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At least 307 records · Page 17Linked to original sources

PubMed1990

Screening for hypertension.

PURPOSE: To review the evidence on four questions about screening asymptomatic adults for arterial hypertension: Is hypertension a significant health problem? Is it detectable at an early, presymptomatic stage? Is treatment available and effective? Do the benefits of screening outweigh the costs and risks? DATA IDENTIFICATION AND SELECTION: We did a computerized search of the MEDLARS data base to identify community-based trials of drug therapy for mild hypertension; other relevant citations are included when appropriate. DATA SYNTHESIS: We approached the preliminary questions in our analysis by narrative review and argument. The estimates of therapeutic efficacy are based on previously published meta-analyses. The cost-effectiveness of screening was addressed by formal mathematical modeling of the effect of screening on various U.S. populations. RESULTS OF ANALYSIS: Hypertension is clearly a significant health problem. It can be detected early, and effective treatment is available. Screening asymptomatic adults for hypertension has benefits that compare favorably to the risks and costs involved. According to our estimates, screening is most cost-effective for older adults compared with younger adults and for men compared with women and is highly sensitive to the cost of therapy for mild hypertension. CONCLUSIONS: We recommend hypertension screening for all adults. We also discuss the frequency and setting of screening activities. When a low-cost therapy is used, the cost-effectiveness of screening for hypertension compares favorably with other cardiovascular interventions.

Adult↗

PubMed1992

A consumer's guide to subgroup analyses.

The extent to which a clinician should believe and act on the results of subgroup analyses of data from randomized trials or meta-analyses is controversial. Guidelines are provided in this paper for making these decisions. The strength of inference regarding a proposed difference in treatment effect among subgroups is dependent on the magnitude of the difference, the statistical significance of the difference, whether the hypothesis preceded or followed the analysis, whether the subgroup analysis was one of a small number of hypotheses tested, whether the difference was suggested by comparisons within or between studies, the consistency of the difference, and the existence of indirect evidence that supports the difference. Application of these guidelines will assist clinicians in making decisions regarding whether to base a treatment decision on overall results or on the results of a subgroup analysis.

Causality↗

PubMed2026

Evolving Role of Immunotherapy in Advanced Esophageal Squamous Cell Carcinoma: Are Programmed Death-Ligand 1 (PD-L1) Cutoffs Still Relevant?

Immune checkpoint inhibitors have transformed the management of advanced esophageal squamous cell carcinoma (ESCC) across first-line, second-line, and perioperative settings. Programmed death-ligand 1 (PD-L1) expression has served as the principal biomarker guiding patient selection for these agents, yet it is measured inconsistently across trials and antibody platforms, and its predictive value has come under renewed scrutiny as follow-up data have matured. This review synthesizes the pivotal randomized trials that established anti-programmed cell death protein-1 therapy in ESCC, critically appraises the pooled and patient-level meta-analyses that have re-examined outcomes across biomarker subgroups, and situates recent regulatory reassessment of PD-L1 thresholds within this broader evidence base. Assay heterogeneity between scoring systems, discordance across antibody clones, and the biological distinction between PD-L1 as a prognostic versus a predictive marker are examined as sources of continued uncertainty. The review concludes by considering emerging genomic and microenvironmental biomarkers that may eventually complement or refine PD-L1-based patient selection, and offers a framework for interpreting a single expression threshold as an approximate, assay-dependent stratifier rather than a precise biological boundary.

combined positive score↗

PubMed1992

[Mishaps with anti-arrhythmic agents used to reduce mortality after infarction].

The presence of isolated and/or repetitive ventricular arrhythmias following myocardial infarction identifies a group of patients at increased risk of death. The availability of anti-arrhythmic drugs, noticeably drugs with class I activity, efficient at suppressing arrhythmias has led to the hope that their administration could reduce post-myocardial infarction mortality. However, this hypothesis has not been confirmed. The Cardiac Arrhythmia Suppression Trial, which was designed to have the power to test the hypothesis that suppression of ventricular arrhythmias is associated with a decrease in mortality following myocardial infarction, even showed an increase in mortality with two drugs with class I activity. Several meta-analyses have confirmed that administration of class I antiarrhythmic drugs is of no clinical benefit in patients with non sustained ventricular arrhythmias following myocardial infarction. Ongoings studies are testing the hypothesis that such benefit could exist with amiodarone. The clinical benefit of beta-blockers, in terms of reduction of both total and sudden death post-myocardial infarction, has been clearly documented and mandates their administration in this setting. Futures studies of anti-arrhythmic drugs will have to focus on groups of patients at increased risk of arrhythmic death.

