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Biomedical subjects

N Klar

Publications and source records attributed to N Klar.

17 recordsLinked to original sources

Predicting costs of stem-cell transplantation.

PURPOSE: Few studies have formally evaluated the relationship between costs, baseline patient characteristics, and major complications of stem-cell transplantation. We sought (1) to determine whether obtaining baseline information enabled identification of patients whose treatments would be the most costly and (2) to estimate inpatient costs for managing specific transplantation complications. PATIENTS AND METHODS: We collected inpatient costs and clinical information for 236 consecutive patients undergoing transplantation at a single institution between July 1, 1994, and February 20, 1997. Multivariable linear regression was used to evaluate the associations between baseline patient characteristics and costs of hospitalization for initial transplantation and between clinical events and such costs. RESULTS: The median initial inpatient cost in 1997 dollars was $55,500 for autologous transplantation (range, $28,200 to $148,200) and $105,300 for allogeneic transplantation (range, $32,500 to $338,000). When only baseline variables were considered, use of a mismatched allogeneic donor and year of transplantation were significant predictors of costs. No characteristics predicted which patients would incur the highest 10% of costs. When clinical events were considered, infection and in-hospital death were associated with higher costs in autologous transplant recipients ($18,400 and $20,500, respectively), whereas infection, veno-occlusive disease, acute graft-versus-host disease, and death were predicted to add between $15,300 and $28,100 each to allogeneic transplantation costs. CONCLUSION: We were not able to identify before transplantation the patients whose treatments would be the most costly. However, the association between clinical complications and higher costs suggests that prevention may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios even if they do not affect overall survival.

Adolescent

The merits of matching in community intervention trials: a cautionary tale.

Concern about potential imbalance on risk factors in community intervention trials often prompts researchers to adopt a pair-matched design in which similar clusters of individuals are paired and one member of each matched pair is then randomly assigned to the intervention group. It is known that if there are few clusters in trial, it becomes increasingly difficult to obtain close matches on all potential risk factors. One may thus offset any gain in precision with loss in degrees of freedom due to matching. We shown in this paper that there are also several analytic limitations with pair-matched designs. These include: the restriction of prediction models to cluster-level baseline risk factors (for example, cluster size), the inability to test for homogeneity of odds ratios, and difficulties in estimating the intracluster correlation coefficient. These limitations lead us to present arguments that favour stratified designs in which there are more than two clusters in each stratum.

Cluster Analysis

Comparison of methods for analyzing binary data arising from two-sample twin studies.

The study of twins is widely used for research into genetic and environmental influences on human outcome measurements. For the study design in which independent samples of monozygotic and dizygotic twins are compared with respect to their similarity on a binary trait, several statistical methods have been proposed. Using a Monte Carlo simulation, we compare the five following procedures: 1) goodness-of-fit method based on the common correlation model, 2) normal approximation of the maximum likelihood estimators of the common correlation coefficients, 3) Ramakrishnan et al. [(1992) Genet Epidemiol 9:273-282] method of odds ratio comparison, 4) generalized estimating equations method of odds ratio estimation, and 5) tetrachoric correlation method. The results show that the goodness-of-fit approach has similar or better performance in both type-one error rates and power than the other methods in all parameter settings. Its advantage with respect to type-one error rates is particularly clear under conditions of small sample sizes, extreme prevalences, or high values of the intraclass correlation coefficients. Therefore, the goodness-of-fit method is recommended for the two-sample twin study design.

Coronary Disease

Statistical considerations in the design and analysis of community intervention trials.

Community intervention trials are often characterized by the allocation of intact social units to different intervention groups. The assessment of adequate sample size for such trials must take into account the statistical dependencies among responses observed within an allocated unit. However, the small numbers of units typically involved in such trials imply that many methods of analysis that have been proposed for analyzing correlated data, particularly in the case of a dichotomous outcome variable, are not applicable to such designs. In this article we investigate this issue and determine the minimum number of units required per group, for the case of both a dichotomous and a continuous outcome variable, needed to provide adequate statistical power for detecting various levels of treatment effect. The use of significance testing as a method of detecting intracluster correlation is also investigated, and, in general, discouraged.

Adolescent

The statistical analysis of kappa statistics in multiple samples.

