State accountability for wife-beating: the Indian challenge.
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Culture↗
Biomedical subjects
R J Cook
Publications and source records attributed to R J Cook.
Modeling two-state disease processes with random effects.
Many chronic medical conditions are manifested by alternating sojourns in symptom-free and symptomatic states. In many cases, in addition to their relapsing and remitting nature, these conditions lead to worsening disease patterns over time and may exhibit seasonal trends. We develop a mixed-effect two-state model for such disease processes in which covariate effects are modeled multiplicatively on transition intensities. The transition intensities, in turn, are functions of three time scales: the semi-Markov scale involving the backward recurrence time for the cyclical component, the Markov scale for the time trend component, and a seasonal time scale. Multiplicative bivariate log-normal random effects are introduced to accommodate heterogeneity in disease activity between subjects and to admit a possible negative correlation between the transition intensities. Maximum likelihood estimation is carried out using Gauss-Hermite integration and a standard Newton-Raphson procedure. Tests of homogeneity are presented based on score statistics. An application of the methodology to data from a multi-center clinical trial of chronic bronchitis is provided for illustrative purposes.
Anti-Infective Agents↗
Pharmacokinetics and efficacy of long-term epidural ropivacaine infusion for postoperative analgesia.
UNLABELLED: The aim of this study was to evaluate the pharmacokinetics and efficacy of the new local anesthetic ropivacaine when used for epidural infusion for up to 72 h after major orthopedic surgery. Immediately after surgery, an epidural infusion of ropivacaine 2 mg/mL was begun at a rate of 6 mL/h in 11 patients. The infusion rate was then adjusted according to patient analgesic needs or side effects. Blood samples were taken during and after the infusion to determine total and unbound ropivacaine and alpha1-acid glycoprotein (AAG) concentrations. Patients were assessed regularly for sensory and motor block and pain using a visual analog scale (VAS) score (0-100 mm). Ten patients received 63-72 h of infusion. Total plasma concentrations of ropivacaine and binding protein (AAG) increased during the infusion such that free concentrations plateaued or began to fall over time. VAS values during mobilization were less than 40 mm in 93% of patients. The majority of patients had no measurable motor block once the surgical block had regressed. When epidural ropivacaine was titrated to achieve a stable sensory block, there was a low incidence of motor block, and free plasma ropivacaine levels were well below the toxic range. IMPLICATIONS: The pharmacokinetics of continuous epidural infusions of ropivacaine are described in patients for up to 72 h postoperatively. Clinical efficacy and side effects are also reported. An understanding of the plasma concentrations obtained and modes of elimination during prolonged epidural infusion is important for safe, routine clinical use in postoperative analgesia.
Adolescent↗
Localization of language cortices by functional MR imaging compared with intracarotid amobarbital hemispheric sedation.
OBJECTIVE: We undertook this study to investigate functional MR imaging as a new clinical method for determining hemispheric language dominance. Seven patients undergoing surgical evaluation for chronic intractable epilepsy were studied. Intracarotid amobarbital injection was also performed and the findings compared with the functional MR imaging results. CONCLUSION: Functional MR imaging studies enabled localization of the frontal and temporal lobe language cortices. The results of functional MR imaging and intracarotid amobarbital testing of hemispheric language dominance agreed in all seven patients, including two right-handed patients with right-hemisphere language dominance. These preliminary results show that functional MR imaging is an accurate noninvasive method of determining language dominance that may replace the amobarbital test for some purposes if confirmed by additional research.
Adult↗
Covalent binding of acetaminophen to N-10-formyltetrahydrofolate dehydrogenase in mice.
The analgesic acetaminophen is frequently used as a model chemical to study hepatotoxicity; however, the critical mechanisms by which it produces toxicity within the cell are unknown. It has been postulated that covalent binding of a toxic metabolite to crucial proteins may inhibit vital cellular functions and may be responsible for, or contribute to, the hepatotoxicity. To further understand the importance of covalent binding in the toxicity, a major cytosolic acetaminophen-protein adduct of 100 kDa has been purified by a combination of anion exchange chromatography and preparative electrophoresis. N-Terminal and internal amino acid sequences of peptides from the purified 100-kDa acetaminophen-protein adduct were found to be homologous with the deduced amino amino acid sequence from the cDNA of N-10-formyltetrahydrofolate dehydrogenase. Antiserum specific for N-10-formyltetrahydrofolate dehydrogenase and acetaminophen react in a Western blot with the purified 100-kDa acetaminophen-protein adduct. Administration of a toxic dose of acetaminophen (400 mg/kg) to mice resulted in a 25% decrease in cytosolic N-10-formyltetrahydrofolate dehydrogenase activity at 2 hr. The covalent binding of acetaminophen to proteins such as N-10-formyltetrahydrofolate dehydrogenase and the subsequent decreases in their enzyme activity may play a role in acetaminophen hepatotoxicity.
