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PubMedDate not supplied

Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review.

Penicillin has been first-line therapy for the treatment of streptococcal pharyngitis for more than 40 years. Since the 1980s, there have been a number of reports suggesting that bacteriologic failure rates with penicillin may be rising. A number of alternative therapies have been proposed, including oral cephalosporins. To evaluate the efficacy of these agents, two meta-analyses have recently been performed. In the meta-analysis performed by Pichichero and Margolis, oral cephalosporins were reported to achieve a significantly greater bacteriologic cure rate than penicillin (92% with cephalosporins vs 84% with penicillin, P < 0.0001) when results from 19 studies were analyzed. A separate meta-analysis performed by Deeter et al reported that the oral cephalosporin cefadroxil monohydrate achieved significantly greater bacteriologic cure rates (94.8% cefadroxil vs 87.5% penicillin, P < 0.05) than oral penicillin when 9 trials in 1406 patients with streptococcal pharyngitis were analyzed. A review of 65 studies of the use of penicillin for the treatment of streptococcal pharyngitis has shown that bacteriologic failure rates in the period 1980 to 1993 were approximately 12% to 13%, slightly but not significantly greater than during the period 1953 through 1979. Oral cephalosporins such as cefadroxil monohydrate provide reasonable alternatives for the treatment of streptococcal pharyngitis.

Administration, Oral↗

PubMed1994

[Research in psychotherapy].

Psychotherapy is an empirical discipline and is therefore open to exact investigations which is one of the prerequisites of its further development. The beginnings of exact research are associated with the names of H. J. Eysenck and C. R. Rogers. The contemporary research based frequently on the generic model of psychotherapy whose authors are D. E. Orlinsky and K. J. Howard is concerned in particular with the effectiveness of psychotherapy; it compares the action of different procedures, deals with differentiated indications and "mechanisms" inducing changes. The most frequent research strategies are an experimental approach, comparative (correlating) research and intensive research strategy. The most important source of information on research are meta-analyses which make it possible to summarize and compare an unlimited amount of mutually independent investigations. The hitherto most extensive meta-analytic processing of research projects was implemented in the Institute of Psychology of Bern University headed by K. Graw. It was revealed among others that psychotherapy exerts a very differentiated action and that in neurotic patients and patients with personality disorders cognitive behavioural psychotherapy, Rogers psychotherapy and psychoanalytic psychotherapy, cca 100 sessions, proves definitely effective. Close to the criterium of objectively effective psychotherapy is also shape psychotherapy and systematically oriented family therapy. In the Czech Republic research is conducted on a small scale but the work is demanding as regards methods and is of a high standard. Exact research of the psychotherapeutic process and therapeutic results contributes to the gradual shaping of a psychotherapeutic model which is internally differentiated and which integrates verified findings of various psychotherapeutic schools and trends.

Humans↗

PubMed1994

[From clinical trials to routine treatment. General aspects of clinical trials in cardiovascular diseases].

The first of two articles deals with general aspects of clinical cardiological research: hard end points -mortality and morbidity-in relation to intermediate end points, power of clinical studies, multicentre studies, meta-analyses, and the relationship between the trial population and the total patient population. The article takes up the kind of problems that are addressed in clinical research, and the relationship between the medical profession and the pharmaceutical industry. The author discusses the situation as regards clinical research in Norway, and emphasizes the need for greater efforts in this field.

Cardiovascular Diseases↗

PubMed1993

A study to determine the efficacy and safety of tenoxicam versus piroxicam, diclofenac and indomethacin in patients with osteoarthritis: a meta-analysis.