Amiodarone↗

PubMed1992

Review articles and publication bias.

Publication bias occurs if the results from studies which have not been published are different from the published ones. From a Bayesian viewpoint, it also concerns non-publication of studies with similar results as the published ones because the strength of the evidence will be influenced. Publication bias complicates the interpretation of reviews and meta-analyses. If favourable results are published more often there will be an overestimation of the effects of a treatment. There have been several attempts to assess the magnitude of publication bias. Unpublished trials could be identified by means of a survey among researchers, and the results could subsequently be compared with the outcomes of published trials. Also, the results from published trials could be compared with trials from a registry. Furthermore, the results from registered but unpublished trials could be compared with those of registered and subsequently published trials. Studies addressing publication bias have shown that it is a serious problem which complicates the interpretation of reviews. In assessments of publication bias other factors must be taken into account. These include the mode of publication: refereed journals, other journals, books, etc. Differences could also be related to the quality of trials. Finally, the source of funding may influence both the results and subsequent publication. Publication bias can only be avoided by registration of all trials before data collection is started; several of such registries have already been installed. Perhaps, if more of such registries exist, reviewers could only use registered trials for their main conclusions. All other information could then be considered sensitive to publication bias.

Meta-Analysis as Topic↗

PubMed1992

Paroxetine in the treatment of melancholia and severe depression.

Meta-analyses of the worldwide paroxetine database assessed the efficacy of this compound in the treatment of both DSM-III defined melancholia and hospitalised patients with severe depression (HAMD > or = 25). The analysis for melancholia included 178 paroxetine treated patients and 66 patients treated with placebo. Paroxetine was significantly superior to placebo in the treatment of melancholia and a clear dose-response relationship was established. The meta-analysis for severely depressed hospitalised patients included 109 paroxetine treated patients and 107 patients treated with a tricyclic/tetracyclic control. Paroxetine and active controls showed comparable efficacy in the treatment of severely depressed hospitalised patients.

Adult↗

PubMed1992

The exclusion of the elderly and women from clinical trials in acute myocardial infarction.

OBJECTIVE: To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infarction, to identify factors associated with such exclusions, and to explore the relationship between the exclusion of elderly and the representation of women. DATA SOURCES: We conducted a systematic search of the English-language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infarction. To accomplish this, we searched MEDLINE, major cardiology textbooks, meta-analyses, reviews, editorials, and the bibliographies of all identified articles. STUDY SELECTION: Only trials in which patients were randomly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review. DATA EXTRACTION: Studies were abstracted for year of publication, source of support, performance location, drug therapies to which patients were randomized, use of invasive diagnostic tests or therapeutic procedures, exclusion criteria, size and demographic characteristics of the randomized study population, and principal outcome measures. DATA SYNTHESIS: A total of 214 trials met inclusion criteria, involving 150,920 study subjects. Over 60% of trials excluded persons over the age of 75 years. Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 (adjusted odds ratio, 4.92; 95% confidence interval, 2.33 to 10.54). Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies (adjusted odds ratio, 2.45; 95% confidence interval, 1.10 to 5.47). Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions (18% vs 23%; P = .0002), with the mean age of the study population significantly associated with the proportion of women participants (P = .0001, R2 = .29). CONCLUSIONS: Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infarction. Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infarction.

Age Factors↗

PubMed1992

The impact of stopping rules on heterogeneity of results in overviews of clinical trials.

This paper explores the extent to which application of statistical stopping rules in clinical trials can create an artificial heterogeneity of treatment effects in overviews (meta-analyses) of related trials. For illustration, we concentrate on overviews of identically designed group sequential trials, using either fixed nominal or O'Brien and Fleming two-sided boundaries. Some analytic results are obtained for two-group designs and simulation studies are otherwise used, with the following overall findings. The use of stopping rules leads to biased estimates of treatment effect so that the assessment of heterogeneity of results in an overview of trials, some of which have used stopping rules, is confounded by this bias. If the true treatment effect being studied is small, as is often the case, then artificial heterogeneity is introduced, thus increasing the Type I error rate in the test of homogeneity. This could lead to erroneous use of a random effects model, producing exaggerated estimates and confidence intervals. However, if the true mean effect is large, then between-trial heterogeneity may be underestimated. When undertaking or interpreting overviews, one should ascertain whether stopping rules have been used (either formally or informally) and should consider whether their use might account for any heterogeneity found.

