Immunotherapy by the subcutaneous injection of increasing doses and then maintenance doses of extracts of inhalant allergens has been practiced for 100 years. Controlled clinical trials have ...established its efficacy in treating allergic rhinitis, asthma, and stinging insect sensitivity, and there are preliminary data to suggest a favorable response in some patients with atopic dermatitis. The response to subcutaneous injection immunotherapy is dose dependent. Disease-modifying actions include blocking development of new sensitivities in monosensitized patients, blocking progression to asthma in patients with allergic rhinitis, and persistence of treatment effects for up to 7 to 10 years after an initial course.
A controlled-release (CR) formulation of zileuton was developed to simplify administration from 600 mg 4 times daily (Zyflo) to 1,200 mg twice daily.
To evaluate the efficacy of zileuton CR, two ...600-mg tablets twice daily, compared with placebo.
Patients with moderate asthma treated with short-acting beta-agonists only were randomized to receive zileuton CR, 1,200 mg twice daily (n = 206); placebo CR, twice daily (n = 203); zileuton immediate-release (IR), 600 mg 4 times daily (n = 101); or placebo IR, 4 times daily (n = 103), for 12 weeks. The primary efficacy variable was change from baseline in morning trough forced expiratory volume in 1 second (FEV1).
Improvement in trough FEV1 was observed after 2 weeks of treatment (P = .001) and was maintained throughout the study. After 12 weeks of dosing, FEV1 improved by a mean of 0.39 L (20.8%) in the zileuton CR group vs 0.27 L (12.7%) in the placebo CR group (P = .02). A significant decline in beta-agonist use and a smaller proportion of patients reporting asthma exacerbations were observed in the zileuton CR group vs the placebo CR group. Adverse event profiles were similar across treatment groups. Elevations in alanine aminotransferase levels at least 3 times the upper limit of normal that reversed after drug withdrawal were seen in 5 zileuton CR-treated patients (2.5%) vs 1 placebo CR-treated patient (0.5%).
Treatment with zileuton CR, 1,200 mg twice daily, resulted in a significant improvement in asthma control, and the safety and efficacy profile was similar to that observed with zileuton IR, 600 mg 4 times daily (Zyflo).
Sensitivity was defined as specific IgE >0.35 kU/L to any allergen tested including: 6 grasses, cat dander, dog epithelium, house dust mites (HDM), 13 trees, short ragweed, and 6 molds.
Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates ...excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype.
Prospective cohort study.
A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study.
Baseline plasma FGF23.
Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction EF ≥ 50%), HF with reduced EF (HFrEF, EF<50%) and HF with unknown EF (HFuEF).
Multivariable-adjusted cause-specific Cox proportional hazards models were used to investigate associations between FGF23 and incident hospitalizations for HF by subtype. The Lunn-McNeil method was used to compare hazard ratios across HF subtypes. Poisson regression models were used to evaluate the total rate of HF.
During a median follow-up time of 10.8 years, 295 HFpEF, 242 HFrEF, and 156 HFuEF hospitalizations occurred. In multivariable-adjusted cause-specific Cox proportional hazards models, FGF23 was significantly associated with the incidence of HFpEF (HR, 1.41; 95% CI, 1.21-1.64), HFrEF (HR, 1.27; 95% CI, 1.05-1.53), and HFuEF (HR, 1.40; 95% CI, 1.13-1.73) per 1 standard deviation (SD) increase in the natural log of FGF23. The Lunn-McNeil method determined that the risk association was consistent across all subtypes. The rate ratio of total HF events increased with FGF23 quartile. In multivariable-adjusted models, compared with quartile 1, FGF23 quartile 4 had a rate ratio of 1.81 (95% CI, 1.28-2.57) for total HF events.
Self-report of HF hospitalizations and possible lack of an echocardiogram at time of hospitalization.
In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risks for all HF subtypes.
Heart failure (HF) is a prominent cause of morbidity and mortality in individuals with chronic kidney disease (CKD). Identifying potential pathways in the development of HF is essential in developing therapies to prevent and treat HF. In a large cohort of individuals with CKD, the Chronic Renal Insufficiency Cohort (N=3,502), baseline fibroblast growth factor-23 (FGF23), a hormone that regulates phosphorous, was evaluated in relation to the development of incident and recurrent HF with reduced, preserved, and unknown ejection fraction. In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risk of all HF subtypes. These findings demonstrate the need for further research into FGF23 as a target in preventing the development of HF in individuals with CKD.
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Are meta-analysis–based comparisons solid evidence? Calderon, Moises A., MD; Andersen, Jens S., PhD; Nelson, Harold S., MD
Journal of allergy and clinical immunology,
08/2013, Letnik:
132, Številka:
2
Journal Article
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Odprti dostop
Because small single-center trials commonly have less variation, their SMDs will be large, not because of a larger effect but because of less variation. ...the random-effects model favors ...single-center trials and not the guideline-compliant, multinational, multisite confirmatory trials used in modern development of specific immunotherapy. ...moving toward evidence-based medicine implies the integration of individual clinical expertise with the best available external clinical evidence from systematic research.
The gate control theory of pain is now widely accepted.2 It probably explains the effectiveness of many forms of home remedies, such as massage and application of heat and cold, as well as providing ...the theoretic basis for treatments such as acupuncture and transcutaneous electrical nerve stimulation.3 A commercially available skin test device, the MultiTest (Lincoln Diagnostics, Decatur, Ill), has been modified to apply light pressure before the tines penetrate the skin, with the intent to reduce the pain produced by penetration of the tines (Fig 1). The new device is based on the gate control theory of pain, which proposes that light pressure will activate nerve fibers that reduce or block the sensation of pain.
