Acamprosate efficacy in alcohol-dependent patients: summary of results from three pivotal trials

In 2004, the United States Food and Drug Administration (FDA) approved acamprosate for use in conjunction with psychosocial support in the maintenance of abstinence in alcohol-dependent patients who are abstinent at treatment initiation. That approval was based primarily on a re-analysis of three European double-blind, placebo-controlled trials in which complete abstinence was the primary outcome measure. The current report presents data from the re-analysis of the pivotal trials, which were 13-, 48-, and 52-week studies. A total of 998 DSM-III-R alcohol-dependent patients were included in the studies, with the majority abstinent at randomization. Using a more stringent definition of abstinence, re-analysis of the rate of complete abstinence, percent days abstinent, and the time to first drink confirmed the original findings for the efficacy of acamprosate in the treatment of alcohol dependence. Rate of complete abstinence was significantly higher with acamprosate than placebo (p < .05); both percent days abstinent and time to first drink were also significantly greater among acamprosate-treated than placebo-treated patients (p < .01). These findings support the use of acamprosate in the treatment of alcohol dependence and illustrate some of the issues that can arise in the FDA process for approval of medications to treat the disorder.     

Under the Microscope Yet Again: A Commentary on Walker and Roach's Critique of the Dickens Committee's Enquiry into our Research

In this issue, Walker and Roach present their critique of the Dickens Committee's investigation of our research. In their critique, Walker and Roach confound criticism of the Dickens Committee with criticism of the study‘Individualized behavior therapy for alcoholics'. We respond to the specific issues raised to demonstrate the misconceptions, and erroneous assumptions upon which Walker and Roach base their critique. The alcohol field will not be advanced by polemics.     

Under the Microscope Yet Again: A Commentary on Walker and Roach's Critique of the Dickens Committee's Enquiry into our Research

In this issue, Walker and Roach present their critique of the Dickens Committee's investigation of our research. In their critique, Walker and Roach confound criticism of the Dickens Committee with criticism of the study ‘Individualized behavior therapy for alcoholics’. We respond to the specific issues raised to demonstrate the misconceptions, and erroneous assumptions upon which Walker and Roach base their critique. The alcohol field will not be advanced by polemics.     

The ISCE ECG genome pilot challenge: A 2004 progress report

The International Society for Computerized Electrocardiography (ISCE) “genome project” began in 2000 as an open-ended discussion of ECG database needs and opportunities. Cooperation within ISCE led to a “pilot challenge” of the database concept, which called for establishment of methodology for transmission, storage, and integrated re-analysis of digitized waveforms of three different ECG manufacturers. The present report documents the early implementation of that goal.     

Calcium antagonists post-infarction: The significance of experimental studies on potentially lethal early ischemic ventricular arrhythmias

The DAVIT-II trial has shown that the verapamil type of calcium antagonist can beneficially be used in post-infarct patients. A recent re-analysis suggests that verapamil may also prevent post-infarct sudden death. There are good theoretical reasons to suppose that calcium antagonists should help prevent ventricular fibrillation. If calcium antagonist agents could be found which have negligible negative inotropic effects, such drugs might be ideal for further testing in the post-infarct phase.     

The total time principle as a substitute for the pacing variable in paired-associate tasks with the aged

Abstract

Winn, F.J., Jr. and J.W. Elias. The total time principle as a substitute for the pacing variable in paired-associate tasks with the aged. Experimental Aging Research, 1975, 1 (2), 307–312. Information provided by Monge and Hultsch in support of the pacing variable was reinterpreted in terms of the total time principle. The re-analysis of the transformed data suggests that the total time principle provides a more parsimonious explanation of the data.     

Family Advocacy Roles and Highly Dependent Residents in Nursing Homes

A developing critique has questioned the practical utility of user rights policy initiatives for highly dependent residents of nursing homes. This paper seeks to extend this critique to the advocacy roles that families have been accorded within the policy initiatives. The discussion is based on a qualitative research study of family participation in six aged care units. The paper argues that the capacity of families to act as advocates for highly dependent nursing home residents is limited by the their weak position within the organisations and the complexity of their relations with staff. It questions both the applicability and the appropriateness of rights models which do not take sufficient account of the structure and meaning of care.     

Mural thrombi in coronary artery disease. Recent advances in pathogenesis, diagnosis, and approaches to treatment

Detection of ventricular mural thrombi has been facilitated by the introduction of echocardiography, nuclear angiography, and radioactive labeling of platelets. Most of the data regarding the incidence of mural thrombi, pathogenesis of thrombus formation, and predisposing factors for systemic emboli after myocardial infarction that were reported on postmortem studies in the past can now be reexamined in the living patient with these noninvasive methods. The data accumulated from such investigations are now available and the results are reviewed herein. A critique of the usefulness of echocardiography and nuclear methods is also presented.     

