecholamines and to an improved outcome in septic patients. However, there are no data on the use of hydrocortisone in burn patients although in these patients reduction of vasopressors might be even more crucial for outcome due to improvement of skin perfusion. This study presents the first results on the impact of hydrocortisone administration in norepinephrine dependent severely burned patients. In a prospective cohort study fourteen consecutive severely burned patients received, 12h after norepinephrine dependency, a hydrocortisone bolus of 100mg followed by 0.18mg/(kgh) hydrocortisone. The course of the necessary norepinephrine dose, as well as the fluid balance was documented 12h prior and after the first dosage of hydrocortisone. Statistical analysis showed an unexpected increase of the required norepinephrine dosage. A statistical post hoc evaluation of surviving and non-surviving patients revealed a significant increase of norepinephrine in non-survivors whereas in survivors it was possible to reduce norepinephrine significantly. Furthermore, the median fluid requirement of surviving patients could be significantly reduced whereas in the group of non-survivors there was no change of volume needed. Our data suggests that hydrocortisone might be useful in selected patients with severe burn injuries. However, patients not responding to hydrocortisone administrations seem to have a poor prognosis. Our findings are in contrast to previously published data on septic patients, in whom hydrocortisone administration resulted in a reduction of norepinephrine. In burned patients the severity of trauma seems to have more profound influence on the pathophysiological mechanism of sepsis. Due to the high number of non-responders, the potential immune suppression and impaired wound healing caused by the side effects of hydrocortisone, further selection criteria seem to be necessary. A short ACTH-test might be considered prior to hydrocortisone administration to select patients who might benefit from this therapy. In summary, further prospective controlled studies will be necessary to establish hydrocortisone in the routine therapy of severely burned patients.

Adult↗

PubMed2003

Indocyanine green video angiographies help to identify burns requiring operation.

The key decision in the treatment of thermal injuries is the determination of the depth of the burn wound and the resultant decision on treatment options. The trend in the treatment of deep dermal and full thickness burns is toward very early excision and grafting to reduce the risk of infection, decrease scar formation, shorten hospital stay, and thereby reducing costs. Traditionally, this has involved serial clinical examinations, which involves primarily subjective judgment. Various objective examination techniques, supplementing the clinical diagnosis, have been suggested, but none has yet achieved widespread clinical acceptance. It has frequently been postulated that the blood flow in injured tissue indicates the extent of tissue damage. In this study, the clinical and scientific impact of indocyanine green (ICG) video angiography was tested in 20 patients. A wide range of depth of injury and etiology was included and analyzed. In all cases considered, video angiography was possible. The measurements and observations correlated well with the actual burn depth, which was assessed clinically (pre- and intraoperative assessment) and histologically (biopsies). In conclusion, ICG video angiography seems to be a practical method to describe vascular patency in a burn wound. The results indicate that ICG fluorescence angiography is a practical, accurate, and effective adjunct to clinical methods for estimating burn wound depth and thereby to assist in the rational assessment of treatment options. Furthermore, it allows an objective, qualitative and quantitative observation of the dynamic changes in burn wound depth, which are observed during the acute post-burn period, thereby indicating optimal timing of the first operation.

Adult↗

PubMed2003

A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity.

We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40-50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity-index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t-test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.

Adult↗

PubMed2002

Patient versus injury factors as predictors of pain and disability six months after a distal radius fracture.

A prospective cohort of 120 patients with distal radius fractures completed a baseline evaluation that determined their age, sex, education level, injury compensation status, AO fracture type, prereduction radial shortening, and postreduction radial shortening. Six months later patients self-reported pain and disability using the Patient-Rated Wrist Evaluation, and were tested for physical impairment (grip, wrist range of motion, and dexterity). Univariate and forward stepwise regression analyses agreed that the most influential predictor of pain and disability at 6 months was injury compensation. Patient education level and prereduction radial shortening also contributed predictive information (R squared = 25%). Wrist impairment was moderately correlated with patient reported pain and disability (r = 0.50). Both impairment and disability measures are required to fully describe outcomes. Further work is required to delineate additional factors that contribute to outcome.

Adult↗

PubMed2001

Current and future challenges in the design and analysis of cluster randomization trials.

Randomized trials in which the unit of randomization is a community, worksite, school or family are becoming widely used in the evaluation of life-style interventions for the prevention of disease. The increasing interest in adopting a cluster randomization design is being matched by rapid methodological developments. In this paper we describe several of these developments. Brief mention is also made of issues related to economic analysis and to the planning and conduct of meta-analyses for cluster randomization trials. Recommendations for reporting are also discussed.

Adult↗

PubMed2001

Meta-analyses in systematic reviews of randomized controlled trials in perinatal medicine: comparison of fixed and random effects models.

There is a need for empirical work comparing the random effects model with the fixed effects model in the calculation of a pooled relative risk in the meta-analysis in systematic reviews of randomized controlled trials. Such comparisons are particularly important when trial results are heterogeneous. We considered 84 independent meta-analyses in which each trial included a set of different women/newborns. These meta-analyses were included in systematic reviews published in the Cochrane Library's pregnancy and childbirth module. Twenty-one of these 84 meta-analyses demonstrated statistical heterogeneity at p<0.10. The random effects model estimates showed wider confidence intervals, particularly in those meta-analyses showing heterogeneity in the trial results. The summary relative risk for the random effects model tended to show a larger protective treatment effect than the fixed effects model in the heterogeneous meta-analyses. In this set of meta-analyses, statistical evaluation of publication bias cannot be shown to account for heterogeneity. Our empirical conclusion is that there may be opposing effects if the random effects model is used in the meta-analysis of clinical trials showing heterogeneity in the results: stronger treatment effects reflected in the summary relative risk, but wider confidence intervals about this summary measure.

