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PubMed1996

Implications of the links between hypertension and myocardial infarction for choice of drug therapy in patients with hypertension.

Meta-analyses of major outcome trials have demonstrated that the benefits of antihypertensive treatment for reduction of the incidence of stroke are entirely consistent with the benefits predicted from epidemiologic data; however, there remains a shortfall in the expected reduction of the incidence of coronary heart disease. Several explanations have been proffered to account for this shortfall, including the potential deleterious metabolic effects of long-term antihypertensive treatment; this has led to the speculation that antihypertensive agents with beneficial ancillary properties might confer additional significant advantage. However, with the exception of the angiotensin-converting enzyme inhibitors, few of these agents have translated into clinical benefit for humans. In addition, sound reasons exist to justify a focus on maintaining and improving the "quality" of blood pressure control. Current evidence suggests that optimal benefit is likely to result from the use of pharmacologic strategies that lower blood pressure consistently over a 24-hour period while at the same time maintaining the "normal" circadian pattern of blood pressure. This result will only be achieved with drugs and drug regimens that genuinely offer long duration of action with the additional potential benefit of maintaining a significant blood pressure lowering effect beyond the end of the dosage interval. This factor is particularly important because many patients with hypertension demonstrate poor adherence to prescribed dosage regimens.

Antihypertensive Agents↗

PubMed1995

[Magnesium sulfate in acute myocardial infarction].

Magnesium sulphate has antiarrhythmic and antithrombotic properties, a coronary and systemic vasodilating action, a direct myocardial protective effect in experimental and clinical models of ischemia-reperfusion injury. Two meta-analyses have pooled the results of several small studies that had analyzed the effect of controlled hypermagnesiemia in acute myocardial infarction before the advent of thrombolytic and antithrombotic therapies. The results have shown a more than 50% mortality reduction, with a minimum estimated benefit of about 30%, and a reduction in ventricular arrhythmias of about 50%. In LIMIT-2, a double-blind trial of 2,316 patients where magnesium was administered as a 8 mMol bolus followed by a 24-hour infusion of 65 mMol, a 24% reduction in mortality was observed. However, these data have not been confirmed in the more than 58,000 patients of the ISIS-4 trial. In this study magnesium, at the same dose of the LIMIT trial, did not reduce 5-week mortality, neither in the general population (7.64% versus 7.24% in control patients, p = n.s.) nor in specific subgroups. The results of ISIS-4 have excluded the routine use of magnesium sulphate in acute myocardial infarction in the era of fibrinolysis and aspirin, beta-blockers and ACE-inhibitors. Nevertheless, magnesium administration could still be considered in certain clinical situations, such as 1) the presence of contraindications to fibrinolysis and aspirin, 2) the treatment of ventricular tachyarrhythmias unresponsive (or as an alternative) to lidocaine, 3) severe hypertension when beta-blockers are not indicated.

Adrenergic beta-Antagonists↗

PubMed1995

Integration of vinorelbine into chemotherapy strategies for non-small-cell lung cancer.

Meta-analyses of randomized clinical studies comparing combination chemotherapy versus "best supportive care" for advanced non-small-cell lung cancer have revealed a small, but statistically significant survival advantage for patients who receive chemotherapy. However, overall increases in lifespan have been short, and the great majority of patients die within 1 year of diagnosis. In the last few years, several new drugs with promising activity have been identified. Of these, vinorelbine has already been shown to increase survival rates in randomized clinical trials. In particular, one such trial showed the combination of vinorelbine and cisplatin to result in statistically superior survival rates, compared with "standard" therapy of cisplatin and vindesine, and with single-agent vinorelbine. A second study comparing vinorelbine to fluorouracil/leucovorin also demonstrated a survival benefit for patients treated with vinorelbine. Therefore, the combination of vinorelbine and cisplatin represents one new option for initial therapy of newly diagnosed stage IV non-small-cell lung cancer.

Antineoplastic Agents↗

PubMed1996

The importance of diet and physical activity in the treatment of conditions managed in general practice.

Evidence from meta-analyses, physiological data and individual studies suggests that diet and exercise are important in the aetiology and treatment of many of the conditions that are managed predominantly in primary care (hypercholesterolaemia, hypertension, diabetes, obesity and excess alcohol intake). However, much of the evidence comes from outside primary care, and it is doubtful whether those studies done in primary care used optimal intervention strategies. A priority for future research should be to demonstrate the feasibility, efficacy and efficiency of lifestyle interventions in a general practice setting.

Adult↗

PubMed1996

Adjuvant drug therapy for operable breast cancer.

Breast cancer-the most common malignancy of lethal potential for women in the developed world-presents as two interrelated problems: (1) local disease in the breast and axillary lymph nodes, and (2) micrometastatic disease in distant sites. During the last century, advances in surgery and radiotherapy have led to high rates of control over local disease. In addition, heightened public awareness and the more widespread use of mammography have led to the more frequent detection of smaller cancers with better prognosis. Nevertheless, the problem of distant recurrence, leading almost inevitably to death, persists. Hence, there is considerable interest in integrating systemic therapy, which since mid-century has been shown to be active against advanced disease, into the treatment of primary breast cancer. The long-standing theoretical prediction of benefit from drug therapy as an adjunct to local control procedures has now been confirmed by several decades of clinical investigation. Long-term follow-up of seminal trials and the conduct of a crucial series of meta-analyses have established the ability of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. Although the relative and absolute influences of drug therapies remain modest, if these were properly applied to the hundreds of thousands of patients diagnosed worldwide per year, the potential impact on public health would be significant. In addition, recent laboratory advances and clinical trial data have indicated several new directions that promise greater impact against occult disseminated disease. These include novel dosing and scheduling strategies, newer active agents, fresh biochemical targets, and different combinations of chemotherapy with hormonal therapy.

Age Distribution↗

PubMedDate not supplied

[Psychotherapy in children and youths].

Child and adolescent psychotherapy form a large proportion of the total amount of psychotherapeutic efforts. Because of the age of the patients, the positive or negative impact is considerable. From the literature we learn that the efforts made to evaluate psychotherapy effects are not in balance with the amount of executed therapies. Meta-analyses of the available controlled therapy-evaluation studies offer a limited but rather encouraging view on the effectiveness of child and adolescent psychotherapy. Also on the differences in effectiveness according to the therapeutic orientation or the treated disturbance some interesting conclusions can be drawn. Unfortunately, these conclusions are based on a limited number of studies, because few clinicians conduct systematic research on therapy effectiveness. Systematic therapy evaluation requires some explicit decisions. The clinician has to decide on the description of the disturbance and the use of a diagnostic system, on the choice of standardized assessment procedures, on the operationalization of his therapeutic techniques and on the availability of norm groups and/or appropriate control conditions. In our psychology and psychotherapy training programs, attention for therapy evaluation is rather limited. Only a small number of students or trainees is explicitly trained in this aspect of therapeutic work. The available literature offers some interesting suggestions to enhance the quantity and the quality of the research in this area.

Adolescent↗

PubMed1996

[Risk of second primary cancer in two-year survivors of small cell lung cancer].

A total of 498 patients with small cell lung cancer received chemotherapy with or without chest irradiation at Osaka Prefectural Habikino Hospital from October 1977 through December 1991. Sixty-one who survived for more than two years were evaluated to determine the incidence and anatomic patterns of redevelopment of small cell lung cancer and development of second primary cancers. The numbers of expected cancers were estimated by cumulating person years of observation from 2 years after the start of treatment for small cell lung cancer to the date of death. Second primary cancers were observed in seven patients (four cases of non-small cell lung cancer, two of gastric cancer, and one of prostate cancer). The risk of a second primary cancer was 3.2 times greater than in the general population (95% Cl: 1.3-6.6). the relations between occurrence of a second primary cancer and family history of cancer, smoking history, smoking cessation after treatment of small cell lung cancer, and thoracic irradiation were studied. Occurrence of a second primary cancer correlated with family history (relative risk 7.5, 95% Cl: 1.5-22) and smoking cessation (relative risk 3.2, 95% Cl: 1.2-6.9). Long-term survivors were more likely to have a second primary cancer than a relapse of small cell lung cancer. Therefore, long-term survivors should be closely monitored for second primary cancers. Meta-analyses of studies done at several institutions may provide more detailed information on the occurrence of second primary cancers after small cell lung cancer.

Adenocarcinoma↗

PubMed1996

Calcium channel blockers in the dock: innocent or guilty?