Descriptions of members of the Simulium damnosum complex (Diptera: Simuliidae) from southern Africa, Ethiopia and Tanzania

This paper presents cytotaxonomic details of five populations of the Simulium damnosum complex from South Africa, Swaziland and Ethiopia. The 'Nkusi SW' and 'Pienaars' forms are newly designated members of the complex from South Africa, but the taxonomic rank of an isolate indistinguishable chromosomally from the 'Nkusi' cytoform remains unclear. From Ethiopia two cytoforms were identified, one of which shares two diagnostic chromosome inversions with the cytoform 'Kisiwani' from Tanzania. The second form belongs to S. kaffaense, and is the suspected local vector of Onchocerca volvulus. In addition, a re-analysis of the cytoform 'Kibwezi' from north-eastern Tanzania provided further insights into its population subdivision, and its genetic and morphological characteristics. Cytotaxonomic similarities between 'Kibwezi', S. mengense and S. pandanophilum, along with their biogeography, indicate a relict status of each of these taxa.     

Low-protein overfeeding: a tool to unmask susceptibility to obesity in humans

In search for an approach to identify physiological targets for therapeutic intervention in obesity management, we have revisited the classic human overfeeding studies of the 1960s, with new emphasis on a 'subgroup' of volunteers who were shifted between overfeeding on a typical affluent (normal-protein) diet and overfeeding on a low-protein diet. Following a re-analysis of these data, the arguments are put forward that since low-protein overfeeding is not only a potent stimulus of thermogenesis, but also an amplifier (or magnifier) of the small inter-individual variations in thermogenesis on the affluent (normal-protein) diet, it can be used as a tool to unmask some of the genetic and metabolic basis underlying human susceptibility to leanness and fatness.     

Intravascular ultrasound radiofrequency analysis of coronary atherosclerosis: an emerging technology for the assessment of vulnerable plaque.

Evaluation of atherosclerotic plaque composition and morphometry may yield insight into plaque biology and the mechanisms of plaque-associated thrombosis. Analysis of intravascular ultrasound radiofrequency (IVUS-RF) backscatter signal is one technology that provides in vivo assessment of both atherosclerotic plaque composition and morphometry. We summarize three different approaches to IVUS-RF and critique the studies using this technology. In addition, we address the potential application of IVUS-RF to assess vulnerable plaque.     

Adjuncts to thrombolysis for myocardial reperfusion.

OBJECTIVE: To discuss adjunctive pharmacologic agents for acute myocardial infarction, to critique their initial effects in clinical trials, and to review their potential for improving the clinical conditions of patients with acute myocardial infarction. DATA SOURCES: Relevant studies reported from January 1985 to December 1990 were identified through a MEDLINE search of the English-language literature and through a manual search of the bibliographies of all identified articles. STUDY SELECTION: Peer-reviewed experimental and clinical studies evaluating the role of pharmacologic adjuncts to thrombolytic therapy in experimental models of coronary occlusion and clinical trials of patients with acute myocardial infarction were selected for review. DATA EXTRACTION AND SYNTHESIS: The data presented were abstracted by the investigators. Differences with a univariate P value of less than 0.05 were considered to be statistically significant. CONCLUSIONS: Current clinical data suggest that adjunctive pharmacologic therapy to thrombolytic agents should include aspirin, at least 160 mg administered as soon as possible after the onset of symptoms; intravenous heparin; and, in selected patients without contraindications, intravenous beta-blockading agents.     

Decision analysis and economic modelling: a primer

In this primer, the reader is introduced to the concepts governing decision analysis and cost-effectiveness analysis. The construction of decision trees and Markov models is presented to provide the necessary background to critique research articles in published literature. Specific sub-topics related to cost-effectiveness analysis are discussed including quality adjustment and utilities (patient preferences for health states), discounting, and sensitivity analysis including Monte Carlo simulation. Evidence based methods to critique decision and cost-effectiveness analysis are provided, and limitations to these analytic methods are examined. In summary, the major functions of decision analysis and cost-effectiveness analysis are to provide: (1) a quantitative summary of existing data, and (2) hypothesis generation for further research.     

An integrated approach to meta-analysis in alcohol studies*

The research design and methods utilised by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta-analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sixes, and random effects models.     

Alcoholism and Social Policy: are we on the right lines?

A critique is presented of a recent Home Office Research Unit review of alcohol distribution theory, and the bearing of the scientific evidence on health policy. The Home Office paper is loaded with errors and mis-understandings.     

The death spiral: predicting death in <Emphasis Type="Italic">Drosophila</Emphasis> cohorts

Drosophila research has identified a new feature of aging that has been called the death spiral. The death spiral is a period prior to death during which there is a decline in life-history characters, such as fecundity, as well as physiological characters. First, we review the data from the Drosophila and medfly literature that suggest the existence of death spirals. Second, we re-analyze five cases with such data from four laboratories using a generalized statistical framework, a re-analysis that strengthens the case for the salience of the death spiral phenomenon. Third, we raise the issue whether death spirals need to be taken into account in the analysis of functional characters over age, in aging research with model species as well as human data.     

Sleep apnea and systemic hypertension: a causal association review.