Acetaminophen↗
Validating the SF-36 health survey questionnaire in patients with psoriatic arthritis.
OBJECTIVE: To assess the reliability and validity of the SF-36 in patients with psoriatic arthritis (PsA). METHODS: The SF-36 was administered to all patients attending the University of Toronto Psoriatic Arthritis Clinic between January and December 1994. Clinical and radiological assessments were performed during the clinic visits. RESULTS: We studied 113 patients, 43 women and 70 men, with a mean age of 50.5 years and a mean arthritis duration of 14.2 years. The reliability of the SF-36 was high, with the Cronbach alpha coefficient exceeding 0.90 for all the 8 health scales. The SF-36 was able to detect meaningful differences in health status between patients with PsA and individuals from the general population. As predicted, patients with PsA reported substantially lower scores on the physical functioning, role limitations due to physical problems, and pain scales. They also reported significantly lower scores on the role limitations due to emotional problems and general health perception scale. In general all scales were moderately to highly correlated with measures of function and pain (r = 0.33-0.67), while the physical functioning, pain, and vitality scales were also moderately correlated with disease activity (r = 0.34-0.42). With one exception the scales were unrelated to disease severity. CONCLUSION: The SF-36 questionnaire is reliable and valid for use in PsA, supporting its use as an adjunct outcome measure for clinical trials in PsA. Because the SF-36 can be used to compare health status across different patient populations, its application can also help to clarify the disease burden associated with PsA.
Adult↗
A logistic model for trend in 2 x 2 x kappa tables with applications to meta-analyses.
There recently has been an increased interest in examining the relationship between the baseline (control) risk of an adverse outcome and the magnitude of the treatment effect (Brand and Kragt, 1992, Statistics in Medicine 11, 2077-2082; Davey Smith, Song, and Sheldon, 1993, The British Medical Journal 306, 1367-1373; Senn, 1994, Statistics in Medicine 13, 293-294). To facilitate such an examination, we propose a logistic model in which the relationship between the treatment effect, as measured by the log odds ratio, and the baseline risk is specified parametrically. This procedure is founded on a product-binomial likelihood and generates maximum likelihood estimates of the baseline event rates and two parameters characterizing the trend in the treatment effect. We fit this model to data from a meta-analysis involving the treatment of women at risk of preterm labor and contrast our findings with those of an earlier analysis.
Biometry↗
A logistic-bivariate normal model for overdispersed two-state Markov processes.
We describe a logistic-bivariate normal mixture model for a two-state Markov chain in which each individual makes transitions between states according to a subject-specific transition probability matrix. The use of the bivariate normal mixing distribution facilitates inferences regarding the correlation of the random effects and hence provides insight as to the nature of the subject-to-subject variability in the transition probabilities. Tests regarding the correlation can be based on likelihood ratio, score, or Wald statistics. Estimates of the transition intensities of a latent continuous time conditionally Markov process may also be computed. We illustrate this methodology by application to a parasitic infection field study and contrast our findings with those previously published on this data set.
Biometry↗
Reproductive health law: where next, after Cairo and Beijing?
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Family Planning Services↗
Methodology for clinical trials in rheumatology: logical foundations.
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Clinical Trials as Topic↗
Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials.
