Efficacy of nasal mometasone for the treatment of chronic sinonasal disease in patients with inadequately controlled asthma.

BACKGROUND: Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control. OBJECTIVE: We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively. METHODS: A 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation. RESULTS: Two hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo, and 319 participants completed the study. There was no difference in the Childhood Asthma Control Test score (difference in change with mometasone - change with placebo [ΔM - ΔP], -0.38; 95% CI, -2.19 to 1.44; P = .68; age 6-11 years) or the Asthma Control Test score (ΔM - ΔP, 0.51; 95% CI, -0.46 to 1.48; P = .30; age ≥12 years) in those assigned to mometasone versus placebo. In children and adolescents (age 6-17 years) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow. In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index (ΔM - ΔP, 0.06; 95% CI, 0.01 to 0.11; P < .01) and in nasal symptoms (sinus symptom score ΔM - ΔP, -3.82; 95% CI, -7.19 to -0.45; P = .03) but no difference in asthma quality of life, lung function, or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo. CONCLUSIONS: Treatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control. Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control.

Vitamin A and fish oils for retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP. OBJECTIVES: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2013. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating the effectiveness of vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials. DATA COLLECTION AND ANALYSIS: We pre-specified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one year; as well as mean change in visual acuity at five-year follow-up. Two authors independently evaluated risk of bias for all included trials and extracted data from the publications. We also contacted study investigators for further information on trials with publications that did not report outcomes on all randomized patients. MAIN RESULTS: We reviewed 394 titles and abstracts and nine ClinicalTrials.gov records and included three RCTs that met our eligibility criteria. The three trials included a total of 866 participants aged four to 55 years with RP of all forms of genetic predisposition. One trial evaluated the effect of vitamin A alone, one trial evaluated DHA alone, and a third trial evaluated DHA and vitamin A versus vitamin A alone. None of the RCTs had protocols available, so selective reporting bias was unclear for all. In addition, one trial did not specify the method for random sequence generation, so there was an unclear risk of bias. All three trials were graded as low risk of bias for all other domains. We did not perform meta-analysis due to clinical heterogeneity of participants and interventions across the included trials.The primary outcome, mean change of visual field from baseline at one year, was not reported in any of the studies. No toxicity or adverse events were reported in these three trials. No trial reported a statistically significant benefit of vitamin supplementation on the progression of visual field loss or visual acuity loss. Two of the three trials reported statistically significant differences in ERG amplitudes among some subgroups of participants, but these results have not been replicated or substantiated by findings in any of the other trials. AUTHORS' CONCLUSIONS: Based on the results of three RCTs, there is no clear evidence for benefit of treatment with vitamin A and/or DHA for people with RP, in terms of the mean change in visual field and ERG amplitudes at one year and the mean change in visual acuity at five years follow-up. In future RCTs, since some of the studies in this review included unplanned subgroup analysis that suggested differential effects based on previous vitamin A exposure, investigators should consider examining this issue. Future trials should take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review, in addition to previous cohort studies, when calculating sample sizes to assure adequate power to detect clinically and statistically meaningful difference between treatment arms.

Bivalirudin for anticoagulation in children.

BACKGROUND: Thromboembolism in children is typically treated with unfractionated heparin (UH) or low molecular weight heparin (LMWH). Both rely on antithrombin (AT) for their action. In addition, heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin use in children. Bivalirudin or other direct thrombin inhibitors may be a useful alternative to heparins in treating thrombosis in children. PROCEDURE: We report a retrospective review to assess the efficacy and safety of bivalirudin in pediatric patients with thrombosis. RESULTS: Sixteen children received bivalirudin for thrombosis or prevention of thrombosis at the Children's Hospital of Illinois from January 2005 to January 2007. Patients received a bolus dose of 0.25 mg/kg followed by a continuous infusion (0.16 +/- 0.07 mg kg(-1) hr(-1)) titrated to 1.5-2.5 times the baseline activated partial thromboplastin time (aPTT). Positive correlation between the bivalirudin average infusion rate and aPTT was observed in twelve patients. Ultrasonographic evidence of thrombus regression was noted at 72 hr in 10 of 10 patients. One patient experienced hematuria after catheterization of the urethra. CONCLUSION: Bivalirudin was effective and well-tolerated in these patients. Further studies should be conducted to better define safety and efficacy of bivalirudin in pediatric patients.

Correction: Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0163716.].

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

BACKGROUND: COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2). METHODS: This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 µmoles, or 150 µmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests. RESULTS: Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels. CONCLUSION: Sulforaphane administered for four weeks at doses of 25 µmoles and 150 µmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01335971.