Traitement pharmacologique de la schizophrénie: évaluation comparative de la qualité des recommandations de pratique clinique [Comparative evaluation of clinical practice guidelines for the treatment of schizophrenia]

INTRODUCTION: Many clinical practice guidelines (CPG) have been published in reply to the development of the concept of "evidence-based medicine" (EBM) and as a solution to the difficulty of synthesizing and selecting relevant medical literature. Taking into account the expansion of new CPG, the question of choice arises: which CPG to consider in a given clinical situation? It is of primary importance to evaluate the quality of the CPG, but until recently, there has been no standardized tool of evaluation or comparison of the quality of the CPG. An instrument of evaluation of the quality of the CPG, called "AGREE" for appraisal of guidelines for research and evaluation was validated in 2002. AIM OF THE STUDY: The six principal CPG concerning the treatment of schizophrenia are compared with the help of the "AGREE" instrument: (1) "the Agence nationale pour le développement de l'évaluation médicale (ANDEM) recommendations"; (2) "The American Psychiatric Association (APA) practice guideline for the treatment of patients with schizophrenia"; (3) "The quick reference guide of APA practice guideline for the treatment of patients with schizophrenia"; (4) "The schizophrenia patient outcomes research team (PORT) treatment recommendations"; (5) "The Texas medication algorithm project (T-MAP)" and (6) "The expert consensus guideline for the treatment of schizophrenia". RESULTS: The results of our study were then compared with those of a similar investigation published in 2005, structured on 24 CPG tackling the treatment of schizophrenia. The "AGREE" tool was also used by two investigators in their study. In general, the scores of the two studies differed little and the two global evaluations of the CPG converged; however, each of the six CPG is perfectible. DISCUSSION: The rigour of elaboration of the six CPG was in general average. The consideration of the opinion of potential users was incomplete, and an effort made in the presentation of the recommendations would facilitate their clinical use. Moreover, there was little consideration by the authors regarding the applicability of the recommendations. CONCLUSION: Globally, two CPG are considered as strongly recommended: "the quick reference guide of the APA practice guideline for the treatment of patients with schizophrenia" and "the T-MAP".

Quoi de neuf pour le traitement de l'hépatite B [What's new in the treatment of hepatitis B infection?]

Although the number of available antiviral drugs for hepatitis B infection (VHB) today is higher than ever, treatment of chronic VHB infection is still often managed by specialists because of the complex natural history of this viral infection and of the risk of selecting viral strains that are resistant to therapy. Different clinical and virological aspects need to be considered to establish a correct indication for therapy. Once antiviral therapy has been started, patients need close monitoring to guarantee adequate compliance and to detect promptly the selection of viral variants resisting to therapy.

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing external-beam radiotherapy (EBR) and/or enucleation in patients with retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly diagnosed unilateral or bilateral Rbl received CT associated with local treatment (LT). Two to five courses of etoposide and carboplatin were administered at 3- to 4-week intervals, depending on tumor response, and were completed each time by LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients showed a complete response (CR) that persisted at a median follow-up (FU) of 31 months (range, 4 to 41 months). Among the three patients who relapsed, two were lost to FU and one died of progressive disease. CR was achieved by CT and LT alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III). Six other patients with advanced disease (groups IV and V) experienced treatment failure and needed salvage treatment by EBR and/or enucleation. The difference between the two patient groups with regard to disease stage was statistically significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who presented with groups I to III (15 eyes) and group V (one eye) disease, whereas enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined with intensive LT is effective in patients with groups I to III Rbl, permitting the avoidance of EBR in the majority of these young children and, thus, reducing the risk of long-term sequelae. This is in contrast with the disappointing results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was needed.

Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine?

In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.

Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.

BACKGROUND: A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. METHODS: In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. RESULTS: Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001). CONCLUSIONS: A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.)

Surfactant protein-D and exposure to bioaerosols in wastewater and garbage workers.

PURPOSE: Bioaerosols and their constituents, such as endotoxins, are capable of causing an inflammatory reaction at the level of the lung-blood barrier, which becomes more permeable. Thus, it was hypothesized that occupational exposure to bioaerosols can increase leakage of surfactant protein-D (SP-D), a lung-specific protein, into the bloodstream. METHODS: SP-D was determined by ELISA in 316 wastewater workers, 67 garbage collectors, and 395 control subjects. Exposure was assessed with four interview-based indicators and by preliminary endotoxin measurements using the Limulus amoebocyte lysate assay. Influence of exposure on serum SP-D was assessed by multiple linear regression considering smoking, glomerular function, lung diseases, obesity, and other confounders. RESULTS: Overall, mean exposure levels to endotoxins were below 100 EU/m(3). However, special tasks of wastewater workers caused higher endotoxin exposure. SP-D concentration was slightly increased in this occupational group and associated with the occurrence of splashes and contact to raw sewage. No effect was found in garbage collectors. Smoking increased serum SP-D. No clinically relevant correlation between spirometry results and SP-D concentrations appeared. CONCLUSIONS: These results support the hypothesis that inhalation of bioaerosols, even at low concentrations, has a subclinical effect on the lung-blood barrier, the permeability of which increases without associated spirometric changes.

Recent developments in the use of chemotherapy in brain tumours.