OBJECTIVE: To review the effect of calcium supplementation during pregnancy on blood pressure, preeclampsia, and adverse outcomes of pregnancy. DATA SOURCE: We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. STUDY SELECTION: Fourteen randomized trials involving 2459 women were eligible. DATA EXTRACTION: Reviewers working independently in pairs abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: Each trial yielded differences in blood pressure change between calcium supplementation and control groups that we weighted by the inverse of the variance. The pooled analysis showed a reduction in systolic blood pressure of -5.40 mm Hg (95% confidence interval [CI], -7.81 to -3.00 mm Hg; P<.001) and in diastolic blood pressure of -3.44 mm Hg (95% CI, -5.20 to -1.68 mm Hg; P<.001). The odds ratio for preeclampsia in women with calcium supplementation compared with placebo was 0.38 (95% CI, 0.22 to 0.65). CONCLUSIONS: Calcium supplementation during pregnancy leads to an important reduction in systolic and diastolic blood pressure and preeclampsia. While pregnant women at risk of preeclampsia should consider taking calcium, many more patient events are needed to confirm calcium's impact on maternal and fetal morbidity.
Blood Pressure↗
Effects of dietary calcium supplementation on blood pressure. A meta-analysis of randomized controlled trials.
OBJECTIVE: To review the effect of supplemental calcium on blood pressure. DATA SOURCE: We searched MEDLINE and EMBASE for 1996 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. STUDY SELECTION: We included any study in which investigators randomized people to calcium supplementation or placebo and measured blood pressure for at least 2 weeks. Fifty-six articles met the inclusion criteria, and 33 were eligible for analysis, involving a total of 2412 patients. DATA EXTRACTION: Two pairs of independent reviewers abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: We calculated the differences in blood pressure change between the calcium supplementation group and the control group and pooled the estimates, with each trial weighted with the inverse of the variance using a random-effects model. Predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodological quality of the studies. The pooled analysis showed a reduction in systolic blood pressure of -1.27 mm Hg (95% confidence interval [CI], -2.25 to -0.29 mm Hg; P=.01) and in diastolic blood pressure of -0.24 mm Hg (95% CI, -0.92 to 0.44 mm Hg; P=.49). None of the possible mediators of blood pressure reduction explained differences in treatment effects. CONCLUSIONS: Calcium supplementation may lead to a small reduction in systolic but not diastolic blood pressure. The results do not exclude a larger, important effect of calcium on blood pressure in subpopulations. In particular, further studies should address the hypothesis that inadequate calcium intake is associated with increased blood pressure that can be corrected with calcium supplementation.
Blood Pressure↗
Criteria for the evaluation of treatment planning systems.
Radiation treatment planning systems (RTPS) are evolving on a rapid and continual basis. After the evaluation of several commercial systems, we have developed a list of features we consider desirable in a product. The goal in the compilation of these criteria was a comprehensive worksheet which categorized the characteristics of RTPS into hardware (computer and peripheral devices), 2-D planning tools, 3-D planning tools, irregular field planning tools, and brachytherapy planning. With these distinctions, one can evaluate a system conforming to the specific planning needs, e.g., conformal therapy, dynamic therapy capabilities, or optimized remote afterloading brachytherapy, of a department. The rationales of the special requirements are provided for justification.
Brachytherapy↗
Conservation of the 2,4-diacetylphloroglucinol biosynthesis locus among fluorescent Pseudomonas strains from diverse geographic locations.
The broad-spectrum antibiotic 2,4-diacetylphloroglucinol (PHL) is a major determinant in the biological control of a range of plant pathogens by many fluorescent Pseudomonas spp. A 4.8-kb chromosomal DNA region from Pseudomonas fluorescens Q2-87, carrying PHL biosynthetic genes, was used as a probe to determine if the PHL biosynthetic locus is conserved within PHL-producing Pseudomonas strains of worldwide origin. The phl gene probe hybridized with the genomic DNA of all 45 PHL-producing Pseudomonas strains tested, including well-characterized biocontrol strains from the United States and Europe and strains isolated from disease-suppressive soils from Switzerland, Washington, Italy, and Ghana. The PHL producers displayed considerable phenotypic and genotypic diversity. Two phenotypically distinct groups were detected. The first produced PHL, pyoluteorin, and hydrogen cyanide and consisted of 13 strains from almost all locations sampled in the United States, Europe, and Africa. The second produced only PHL and HCN and consisted of 32 strains from the U.S. and European soils. Analysis of restriction patterns of genomic DNA obtained after hybridization with the phl gene probe and cluster analysis of restriction patterns of amplified DNA coding for 16S rRNA (ARDRA) and randomly amplified polymorphic DNA (RAPD) markers indicated that the strains that produced both PHL and pyoluteorin were genetically highly similar. In contrast, there was more diversity at the genotypic level in the strains that produced PHL but not pyoluteorin. ARDRA analysis of these strains indicated two clusters which, on the basis of RAPD analysis, split into several subgroups with additional polymorphisms. In general, the occurrence of phenotypically and genotypically similar groups of PHL producers did not correlate with the geographic origin of the isolates, and highly similar strains could be isolated from diverse locations worldwide.