Chi-Square Distribution↗

PubMed2001

A general goodness-of-fit approach for inference procedures concerning the kappa statistic.

The kappa statistic is frequently used as a measure of agreement among two or more raters. Although considerable research on statistical inferences for this statistic has been published for the case of two raters and a binary outcome, relatively little work has appeared on inference problems for the case of multiple raters and/or polytomous nominal outcome categories. In this paper we propose a new procedure for constructing inferences for the kappa statistic that may be applied to this general case. The procedure is based on a chi-square goodness-of-fit test as applied to the Dirichlet multinomial model, and is a natural extension of previously proposed procedures that apply to more restricted cases. A simulation study shows that the new procedure provides confidence interval coverage levels and type I error rates close to nominal over a wide range of parameter combinations. We also present a sample size formula which may be used to determine the required number of subjects and raters for a given number of outcome categories.

Bias↗

PubMed2001

Evaluation of an adjusted chi-square statistic as applied to observational studies involving clustered binary data.

A simple adjustment to the Pearson chi-square test has been proposed for comparing proportions estimated from clustered binary observations. However, the assumptions needed to assure the validity of this test have not yet been thoroughly addressed. These assumptions will hold for experimental comparisons, but could be violated for some observational comparisons. In this paper we investigate the conditions under which the adjusted chi-square statistic is valid and examine its performance when these assumptions are violated. We also introduce some alternative test statistics that do not require these assumptions. The test statistics considered are then compared through simulation and an example presented based on real data. The simulation study shows that the adjusted chi-square statistic generally produces empirical type I errors close to nominal under the assumption of a common intracluster correlation coefficient. Even if the intracluster correlations are different, the adjusted chi-square statistic performs well when the groups have equal numbers of clusters.

Chi-Square Distribution↗

PubMed2001

WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care.

BACKGROUND: We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. METHODS: Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. FINDINGS: Women attending clinics assigned the new model (n=12568) had a median of five visits compared with eight within the standard model (n=11958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. INTERPRETATIONS: Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost.

Adult↗

PubMed2001

Statistical inferences for a twin correlation with multinomial outcomes.

Current methods for statistical analysis of twin studies focus on continuous and dichotomous data, while only limited methodology exists for analysing multinomial data. As a consequence, investigators are often tempted to collapse multinomial data into two categories simply to facilitate the analysis. We address this problem by developing and evaluating two approaches to the assessment of twin correlation for an outcome variable having more than two nominal categories. One method developed is an extension of the goodness-of-fit approach, while the other method is based on large sample normal theory. Procedures for confidence interval construction are developed and compared using Monte Carlo simulation. The results show that either method may be safely used for confidence interval construction provided the number of twin pairs is large (> or =100) but that in smaller sample sizes the goodness-of-fit procedure is to be preferred on the grounds of validity. Other inference problems are also discussed, including point estimation, hypothesis testing and sample size estimation. An example is included.

Computer Simulation↗

PubMed2001

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Adult↗

PubMed2001

Peritoneal sclerosis in peritoneal dialysis patients related to dialysis settings and peritoneal transport properties.

BACKGROUND: Peritoneal sclerosis is a histopathologic finding that is probably causative of long-term system failure in peritoneal dialysis (PD). It may be due to uremic toxicity and the influence of peritoneal dialysate components. We intended to clarify to which degree peritoneal fibrosis and vascular changes were associated with the modalities of PD and the peritoneal transport characteristics. METHODS: Peritoneal biopsies of 41 patients suffering from end-stage renal disease were examined. Sixteen patients were at the initiation of dialysis treatment, and 25 patients were studied during chronic PD treatment [9 patients on continuous ambulatory PD (CAPD) and 16 patients on automatic PD (APD)]. Twenty nonuremic patients undergoing abdominal surgery served as the controls. Samples were taken from the parietal peritoneum under standardized conditions and were examined by light microscopy using different staining techniques, semiquantitative grading, and computer-based histomorphometry. RESULTS: A marked loss of mesothelial cells during PD treatment was only observed in cases with two or more preceding episodes of peritonitis, but an increase of the submesothelial fibrous tissue was a common finding and was related to the cumulative glucose load on PD. Patients on PD also had a significantly increased density of small vessels and capillaries in the submesothelial peritoneal layer (12.8 +/- 6.9 per field vs. 6.6 +/- 2.9 in normal controls, P < 0.01). The wall/lumen index of the vessels was increased indicating vascular sclerosis. The degree of vascularization correlated with the amount of fibrous tissue. Patients characterized as high transporters according to the peritoneal equilibration test (PET) had an increased submesothelial fibrous layer. Patients on APD tended to have an increased membrane diameter submesothelial stroma and vascularization (P = NS), although they were treated for a shorter period of time than the CAPD group. Some of the morphologic changes described could already be observed in uremic patients before the onset of dialysis. CONCLUSION: Further research focusing on the clinical and biochemical backgrounds leading to peritoneal membrane changes is of major importance for developing strategies to improve long-term survival on PD.

Adult↗