Several studies have recently been published which have raised doubts over the long-term safety of calcium channel blockers (CCB). These have included retrospective case control studies in hypertension and meta-analyses of small scale studies in unstable angina and myocardial infarction (MI). Most of the reports were primarily concerned with the use of the short acting dihydropyridine nifedipine. Despite wide media coverage of these reports, the results are by no means irrefutable and, because of the nature of the studies themselves, are open to several criticisms. Calcium channel blockers are currently being evaluated in large-scale, prospective, randomised controlled studies, but results are unlikely to be available within the next few years. Meanwhile, the consensus view seems to be that short acting dihydropyridines should in general be avoided and have no place in the management of unstable angina and post MI. In the setting of stable angina, long acting dihydropyridines should generally be used in conjunction with a beta-blocker. In hypertensive patients, long acting dihydropyridines may be used as alternative antihypertensive agents in patients in whom the first line agents (diuretics and beta-blockers) are poorly tolerated, contra-indicated or ineffective.

Calcium Channel Blockers↗

PubMed1996

Geriatric work-up in the Nordic countries. The Nordic approach to comprehensive geriatric assessment.

A group established by the Nordic professors of geriatrics has developed a position document presenting a shared and updated review of geriatric work-up as a way of comprehensive geriatric assessment in the Nordic countries. The main intention is that the document will serve as support and help for the clinician concerned with hospital based geriatric medicine. It may also be useful for quality control and teaching. Not least, it may be useful for health professionals other than geriatricians. To some extent, the position of geriatric medicine in the Nordic countries varies between the countries. However, the background for developing a Nordic version of geriatric work-up is shared attitudes and principally the same organization of the health care system, and collaboration within geriatrics for many years. Several trials on comprehensive geriatric assessment and management performed in different settings have shown favourable outcomes. Results from controlled Nordic trials are compiled and summaries of meta-analyses are presented. The concept of Nordic geriatric work-up is based on a model defining health and disease in old age as dimensions of pathology, impairments, functional limitations, and disability, all being modified by extra- and intraindividual factors. Handicap is defined as the disability gap. Different health professionals have varying responsibilities in the geriatric team-work, but all should be dedicated to establish common goals. The geriatric work-up is presented with success factors and barriers, stating important differences between multidisciplinary and interdisciplinary processes. Checklists and assessment scales may be very useful when performing a geriatric work-up, but they should be used with caution. Specific scales covering different functional areas of the geriatric patient are recommended for clinical practice. Such scales must be valid, reliable, acceptable to the patient, responsive to change, and should be in an appropriate format, as well as easy to administer. Prior to the use among geriatric teams in the Nordic countries the scales should be translated into all the Nordic languages, and the translated versions should ideally have been subjected to validity and reliability testing. However, so far no scale meets these demands regarding all the five Nordic languages.

Aged↗

PubMed1996

Controversies: synthetic or natural surfactant treatment for respiratory distress syndrome? The case for synthetic surfactant.

The choice of surfactant for prophylactic or "rescue" treatment of RDS is dependent on a number of different considerations: a) Randomised controlled trials have shown that natural and synthetic surfactants increase survival whether used prophylactically or as rescue. No statistically significant difference in mortality has been shown when the two types of surfactant have been compared in randomised trials. b) Possible adverse effects of surfactant treatment include: (i) Intraventricular haemorrhage (IVH). Two randomised trials of natural surfactant have shown a significant increase in IVH with natural surfactant treatment. In meta-analyses, IVH has not been significantly reduced despite decreased mortality. Acute changes in cerebral haemodynamics and EEG have been demonstrated following natural surfactant administration. These changes are less marked or absent with synthetic surfactant. (ii) The antigenicity of animal surfactant has not been shown to have clinical consequences. (iii) Prions are infectious particle (resistant to some sterilising techniques) which are responsible for slow encephalopathies, some of which have crossed species barriers. Contamination of bovine surfactant with prion particles from nervous tissue has been a theoretical concern. Synthetic surfactant has no risk of prion contamination. (iv) One natural surfactant has been shown to contain platelet activating factor (PAF). Synthetic surfactants can be made with greater chemical purity. c) Natural surfactants improve oxygenation faster than do synthetic surfactants. A rapid effect is not necessarily better with respect to later outcomes. d) Synthetic surfactant preparations are generally cheaper per dose than natural surfactant preparations. Synthetic surfactant treatment increases survival with less concern about adverse effects and generally lower cost per dose than natural surfactant.