Antifungal Agents↗
Coupled error spending functions for parallel bivariate sequential tests.
Sequential procedures are developed to facilitate marginal monitoring of bivariate response vectors in clinical trials. The general approach is based on an extension of the error spending function methodology of Lan and DeMets (1983, Biometrika 70, 659-663) and is sufficiently flexible that one may elect to fix the experimental type I error rate (Cook, 1994, Controlled Clinical Trials 15(3), 187-200) or the marginal type I error rates. Sample size calculations are described to ensure power requirements are satisfied for marginal tests of significance. Reformulating the procedures in terms of repeated confidence intervals (Jennison and Turnbull, 1989, Journal of the Royal Statistical Society, Series B 51, 305-361) lends added flexibility to the monitoring process. The developments are discussed in the context of responses with a bivariate normal distribution. Data from an asthma intervention trial are used for illustrative purposes.
Asthma↗
Robust tests for treatment comparisons based on recurrent event responses.
Robust nonparametric tests are considered for use in longitudinal studies in which the response of interest is a recurrent event. The tests are robust in the sense that they do not rely on distributional assumptions regarding the processes generating the events. The methods we describe are presented in the context of a clinical trial with attention initially directed at the two-sample problem in which a single experimental treatment is compared to a control. We investigate a family of generalized pseudo-score statistics (Lawless and Nadeau, 1995, Technometrics 37, 158-168) in which weight functions may be chosen to generate tests sensitive to various types of departure from the null hypothesis that the mean functions for the treatment and control groups are identical. All tests we consider are evaluated by simulation with respect to the type I error rate and power under a variety of practical scenarios. An application involving data from a kidney transplant study illustrates these procedures. For trials with multiple treatment arms, we generalize these approaches and indicate test statistics appropriate for unstructured alternatives and tests based on linear contrasts of the treatment-specific mean functions. Extensions of this methodology for stratified designs are also indicated.
Antibodies↗
Design considerations in crossover trials with a single interim analysis and serial patient entry.
A two-stage sequential design is presented to facilitate a single interim analysis in crossover trials with serial patient entry. The interim analysis is based on a linear statistic that combines data from individuals observed for only one treatment period with data from those observed for both periods (Cook, R. J., 1995, Biometrics 51, 932-945). The final analysis is based on the usual test statistic used in crossover trials. The size of this procedure is controlled by partitioning the experimental type I error rate over the two analyses and deriving the appropriate critical values. We investigate the design implications of adopting this procedure over the usual analysis for crossover trials by examining the necessary sample size inflation factors to maintain power, and indicate the expected savings in terms of the number of responses required. Data from a study designed to compare two antiemetic therapies for previously untreated chemotherapy patients (Osaba, D., et al., 1986, Clinical and Investigative Medicine 9, 225-231) are used to illustrate the procedure.
Antineoplastic Agents↗
Interim monitoring of longitudinal comparative studies with recurrent event responses.
A method of interim monitoring is described for longitudinal comparative studies in which the outcome of interest is a recurrent event and treatment comparisons are based on expected numbers of events. The nonparametric methods described by Cook, Lawless, and Nadeau (1996, Biometrics 52, 116-130) are generalized to provide a robust estimate of the covariance matrix for a sequence of test statistics calculated over time. The error spending function methodology of Lan and DeMets (1983, Biometrika 70, 659-663) is adopted to control the experimental type I error rate. A simulation study indicates satisfactory frequency properties of this procedure for the moderate to large scale trials for which it is intended. Extensions of this approach to handle stratified designs and studies with multitype recurrent events are indicated. Data from a kidney transplant study (Cole et al., 1994, Transplantation 57, 60-67) are used for illustrative purposes.
Antilymphocyte Serum↗