Metaanalytic revision of endpoints.
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Empirical antifungal treatment (EAT) in neutropenia is mainly aimed at improving the poor prognosis of patients with invasive fungal infection through early treatment. The Infectious Diseases Society of America recommends initiating EAT in patients with persistent fever after 5-7 days of antibacterial treatment, and in those in whom remission of neutropenia is not imminent. Nevertheless, EAT has not been shown to be more effective than a placebo, it does not show better results than directed antifungal treatment, its effectiveness is minimal, it is not innocuous, and it is not very efficient with the use of most antifungal agents. All considered, we believe that the aforementioned recommendation for EAT treatment is unjustified. In its place we propose the application of EAT in patients selected on the basis of clinical criteria and risk factors.
Pharmaceuticals represent an increasing share of private and public health care expenditures. However, while most governments are interested in ensuring availability and access to drugs, the issue of adequate use of drugs remains a low priority in most third world countries. This paper summarizes the results of interventions conducted in developing countries aimed at improving patients' compliance with the advice of health professionals and/or to decrease the unnecessary use of drugs by the general population. Forty-five studies were identified through literature searches and networking; and only about a third of them fulfilled the eligibility criteria for inclusion in the review. Given the paucity of information available and the importance of the topic the authors report on all 45 studies identified. Although much remains to be explored there are several interventions that deserve to be highlighted. The authors argue that improving the use of pharmaceuticals through interventions directed only to consumers may have a small impact and suggest that in order to obtain meaningful changes it might be necessary to design interventions to modify the behavior of all the actors in the medication cycle (manufacturers, health professionals, retailers, consumers and governments). They suggest that the extraordinary therapeutic effects of antibiotics, coupled with the problems that may arise when they are inappropriately used and with the extraordinary amount of resources spent on antibiotics worldwide justify a global effort to reduce their inappropriate use and promote their adequate administration. The complexity of this type of intervention would require the support of the pharmaceutical industry, governments, private foundations, and international organizations.
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Psoriatic arthritis is an inflammatory and possibly destructive form of arthritis. As in rheumatoid arthritis and ankylosing spondylitis, the use of biological therapy in psoriatic arthritis is a therapeutic revolution: both articular and cutaneous efficacy have been shown, and some improvement is visible on radiography. The benefit-risk ratio will improve when we learn to identify more accurately the patients likely to benefit from these treatments.
Over the past decade, new biological therapies have been developed to treat systemic autoimmune diseases. These new treatments, which target various steps of the immune response, include: B lymphocyte (BL) inhibitors, such as anti-CD20 monoclonal antibodies, BlyS antagonists, and tolerogens that inhibit specific BLs that produce pathogenic antibodies; inhibitors of costimulation between antigen-presenting cells and T lymphocytes (TL), such as monoclonal antibodies against CD40 ligand and CTLA4-Ig (abatecept); TL antagonists, which can inhibit proliferation of autoreactive T cells; cytokine antagonists; chemokine and adhesin antagonists, which inhibit trafficking of immunocompetent cells to target organs. These new approaches are based on a deeper understanding of the autoimmune response.
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The validity of meta-analyses has recently been examined by comparing their results with those of megatrials on the same topic. We investigated the reliability of this gold standard by identifying megatrials, defined as ones involving more than 1000 subjects, in the recent issue of the Cochrane Library and in the article by LeLorier et al. (N Engl J Med 1997;337:536-42). In the former set, 289 pairs of megatrials were identified which studied the same patient-intervention-outcome combinations. Of these, 210 (73%, 95% CI: 67-77%) reported odds ratios or weighted mean differences that were not statistically significantly different from each other. The agreement of statistical conclusions regarding outcomes was a quadratic weighted kappa of 0.40 (95% CI: 0.29-0.51). The article by LeLorier et al. yielded 133 comparisons, of which 97 (73%, 95% CI: 64-79%) reported mutually compatible odds ratios. The agreement of statistical conclusions was a kappa of 0.33 (95% CI: 0.18-0.47). Agreement among megatrials was approximately as large as that reported between meta-analyses and megatrials. These findings suggest that taking megatrials as the gold standard can be problematic and that there is no substitute for clear and hard thinking for any study, be it a meta-analysis or a megatrial.
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The use of beta-blockers in addition to digoxin, diuretics, and ACE inhibitors was shown to be beneficial for patients with chronic heart failure. Benefits include decreased hospitalizations, decreased need for heart transplant, and decreased mortality. The fact that beta-blockers may improve a sense of well-being, as well as quality of life, for patients with chronic heart failure, is perhaps the greatest advantage to including these drugs in HF therapy.
The Brief Psychiatric Rating Scale (BPRS) anxiety/depression subscore has been used to assess affective symptoms in three studies (n = 612) comparing amisulpride (400-800 mg/day, n = 339) with haloperidol (15-20 mg/day, n = 160) and risperidone (8 mg/day, n = 113) in the treatment of acute exacerbations of schizophrenia. At endpoint, the mean improvement in the anxiety/depression subscore showed a significant (P = 0.011) difference in favour of amisulpride (5.6+/-6.1) compared with haloperidol (4.4+/-5.5) and risperidone (3.7+/-4.7). Amisulpride provided a significantly greater improvement compared both to haloperidol and risperidone in more severely depressed patients (BPRS anxiety/depression subscore > or = 16 at baseline, P = 0.001). This significant advantage in favour of amisulpride is seen from the 2nd week of treatment.
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