OBJECTIVE: To obtain a better quantitative and qualitative estimate of the effect of tenoxicam (Tx) compared to piroxicam (Px), diclofenac (Dcl) and indomethacin (Ind) in the treatment of osteoarthritis (OA). METHODS: Relevant studies were identified using computerized Medline search, manual search of cited references and correspondence with investigators, colleagues and the manufacturer of Tx. Once the studies were selected and chosen on the basis of predetermined methodologic criteria, the required data were extracted by 2 authors, independently. Eighteen studies met the required eligibility criteria. Meta-analyses were undertaken on 12 studies of Tx vs Px, 3 studies of Tx vs Dcl, and 2 studies of Tx vs Ind. Efficacy was measured in 2 ways: (1) physician global rating scale and (2) pain scale. Safety was measured in 3 ways: (1) physician global rating scale, (2) number of patients with adverse events, and (3) dropouts due to adverse events. RESULTS: The following findings of the meta-analysis were statistically significant: In Tx vs Px comparisons, efficacy-(1), safety-(1) and safety-(3) were all better with Tx; in Tx vs Ind comparisons, safety-(1) and safety-(2) were better with Tx. All other findings showed no statistically significant differences between Tx and the comparison drug. CONCLUSIONS: Compared to Px, Tx performs better on physician assessment of efficacy and tolerability, but the other comparisons remain inconclusive. Compared to Dcl, there appears not to be a difference. Compared to Ind, Tx is safer.

Aged↗

PubMed1994

Meta-analysis in dental research: a paradigm for performance and interpretation.

Applications of meta-analysis have begun to appear with some regularity in the dental research literature. Recently, a meta-analysis played a high-profile role in the ongoing academic debate concerning the relative anticaries efficacy of dentifrices containing fluoride as sodium fluoride and as sodium monofluorophosphate, engendering a controversy concerning the methodology employed. This has given rise to the need for a careful consideration of the principles involved in the meta-analytic process to provide a basis of understanding upon which such controversies may be resolved. The present report endeavors to meet this need by enumerating the steps involved in a meta-analysis, and contrasting them with the analogous steps in the more widely-understood "usual" inferential process, bringing to light both the similarities and differences between these two types of analyses. Within this context, the conflicting meta-analyses associated with the current controversy are discussed and compared, and the source of the difference between them is readily identified. This process reaffirms the need for close collaboration between statisticians and other scientists in the performance of a meta-analysis, and the value of such close collaboration in the evaluation and interpretation of a meta-analysis performed by others, as well.

Dental Caries↗

PubMedDate not supplied

[Hypercholesterolemia: to treat or not to treat? That is the question].

Numerous epidemiological studies have confirmed the positive correlation of elevated serum cholesterol levels to increased coronary risk. Clinical and angiographical trials have shown that modification of hypercholesterolaemia by diet or drugs can lower cardiovascular morbidity and mortality. No good evidence exists that lowering serum cholesterol is harmful. In some meta-analyses enhancing statistical power, total mortality appears to be decreased in primary prevention trials if hypercholesterolaemia is sufficiently reduced. Current guidelines for cholesterol modification should include the primary prevention with identification of individuals at high risk, combined with population information, and the secondary prevention for the patients with symptomatic coronary heart disease.

Age Factors↗

PubMedDate not supplied

1992 Bonica Lecture. Advances in chronic pain management since gate control.

OBJECTIVE: Two pain treatment systems that developed soon after the publication of the gate theory are probably a direct result of its publication: neuraxial opiate administration and electrical stimulation of the spinal cord and peripheral nerves and receptors. Although the use of these modalities has become widespread in managing chronic pain, there is disagreement about their long-term efficacy. This presentation will attempt to review the data regarding the mechanisms of action of these modalities and their efficacy in treating chronic pain of malignant and nonmalignant origin. DATA SOURCES: Data were derived almost entirely from original articles reporting experimental data from both animal and human studies and from series of patients undergoing treatment with the modalities reviewed. STUDY SELECTION: Where possible, controlled studies were selected. However, much of the available data regarding treatment results are uncontrolled. DATA EXTRACTION AND SYNTHESIS: Selected data from studies that were felt to be reasonably well conducted are presented or summarized. Because of the lack of control groups in many of the clinical trials, meta-analyses were not carried out. CONCLUSIONS: Long-term spinal opiate administration has been shown to be more effective than systemic opiates in some patients with cancer pain, but often must be combined with local anesthetics to provide satisfactory pain relief. Loss of effect over time is a significant problem. Since the identification of spinal opiate receptors and the introduction of spinally administered narcotics, a number of other receptors that are important in both sensitization and suppression of pain projection systems have been characterized. Agonists and antagonists to many of these receptors are being developed, and a few are available for clinical trials. Long-term electrical stimulation of the spinal cord produces substantial analgesia below the stimulated spinal segments in some patients with chronic pain. Although initial results are usually encouraging, long-term efficacy may be disappointing. It is postulated that analgesia associated with spinal stimulation is associated with both stimulation of large fiber ascending tracts and blockade of spinothalamic pathways. Transcutaneous electrical nerve stimulation (TENS) has come into widespread use in managing chronic pain and has had limited trials in cancer pain patients. It is well accepted by patients and physicians, but clinical studies of long-term efficacy have yielded variable results. The analgesic action is probably the result of both large afferent fiber activation and blockade of peripheral nociceptors.