Cerebrovascular Circulation↗

PubMed1996

Infection and prematurity: evidence-based approaches.

The real cost savings arising from effectively preventing or treating preterm birth ascribable to prevalent reproductive tract infections are demonstrated in the lives of children saved from premature death and personal, biologic and economic impairment. Three meta-analyses demonstrate neonatal and maternal benefits from adjunctive antibiotic treatment of mothers suffering preterm premature rupture of membranes. The effects of adjunctive antibiotic treatment of women with preterm labor are inconsistent, but single-agent regimens using erythromycin and clindamycin are effective and provide coverage for group B streptococcus. Providers and payers now have evidence-based, clinically proven and cost-saving opportunities to prevent important numbers of preterm births, as well as preventing individual children suffering from being 'born too soon'.

Anti-Bacterial Agents↗

PubMed1996

Who needs antiplatelet therapy?

A series of overviews or meta-analyses of randomized clinical trials prepared by the Antiplatelet Trialists' Collaboration were published in the British Medical Journal in January 1994. They demonstrated that prolonged courses of medium-dose aspirin were very effective at preventing both fatal and non-fatal myocardial infarction and stroke in patients at high risk of occlusive vascular disease. The aim of this review is to provide the general practitioner with a practical guide to the use of aspirin in patients at high and low risk of occlusive vascular disease and to discuss appropriate dosages and contraindications to treatment in the light of all the recent evidence.

Aspirin↗

PubMed1996

Random versus nonrandom assignment in controlled experiments: do you get the same answer?

Psychotherapy meta-analyses commonly combine results from controlled experiments that use random and nonrandom assignment without examining whether the 2 methods give the same answer. Results from this article call this practice into question. With the use of outcome studies of marital and family therapy, 64 experiments using random assignment yielded consistently higher mean post-test effects and less variable posttest effects than 36 studies using nonrandom assignment. This difference was reduced by about half by taking into account various covariates, especially pretest effect size levels and various characteristics of control groups. The importance of this finding depends on (a) whether one is discussing meta-analysis or primary experiments, (b) how precise an answer is desired, and (c) whether some adjustment to the data from studies using nonrandom assignment is possible. It is concluded that studies using nonrandom assignment may produce acceptable approximations to results from randomized experiments under some circumstances but that reliance on results from randomized experiments as the gold standard is still well founded.

Family Therapy↗

PubMed1996

[Large trials in the secondary prevention of stroke].

To date, no drug has been demonstrated as efficacious in the treatment of acute ischemic stroke. Therefore, primary and secondary prevention play a fundamental role. Besides adequate control of risk factors, trials and meta-analyses have demonstrated that both medical and surgical therapy are effective in secondary prevention of stroke. In patients with atherothrombotic transient ischemic attack (TIA) or minor stroke and carotid stenosis > 70%, surgical therapy (endarterectomy) is the treatment of choice, while antiplatelet drugs are the elective treatment in the case of stenosis < 70%. Acetylsalicylic acid is the first choice medical treatment, but the optimal dosage is still a matter of debate. Ticlopidine has an efficacy similar to that of aspirin, but shows a certain number of side effects; recently a European study has shown the efficacy of dipyridamole, and the superiority of the combination dipyridamole-aspirin vs low-dose aspirin. In the secondary prevention of cardioembolic stroke, oral anticoagulants have higher efficacy than antiplatelet drugs, at least in selected groups of patients.

Anticoagulants↗

PubMed1996

Renal protection and angiotensin converting enzyme inhibition in microalbuminuric type I and type II diabetic patients.

