European cooperation for clinical practice guidelines in cancer.
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Biomedical subjects
Publications and source records attributed to M Haugh.
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OBJECTIVE: An assessment of the quality of health information on the Internet is an absolute necessity. In this study 'sensitive' information was defined as information found in documents published on the Internet, which could be used in a medical decision. For sensitive information, the main criterion chosen for the quality of the information was an indication of the level of evidence. A survey was conducted using the CISMeF health catalogue to assess how often a score of the level of evidence is mentioned in the information accessible on the Internet in French-language health resources. METHODS: Since 1999, members of the CISMeF team have systematically been searching for all documents containing 'sensitive' information and verifying whether the level of evidence was explicitly indicated as a score at least once in the document. RESULTS: As of June 2001, 10,190 resources were included in CISMeF; including 2964 textual 'sensitive' resources (29.1%). Out of all these resources, only 4.7% (95% confidence interval: 4.0 - 5.5%) indicated the level of evidence. A statistically significant difference in the prevalence of indicating the level of evidence according to resource types (e.g., 18.1% for guidelines compared to 0.0% for teaching material), year of publication (almost three times greater in 1997-2001 compared with 1990-1996) and publishers was observed. CONCLUSION: As the number of people accessing the growing amount of information on the Internet is increasing daily, publishers have an ethical obligation to inform their readers about the validity of 'sensitive' information their sites contain. However, the vast majority of the French language Internet resources that were surveyed do not mention a score of the level of evidence for their sensitive information.
BACKGROUND: Historically, there has been a general resistance to treating onychomycosis on the basis that such treatments were protracted and of uncertain outcome. However, modern treatments act more promptly and reliably. OBJECTIVES: To carry out a meta-analysis to evaluate the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin. METHODS: The analysis used data from published trials, supplemented where necessary by reference to the original trial reports. RESULTS: Three trials were included in which terbinafine was compared with placebo. From four trials comparing terbinafine with itraconazole, a statistically significant advantage in favour of terbinafine was observed for negative culture and microscopy at the end of the trials. Furthermore, both patients and physicians reported terbinafine to be better tolerated than itraconazole. From two trials comparing terbinafine with griseofulvin, a significantly higher rate of negative microscopy and culture was observed with terbinafine. CONCLUSIONS: A significant advantage in favour of treatment with terbinafine was observed.
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Systematic reviews and meta-analyses are the best approaches available for summarizing the available evidence concerning the efficacy of therapies. Although the renal field has been slow to use these techniques, they are being used increasingly. In March 1997, the Cochrane Renal Group was formed, and this group aims to produce and maintain up to date systematic reviews of the evidence on the effectiveness of therapies used to treat patients with renal diseases. This group is part of the Cochrane Collaboration which is an international structure grouping collaborators together, with the aim of preparing, maintaining and disseminating systematic reviews of the effects of health care in all areas of medicine.
BACKGROUND: The aim of this meta-analysis was to assess the efficacy of antiviral agents to prevent, in solid organ transplant recipients, cytomegalovirus infection and symptomatic disease and to decrease the incidence of acute rejection, graft loss, and death. METHODS: Of the studies identified, 13 met the following inclusion criteria: prospective randomized study, in adults or pediatric recipients of a solid organ transplant, where one group in the study received a prophylactic treatment with acyclovir and/or ganciclovir begun before the cytomegalovirus infection and a control group was not treated or receive placebo. RESULTS: Prophylactic treatment was found to be associated with a significant decrease of cytomegalovirus disease compared with placebo or no treatment, using the logarithm of relative risk method (relative risk=0.50; 95% confidence interval, 0.40-0.62; P-value for chi-square association <0.001). Prophylactic treatment decreased also the rate of cytomegalovirus infection (relative risk=0.74; 95% confidence interval, 0.62-0.88; P<0.001). Our analysis failed to show a significant decrease of graft loss, acute rejection, and death in the prophylactic treatment group. Subgroup analysis based on the type of antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or liver) gave comparable results. CONCLUSION: The use of antiviral agents for the prevention of cytomegalovirus disease and cytomegalovirus infection in solid organ transplantation is supported by this meta-analysis.
