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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↗

PubMed1993

Cyclosporin A in rheumatoid arthritis: overview of efficacy.

Five clinical trials of cyclosporin A (CyA) in the treatment of RA were reviewed and an initial evaluation made of clinical endpoints across the studies. A composite effect score for efficacy and the rates of dropout due to toxicity were each compared to earlier meta-analyses evaluating the relative efficacy and toxicity of second-line drugs for RA. The overall percentage improvements over a 6-month assessment period for the various clinical endpoints were all found to meet a minimal clinical improvement of 20%: tender joints, 20%; grip strength, 22%; swollen joints, 29%; functional index, 29%; morning stiffness, 40%; and CRP, 45%. The exception was ESR (16%). The composite effect for CyA indicated significant improvement over placebo (P < 0.001). This effect in excess of placebo was in the range of that found for antimalarial drugs. The toxicity associated with CyA was similar to that found with drugs with low toxicity, such as auranofin. A more detailed analysis using individual patient data and the results of two studies is planned.

Arthritis, Rheumatoid↗

PubMed1993

High-osmolar and low-osmolar contrast media. An update on frequency of adverse drug reactions.

During the past 3 years a great number of papers about adverse drug reactions to intravascular injection of high-osmolar and low-osmolar iodinated contrast media (CM) have been published. They include observational studies, randomized trials, meta-analyses and committee reports. Thorough analysis of this material substantiates an improvement in safety of at least 6-fold using nonionic low-osmolar CM compared with ionic high-osmolar CM. The point where only a small minority is continuing to argue effectively that low-osmolar CM are not better than conventional high-osmolar CM has now been reached. High-osmolar CM are used less and less for intravascular purposes, and, in fact, have been totally replaced by low-osmolar CM in 4 countries.

Clinical Trials as Topic↗

PubMed1993

Effect of antibiotic therapy and etiologic microorganism on the risk of bacterial meningitis in children with occult bacteremia.

OBJECTIVE: To quantify the effect of antibiotic therapy on the probability of subsequent bacterial meningitis in children with fever without source treated as outpatients. DESIGN: Bayesian meta-analyses. REPORTS INCLUDED: All reports of the organism-specific prevalence of occult bacteremia in children with fever without source treated as outpatients, and the organism-specific prevalence of subsequent meningitis in children with occult bacteremia initially treated as outpatients stratified by type of antibiotic therapy. RESULTS: The mean probabilities of subsequent meningitis in children with occult bacteremia were 9.8%, 8.2%, and 0.3% in the no antibiotic, oral antibiotic, and parenteral antibiotic therapy groups, respectively. All cases of bacterial meningitis in children with occult bacteremia treated with oral antibiotics were due to Haemophilus influenzae. There were no cases of culture-positive bacterial meningitis in 139 bacteremic children treated with ceftriaxone (mean probability, 0.3%; 95% confidence interval, 0.0% to 1.5%). The mean probabilities of bacterial meningitis in a child with fever without source treated as an outpatient without antibiotics were: Streptococcus pneumoniae, 0.21%; and H influenzae, 0.06%. CONCLUSIONS: Antibiotic therapy is effective in preventing meningitis in children at risk of occult bacteremia.

Administration, Oral↗

PubMed1995

Clinical efficacy of sulphasalazine--a review.

This review of the use of sulphasalazine (SASP) in the therapy of rheumatoid arthritis refers to the placebo-controlled trials of SASP and the randomized comparative studies with other second-line drugs that have been published over the past decade. The questions relating to appropriate selection of patients for this treatment and the possible relevance of drug interactions are addressed. The favourable effect of SASP on functional, radiological and extra-articular outcome measures is highlighted, as is the reproducibility of published studies. Finally, the results from combination studies and meta-analyses are outlined.

Antirheumatic Agents↗

PubMed1996

Cost efficacy of the diagnosis and therapy of renovascular hypertension.

