An integrated analysis of the efficacy of fluticasone furoate nasal spray versus placebo on the nasal symptoms of perennial allergic rhinitis.

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The aim of this analysis was to determine whether the beneficial effects of once-daily (q.d.) fluticasone furoate nasal spray (FFNS) effectively improved individual nasal symptoms of PAR. An integrated analysis was performed on data from three randomized, double-blind, placebo-controlled, parallel-group trials designed to evaluate the efficacy and safety of FFNS at 110 micrograms, q.d. in subjects with PAR. The analysis included 460 subjects who received FFNS and 459 who received placebo for 4 weeks. All subjects evaluated the severity of individual nasal symptoms of nasal congestion, nasal itching, rhinorrhea, and sneezing on a four-point categorical scale. The main efficacy measures included change from baseline in daily reflective total nasal symptom score (rTNSS), reflective daily scores for each individual symptom, and predose instantaneous TNSS (iTNSS). Over 4 weeks of treatment, FFNS significantly improved rTNSS, iTNSS, and the reflective scores for each individual symptom compared with placebo. The least squares (LS) mean treatment difference over weeks 1-4 between FFNS and placebo for rTNSS was -0.93, ranging from -0.20 to -0.28 for the individual nasal symptoms (p < 0.001 for all versus placebo). For the iTNSS, the LS mean treatment difference between FFNS and placebo over weeks 1-4 was -0.95 (95% CI,-1.24, -0.66; p < 0.001). FFNS at 110 micrograms q.d. effectively relieved all nasal symptoms of PAR including nasal congestion over a 24-hour period.

Primary care physician perceptions on the diagnosis and management of chronic obstructive pulmonary disease in diverse regions of the world.

Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality. Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care. A web-based pilot survey was conducted to evaluate the primary care physician's, or general practitioner's (GP's), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory. The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant. This survey demonstrated that the GPs' understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management. A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa. Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%). Management of COPD was well below guideline-recommended levels in most of the regions investigated. The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied.

An integrated analysis of the efficacy of fluticasone furoate nasal spray on individual nasal and ocular symptoms of seasonal allergic rhinitis.

Intranasal steroids have been shown to affect ocular symptoms of allergic rhinitis (AR). The results of the published literature, however, are not uniform across all products. This study was designed to evaluate whether the effects of fluticasone furoate nasal spray (FFNS) are consistent across different allergy seasons and different geographic regions for individual nasal and ocular symptoms of seasonal allergic rhinitis (SAR). An integrated analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group, multicenter trials, designed to evaluate the efficacy and safety of FFNS, 110 micrograms, once daily for 14 days in 1141 adult and adolescent SAR patients exposed to mountain cedar, ragweed, or grass pollen allergen. All patients evaluated severity of seven individual nasal and ocular symptoms on a 4-point categorical scale. The main efficacy measures included change from baseline in daily reflective, morning (A.M.) predose instantaneous, and daily A.M. and evening (P.M.) reflective score for each nasal/ocular symptom. FFNS significantly improved daily mean reflective, A.M. predose instantaneous, and daily A.M. and P.M. reflective scores for nasal itching, sneezing, congestion, rhinorrhea, and ocular itching/burning, tearing/watering, and redness, compared with placebo (p < 0.001 for all versus placebo). The least square (LS) mean treatment differences ranged from -0.44 to -0.33 (p < 0.0001) for the individual nasal symptoms and from -0.22 to -0.19 (p < 0.0001) for the individual ocular symptoms. FFNS also significantly improved daily reflective total nasal symptom scores (TNSS)/reflective total ocular symptom scores (TOSS), and A.M. predose instantaneous TNSS and instantaneous TOSS, compared with placebo (LS mean treatment differences = -1.47, -0.65, -1.49, and -0.63, respectively; p < 0.001 for all). FFNS, 110 micrograms, once daily consistently relieved all nasal and ocular symptoms of SAR across different allergy seasons and geographical locations.

Pudendal nerve stimulation of a preparation of isolated guinea-pig urethra.

OBJECTIVE: To assess the functional response of the urethral striated muscle to activation of its nerves, using a novel isolated organ-bath preparation. MATERIALS AND METHODS: The urethra of the female guinea-pig was chosen as a suitable model for investigation, as it is functionally and structurally similar to the human urethra. Female Dunkin-Hartley guinea-pigs (400-500 g) were used; for the histochemical and immunohistochemical experiments, unfixed urethras were cryo-sectioned (14 microm thick) and were stained using established methods. For in vitro experiments, whole urethras were suspended vertically, with pudendal nerves intact, for isometric tension and intraluminal pressure recording in a 40-mL organ bath. Drugs were applied directly to the bathing solution. RESULTS: In the striated muscle layer of the urethra there was positive beta-NADPH-diaphorase activity. In organ-bath studies the pudendal nerve-evoked contractions (0.2 ms pulses, 5 s trains, 70 V and 1-100 Hz) were abolished in the presence of tubocurarine (10(-6)m), and unaffected by guanethidine and atropine (both 10(-6)m). Pre-incubation with sodium nitroprusside and SIN-1 chloride significantly reduced the initial peak pressure responses (P < 0.05, anova for paired data) evoked by electrical field stimulation of the pudendal nerves at stimulus parameters of 0.2 ms pulses, 5 s trains, 70 V and 25 Hz. CONCLUSION: Electrically induced contractions were abolished by tubocurarine, confirming that the pudendal nerve innervates the striated muscle of the guinea-pig external urethral sphincter via nicotinic receptors. beta-NADPH-diaphorase histochemistry gave positive staining around guinea-pig striated muscle cells and possibly identified neuromuscular junction sites staining positively for the nitric oxide synthase marker. Together with the results of the organ-bath experiments, the results suggest that the striated muscle cells of the guinea-pig urethra have the machinery to respond to nitric oxide.