Eva Montané

Epidemiology of aplastic anemia : a prospective multicenter study

Aplastic anemia is a rare disease whose incidence varies considerably worldwide. In this study conducted in the metropolitan area of Barcelona, the overall incidence was 2.34 per million inhabitants per year. The survival rate at 2 years was 57%, confirming the severity of this condition. See related perspective article on page 489. Background Aplastic anemia is a rare and severe disease. Its incidence varies considerably worldwide. We aimed at describing the epidemiology of this disease, including the incidence, mortality and survival trends, in a well-defined population. Design and Methods Since 1980, a case-control surveillance study of aplastic anemia has been carried out by a cooperative group, in the metropolitan area of Barcelona. Inclusion is dependent on the patient having at least two of the following features: white blood cell count ≤3.5×109/L, platelet count ≤50×109/L, hemoglobin <10 g/L or hematocrit of <30%; when only one of these last two criteria is fulfilled, a reticulocyte count of ≤30×109/L is also required. The bone marrow biopsy has to be compatible with the diagnosis of aplastic anemia. Results Between 1980 and 2003, a total of 235 cases of aplastic anemia were identified. The overall incidence was 2.34 per million inhabitants per year and the incidence increased with age. Most of the cases were classified as severe or very severe aplastic anemia. Survival rates at 3 months, and at 2 and 15 years after the diagnosis were 73%, 57%, and 51%, respectively. Advanced age and more severe disese at the time of diagnosis were associated with a lower survival rate. There was a trend to a better 2-year survival rate among patients treated with bone marrow transplantation. Forty-nine cases (20.8%) were exposed to drugs reported to be associated with aplastic anemia, and 21 (8.9%) to toxic agents. Conclusions The incidence of aplastic anemia in Barcelona is low but the case fatality rate is high. Advanced age and severe disease at the time of diagnosis were associated with decreased survival.

Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI®

A Phase I interventional Clinical Trial was performed with a potential tuberculosis vaccine, based on detoxified cellular fragments of M. tuberculosis, named RUTI. The objective was to evaluate the safety profile and T-cell immune responses over a 6-month period following subcutaneous inoculation. The double-blind, randomized and placebo-controlled trial was conducted in healthy volunteers, all recruited at one site. RUTI, at each of the four tested doses, starting from 5microg and going up to 200microg, and placebo were inoculated to groups of 4 and 2 volunteers respectively, consecutively. RUTI appeared to be well tolerated as judged by local and systemic clinical evaluation, though vaccine dose dependent local adverse reactions were recorded. T-cell responses of blood lymphocytes to PPD and a number of antigen subunits were elevated, when compared with controls subjects. These results support the feasibility of future evaluation, to be targeted at subjects with latent tuberculosis infection (LTBI).

Oral antispastic drugs in nonprogressive neurologic diseases: A systematic review

Objective: To assess the efficacy of oral drugs in the treatment of spasticity in patients with nonprogressive neurologic disease (NPND). Methods: Systematic review of double-blind randomized controlled trials of antispastic oral drugs in the treatment of spasticity in NPND. Data sources: Electronic MEDLINE, PubMed, Cochrane Library, and hand searches. Results: Twelve studies (469 patients) were included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy). Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and gabapentin in one (28, all exposed). Most trials were of small size, of short duration, and their methodologic quality was inadequate. Ten trials were controlled with placebo and only two were direct comparisons between drugs. Efficacy outcome variables were heterogeneous. Only four reports described the magnitude of the antispastic effect. The incidence of adverse drug effects (drowsiness, sedation, and muscle weakness) was high. Conclusion: Evidence on the efficacy of oral antispastic drugs in NPND is weak and does not include evaluation of patients’ quality of life. If any, efficacy is marginal. Adverse drug reactions were common. Better methodologic instruments are needed for the evaluation of antispastic treatment.

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

BackgroundSeveral randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS.MethodsReports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded.ResultsA total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001).ConclusionQuality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years.