UNLABELLED: Numerous competing diagnostic modalities and the lack of data about therapeutic benefit result in controversy concerning the identification and treatment of renovascular hypertension. METHODS: Meta-analyses were used to examine the cost efficacy of renovascular hypertension diagnosis and treatment. Sensitivity, specificity and predictive value were calculated for captopril renography, Doppler, the captopril test and arteriography. Sensitivities and specificities were used to project cost per patient cured or improved for each modality. This was compared with the lifetime cost of medical therapy. Cost efficacy was calculated using a hypothetical population (1000 patients, a prevalency rate of 30% for renal artery stenosis, expected cure or improvement rate of 0.77 after angioplasty). RESULTS: The sensitivity, specificity and positive predictive values were similar for all modalities except the captopril test, which had a significantly lower sensitivity. The specificity was similar for all procedures; Doppler was highest but was mitigated by a 17% technical failure rate. The cost per patient cured or improved is greatest for arteriography and lowest for the captopril test. The relationship between cost per patient cured and the number of patients diagnosed in the population was calculated (relative value = (1/cost) x number patients detected). The relative value of captopril renography and arteriography is similar. Doppler and the captopril test have the lowest relative value. If angioplasty reduces medication by three drugs, the savings is $5807 to $8046 per patient. Surgical therapy is not cost-effective. CONCLUSION: Screening for renovascular hypertension is not cost-effective at a prevalence less than 30%, but captopril renography is equally cost-effective as arteriography and obviates the need for an arteriogram in many patients.

Captopril↗

PubMed1996

Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials.

BACKGROUND: Numerous studies demonstrate the efficacy of the combination therapy of insulin and sulfonylurea in subjects with type II diabetes mellitus. However, two recent meta-analyses of randomized trials during the last decade provided inconsistent conclusions and failed to resolve the controversy. OBJECTIVE: To assess the efficacy of insulin and sulfonylurea combination therapy in type II diabetes mellitus by performing meta-analysis of only the controlled studies selected according to specific strict criteria. METHODS: A computerized literature survey was conducted using the MEDLINE database from January 1980 through March 1992 with the search headings of "sulfonylurea" and "insulin" and "combination therapy in diabetes mellitus. "A manual search was also performed using references from each retrieved report. Case reports, review articles, editorials, and citations reported in non-English-language journals without English translations were excluded. Forty-three citations were obtained. Four strict inclusion criteria were used to select studies: randomized, placebo-controlled trials (oral agent plus insulin vs placebo plus insulin); homogeneous target population (subjects with type II diabetes); intervention using the same sulfonylurea agent in a combination therapy; and uniform outcome measures to evaluate efficacy such as body weight; values for serum glucose, glycohemoglobin, and C peptide; daily insulin dosage; and lipid concentrations. More stringent qualitative subcriteria were then used to eliminate bias in the final unanimous selection by two blinded reviewers. Data were pooled and analyzed using Student's t test and Winer's combined test. RESULTS: Sixteen studies satisfied the inclusion criteria. Metabolic control improved with the combination therapy as reflected by a significant lowering of fasting serum glucose values (P < .01) and glycohemoglobin concentrations (P < .025). Moreover, improved metabolic control was achieved with a significantly smaller daily insulin dose (P < .01) and without a significant change in body weight. Finally, the combination therapy enhanced the endogenous insulin secretion as expressed by an increase in fasting serum C peptide concentration (P < .05). CONCLUSIONS: Combination therapy with insulin and sulfonylurea may be a more appropriate and a suitable option to insulin monotherapy in subjects with non-insulin-dependent diabetes in whom primary or secondary failure to sulfonylurea developed. It may also be a more cost-effective way of long-term management in this group of subjects, especially in the elderly.

Blood Glucose↗

PubMed1996

The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices.

