Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma

Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.status: publishe

Overcoming phase 1 delays: the critical component of obstetric fistula prevention programs in resource-poor countries

<p>Abstract</p> <p>Background</p> <p>An obstetric fistula is a traumatic childbirth injury that occurs when labor is obstructed and delivery is delayed. Prolonged obstructed labor leads to the destruction of the tissues that normally separate the bladder from the vagina and creates a passageway (fistula) through which urine leaks continuously. Women with a fistula become social outcasts. Universal high-quality maternity care has eliminated the obstetric fistula in wealthy countries, but millions of women in resource-poor nations still experience prolonged labor and tens of thousands of new fistula sufferers are added to the millions of pre-existing cases each year. This article discusses fistula prevention in developing countries, focusing on the factors which delay treatment of prolonged labor.</p> <p>Discussion</p> <p>Obstetric fistulas can be prevented through contraception, avoiding obstructed labor, or improving outcomes for women who develop obstructed labor. Contraception is of little use to women who are already pregnant and there is no reliable screening test to predict obstruction in advance of labor. Improving the outcome of obstructed labor depends on prompt diagnosis and timely intervention (usually by cesarean section). Because obstetric fistulas are caused by tissue compression, the time interval from obstruction to delivery is critical. This time interval is often extended by delays in deciding to seek care, delays in arriving at a hospital, and delays in accessing treatment after arrival. Communities can reasonably demand that governments and healthcare institutions improve the second (transportation) and third (treatment) phases of delay. Initial delays in seeking hospital care are caused by failure to recognize that labor is prolonged, confusion concerning what should be done (often the result of competing therapeutic pathways), lack of women’s agency, unfamiliarity with and fear of hospitals and the treatments they offer (especially surgery), and economic constraints on access to care.</p> <p>Summary</p> <p>Women in resource-poor countries will use institutional obstetric care when the services provided are valued more than the competing choices offered by a pluralistic medical system. The key to obstetric fistula prevention is competent obstetrical care delivered respectfully, promptly, and at affordable cost. The utilization of these services is driven largely by trust.</p

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group