Cochrane collaboration has been developing since 1992 as an international network aiming at performing systematic reviews of available data on therapeutic effectiveness. The fundamental principles of this organisation are trying to avoid duplication of efforts, seeking the best reliability, using reproducible and quantitative synthesis techniques, offering constantly updated results. All health domains are progressively covered. The production unit in one domain is the review group. The Hypertension Cochrane Review Group (HTN CRG) has been officially registered on May 15th 1996. Information and products from the group are available through its news letter, through the Cochrane Library CD-ROM, regularly updated, and on the Internet (http://merece.uthscsa.edu/htncrg). The Hypertension Cochrane Review Group includes an editorial board (with an administrator and three editors), the authors of systematic reviews, internal and external reviewers. The geographic link is the San Antonio Cochrane Centre (Texas, USA). Invitations to participate have been sent to people interested in hypertension and who where known to the Cochrane collaboration, and to authors of previous reviews in hypertension. It is possible to collaborate with the HTN CRG through: performing a systematic review; reviewing protocols and systematic reviews; hand-searching medical journals; being a member of the editorial team. The first protocol for a systematic review edited by the group concerns antihypertensive treatment in the elderly, and is available in the 1996 and subsequent editions of the Cochrane Library. The group welcomes other reviews from domains awaiting registration, and collaborates with related domains review groups such as Diabetes CRG, or Stroke CRG. The group contributes to the effort of hand-searching medical literature, Pr Plouin being responsible for the Archives des Maladies du Coeur et des Vaisseaux. The second edition in 1996 of the Cochrane Library included 114 systematic reviews and 131 protocols, being the only media with similar objectives.
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Protocols for dose ranging trials in healthy volunteers or patients can be described by the combination of an experimental design and one or more decision rules. Generally, the doses are chosen on the basis of an up-and-down method, until the maximum tolerated (affecting one or more physiological parameters) and the minimum effective doses are found. Despite the large number of possible protocols there is no standard for the description of the experimental design or the decision rule(s). We propose a series of variables that can be used to facilitate data collection and that can adequately and uniquely characterize most dose ranging protocols.
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In clinical trials, the clinical endpoint is often replaced by an intermediate endpoint, known in some instances as a "surrogate" endpoint. The reasons for the substitution are often both practical and financial. At present, no theoretical basis or practical guidelines exist to help in the choice of surrogate endpoints. An approach is proposed here, based on three provisos which can be verified using one of a series of equations, if sufficient data on the pathophysiology and epidemiology of the disease are available. It is shown that even a strong statistical correlation is not a sufficient criterion for the definition of a surrogate endpoint. It is apparent that results obtained with the commonly used "surrogate" endpoints should be cautiously considered, and that the assessment of treatments should, when possible, be based on clinical rather than intermediate endpoints.
Sections of formaldehyde-fixed paraffin-embedded cortical and hippocampal brain tissue from five cases with senile dementia of Alzheimer type (SDAT) and five cases with Pick's disease (PD) were immunostained with the monoclonal antibodies (mabs) 147, RT 97, BF 10 and 8D8 with and without pretreatment with alkaline phosphatase (AP) or trypsin (Tr). The mabs 147, RT 97 and BF 10 had previously been demonstrated to bind exclusively to phosphorylated epitopes of neurofilament proteins, while mab 8D8 is shown in this report to bind mainly, but not exclusively, to phosphorylated neurofilament epitopes. The mabs RT 97, BF 10 and 8D8, but not 147 stain most, if not all, Pick bodies (PB) and Alzheimer neurofibrillary tangles (NFT). When sections are pretreated with AP or Tr the immunostaining with mab BF 10 is very resistent in both PB and NFT. This resistance of PB and NFT is in contrast to the reduced staining of axons and of swollen cells in PD by the same enzymatic pretreatment. Immunostaining with mab RT 97 of PB and NFT is reduced moderately by AP and considerably by Tr. Only when stained with mab 8D8 is there a discrepancy between PB and NFT in their reaction to the pretreatment with AP: NFT staining with mab 8D8 is not affected, while that of PB is abolished. Thus, in spite of their different ultrastructure, PB and NFT are very similar immunocytochemically and in the accessibility of their phosphorylated epitopes to enzymatic treatment.