Analysis of Variance↗

PubMed1992

Directory of registries of clinical trials.

Registries of clinical trials are a potentially useful resource for the planning of new studies, the promotion of communication and collaboration between researchers, the conduct of meta-analyses, and the facilitation of patient access and recruitment to trials. However, many physicians and researchers are unaware of their existence, and as a result they remain underused. A directory of registries of clinical trials has been developed as a result of an international survey of 63 organizations and 51 individuals in 13 different countries to identify the existence of such registries. This is intended as a resource to keep physicians, researchers, trial organizers, funding bodies and government agencies abreast of the growing number of registries available, and to assist in the planning of future registries. Twenty-four current and six planned registries of clinical trials have been identified. Most focus on AIDS or oncology, but such diverse areas as neurosurgery, cardiovascular disease, dentistry and perinatology are also represented. This paper presents a descriptive profile on each registry and discusses the relative merits of their different organizational features. Recommendations are given for the establishment of future registries.

Clinical Protocols↗

PubMed1991

[Class I anti-arrhythmia agents and prevention of sudden death following myocardial infarction].

The results of therapeutic trials of Class I antiarrhythmic agents after myocardial infarction are not identical or always compatible with those of the CAST. It is important to determine the reason for this disparity in order to try and identify the patients who should not be given these drugs and those in whom they could be beneficial, providing these benefits are clearly demonstrated. Meta-analyses of controlled therapeutic trials of Class I antiarrhythmics after myocardial infarction have been performed. Depending on the study protocol used, the results of the CAST are compatible or incompatible with those of other trials. A possible reason for this apparent discordance from meta-analysis could be the particularly low cardiac risk in the CAST patients.

Anti-Arrhythmia Agents↗

PubMed1991

Treatment of hypertension: a clinical epidemiologist's view.

The majority of deaths attributable to hypertension are coronary artery disease (CAD) deaths and, consequently, the prevention of CAD should be the primary aim of hypertension management. Recent meta-analyses confirm the results of the individual hypertension intervention trials, which demonstrated a disappointing shortfall in the observed prevention of CAD events and mortality from lowering blood pressure compared with the expected benefits. These trial results, rather than challenging the validity of the causal nature of the association between hypertension and CAD may be interpreted to suggest that the management of hypertension in the trials was suboptimal. The drugs used in the trials were almost exclusively thiazide diuretics and to a lesser extent beta-blockers. Both of these drug groups have been shown to have adverse effects on lipid profiles--a pivotal risk factor for CAD. In addition to the effects on lipids, diuretics also adversely affect potassium, uric acid, glucose metabolism, and insulin resistance, all of which directly or indirectly affect the incidence of CAD. In the face of a major shortfall in the overall benefit from managing hypertension with diuretics and to a lesser extent beta-blockers, it therefore seems more logical to recommend for the management of hypertension the use of agents with a more metabolic-friendly profile.

Coronary Disease↗

PubMed1991

Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. The Danish Study Group on Verapamil in Myocardial Infarction.

The effect of verapamil on death and reinfarction after an acute myocardial infarction was studied in two double-blind, randomized, placebo-controlled multicenter trials, the Danish Verapamil Infarction Trials I and II (DAVIT I and II). The studies demonstrated that verapamil 360 mg/day from the 2nd week after an acute myocardial infarction, prevented death and reinfarction. Meta-analyses of the results of DAVITs I and II resulted in a reduction of pooled ratios of 22% (95% confidence limits 1-37, p = 0.04) for death, 21% (5-35, p = 0.02) for first major events (first reinfarction or death), and 27% (6-43, p = 0.02) for first reinfarctions. The effect of verapamil was to prevent myocardial ischemia and reduce sudden death and reinfarction. It is concluded that long-term treatment with verapamil after an acute myocardial infarction may be recommended with the object of reducing overall mortality, major events and reinfarction.

Arrhythmias, Cardiac↗

PubMed1991

Prophylaxis of deep venous thrombosis and pulmonary embolism.

Clinically silent deep venous thrombosis (DVT) develops in up to 25% of patients who undergo general surgical procedures. Approximately 10% of these thromboses are complicated by potentially fatal pulmonary embolism. Two recent meta-analyses of more than 70 published trials of DVT prophylaxis in general surgery have demonstrated conclusively that prophylaxis significantly reduces rates of DVT and fatal pulmonary embolism and results in improved overall survival. Physical methods of prophylaxis, including compression stockings and intermittent pneumatic compression, are as effective as pharmacologic prophylaxis (the most common regimen being heparin, 5000 units subcutaneously ever 8 to 12 hours). Bleeding complications are increased with the use of heparin, although they are clinically minor. Deep venous thrombosis prophylaxis should be routinely instituted for all general surgical patients who undergo major operative procedures.