Adrenergic alpha-Agonists↗

PubMed1993

[Antihypertensive treatment and left ventricular hypertrophy].

Left ventricular hypertrophy in arterial hypertension can be considered as an adaptive response of the heart to the increased afterload, in order to reduce wall stress; however, cardiac hypertrophy can also represent the first step toward a pathological process that leads to the development of congestive heart failure. Epidemiological studies have documented that left ventricular hypertrophy in essential hypertension represents an independent risk factor for cardiovascular morbidity and mortality. The possibility of reversing, or even preventing, left ventricular hypertrophy through a reduction in elevated blood pressure values and modification of some other pathogenetic factors should represent a major therapeutic need in the treatment of hypertensive patients. It has been demonstrated that different classes of antihypertensive drugs do not have the same effect in reducing left ventricular mass, probably because beyond control of blood pressure, the pharmacological interference with adrenergic system, the renin-angiotensin-aldosterone system or other growth factors can influence the development and the reduction of cardiac hypertrophy. Two recent meta-analyses of the principal regression studies have shown that ACE-inhibitors, followed by calcium antagonists and drugs capable of reducing sympathetic nervous system activity, are more effective in decreasing left ventricular mass. The results of experimental and clinical studies have demonstrated that the reversal of cardiac hypertrophy is associated with an improvement of the functional consequences of an increased left ventricular mass. Further studies are needed in order to verify whether the reversal of left ventricular hypertrophy per se increases survival in essential hypertensive patients.

Adaptation, Physiological↗

PubMed1994

The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer.

OBJECTIVE: To determine the effect of oral contraceptive (OC) use on the cumulative incidence of epithelial ovarian cancer from ages 20-40, 20-50, and 20-55 years among four groups of women: positive family history, negative family history, parous, and nulliparous. METHODS: Cancer and Steroid Hormone Study data were combined with data from the Surveillance, Epidemiology, and End Results Network to provide estimates of the age-specific incidence rates of epithelial ovarian cancer among never-users of OCs in the four specified groups of women. These rates provided the basis for calculating cumulative incidences. The rates in women using OCs were estimated from meta-analyses of the epidemiologic literature, using regression equations expressing the log-relative rate of epithelial ovarian cancer as a function of duration of use and recency. RESULTS: In all four groups, the cumulative number of epithelial ovarian cancer cases estimated to occur per 100,000 OC users, compared to never-users, decreased with increasing duration of OC use. Our results suggest that 5 years of OC use by nulliparous women can reduce their ovarian cancer risk to the level seen in parous women who never use OCs, and that 10 years of OC use by women with a positive family history can reduce their risk to a level below that for women whose family history is negative and who never use OCs. CONCLUSION: These data represent the first published estimates of the effect of OC use on the cumulative incidence of epithelial ovarian cancer by family history and by parity. The demonstrated substantial noncontraceptive benefit from OCs justifies their judicious use as a potentially powerful resource for primary prevention in women at high risk of ovarian cancer.

Adult↗

PubMed1993

Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion. A meta-analytic attempt to resolve the brouhaha.