Several recent studies have further clarified the role of chemotherapy in newly diagnosed anaplastic glioma. For newly diagnosed glioblastoma, combined daily radiotherapy with daily temozolomide followed by six cycles of adjuvant temozolomide improves overall survival. This benefit is especially observed in patients with a methylated promotor of the MGMT gene which encodes an alkyltransferase; this observation however, needs confirmation. Although oligodendroglial tumours are sensitive to chemotherapy, classical adjuvant nitrosourea-based chemotherapy does not improve overall survival in newly diagnosed anaplastic oligodendroglioma, even in the subset of 1p/19q loss tumours. It may increase progression-free survival however, and further studies must show if combined modality treatment with daily chemotherapy during radiotherapy increases survival. Trials exploring the role of chemotherapy in low-grade glioma are ongoing. No standard chemotherapy is currently available for highly anaplastic glioma failing first-line temozolomide-based therapy.

Gas emission during laparoscopic colorectal surgery using a bipolar vessel sealing device: A pilot study on four patients.

BACKGROUND: Dissection during laparoscopic surgery produces smoke containing potentially toxic substances. The aim of the present study was to analyze smoke samples produced during laparoscopic colon surgery using a bipolar vessel sealing device (LigaSuretrade mark). METHODS: Four consecutive patients undergoing left-sided colectomy were enrolled in this pilot study. Smoke was produced by the use of LigaSuretrade mark. Samples (5,5l) were evacuated from the pneumoperitoneum in a closed system into a reservoir. Analysis was performed with CO2-laser-based photoacoustic spectroscopy and confirmed by a Fourier-transform infrared spectrum. The detected spectra were compared to the available spectra of known toxins. RESULTS: Samples from four laparoscopic sigmoid resections were analyzed. No relevant differences were noted regarding patient and operation characteristics. The gas samples were stable over time proven by congruent control measurements as late as 24 h after sampling. The absorption spectra differed considerably between the patients. One broad absorption line at 100 ppm indicating H2O and several unknown molecules were detected. With a sensitivity of alpha min ca 10-5 cm-1 no known toxic substances like phenol or indole were identified. CONCLUSION: The use of a vessel sealing device during laparoscopic surgery does not produce known toxic substances in relevant quantity. Further studies are needed to identify unknown molecules and to analyze gas emission under various conditions.

Statin-associated myasthenia gravis: report of 4 cases and review of the literature.

A few recent individual case reports have suggested that a myasthenic syndrome may be associated with statin treatment, but this association is not well described. We report 4 patients who developed symptoms of myasthenia gravis within 2 weeks of starting treatment with a statin drug. In 1 case the drug appears to have exacerbated underlying myasthenic weakness, whereas in the other 3 cases, de novo antibody formation appears to be most likely. In each case, some degree of recovery followed discontinuation of the statin medication.

Screening of the antimalarial activity of plants of the Cucurbitaceae family

Crude ethanolic extracts (CEEs) from two species of Cucurbitaceae, Cucurbita maxima and Momordica charantia (commonly called "abóbora moranga" and melão de São Caetano", respectively) were assayed for antimalarial activity by the 4-d suppressive test. The CEE of dry C. maxima seeds showed strong antimalarial activity following oral administration (259 and 500 mg/kg), reducing by 50% the levels of parasistemia in Plasmodium berghey-infected mice. Treatment of normal animals with 500 mg/Kg of the extract three days before intravenous injection of P. berghei caused a significant 30% reduction in parasitemic levels. No effect was observed when the animals were treated with the CEE only on the day of inoculation. Oral administration of the CEE of dry M. charantia leaves adminstered orally was ineffective up to 500 mg/Kg in lowering the parasitemic levels of malarious mice.

Molecular epidemiology of predominant clones and sporadic strains of methicillin resistant Staphylococcus aureus in Switzerland and comparison with European epidemic clones.

OBJECTIVE: To assess the molecular epidemiology and risk factors of predominant clones and sporadic strains of methicillin-resistant Staphylococcus aureus (MRSA) in Swiss hospitals and to compare them with European strains of epidemic clones. MATERIAL AND METHODS: One-year national survey of MRSA cases. Analysis of epidemiological and molecular typing data (PFGE) of MRSA strains. RESULTS: In 1997, 385 cases of MRSA were recorded in the five Swiss university hospitals and in 47 community hospitals. Half of the cases were found in Geneva hospitals where MRSA was already known to be endemic. Molecular typing of 288 isolates (one per case) showed that 186 (65%) belong to four predominant clones, three of which were mostly present in Geneva hospitals. In contrast, the fourth clone (85 cases) was found in 23 hospitals (in one to 16 cases per hospital). The remaining 35% of the strains were clustered into 62 pulsed field gel electrophoresis types. They accounted for one to five patients per hospital and were defined as sporadic. Multivariate analysis revealed no independent risk factors for harboring a predominant versus a sporadic strain, except that transfer from a foreign hospital increases the risk of harboring a sporadic strain (OR, 42; 95% CI, 5-360). CONCLUSION: While cases with predominant clones were due to the local spread of these clones, most sporadic cases appear to be due to the continuous introduction of new strains into the country. With the exception of a transfer from a hospital outside Switzerland, no difference in the clinical or epidemiological characteristics was observed between patients harboring a predominant clone and those with a sporadic strain.