Combination conventional DMARDs compared to biologicals: what is the evidence?

PURPOSE OF REVIEW: Dramatic improvement seen in the prognosis of rheumatoid arthritis has been driven by higher expectations, led by newer drugs and more intensive use of the older drugs. Although methotrexate has retained its place as the first-line agent, there has been great interest in comparing biologicals to conventional Disease Modifying Anti Rheumatic Drugs (DMARDs) over the past few years with the updated guidelines from both the American College of Rheumatology and European League Against Rheumatism. We have tried to critically summarize the findings of some landmark trials that compare these two approaches. RECENT FINDINGS: Treatment of Early Rheumatoid Arthritis, The Swedish Pharmacotherapy study and Rheumatoid Arthritis Comparison of Active Therapies are landmark trials that were designed to compare strategies using biologicals vs. conventional DMARDs. We will review the safety and efficacy data from these three trials here and also briefly the important cost differential. CONCLUSION: Methotrexate should be the first-line therapy for most rheumatoid arthritis patients and will produce the desired results in greater than one-third of the patients. When methotrexate is not adequate, triple DMARD therapy should be added which will result in control of approximately another one-third of the patients. Ultimately, and usually before 1 year of disease, the remainder of patients will require biological therapies usually added to conventional DMARDs. There is no evidence that this step-up approach results in any long-term disadvantage and good evidence that it results in substantial cost savings.

Diagnosis of ventilator-associated pneumonia in children in resource-limited setting: a comparative study of bronchoscopic and nonbronchoscopic methods.

OBJECTIVES: To compare the available methods for the diagnosis of ventilator-associated pneumonia in intubated pediatric patients and to suggest less costly diagnostic method for developing countries. DESIGN: Prospective study. SETTING: Pediatric intensive care unit of a tertiary care, multidisciplinary teaching hospital located in northern India. PATIENTS: All consecutive patients on mechanical ventilation for >48 hrs were evaluated clinically for ventilator-associated pneumonia. INTERVENTIONS: Four diagnostic procedures (tracheal aspiration, blind bronchial sampling, blind bronchoalveolar lavage, and bronchoscopic bronchoalveolar lavage) were performed in the same sequence within 12 hrs of clinical suspicion of ventilator-associated pneumonia. The bacterial density > or =104 colony-forming units/mL in a bronchoscopic bronchoalveolar lavage sample was taken as reference standard. MEASUREMENTS AND MAIN RESULTS: Thirty patients with 40 episodes of ventilator-associated pneumonia were included in the study. Tracheal aspirate at the cutoff of > or =105 colony-forming units/mL was found to have sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 84%, 77%, 87.5%, 73%, and 80%, respectively. For blind bronchial sampling at > or =104 colony-forming units/mL cutoff, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88%, 82%, 88%, 83%, and 87%, respectively; the most reliable results were obtained with blind bronchoalveolar lavage at the cutoff of > or =103 cfu/mL (sensitivity 96%, specificity 80%, positive predictive value 88%, negative predictive value 92%, and accuracy 90%). The area under the receiver operating characteristic curve of tracheal aspiration, blind bronchial sampling, and blind bronchoalveolar lavage was 0.87 +/- 0.06, 0.89 +/- 0.06, and 0.89 +/- 0.05, respectively. The cost of balloon-tip pressure catheter used for blind bronchoalveolar lavage was INR 1600.00 (US$40) whereas that for blind bronchial sampling was only INR 35.00 (<1 US$). CONCLUSIONS: Blind bronchoalveolar lavage was the most reliable method followed closely by blind bronchial sampling for the diagnosis of ventilator-associated pneumonia. Considering the difference of the cost in the two procedures, blind bronchial sampling may be the preferred method in the pediatric intensive care unit of a developing country.

Neighbourhood socioeconomic circumstances, adiposity and cardiometabolic risk measures in children with severe obesity.

BACKGROUND: It has recently been shown that neighbourhood socioeconomic disadvantage in childhood is associated with obesity, hypertension, fatty liver, and type 2 diabetes in adulthood. However, it is largely unknown whether neighbourhood socioeconomic circumstances are important predictors of adiposity and associated measures in children, especially in those with severe obesity. Therefore, we evaluated the associations between neighbourhood socioeconomic factors with the severity of obesity, and related cardiometabolic risk factors in a cohort of obese children. METHODS: The Childhood Overweight BioRepository of Australia (COBRA) cohort study comprises 444 children (mean age 11.1years, mean BMI z-score 2.5). Neighbourhood socioeconomic advantage/disadvantage was evaluated based on postcode information by the national Australian Socio-Economic Indexes for Areas (SEIFA) scores. Participants/parents also completed self-administered questionnaires on neighbourhood related facilities, family education and family income. RESULTS: In analyses adjusted for age, sex and pubertal status, SEIFA indicating neighbourhood education/occupation was negatively associated with BMI, waist circumference and body fat%. Higher family education was associated with lower BMI. Neighbourhood walkability was related to lower waist circumference. Good shopping facilities in the neighbourhood were associated with increased risk of dyslipidemia and fatty liver, and the existence of parks and playgrounds nearby was related to dyslipidemia. CONCLUSIONS: The present data suggest that neighbourhood-related issues are associated with less severe adiposity among children with established obesity. Concerning cardiometabolic risk factors, shopping facilities were related to dyslipidemia and fatty liver. These findings suggest that increased awareness and efforts are needed to diminish socioeconomic inequalities between neighbourhoods.