OBJECTIVE: To determine the efficacy of antibiotics for prophylaxis of recurrent otitis media and treatment of otitis media with effusion (OME) in children. DATA SOURCES: MEDLINE from 1966 through April 1993, textbooks, Current Contents, and bibliographies of selected articles. STUDY SELECTION: Thirty-three studies initially identified were reviewed by three blinded reviewers assessing study quality and suitability for inclusion. Twenty-seven met inclusion criteria for the meta-analyses. DATA EXTRACTION: We abstracted quantitative data and calculated rate differences (RDs) using tympanometry as the preferred outcome measure. DATA SYNTHESIS: Nine studies of antibiotic prophylaxis of recurrent otitis media with 958 subjects had an RD of 0.11 (95% confidence interval [Cl], 0.03 to 0.19) favoring antibiotic treatment. Twelve studies of short-term patient outcomes of OME with 1697 subjects had an RD favoring antibiotics of 0.16 (95% Cl, 0.03 to 0.29), while eight studies using the ear as the outcome measure with 2052 ears studied had an RD of 0.25 (95% Cl, 0.10 to 0.40). No significant difference was shown between placebo and antibiotics (RD, 0.06; 95% Cl, -0.03 to 0.14) in the eight studies of longer-term outcome of OME. Subgroup analyses by antibiotic grouping, duration of treatment, and duration of disease did not show significant differences. CONCLUSIONS: Antibiotics appear to have beneficial but limited effect on recurrent otitis media and short-term resolution of OME. Longer-term benefit for OME has not been shown. The findings are limited by the failure of most studies to consider potential confounders and by inability to identify groups of patients most likely to benefit.

Acute Disease↗

PubMedDate not supplied

Cisplatin-etoposide based chemoradiation treatment for limited small cell lung cancer: the current situation.

Although the role of thoracic radiotherapy in limited small cell lung cancer has been established by two meta-analyses, optimization of radiotherapy with chemotherapy requires a full understanding of the chemotherapeutics used and the factors involved in administration of thoracic radiotherapy. The Cisplatin-Etoposide (PE) combination has replaced the cyclophosphamide or doxorubicin as the combination of choice, but it isn't clear whether the addition of the other agents add to benefit or toxicity. New agents continue to be sought to improve systemic failure. This paper focuses on the radiotherapy variables: dose, volume, fractionation, temporal sequencing, and variety of methods of combining the modalities are discussed. Results of a variety of pilot studies using thoracic radiotherapy and the PE combination are discussed. A randomized trial of accelerated radiotherapy versus standard fractionation has been completed within the past year, but results are not yet available. Further trials are warranted to improve integration of modalities in order to increase survival and reduce local and systemic failure without increasing untoward effects.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Resolving discrepancies among studies: the influence of dose on effect size.

In conducting reviews or meta-analyses, epidemiologists frequently must reconcile conflicting results. This paper addresses heterogeneity in nonexperimental studies. The emphasis is on simple exploratory methods rather than formal approaches. Five examples illustrate how quantitative concordance among studies is possible, even when measured effects appear discrepant. The examples concern ethylene oxide and leukemias, methylene chloride and liver cancer, saccharin and bladder cancer, prenatal lead exposure and birthweight, and aspirin and bleeding tendencies in labor and delivery. Data examined here indicate that differences in dose levels frequently explain heterogeneous effect measures, often outweighing other sources of variability among studies. We present simple methods for combining dose information from the study of interest with dose-response data from other epidemiologic studies or animal studies to derive plausible hypothesized effect levels. These plausible effect sizes are the measures of association that would be predicted, for the actual exposures, by extrapolating from other studies with possibly differing exposure levels. Post hoc power calculations and comparisons of confidence intervals for overlap to reconcile "positive" and "null" studies may be misleading, since these approaches assume a uniform true association obscured by random fluctuations only. Whenever it can be estimated, a plausible effect size should be the starting point to assess findings of either positive or null studies. Without such calculations, comparisons among conflicting studies may not be meaningful.

Aspirin↗

PubMed1993

[The effect of lowering cholesterol on mortality].