We have used a monoclonal antibody to label and purify neurofibrillary tangles using a cell sorter. The method should prove invaluable in future analyses of the biochemical makeup of neurofibrillary tangles, which in turn will greatly assist our comprehension of tangle pathology.
A panel of monoclonal antibodies to neurofilaments have been investigated with regard to the location of their respective epitopes on neurofilament polypeptides and their ability to label the neurofibrillary tangles and paired helical filaments (PHF) which are characteristic of Alzheimer's disease. All of the neurofilament monoclonal antibodies that label tangles and PHF are directed against epitopes in the side arm domains of the two larger neurofilament polypeptides, NF-H and NF-M, and do not recognise the alpha-helical rod domains of these proteins. Immuno-electron microscopy demonstrates that the neurofilament antibodies label the constituent PHF per se and do not simply stain neurofilaments that might be admixed with PHF. These neurofilament epitopes are differentially retained by PHF, following isolation. Thus, antibody labelling of PHF is not simply due to the presence of normal neurofilament polypeptides. We propose that in tangle-bearing neurons, neurofilaments are degraded by proteases and that it is fragments of the side arms which contribute to the composition of PHF.
The origin of the paired helical filaments (PHF) that accumulate in human neurons during aging and in Alzheimer's disease and their relationship to normal neurofilaments remain unclear. The observation that a rabbit antiserum to highly enriched PHF fractions specifically labeled PHF in Alzheimer neurofibrillary tangles but showed no reaction with neurofilaments or other normal cytoskeletal proteins led us to compare this antiserum to two monoclonal antibodies, RT97 and BF10, previously found to cross-react with tangles and with the 210,000 and 155,000 mol. wt. neurofilament proteins, respectively. Both alpha-PHF serum and the neurofilament monoclonals strongly immunolabel almost all neurofibrillary tangles in Alzheimer cortical sections. Double-immunolabeling studies show that both reagents recognize the same tangles and usually show identical patterns of staining of intraneuronal fibrous material. Following prolonged extraction of cortex in sodium dodecyl sulfate, a step which removes normal neurofilaments but leaves PHF intact, almost all isolated tangles retain strong immunoreactivity with alpha-PHF serum at an intensity which is slightly reduced from that in cortical sections. In contrast, only a small number of isolated tangles are stained strongly by RT97 and BF10; most show much decreased or no reactivity with these monoclonal neurofilament antibodies. This differential immunoreactivity was confirmed by double-labeling studies. Tangles prepared under gentle extraction conditions show strong reactivity with alpha-PHF antibodies but again only a small number are strongly labeled by RT97 and BF10. We conclude that neurofibrillary tangles in Alzheimer's disease are heterogeneous as regards their filamentous content and contain both antigens cross-reacting with neurofilaments and antigens which are apparently unique to PHF and not shared with normal neurofilaments.
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The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.
Efficacy indices measure the efficacy of therapies. They derive, by definition, from two quantities, the basal or control risk of event, Rc, observed in the control group, and the on-treatment risk, Rt, observed in the treated group. In clinical trials and meta-analyses, each is an unbiased measure of efficacy. Although they are a combination of frequencies, these indices are used in clinical practice to predict the benefit in treated patients. Their relevance to express efficacy depends on the type of clinical condition, and is better for acute diseases than for chronic diseases. In order to be useful for prescribers, they should meet certain specifications. In addition, they should be considered in the more general framework of effect models.