OBJECTIVE: To critically examine the causal association between sleep apnea syndrome and hypertension. METHODS: A retrospective systematic critique of five epidemiologic studies published in the English literature during 1978 to 1989 identified on Medline and manual literature searches. The evidence was evaluated using the standard observational criteria for causation: strength of association, consistency, dose-response relationship, temporal sequence, specificity, and biologic plausibility. RESULTS: We found evidence to support a causal association between sleep apnea syndrome and hypertension in consistency and specificity and some evidence to suggest a dose-response relationship. Review of the data dealing with the mechanisms important in the pathogenesis of sleep apnea and hypertension allowed us to advance several theories to provide support for biologic plausibility. CONCLUSION: We concluded that there is a positive association--relative risk estimate between 1.3 and 40--for sleep apnea syndrome and hypertension, but the risk association is unstable. Thus, we believe that there is insufficient data to justify doing polysomnography as part of the routine diagnostic work-up for patients with hypertension.     

In the European population HLA-class II genes are not associated with Helicobacter pylori infection.

OBJECTIVE : Genetic variability influences susceptibility to several diseases and depends on the specific ethnic background of individuals. HLA-class II genes have repeatedly been investigated as candidate genes for predisposition to Helicobacter pylori infection. Certain HLA-DQA1 alleles have been reported to be associated with gastric and duodenal ulcer disease in infected patients in the Japanese population. But conflicting results were reported on European and Japanese populations. METHODS : HLA-DRB1 typing of 382 German individuals with well-defined H. pylori status and different clinical course of the disease was performed by polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULTS : No association with the infection status itself was observed in the German cohort. Similar results have been found in other European populations. In contrast, re-analysis of published data in a Japanese cohort revealed a highly significant association of DRB1*1501 with uninfected controls (P = 0.00035). In the German population, the carrier frequency of DRB1*15 was higher in H. pylori-positive individuals with gastric or duodenal ulcer but without statistical significance (gastric ulcer: odds ratio, 2.13; chi2 = 3.77; P = 0.05; Bonferroni correction, Pc = not significant; and duodenal ulcer: odds ratio, 2.15; chi2 = 3.4; P = 0.06; Pc = not significant). In infected individuals, autoantibodies to gastric mucosa were investigated, but no statistical significant difference in carrier frequencies of HLA-DRB1 alleles was evident. CONCLUSION : The DRB1*1501-DQA1*01021-DQB1*0602 haplotype seems to provide protection from H. pylori infection in the Japanese population, whereas genetic variability in HLA-class II genes has only a minor impact on H. pylori infection and its clinical course in the European population.     

Contribution of the 24 hour electrocardiogram to the prediction of sudden coronary death.

BACKGROUND--Sudden coronary death is a major public health issue. The identification of patients at high risk should therefore be as efficient as possible. This study compares simple and more elaborate risk stratification procedures. METHODS--Risk functions for the prediction of sudden death were determined in a population of 6693 consecutive patients who had 24 hour electrocardiography for various indications. The functions were based on the clinical and electrocardiographical data on 245 patients who died suddenly during 2 year follow up and 467 patients randomly drawn from the total study population. RESULTS--The model based on history (age, sex, myocardial infarction, congestive heart failure, palpitation, syncope, use of diuretics, and use of nitrates), 12 lead electrocardiography (major intraventricular conduction defect, T wave abnormality, and ST depression > or = 0.05 mV), and standard rhythm analysis of 24 hour electrocardiography (ventricular tachycardia, frequent premature atrial complexes, sinus tachycardia (> 150 min-1), and atrial fibrillation) was almost as efficient in the prediction of sudden death as extended models that also contained information from exercise testing, echocardiography, ventriculography, and computer-aided re-analysis of 24 hour electrocardiography (QT and RR interval variability). CONCLUSIONS--These results indicate that additional information from advanced function tests does little to increase the efficiency of prediction of sudden coronary death over that of tests based on history, the standard 12 lead electrocardiogram, and 24 hour electrocardiography.     

Immunological reclassification of 22 children with a former diagnosis of non-T, non-B ALL

Stored peripheral blood or bone marrow mononuclear cells from 22 pediatric patients with verified acute lymphoblastic leukemia (ALL) previously classified as non-T, non-B ALL were re-investigated by flow cytometric analysis by means of a panel of B cell-specific and -associated monoclonal antibodies (moabs) using a new analytical method described by Platz et al, the so-called Delta Channel Value method. All 22 patients were immunologically re-characterized as pre-B ALL. The reproducibility between the first (acute) and subsequent re-analysis was almost complete. 20 of the tumor cell populations could be assigned to the B cell differentiation scheme recently proposed by Nadler et al. This scheme operates with four stages of pre-B cell differentiation and each stage is defined by the expression of one to four of the following markers: HLA-DR, CD19, CD10 and CD20. Two additional markers, CD24 and CD22, were investigated in our study and allowed further subdivision of the four subgroups proposed by Nadler et al. The composition of a panel of moabs for routine classification of pre-B ALL is proposed.