There is little doubt about the validity of the lipid hypothesis as a pathogenetic theory for atherosclerosis. However, this theory does not allow the conclusion that cholesterol-lowering treatment is necessarily beneficial in practice. As a consequence of the probabilistic nature of risk factors, the classification of plasma cholesterol levels into "normal" and "pathological" can be misleading in clinical practice. The potential benefit of cholesterol-lowering treatment is a direct function of the overall coronary risk, more or less independently of plasma cholesterol. Therefore, plasma cholesterol is of clinical significance only in patients with established CHD and a high overall risk of infarction. Total mortality has been prospectively included as one end-point in addition to infarct mortality in the many intervention studies on cholesterol-lowering. Meta-analyses of these studies show a non-significant decrease in infarct mortality through cholesterol-lowering drug treatment, with a concomitant, highly significant increase in non-infarct mortality. Lowering cholesterol in asymptomatic persons and in coronary patients with a relatively low risk of infarction results in a significant increase in total mortality. Only in a very small group of coronary patients with a very high risk of myocardial infarction, due to the presence of several additional risk factors, may cholesterol-lowering treatment be beneficial.

Anticholesteremic Agents↗

PubMed1993

Defining normal ambulatory blood pressure in relation to target organ damage and prognosis.

It is premature to state that ambulatory blood pressure (ABP) values below a given level should be considered normal, and those above it abnormal, in terms of prognostic implications on cardiovascular (CV) morbidity. We do not know whether CV morbidity in hypertensive subjects with apparently normal ABP (white coat hypertension) is less than that in patients with higher ABP levels and similar to that of healthy normotensive subjects, or whether the effects of antihypertensive drug treatment on CV morbidity are superior to placebo in white coat hypertension. It is important to achieve agreement on a temporary working definition of normal ABP to be used to test two main hypotheses: 1) in subjects with white coat hypertension, CV morbidity is less than that in patients with higher ABP levels; and 2) drug treatment is not superior to placebo in reducing CV morbidity in white coat hypertension. Normal ABP values can be derived empirically from population based samples, in selected groups of healthy subjects, or from meta-analyses. However, the significance of the definition of a normal ABP range is the identification of clinically hypertensive patients at low risk of future CV morbid events. Using echocardiographic left ventricular (LV) mass as a surrogate outcome measure, we found that the coexistence of mean daytime ABP levels < 134 mm Hg systolic and < 90 mm Hg diastolic, regardless of gender (< 136/87 mm Hg in men and 131/86 mm Hg in women) identifies a subgroup of clinically hypertensive subjects with echocardiographic LV mass, and associated prevalence of left ventricular hypertrophy (LVH) similar to those found in healthy normotensive control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

PubMed1993

[Questions and aspects of radiotherapy of adult patients with localized supradiaphragmatic stage (CS I/II) Hodgkin's disease. 1. Questions and aspects on indications for primary and adjuvant radiotherapy].

Important studies of the therapy in patients with early stages of Hodgkin's disease aim at reducing the long-term risks, yet maintaining the high cure rate. Several prospective studies and two large meta-analyses did not observe a significant difference of the ten- or 15-year survival rate after radiotherapy or combined radio- and chemotherapy in the total group of patients with CS I/II A Hodgkin's disease, not withstanding a significant reduction of the recurrence risk after combined therapy. There is some evidence but no proof, that certain subgroups of patients with early stage, have a higher survival after combined therapy compared to that after radiotherapy alone. Most studies of therapy in Hodgkin's disease have a statistical power much too low, in order to demonstrate significant differences of the survival rate in the order of 10 to 15%. Randomized studies of chemo- versus radiotherapy in patients with PS I/II A and some PS III A have shown conflicting results. Patients with supradiaphragmatic Hodgkin's disease and CS I/II can be subdivided according to the recurrence risk after primary radiotherapy in the following subgroups: 1. Patients with a very low or a low recurrence risk of approximately 10 to 20%: patients less than 40 years old and CS I/II A NS/LP with less than three involved regions and no bulky mediastinal mass and an ESR below 30 mm. If there is only unilateral suprahyoidal lymph node involvement, primary radiotherapy of the involved region or a mini-mantle or a mantle field is acceptable and achieves a recurrence free survival of 90% or higher. If there is only non bulky mediastinal involvement, mantle field radiotherapy is acceptable and achieves a recurrence-free survival of at least 90%. In the other patients, primary irradiation of an extended mantle field without a staging laparotomy is an acceptable primary treatment, achieving a recurrence-free survival rate of approximately 80%. Another option is a staging laparotomy with splenectomy and a mantle radiotherapy for PS I/II. Few groups prefer primary chemotherapy alone or some type of a reduced chemotherapy with lesser toxicity combined with localized radiotherapy and long-term observations of a larger group of patients after the last type of treatment have to confirm the excellent early results. 2. Patients with an intermediate recurrence risk of approximately 20 to 40%: patients, who do not belong to group one or group 3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Limitations to standard randomized controlled clinical trials to evaluate combination therapies in rheumatic diseases.