Methods are presented for assessing and comparing the results of k > or = 2 independent samples of measured agreement or concordance, where in each sample a given member of a pair of observations is classified according to the presence or absence of a binary trait. Examples include the assessment of interobserver agreement across different groups of patients in a clinical study, investigations of sibling concordance across different genetic groups, and meta-analyses of observer agreement across different studies. The methodology described is based on application of goodness-of-fit theory to testing hypotheses concerning kappa statistics. Partitioning methods allow a variety of hypotheses to be tested, including an assessment of the degree of agreement within each sample, a testing procedure based on the pooled data, and a test of heterogeneity that may be used to assess the validity of pooling across samples. Three examples are given.

Humans

Testing the homogeneity of kappa statistics.

Procedures are compared for testing the homogeneity of k > or = 2 independent kappa statistics in the case of two raters and a dichotomous outcome. One of the procedures is based on the estimated large sample variance derived under a model frequently adopted for inferences concerning interobserver agreement. The other is based on a goodness-of-fit approach to this model. The results of a Monte Carlo simulation show that the two approaches have similar properties if the number of subjects in each sample is large (> 100), and the prevalence of the underlying trait of interest is not extreme, while the goodness-of-fit approach is recommended for comparisons involving smaller numbers of subjects or in which the prevalence of the underlying trait is small (< 0.3).

Analysis of Variance

Statistical methodology for estimating twin similarity with respect to a dichotomous trait.

Statistical methodology is presented for the estimation of twin similarity with respect to a dichotomous trait. The methodology focuses on the intraclass correlation as the parameter of interest and is analogous to methodology commonly applied to continuous outcome data. For inference problems involving a single sample, confidence interval construction and significance testing are discussed. For two sample problems, test procedures are provided that are an alternative to an approach recently presented by Ramakrishnan et al. [(1992) Genet Epidemiol 9:273-287 (1)]. Two examples based on published data sets are given to illustrate the proposed techniques.

Confidence Intervals

Accounting for cluster randomization: a review of primary prevention trials, 1990 through 1993.

OBJECTIVES: This methodological review aims to determine the extent to which design and analysis aspects of cluster randomization have been appropriately dealt with in reports of primary prevention trials. METHODS: All reports of primary prevention trials using cluster randomization that were published from 1990 to 1993 in the American Journal of Public Health and Preventive Medicine were identified. Each article was examined to determine whether cluster randomization was taken into account in the design and statistical analysis. RESULTS: Of the 21 articles, only 4 (19%) included sample size calculations or discussions of power that allowed for clustering, while 12 (57%) took clustering into account in the statistical analysis. CONCLUSIONS: Design and analysis issues associated with cluster randomization are not recognized widely enough. Reports of cluster randomized trials should include sample size calculations and statistical analyses that take clustering into account, estimates of design effects to help others planning trials, and a table showing the baseline distribution of important characteristics by intervention group, including the number of clusters and average cluster size for each group.

Bias

Methods for comparing event rates in intervention studies when the unit of allocation is a cluster.

The aim of many research investigations is to compare the proportion of individuals in each of several groups that have a certain characteristic. The unit of allocation for such investigations is often an intact social unit, as in randomizing families, medical practices, schools, or entire communities, to different intervention groups. Standard statistical methods are not appropriate for these designs, since they do not take into account the dependencies among individuals within the same cluster. The authors review the strengths and weaknesses of several approaches for dealing with this problem, using data from a school-based smoking cessation trial. A principal conclusion is that the choice of method should depend on whether or not random allocation is used in the assignment of interventions.

Chi-Square Distribution

A comparison of methods for testing homogeneity of proportions in teratologic studies.

We consider teratologic studies in which the aim is to compare the survival rate of animals in a treatment group to the corresponding rate in a control group. The design of such studies often involves the allocation of intact litters of animals to treatment, invalidating the application of standard statistical methods. We review the strengths and weaknesses of several approaches for dealing with this problem including methodology recently developed for the analysis of clustered binary data. A simulation study is conducted in which litter sizes are generated from a distribution having specified mean and degree of imbalance. It is recommended on the basis of this study and on theoretical considerations that the choice of method should depend on whether the comparison of interest is experimental or observational. For experimental comparisons, involving the random assignment of litters to different treatment groups, methods based on the adjustment of standard chi-square statistics are recommended unless the number of litters in each group is very large.

Animals

Initial nonfunction in cadaveric renal transplantation.