Heparin↗

PubMed1991

[Rehabilitation following myocardial infarct].

Today rehabilitation after myocardial-infarction is a routine measure in most countries, yet its effectiveness is still under discussion. Rehabilitation aims at ameliorating the quality of life and at preventing a cardiovascular reevent, in other words at prolonging life. The latter "hard" endpoints is best amenable to quantification. Only recent meta-analyses of pooled data were able to show that rehabilitation in fact does prolong life. The relative importance of physical exercise in mostly complex rehabilitation programs is even less clear. This analyses implies a benefit, yet the exact proof is still missing. If rehabilitation could be shown to improve quality of life, its application would, of course, be justified even if it did fail to prolong life. Important open questions relate to the optimizing of rehabilitation: duration, frequency, intensity as well as age and sex of responders. Answering these will be a challenge for tomorrow's rehabilitation medicine.

Combined Modality Therapy↗

PubMed1991

Aspirin in transient ischemic attacks and minor stroke: a meta-analysis.

An overview analysis of seven randomized controlled trials testing the effectiveness of aspirin in the treatment of patients with transient ischemic attacks and minor strokes was performed. A total of 6409 patients from the seven trials was entered in the analysis; 2182 patients received only aspirin; 1598 patients received an aspirin-combination regimen with either sulfinpyrazone or dipyridamole; and 2629 subjects received a placebo. Aspirin alone produced an 18% decrease in all strokes and cardiovascular deaths. The pooling of studies examining aspirin-combination regimens and the larger grouping of studies of aspirin and aspirin-combination regimens led to more striking results. Indeed, significant risk reductions were observed for three of the four outcomes, namely, total deaths, total strokes, and total strokes and cardiovascular deaths, with odds ratios ranging from 0.59 to 0.78. Suggestive, albeit more modest, results were obtained when examining the impact of these regimens on total cardiovascular mortality. The same tendencies have also been observed in three previously published meta-analyses.

Adult↗

PubMed1991

[The role of surgery in portal hypertension].

Following a historical review of the treatment of portal hypertension, the evaluation of the patient with bleeding esophageal varices is discussed. The aim of preoperative evaluation is to determine the best option for either emergency or elective treatment of bleeding esophageal varices. The most recent medical and surgical randomized studies with meta-analyses are discussed.

Esophageal and Gastric Varices↗

PubMed1990

Secondary prevention of death and reinfarction with verapamil after an acute myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction.

The effect of verapamil on death, reinfarctions, and major events i.e. reinfarction or death, has been investigated in two Danish double-blind, placebo-controlled verapamil infarction trials DAVIT I and II. DAVIT I, which was an early intervention trial, demonstrated that after six months there was a statistically non-significant reduction of mortality and reinfarction. DAVIT II demonstrated a non-significant reduction of mortality rate (P = 0.11, hazard ratio 0.80, 95% confidence limits 0.61-1.05), a significant reduction of reinfarction rate (P = 0.04, 0.77, 0.58-1.03), and major event rate (P = 0.03, 0.80, 0.64-0.99) in the verapamil group compared with the placebo group. Meta-analyses of DAVIT I (including only patients alive on day eight) and of DAVIT II showed a statistically significant reduction of odds ratio of mortality of 22% (P = 0.04), of reinfarctions of 27% (P = 0.02), and of major events of 21% (P = 0.02). It is concluded that long-term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality, major events, and reinfarction rates.

Anti-Arrhythmia Agents↗

PubMed1989

Is it possible to reduce the risk of cardiovascular events in subjects suffering from intermittent claudication of the lower limbs?

This study meta-analysed randomized, double-blind, placebo controlled trials in patients with intermittent claudication of the lower limbs comparing ticlopidine to placebo in order to test the hypothesis that the drug, a pure antiplatelet agent, is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients. A highly significant reduction, from 9% to 3% (p ranging from 0.006 to 0.002), was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients (301 with ticlopidine, 310 with placebo). The duration of follow-up ranged from 6 to 12 months. Side-effects, defined as withdrawal from study medication for any reason but death, cardio-vascular events or cancer, were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo. We concluded that in this high risk population, prevention of cardio-vascular events is likely to be effective.

Cardiovascular Diseases↗