Randomized controlled clinical trials provide the cornerstone of modern research concerning medical therapies. However, important limitations intrinsic to clinical trials may restrict the generalizability of results to usual clinical practice. Limitations which appear particularly prominent in studies of combination therapies in inflammatory rheumatic diseases include: a) appropriate attention to group data which does not address variability of individual patient responses to specific agents; b) exclusion criteria to enter the clinical trial; c) small numbers with insufficient statistical power to identify clinically important trends; d) a time frame too short to recognize clinically meaningful differences between treatment regimens which may emerge over long periods. These limitations present problems in interpretation of studies in polymyositis, systemic lupus erythematosus, and rheumatoid arthritis. Strategies to improve accurate assessment of therapies include meta-analyses, clinical trials over at least five years, and long-term databases concerning consecutive patients seen in usual care.

Arthritis, Rheumatoid↗

PubMed1993

Drug treatment of depression in the frail elderly: discussion of the NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life.

The priorities for future research from the NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life, as republished in the previous article, included recommendations to "conduct clinical trials and observational studies of treatment in the very old, the elderly in institutional setting, and the elderly with medical illnesses," that is, in the frail elderly. The present article reviews recent research in this field and outlines the potential for future developments. The importance of these areas of investigation follows from epidemiological findings suggesting that the prevalence of major depression in community populations, in general, decreases as a function of age but that depressions of all types occur more frequently in the "oldest-old," in patients seen in medical care settings, and in those with chronic disease and disability. The psychopharmacological literature, as summarized for the Consensus Conference in the review by Salzman and the meta-analyses of Klawansky, Greenhouse, and Schneider, indicates that antidepressant medications remain effective in elderly patients with moderate to severe degrees of major depression. Questions remain, however, about the value of drug treatment for those depressions that are most common in late life, including those that occur in extremely old patients and in patients with significant medical illness.

Aged↗

PubMed1993

125I-fibrinogen leg scanning: reassessment of its role for the diagnosis of venous thrombosis in post-operative patients.

OBJECTIVE: To determine the reasons why 125I-fibrinogen leg scanning, a screening test which was reported to be very sensitive for the detection of post-operative thrombosis, has shown poor sensitivity in contemporary studies. STUDY IDENTIFICATION: English-language reports were identified through a Medline computer search (1965-1991), Current Contents, and an extensive manual search of the bibliographies in identified articles. STUDY SELECTION: Studies in orthopaedic or general surgical patients were reviewed that compared 125I-fibrinogen leg scanning with venography in all patients (accuracy studies) or in patients in whom 125I-fibrinogen leg scanning became positive (positive predictive value studies). DATA EXTRACTION: A systematic appraisal of study design and specific descriptive information concerning the selection of patients. RESULTS OF DATA SYNTHESIS: Six of the 15 studies which compared 125I-fibrinogen leg scanning with venography were level 1 studies (potential for bias minimized) and nine were classified as level 2 studies (potential for bias not minimized). In orthopaedic surgical patients, the pooled sensitivity of leg scanning for isolated calf vein thrombosis, for all venous thrombosis, and the pooled specificity were 55%, 45%, and 92% for the level 1 studies, respectively. These indices were 88%, 82%, and 79%, respectively for the level 2 studies (P < 0.001). Only two (level 2) studies were found that evaluated the accuracy of leg scanning for venous thrombosis in general surgical patients. CONCLUSION: We conclude that leg scanning is an insensitive method for the screening of post-operative venous thrombosis in orthopaedic patients. Our findings call into question the validity of the many studies (including meta-analyses) evaluating prophylactic agents for venous thrombosis which used leg scanning as the only test for the assessment of efficacy.

Fibrinogen↗