This report updates and replaces previous recommendations regarding the use of Bacillus of Calmette and Guerin (BCG) vaccine for controlling tuberculosis (TB) in the United States (MMWR 1988;37:663-4, 669-75). Since the previous recommendations were published, the number of TB cases have increased among adults and children, and outbreaks of multidrug-resistant TB have occurred in institutions. In addition, new information about the protective efficacy of BCG has become available. For example, two meta-analyses of the published results of BCG vaccine clinical trials and case-control studies confirmed that the protective efficacy of BCG for preventing serious forms of TB in children is high (i.e., > 80%). These analyses, however, did not clarify the protective efficacy of BCG for preventing pulmonary TB in adolescents and adults; this protective efficacy is variable and equivocal. The concern of the public health community about the resurgence and changing nature of TB in the United States prompted a re-evaluation of the role of BCG vaccination in the prevention and control of TB. This updated report is being issued by CDC, the Advisory Committee for the Elimination of Tuberculosis, and the Advisory Committee on Immunization Practices, in consultation with the Hospital Infection Control Practices Advisory Committee, to summarize current considerations and recommendations regarding the use of BCG vaccine in the United States. In the United States, the prevalence of M. tuberculosis infection and active TB disease varies for different segments of the population; however, the risk for M. tuberculosis infection in the overall population is low. The primary strategy for preventing and controlling TB in the United States is to minimize the risk for transmission by the early identification and treatment of patients who have active infectious TB. The second most important strategy is the identification of persons who have latent M. tuberculosis infection and, if indicated, the use of preventive therapy with isoniazid to prevent the latent infection from progressing to active TB disease. Rifampin is used for preventive therapy for persons who are infected with isoniazid-resistant strains of M. tuberculosis. The use of BCG vaccine has been limited because a) its effectiveness in preventing infectious forms of TB is uncertain and b) the reactivity to tuberculin that occurs after vaccination interferes with the management of persons who are possibly infected with M. tuberculosis. In the United States, the use of BCG vaccination as a TB prevention strategy is reserved for selected persons who meet specific criteria. BCG vaccination should be considered for infants and children who reside in settings in which the likelihood of M. tuberculosis transmission and subsequent infection is high, provided no other measures can be implemented (e.g., removing the child from the source of infection). In addition, BCG vaccination may be considered for health-care workers (HCWs) who are employed in settings in which the likelihood of transmission and subsequent infection with M. tuberculosis strains resistant to isoniazid and rifampin is high, provided comprehensive TB infection-control precautions have been implemented in the workplace and have not been successful. BCG vaccination is not recommended for children and adults who are infected with human immunodeficiency virus because of the potential adverse reactions associated with the use of the vaccine in these persons. In the United States, the use of BCG vaccination is rarely indicated. BCG vaccination is not recommended for inclusion in immunization or TB control programs, and it is not recommended for most HCWs. Physicians considering the use of BCG vaccine for their patients are encouraged to consult the TB control programs in their area.

Adult↗

PubMed1996

Psychosocial interventions for patients with coronary artery disease: a meta-analysis.

BACKGROUND: Narrative review strategies and meta-analyses have shown that drug treatment and exercise rehabilitation regimens can reduce psychological distress and postmyocardial infarction mortality and recurrence. OBJECTIVE: To question whether the addition of psychosocial interventions improves the outcome of a standard rehabilitation regimen for patients with coronary artery disease. METHODS: We performed a statistical meta-analysis of 23 randomized controlled trials that evaluated the additional impact of psychosocial treatment of rehabilitation from documented coronary artery disease. Anxiety, depression, biological risk factors, mortality, and recurrence of cardiac events were the clinical end points that were studied. Mortality data were available from 12 studies, and recurrence data were available from 10 of the 23 studies. RESULTS: The studies had evaluated 2024 patients who received psychosocial treatment vs 1156 control subjects. The psychosocially treated patients showed greater reductions in psychological distress, systolic blood pressure, heart rate, and cholesterol level (with effect size differences of -0.34 [corrected], -0.24, -0.38, and -1.54, respectively). Patients who did not receive psychosocial treatment showed greater mortality and cardiac recurrence rates during the first 2 years of follow-up with log-adjusted odds ratios of 1.70 for mortality (95% confidence interval [CI], 1.09 to 2.64) and 1.84 for recurrence (CI, 1.12 to 2.99). CONCLUSIONS: The addition of psychosocial treatments to standard cardiac rehabilitation regimens reduces mortality and morbidity, psychological distress, and some biological risk factors. The benefits were clearly evident during the first 2 years and were weaker thereafter. At the clinical level, it is recommended to include routinely psychosocial treatment components in cardiac rehabilitation. The findings also suggest an urgent need to identify the specific, most effective types of psychosocial interventions via controlled research.

Coronary Disease↗

PubMed1996

The importance of quality of primary studies in producing unbiased systematic reviews.