Patients who receive a kidney transplant that does not function immediately have more complications and decreased graft survival than patients whose allografts function immediately. To determine the causes of initial nonfunction (INF), the authors reviewed 188 consecutive cadaveric kidney transplants performed between 1985 and 1988 at the University Hospital, London, Ont. Data were collected on 16 putative risk factors for INF, which were divided into three categories: donor, recipient and technical. INF was defined as the need for dialysis within 7 days of transplantation. Forty-eight (26%) of the 188 allografts had INF, 6 of which never functioned. Univariate analysis identified five variables associated with increased risk of INF: no donor dopamine use, back-table flush, single-organ retrieval, exchanged kidney and prolonged cold ischemic time. Multivariate analysis, however, identified only three variables associated with INF: cerebrovascular accident as the cause of donor death, no donor dopamine use and single-organ retrieval. The authors recommend (a) low-dose dopamine therapy for all donors and (b) multiorgan retrieval to produce quality kidneys for transplantation.

Cadaver

Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q.

Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B cells. No significant enhancement of Ig production by B cells was seen in the absence of T cells or PWM. The contribution of T cells or PWM could be replaced by supernatants of PMA and Con A-activated PBMC (T cell growth factor). C1q that had been frozen, in contrast with freshly isolated C1q, was at least 3 times more active in enhancement of the production of Ig by B cells in culture in the presence of suboptimal concentrations of T cell growth factor. The capability of C1q to stimulate B cells could be ascribed to aggregates of C1q. Monomeric C1q was only marginally active to stimulate B cell Ig production, whereas dimeric and tetrameric C1q were able to enhance Ig production by B cells in relation to their size. Furthermore, aggregation of C1q on soluble aggregates of rabbit IgM also increased its potential to enhance B cell Ig production. The interaction of C1q with the B cells occurs via the collagenous tail of C1q, as suggested by inhibition experiments with purified collagenous tails and globular heads of C1q. These results indicate that triggering of C1qR on B cells positively regulates Ig production in vitro.

Antibody Formation

Binding and catabolism of aggregated immunoglobulins bearing C3b or iC3b by U937 cells.

Mononuclear cells play an important role in the elimination of immune complexes (IC). In the presence of complement (C) the binding and degradation of IC by mononuclear cells is enhanced at least two-fold. The enhancement of binding is caused by a synergistic interaction of the IC with cellular Fc and complement receptors (R). In the present study we have investigated the contribution of the complement receptors CR1 and CR3 of human monocyte cell line U937 on the complement-mediated binding and degradation of immune complexes and soluble aggregates of IgG (AIgG) bearing C3b or iC3b. It was found that deposition of C3b on AIgG enhanced the binding of AIgG to U937 cells at least two-fold. The C3b-mediated enhancement of binding was abolished by anti-CR1. iC3b-bound to AIgG also enhanced the binding of AIgG to the cells. This binding was only partially reduced by anti-CR3 antibodies, but the combination of anti-CR1 and anti-CR3 fully abolished the iC3b-mediated enhancement of binding. These results suggest that both CR1 and CR3 contribute to the complement-mediated binding and degradation of soluble IC by mononuclear phagocytes.

Antigen-Antibody Complex

The pathophysiology of protein-overload proteinuria.

Alterations in glomerular function and structure were studied in protein-overload nephrosis in the rat induced by intraperitoneal administration of bovine serum albumin (BSA). Fractional clearance (C/GFR) studies using inulin and tracer proteins of different molecular size and charge revealed in proteinuric rats 1) unchanged glomerular filtration rate and renal plasma flow; 2) a 34-fold increase in C/GFR of rat serum albumin, reaching values similar to BSA; 3) a 2-fold increase in C/GFR for anionic horse radish peroxidase (HRP), but normal values for neutral and cationic HRP, and 4) an 11- and 3-fold increase for heterologous IgG and IgM, respectively. Glomerular epithelial cells showed degenerative changes, but the distribution of anionic sites in the glomerular basement membrane was found to be unaltered, as determined by polyethyleneimine binding studies. In summary, an elevation of serum albumin concentration resulted in an increased transcapillary albumin transport. This was found to lead to degenerative changes of glomerular epithelial cells with development of large pore defects, which were completely reversible.

Animals

Cluster randomization trials in tropical medicine: a case study.

Field trials in tropical medicine are often designed so that intact social units (e.g., families, schools, communities) rather than independent individuals are randomized to an intervention group. Reasons are diverse, but include administrative convenience, a desire to reduce the effect of treatment contamination, and the need to avoid ethical issues that might otherwise arise. Dependencies among cluster members typical of such designs must be considered when determining sample size and analysing the resulting data. Failure to do so can result in false conclusions that the treatment is effective. The purpose of this paper is to compare different methods which can be used to construct tests of the effect of treatment when outcomes are binary (e.g., infected/uninfected). The discussion will be illustrated using data from a trial which randomly assigned families to either a control group or a screening and treatment programme for imported intestinal parasites.

Asia, Southeastern