Prescribing information in 26 countries: a comparative study

This study was set up to document the variability of prescribing information from different sources concerning indications, side effects and cautions of selected drugs. An original method to measure the degree of information agreement among different written materials, such as summaries of product characteristics, package inserts and data sheets, and a widely accepted reference text was developed. The results show that there is substantial disagreement in the materials available to prescribers and patients in different countries. Disagreement was even found within a single country when written materials from different brands of the same drug were compared. The discordance can be explained by the fact that the evidence available for each drug is considered/assessed differently by separate countries. It is argued that the discrepancies found may mislead prescribers, patients and those comparing drug-use patterns across countries. National regulatory authorities have a key role to play in remedying this situation, and a two-pronged approach is proposed. At the international level, national authorities should strengthen collaboration and information interchange and, at the national level, should implement appropriate measures aimed at removing contradictory statements on drug-information materials that have no reason to be different. Finally, further training and continued education aimed at drug regulatory officials could provide the necessary knowledge and enable national authorities to meet the need for drug information that is independent of commercial interests.

Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study

Background During the last decade, the use of 5-aminolevulinic acid (5-ALA) has been steadily increasing in neurosurgery. The studys main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas’ patients. Methods National, multicenter and prospective observational study. Inclusion criteria: authorized conditions of use of 5-ALA. Exclusion criteria: contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities. Results Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%). Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance. Conclusion In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as incomplete resection was not identified as a prognostic factor risk for death. Because optimal fluorescence was correlated to higher complete resection rate, further research is needed to identify patients (or tumors) with more surgery benefits when using the 5-ALA.

Scientific drug information in newspapers: sensationalism and low quality. The example of therapeutic use of cannabinoids

ObjectiveWe aimed to analyse the quality of newspaper articles (NAs) concerning the therapeutic use of cannabis published in Spanish newspapers.MethodsA preliminary questionnaire of the Index of Scientific Quality was used [scores ranged from 0 (no misleading) to 14 (misinformation in each item)].ResultsOf the 29 NAs analysed, 16 (55.2%) were scored as 4 or lower, and 6 (20.7%) scored 7 or higher. Up to 23 NAs (79.3%) did not manage the knowledge related to cannabinoids; 20 (69%) gave a sensationalist message; 11 (37.9%) were able to wrongly influence clinical decision taking; and 8 (27.6%) misled medical concepts.ConclusionThe leading medical journals could play an especially relevant role while preparing their press releases if they specify study limitations and context.

Multiple drug interactions – induced serotonin syndrome: a case report

Serotonin syndrome is a potentially life‐threatening disorder of excessive serotoninergic activity often due to drug interactions. We report a case of serotonin syndrome induced by pharmacokinetic and pharmacodynamic interactions between three different selective serotonin‐reuptake inhibitors (SSRI) and possibly ciprofloxacin. Extreme caution is necessary in patients treated with serotonin‐reuptake inhibitors who need to be switched to another antidepressant or when they require the addition of concomitant drugs, especially serotoninergic drugs and isoenzimes of cytochrome P450 inhibitors.

Gripe A, embarazo y antivíricos inhibidores de la neuraminidasa

Following the explosion of the influenza A pandemic (H1N1) during the first semester of 2009, oseltamivir and zanamivir were used as the treatment of choice in the absence of rigorous clinical studies demonstrating their efficacy in the treatment and prophylaxis of this disease. Knowledge of seasonal influenza, flu pandemics and particularly the H1N1, which produces more severe infection and a higher mortality rate during pregnancy, led to the use of antiviral treatment despite the scarcity of clinical studies on their efficacy and effectiveness, mainly due to the influence of the media. This study reviewed the experimental and clinical studies performed on the safety of oseltamivir and zanamivir in pregnancy. Likewise, the recommendations made by the different health care and governmental authorities as well as other institutions and scientific and health care organizations on the therapeutic management and prophylaxis of influenza A 2009 in pregnant women were reviewed.

Drug‐related deaths in hospital inpatients: A retrospective cohort study

To determine the incidence of drug‐related deaths (DRD) in a university hospital in 2015, to describe their characteristics, and to discover risk factors of DRD.