BACKGROUND: Traditional and largely qualitative reviews of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment. The latter approach is dependent on the quality of primary studies, which may introduce bias if they are of poor methodologic quality. OBJECTIVE: To test the hypothesis that the inclusion of poor-quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect. METHODS: An overview of randomized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis. Data sources included online searching of MEDLINE and Science Citation Index databases between 1966 and 1994, scanning the bibliography of known primary studies and review articles, and contacting experts in the field. After independent, blind assessment, nine of 149 originally identified studies met the inclusion criteria and were selected. We assessed study quality independently. Outcome data from each study were pooled and statistically summarized. RESULTS: There was a marginal improvement in pregnancy rate with antiestrogen treatment (odds ratio, 1.6; 95% confidence interval, 0.9 to 2.6). Sensitivity analyses on the basis of methodologic quality demonstrated that poor-quality studies produced a positive effect with treatment, whereas no benefit was observed with high-quality studies. CONCLUSION: The results of a meta-analysis are influenced by the quality of the primary studies included. Methodologically, poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences.

Bias↗

PubMed1996

Meta-analysis, clinical trials, and transferability of research results into practice. The case of cholesterol-lowering interventions in the secondary prevention of coronary heart disease.

OBJECTIVE: To evaluate, in the comprehensive scenario of "evidence-based" medicine, the transferability of the results of published randomized clinical trials and meta-analyses on cholesterol-lowering interventions to clinical practice. METHOD: Overview of randomized clinical trials on cholesterol-lowering interventions in the secondary prevention of coronary heart disease. RESULTS: The present overview on secondary prevention of coronary heart disease included 34 trials with cholesterol-lowering interventions in 24968 individuals. There was a 12.5% mortality in the group that was allocated active intervention and a 17.2% mortality in the control group (risk reduction, 13%; 95% confidence interval, -19% to -6%). Coronary and cardiovascular odds of deaths were significantly reduced. No clear association was found between noncoronary mortality and cholesterol-lowering interventions. Baseline total cholesterol levels had no clear influence on total mortality. Intermediate (10%-20%) and high ( > 20%) total cholesterol reductions were associated with similar reductions in the odds of death (-23% and -30%, respectively). No conclusion could be reached for patients who were less represented in the studies (ie, women and elderly persons). Patients with more complicated baseline clinical conditions (eg, congestive heart failure) had little nonsignificant benefit from cholesterol-lowering interventions. CONCLUSIONS: The effect of cholesterol-lowering interventions at least in the secondary prevention of coronary heart disease can be considered as established, but the transferability of such results to real-life patients remains the critical, unanswered question.

Anticholesteremic Agents↗

PubMed1996

Lung cancer.

In small cell lung cancer, combination chemotherapy including platinum compounds (cisplatin and carboplatin) and the podophyllotoxins (teniposide and etoposide) continues to be the backbone of therapy. Complete plus partial responses to combination chemotherapy occur in 80-90% of all patients. Median survival is at present 11-17 months depending on the initial tumour stage. Overall 5-year survival is approximately 5%. The duration of treatment has been shortened to 5-6 months. The results of the use of hematopoietic growth factors have hitherto been disappointing with respect to survival, while a definite effect on the degree and number of infections has been documented, when aggressive chemotherapy is administered. For epidermoid-, adenoid- and large cell carcinoma, results are emerging indicating that preoperative and preirradiatory chemotherapy in stage IIIa non-small cell lung cancer might have a substantial role in the overall management based on results from phase III trials. The studies are, however, rather modest in number and longer follow-up is necessary before recommendations for general use can be made. For patients with advanced non-small cell lung cancer (stage IIIb and IV), meta-analyses have yielded a small survival benefit (6 weeks) in favour of patients receiving chemotherapy vs. best supportive care. The treatment of this type of NSCLC should, however, still be considered to be experimental in order to define new innovative treatments. No improvement of the therapy of mesotheliomas has been reported.

Carcinoma, Non-Small-Cell Lung↗

PubMed1995

[How far should blood pressure be lowered in essential hypertension to optimize the results?].

Early studies of the seventies and eighties showed an inverse relationship between blood pressure reduction and incidence of complications and death. Afterwards, in the late eighties, some authors showed that reductions of diastolic blood pressure beyond 85 or 90 mm Hg increased coronary heart disease mortality (J shaped curve). Meta-analyses and recent epidemiological studies have shown that cardiovascular morbidity decreases along with reductions in diastolic blood pressure, if it is kept within normal limits (70-89 mm Hg). Cardiovascular mortality decreases significantly with blood pressure reductions of 7 to 8 mmHg. Some authors have suggested that diastolic blood pressure should be reduced to 85 mmHg or less in individuals with several cardiovascular risk factors, to obtain a better risk reduction. This hypothesis waits for confirmation from follow-up studies.

Blood Pressure↗