BACKGROUND: Many studies have emphasized the role of antihypertensive drugs and in particular angiotension converting enzyme (ACE) inhibitors in the retardation of diabetic nephropathy. Although these studies have focused predominantly on patients with overt proteinuria, more recently a number of investigators have explored the role of ACE inhibitors in both type I and type II diabetic patients with an earlier phase of diabetic renal disease known as microalbuminuria. These agents are now being considered as renoprotective agents not only in hypertensive patients but also in those with 'normal' blood pressure. Initially, studies in type I diabetic patients showed that ACE inhibition was effective in retarding the increase in albuminuria which was observed in placebo treated groups. More recently, several multi-centre placebo controlled studies have been performed suggesting that prolonged treatment not only reduced albuminuria but also preserved renal function. The role of ACE inhibition in microalbuminuric type II diabetic patients is less well characterised although several studies have recently described beneficial effects of ACE inhibition on albuminuria and possibly on renal function. REVIEW: Although ACE inhibitors have been clearly shown to reduce urinary albumin excretion in diabetic patients, the issue as to whether they confer a specific benefit over other classes of antihypertensive agents remains controversial. Several meta-analyses have suggested that ACE inhibitors are more potent at decreasing albuminuria or proteinuria than other antihypertensive agents, for a given reduction in blood pressure. The Melbourne Diabetic Nephropathy Study Group has instituted a study which is placebo-controlled and is confined to normotensive type I and type II diabetic patients. The ACE inhibitor perindopril has been compared not only with placebo but also with the dihydropyridine calcium channel blocker, nifedipine. Preliminary analysis reveals that after 12 and 24 months of treatment, perindopril is more effective in reducing albuminuria than placebo or nifedipine. CONCLUSION: ACE inhibitors are a promising class of antihypertensive agents in diabetic patients with microalbuminuria. These drugs should be considered as first line agents in such patients, even in the absence of systemic hypertension.

Albuminuria↗

PubMed1997

Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis.

OBJECTIVE: To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major disease end points. DATA SOURCES: MEDLINE searches and previous meta-analyses for 1980 to 1995. DATA SELECTION: We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controlled randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluated multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies. DATA SYNTHESIS: Diuretics and beta-blockers have been evaluated in 18 long-term randomized trials. Compared with placebo, beta-blocker therapy was effective in preventing stroke (relative risk [RR], 0.71; 95% confidence interval [CI], 0.59-0.86) and congestive heart failure (RR, 0.58; 95% CI, 0.40-0.84). The findings were similar for high-dose diuretic therapy (for stroke, RR, 0.49; 95% CI, 0.39-0.62; and for congestive heart failure, RR, 0.17; 95% CI, 0.07-0.41). Low-dose diuretic therapy prevented not only stroke (RR, 0.66; 95% CI, 0.55-0.78) and congestive heart failure (RR, 0.58; 95% CI, 0.44-0.76) but also coronary disease (RR, 0.72; 95% CI, 0.61-0.85) and total mortality (RR, 0.90; 95% CI, 0.81-0.99). Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure in hypertensive patients, the clinical trial evidence in terms of health outcomes is meager. For several short-acting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulations and the nondihydropyridine calcium channel blockers are safe and prevent major cardiovascular events in patients with hypertension remains untested and therefore unknown. CONCLUSION: Until the results of large long-term clinical trials evaluating the effects of calcium channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and beta-blockers as firstline agents and low-dose therapy for all antihypertensive agents.

Adrenergic beta-Antagonists↗

PubMed1997

[Behavior and cognitive treatments for insomnia. An alternative to pharmacotherapy].

OBJECTIVE: To familiarize family physicians with cognitive and behavioural treatments for insomnia. DATA SOURCES: MEDLINE was searched from 1983 to 1995 and Psychlit from 1974 to 1995 using the key words "behaviour therapy," "cognitive therapy," "phototherapy," and "insomnia." STUDY SELECTION: We chose randomized trials and meta-analyses on the treatment of insomnia. Information was extracted on time-lag before sleep, frequency and duration of wakeful periods during the night, consumption of hynotics, and subjects' own assessment of their sleep before and after treatment. SYNTHESIS: The most effective interventions were relaxation training, sleep restriction, and stimulus control. Practising good sleeping habits was only somewhat effective and should always be used in conjunction with other interventions. CONCLUSION: Stimulus control for insomnia has been demonstrated to be effective when used by primary care physicians. Other nonpharmacologic treatments should be evaluated in a similar manner.

Behavior Therapy↗

PubMed1997

Cognitive-behavioral therapy for panic disorder: current status.

Controlled clinical trials evaluating cognitive-behavioral approaches for panic disorder are rapidly accumulating. In the aggregate, these studies suggest substantial efficacy for cognitive-behavioral approaches in both the short and long term. Summaries and meta-analyses of these results are briefly described, but new evidence is also presented indicating that, in this chronic condition, patients continue to experience some exacerbations and remissions over the long term. Current attempts to evaluate combination psychosocial and pharmacologic approaches are described as well as the beginnings of efforts to develop more powerful treatments for panic disorder with or without agoraphobia.

Alprazolam↗