The Effect of Statins on Mortality in Septic Patients: a Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. DATA SOURCES AND STUDY SELECTION: Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. DATA EXTRACTION AND SYNTHESIS: Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. CONCLUSIONS: Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.

Estudo Comparativo, Aleatorizado, em Dupla Ocultação, de Orlistat Versus Placebo, de Eficácia e Segurança, em Doentes Obesos com Hipercolesterolemia Ligeira a Moderada

INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

Budesonide Reverses Lung Hyperinflation in Childhood Asthma: a Controlled Study

Budesonide (800 mg bid, for 2 months) was administered to 12 asthmatic children (mean age, 11.293.3 years) with lung hyperinflation (TGV]130% predicted and:or RV]140% predicted) in a randomised, placebo controlled, double blind, crossover study. Body plethysmography (panting frequency controlled at 1·s 1) was performed at the beginning, 2 months afterwards (before crossover) and at the end of the study. Budesonide significantly reduced TGV (2.3590.90 l BTPS or 126924% predicted) compared with placebo (2.5491.08 l BTPS, P 0.014 or 140921% predicted, PB0.05). In addition, budesonide significantly increased mean specific conductance (0.0690.02 cm H2O 1 l s 1 to 0.0790.01 cm H2O 1 l s 1, PB0.05). It was concluded that budesonide reduced lung hyperinflation most likely by decreasing airway inflammation.

Safety and Efficacy of Oral Fexofenadine in Children with Seasonal Allergic Rhinitis - a Pooled Analysis of Three Studies

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

Infecções Urinárias e Gravidez - Diagnóstico, Terapêutica e Prevenção

Objectives: Literature review of classification, epidemiology, pathophysiology, microbiology, clinical presentation, diagnosis, complications, treatment and prevention of urinary tract infections (UTI) in pregnancy. Data Sources and Review Methods: Bibliographic research in Medline, through PubMed and Medscape, of systematic reviews, observational studies, clinical guidelines, meta-analyses and randomized controlled trials published between January 1992 and December 2010. Results: Asymptomatic bacteriuria occurs in 2 to 10% of pregnant women, 30% of which will develop acute pyelonephritis if left untreated. Treatment of asymptomatic bacteriuria has been shown to reduce the risk of pyelonephritis in pregnancy. Therefore, screening and treatment of this form of UTI has become a standard of obstetrical care, although the ideal duration of the treatment is still controverse. Acute pyelonephritis is one of the most common medical complications of pregnancy and may be associated with maternal, obstetric and perinatal complications. There is no clear consensus in the literature regarding antibiotic choice or duration of therapy for symptomatic UTI. Increasing antibiotic resistance complicates the choice of empirical regimens and local resistance rates need to be taken into account when deciding the therapy. Considering the high rate of recurrence of UTI during pregnancy, prophylactic measures need to be taken in pregnant women who have already experienced UTI during their current pregnancy. Conclusions: Although UTI is a generally benign condition in non-pregnant women, it may be a potentially serious complication during pregnancy. Early diagnosis and treatment of UTI during pregnancy are mandatory and can prevent severe maternal and perinatal complications.

Laserterapia de Baixa Potência no Tratamento de Úlceras Diabéticas. Um Problema de Evidência

Introdução: A Diabetes Mellitus representa a principal causa de amputação dos membros inferiores, com importantes custos económicos para os serviços de saúde. O principal factor de risco para a amputação é o desenvolvimento de úlceras diabéticas, sendo acompanhada de uma elevada taxa de mortalidade aos cinco anos. A isquemia por afecção do território macrovascular é um factor fisiopatológico essencial no desenvolvimento de úlceras isquémicas. Os tratamentos existentes são prolongados e associados a elevadas taxas de insucesso e recidiva, exigindo a combinação de múltiplas modalidades terapêuticas. A laserterapia de baixa potência tem sido usada como terapêutica adjuvante do pé diabético, desde a década de 60 do século XX, devido aos seus hipotéticos efeitos estimuladores da microcirculação e da reparação tecidular. Material e Métodos: Identificação de estudos científicos publicados através de uma pesquisa bibliográfica da Pubmed, The Cochrane Library e Cochrane Controlled Trials Register. Discussão e Conclusões: A evidência existente é favorável para modelos celulares in vitro, mas conflituosa em modelos animais e populações humanas. Existe uma grande heterogeneidade metodológica, que pode ser responsável pelos resultados discordantes. São propostas orientações para estudos futuros neste âmbito, nomeadamente a caracterização detalhada das úlceras e os parâmetros de tratamento com laser. São necessários estudos bem controlados, duplamente ocultos e aleatorizados. Seguindo o primum non nocere, a laserterapia pode ser utilizada como terapêutica adjuvante no tratamento do pé diabético, uma vez que é incruenta, de rápida aplicação e de baixo custo, sem efeitos adversos significativos.

Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.

Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study)

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype.