Placebo Spray Research Articles

Treatment of upper respiratory tract infections in primary care: a randomized study using aromatic herbs.

This study is a prospective randomized double-blind controlled trial whose aim was to investigate the clinical effects of aromatic essential oils in patients with upper respiratory tract infections. The trial was conducted in six primary care clinics in northern Israel. A spray containing aromatic essential oils of five plants (Eucalyptus citriodora, Eucalyptus globulus, Mentha piperita, Origanum syriacum, and Rosmarinus officinalis) as applied 5 times a day for 3 days and compared with a placebo spray. The main outcome measure was patient assessment of the change in severity of the most debilitating symptom (sore throat, hoarseness or cough). Sixty patients participated in the study (26 in the study group and 34 in the control group). Intention-to-treat analysis showed that 20 minutes following the spray use, participants in the study group reported a greater improvement in symptom severity compared to participants in the placebo group (P = .019). There was no difference in symptom severity between the two groups after 3 days of treatment (P = .042). In conclusion, spray application of five aromatic plants reported in this study brings about significant and immediate improvement in symptoms of upper respiratory ailment. This effect is not significant after 3 days of treatment.

Cost–Utility Analysis of Topical Intranasal Steroids for Otitis Media with Effusion Based on Evidence from the GNOME Trial

Objectives To estimate the cost-effectiveness of topical intranasal steroids for the treatment of otitis media with effusion (OME) in primary care from the perspective of the UK National Health Service. Methods An economic evaluation was conducted based on evidence from the double-blind, randomized, placebo-controlled GPRF [General Practice Research Framework] Nasal Steroids for Otitis Media with Effusion (GNOME) trial. Participants comprised 217 children aged 4–11 years who had at least one episode of otitis media or related ear problem in the previous 12 months and had tympanometrically confirmed bilateral OME. Children were randomly allocated to receive either mometasone furoate 50 µg or placebo spray once daily into each nostril for 3 months. The main outcome measure was the incremental cost per quality-adjusted life-year (QALY) gained for topical steroids compared with placebo. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative willingness to pay thresholds. Results Children receiving topical steroids accrued nonsignificantly higher costs (incremental cost/child: £11, 95% confidence interval [CI]: −£199 to £222) and nonsignificantly fewer QALYs (incremental QALY gain/child: −0.0166, 95% CI: −0.0652 to 0.0320) than those receiving placebo. Topical steroids had a 24.19% probability of being cost-effective at a £20,000 per QALY gained threshold, a 23.82% probability of being more effective and a 46.25% probability of being less costly. Sensitivity and subgroup analyses showed incremental costs and benefits to be highly sensitive to the methods used and the patient group considered, although differences between groups did not reach statistical significance in any analysis. Conclusions Topical steroids are unlikely to be a cost-effective treatment for OME in general practice.

Assessment of Clinical Efficacy of Intranasal Desmopressin Spray and Diclofenac Sodium Suppository in Treatment of Renal Colic Versus Diclofenac Sodium Alone

To determine the effect of the combination of intranasal desmopressin spray and diclofenac sodium suppository on acute renal colic and compare it with diclofenac sodium suppository alone. A total of 150 patients aged 15-65 years referred to our hospital with acute renal colic were included in a double-blind controlled clinical trial study. Patients in group 1 received desmopressin, 40 microg intranasally plus diclofenac sodium suppository 100 mg, and patients in group 2 received diclofenac sodium suppository 100 mg plus a placebo spray consisting of normal saline 0.9%. Significant differences were found in the pain scores at 15 and 30 minutes between the 2 groups (P < .05). Also, significant differences were found in the mean pain scores in the first 15 and first 30 minutes after treatment between the 2 groups (P < .05). Of the patients in group 1, 37.3% had no pain relief and required pethidine. However, this rate in group 2 was 69.3%. In 17 cases, we prescribed pethidine within 20 minutes after treatment, and these patients were excluded from our study. According to our results, intranasal desmopressin plus diclofenac sodium suppository caused prompt pain relief with significant decreases in pain scores after 15 and 30 minutes. We suggest that intranasal desmopressin spray is a useful supplemental therapy for renal colic in combination with nonsteroidal anti-inflammatory drugs, especially to reduce the use of opioids.

Effects of nicotine patch or nasal spray on nicotine and cotinine concentrations in pregnant smokers

Objective. To examine the short-term effects of the nicotine patch or nasal spray on measures of nicotine exposure, withdrawal symptoms, and on maternal and fetal heart rates in pregnant smokers.Methods. We measured nicotine/cotinine concentrations and maternal and fetal heart rates during an 8-h monitoring session while smoking and again after 4 days of nicotine patch (15 mg/16 h), nasal spray (recommended regimen of 24 doses per day), or placebo treatment. Nicotine withdrawal symptoms were assessed daily.Results. Twenty-one subjects, who smoked an average of 17 cigarettes per day, completed both monitoring sessions. Nicotine concentrations decreased from baseline smoking concentrations in all groups (p = 0.002). Percent change in cotinine concentration differed across groups (reduction = 77% with placebo, 70% with nasal spray, and 48% with patch; p = 0.029). Maternal heart rate decreased in the placebo and nasal spray groups compared with the patch group (p = 0.021). The baseline fetal heart rate decreased in the placebo group throughout the second monitoring session, but increased slightly in the patch and nasal spray groups. The treatment by time interaction was marginally significant (p = 0.052). Daily, cigarette craving decreased more in the patch versus the other groups (p = 0.025).Conclusions. Nicotine patch and nasal spray reduce maternal nicotine exposure compared with smoking and may be effective for smoking cessation.

A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care

To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion (OME). A double-blind randomised placebo-controlled trial with an intention to treat analysis; the 10.6% of patients lost to follow-up at 1 month were censored in the analysis. 76 Medical Research Council General Practice Research Framework practices throughout the UK between 2004 and 2007. A sample of 217 children aged 4-11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry (B B or B C2 types using a modified Jerger classification) at randomisation. Mometasone 50 micrograms in each nostril or placebo spray once daily for 3 months. The primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month. Secondary outcomes included clearance at 3 months and 9 months; adverse events; OM8-30 scores (a functional health status responsive disease-specific measure); hearing loss; days with otalgia; cost-effectiveness; and health utilities. Of the topical steroid group, 40.6% (39/96) demonstrated tympanometric clearance (C1 or A type) in one or both ears at 1 month, compared with 44.9% (44/98) of the placebo group. The absolute risk reduction at 1 month was -4.3% (95% CI -18.05% to 9.26%); the odds ratio (OR) was 0.84 (95% CI 0.48 to 1.48). Four covariates were pre-specified for inclusion in logistic regression analysis: age as a continuous variable (p = 0.94), season (p = 0.70), atopy (p = 0.61) and clinical severity (p = 0.006). The adjusted OR (AOR) at 1 month for the main outcome was 0.93 (95% CI 0.50 to 1.75). Secondary analysis at 3 months showed 58.1% of the steroid group had resolved and 52.3% of the placebo group, AOR 1.45 (95% CI 0.74 to 2.84). At 9 months 55.6% of the treated group remained clear in at least one ear and 65.3% of the placebo group, AOR 0.82 (95% CI 0.39 to 1.75). Adverse events (although relatively minor) occurred in 7-22% of children and included nasal stinging, epistaxis, dry throat and cough. The OM8-30 scores (p = 0.55) reported hearing difficulty (p = 0.08), and days with otalgia (p = 0.46) were not significantly different between groups at 3 months. The economic evaluation found the active treatment arm to be dominated by placebo, accruing slightly (but not significantly) higher costs and fewer quality-adjusted life-years (QALYs), with a 24.2% probability that topical steroids are a cost-effective use of NHS resources at a ceiling ratio of 20,000 pounds per QALY gained. Use of topical intranasal corticosteroids is very unlikely to be a clinically effective treatment for OME (glue ear) in the primary care setting. Current Controlled Trials ISRCTN38988331.

Fluticasone furoate nasal spray reduces the nasal-ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms

Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms associated with allergic nasal symptoms, even though they do not reach the eye. To elucidate a mechanism to explain these observations. We performed a double-blind, placebo-controlled, crossover experiment in 20 subjects with seasonal allergic rhinitis. Nasal antigen challenge was performed consecutively for 3 days after 1 week of treatment with either placebo or fluticasone furoate nasal spray (FFNS). Subjects recorded their nasal and ocular symptoms, and nasal secretions were quantified. Nasal scrapings to quantify eosinophils were obtained before each antigen challenge. Nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex. Priming in the number of sneezes, contralateral nasal secretion weights, and total eye symptoms were observed. Treatment with FFNS reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions. We confirmed that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. FFNS reduced eosinophil infiltration, priming, and ocular symptoms. Furthermore, our results support a mechanism by which control of eye symptoms can be achieved during nasal administration of an intranasal steroid in patients with seasonal allergic rhinitis.

Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: A prospective double-blind randomized placebo-controlled study

Objectives Combination of drugs with different mechanisms of action helps in achieving synergistic analgesic effect in neuropathic pain. Keeping this point in view, the effect and safety aspects of sodium valproate and GTN were assessed alone as well as in combination in this study. Design Prospective double-blind randomized placebo-controlled study. Material and method Eighty-seven type 2 diabetics with painful neuropathy were enrolled. Four were excluded: three with HbA 1c > 11 while one withdrew consent. The remaining 83 were given either sodium valproate and GTN spray (group A) or placebo drug and GTN spray (group B) or sodium valproate and placebo spray (group C) or placebo drug and placebo spray (group D). Quantitative assessment of pain was done by McGill pain questionnaire, visual analogue score (VAS) and present pain intensity (PPI) at the beginning of the study and after 3 months along with motor and sensory nerve conduction velocities measurements. Results All the three treatment groups experienced significant improvement in pain score in their drug phase of trial ( p < 0.001/ < 0.05) along with some of the electrophysiological parameters. The assessment of the magnitude of therapeutic effect of sodium valproate, GTN and their combination gave numbers needed to treat (NNT) of 7, 5 and 4, respectively. Conclusion Sodium valproate and GTN are well tolerated and provide significant improvement in pain scores as well as in electrophysiological parameters.

Topical intranasal corticosteroids in 4-11 year old children with persistent bilateral otitis media with effusion in primary care: double blind randomised placebo controlled trial

Objective To determine the clinical effectiveness of topical intranasal corticosteroids in children with bilateral otitis media with effusion.Design Double blind randomised placebo controlled trial.Setting 76 Medical Research Council General Practice...

Low-Dose Estradiol Spray: a Novel Treatment for Vasomotor Instability in Postmenopausal Women

This article describes a novel transdermal estradiol spray developed for the treatment of menopausal vasomotor instability. The spray delivers estradiol directly into the subcutaneous microcirculation achieving the advantages of estradiol patches, creams and gels but with minimal skin reaction, patient inconvenience or cosmetic shortcomings associated with transdermal methods. In the one published Phase III clinical trial, postmenopausal women (n = 454) with eight or more moderate-to-severe hot flashes per day applied each morning, one, two or three estradiol 90 microl sprays (each containing estradiol 1.53 mg) versus matching placebo sprays. There was a significant decrease in hot flash frequency and intensity at weeks 4 and 12 compared with corresponding placebo groups (p < 0.010). The systemic estradiol delivery rates at week 12 were approximately 0.021, 0.029 and 0.040 mg/day for the 1-, 2- and 3-spray doses, respectively. There were common adverse events similar to those previously reported with transdermal estradiol, except for skin irritation, which was very low. The spray is a well-tolerated, cosmetically attractive and convenient method of delivering low-dose, transdermal estradiol.

Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers

Genetic variation may influence initial sensitivity to nicotine (i.e. during early tobacco exposure), perhaps helping to explain differential vulnerability to nicotine dependence. This study explored associations of functional candidate gene polymorphisms with initial sensitivity to nicotine in 101 young adult nonsmokers of European ancestry. Nicotine (0, 5, 10 microg/kg) was administered through nasal spray followed by mood, nicotine reward (e.g. 'liking') and perception (e.g. 'feel effects') measures, physiological responses, sensory processing (prepulse inhibition of startle), and performance tasks. Nicotine reinforcement was assessed in a separate session using a nicotine versus placebo spray choice procedure. For the dopamine D4 receptor [DRD4 variable number of tandem repeats (VNTR)], presence of the 7-repeat allele was associated with greater aversive responses to nicotine (decreases in 'vigor', positive affect, and rapid information processing; increased cortisol) and reduced nicotine choice. Individuals with at least one DRD4 7-repeat allele also reported increased 'feel effects' and greater startle response, but in men only. Other genetic associations were also observed in men but not women, such as greater 'feel effects' and anger, and reduced fatigue, in the dopamine D2 receptor (DRD2 C957T single nucleotide polymorphism) TT versus CT or CC genotypes. Very few or no significant associations were seen for the DRD2/ANKK1 TaqIA polymorphism, the serotonin transporter promoter VNTR or 5HTTLPR (SLC6A4), the dopamine transporter 3' VNTR (SLC6A3), and the mu opioid receptor A118G single nucleotide polymorphism (mu opioid receptor polymorphism 1). Although these results are preliminary, this study is the first to suggest that genetic polymorphisms related to function in the dopamine D4, and perhaps D2, receptor may modulate initial sensitivity to nicotine before the onset of dependence and may do so differentially between men and women.

Low-Dose Estradiol Spray to Treat Vasomotor Symptoms

To investigate the safety and efficacy of a transdermal estradiol (E2) spray in women with postmenopausal vasomotor symptoms. A randomized, double-blind, placebo-controlled, multicenter, parallel-group clinical trial was conducted. Postmenopausal women (N=454) with at least eight moderate-to-severe hot flushes per day applied daily, one, two, or three E2 (90 microliter spray contains 1.53 mg E2) or matching placebo sprays. The primary efficacy endpoints were mean change from baseline in frequency and severity of moderate-to-severe hot flushes at weeks 4 and 12. All three E2 groups showed a significant decrease in hot flushes at weeks 4 and 12 compared with their placebo groups (P<.010). The mean change in frequency at week 12 was eight fewer flushes per day for women in the E2 groups and between four and six fewer flushes for women in the placebo groups. Women in the three- and two-E2 spray groups demonstrated significant (P<.050) reductions in severity score at weeks 4 and 12; women in the one-spray group showed significant reductions at week 5. At week 12, the majority (74-85%) of women on E2 showed at least a 50% hot flush frequency reduction as compared with 46% in the placebo group. The systemic E2 delivery rates at week 12 were approximately 0.021 mg/d, 0.029 mg/d, and 0.040 mg/d for the one-, two-, and three-spray doses, respectively. Common adverse events were similar to those previously reported with other transdermal products. Treatment-related application site reaction rate was similar to placebo (1.3% compared with 1.8%). The three dose levels of E2 spray achieved efficacy at 0.021-0.040 mg/d delivery rates. The spray is a well-tolerated, new, convenient method of delivering low-dose E2 transdermally. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00122200. I.

News &amp; Notes

AbstractLoop diuretics may increase bone loss in menContinuous use of a loop diuretic could double the rate of bone loss in elderly men, according to a new analysis of the Osteoporotic Fractures in Men study (Arch Intern Med 2008; 168: 735–40).This analysis of a subgroup of 3269 of the original 5995 men over 65 for whom a DEXA scan was available at baseline and after a mean follow‐up of 4.6 years identified 84 who had continuously used a loop diuretic, 181 with intermittent use and 3004 never‐users.After adjustment for risk factors, the mean annual rate of decline in bone mineral density (BMD) at the hip was 0.78 per cent among continuous users, 0.58 per cent with intermittent use and 0.33 per cent among never‐users; there were similar trends at the femoral neck and trochanter.Cochrane reviews finasterideTreatment with finasteride reduces the risk of prostate cancer in men at increased risk by about one‐quarter, a new Cochrane review reveals (Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007091. DOI: 10.1002/ 14651858.CD007091).The risk reduction with finasteride did not vary with age, ethnicity or family history but was not evident in men with prostate‐specific antigen &gt;4ng/ml. The analysis was dominated by the Prostate Cancer Prevention Trial, which reported an increase in men with high‐grade tumours during finasteride therapy.Only one report of dutasteride was included, suggesting a 51 per cent risk reduction in cancers detected.New GnRH antagonistsGermany is the first country in Europe to have the new GnRH receptor antagonist abarelix (Plenaxis) for the treatment of hormone‐dependent prostate cancer. Manufacturer Speciality European Pharma says that abarelix, by contrast with agonist therapies, reduces testosterone levels rapidly and is not associated with hormonal surge or flare. Registration is now underway across Europe.Phase III data presented at the 23rd Annual European Association of Urology Congress in Milan revealed the rapid onset of effect with Ferring's GnRH antagonist degarelix. After 14 days, serum testosterone was &lt;5ng/ml in all patients treated with degarelix and in 18 per cent of those assigned to monthly leuprorelin. The median reduction in prostate‐specific antigen was 64 per cent with degarelix and 18 per cent with the LHRH analogue.Transdermal testosterone little benefit for womenWomen who report decreased sexual satisfaction derive little benefit from transdermal testosterone, an Australian trial has shown (Ann Intern Med 2008; 148: 569–77).261 women aged 35–46 who reported decreased sexual satisfaction compared with historical experience were randomised to receive placebo or testosterone spray at doses of 56, 90 or 180µl for 16 weeks. Baseline morning serum free testosterone level was less than 3.8pmol/l.The primary endpoint was the number of satisfactory sexual events (SSEs) in the 28 days up to week 16.The rate ratios of SSEs compared with placebo for 56, 90 and 180µl doses were 1.34, 1.48 and 1.38, respectively; of these, only the response to the 90µl dose was statistically significant but the absolute difference was small – equivalent to an increase of 0.8 SSE per month. The commonest adverse effect was dose–related hypertrichosis at the site. Copyright © 2008 Wiley Interface Ltd

Sublingual hyoscyamine spray as premedication for colonoscopy: a randomized double-blinded placebo-controlled trial

Background Colonic motility and spasm during colonoscopy may affect duration and quality of the examination as well as patient comfort during and after the procedure. Previous studies assessing the utility of antispasmodic agents in colonoscopy demonstrated conflicting results. The aim of this study was to determine the effect of sublingual hyoscyamine spray (IB-Stat, Inkine Pharmaceutical) on the performance of colonoscopy. Methods One hundred patients undergoing elective colonoscopy were randomized in a double-blind study to receive .25 mg sublingual hyoscyamine spray (n = 50: 25 men and 25 women, mean age 60) or placebo spray (n = 50: 23 men and 27 women, mean age 56) 15 to 30 minutes before the procedure. Parameters measured included time required to reach the cecum, total procedure time, endoscopist perception of colonic motility and difficulty of the procedure, and patient assessment of discomfort after the procedure. The latter parameters were measured using a 100-mm visual analog scale. A single endoscopist performed all of the procedures. Results After adjustment for age, procedural difficulty scores and colonic motility scores were significantly lower in the hyoscyamine group compared with placebo (differences of 5.589 mm [ P = .047] and 5.685 mm [ P = .040], respectively). Mean time to cecal intubation and percentage of patients with discomfort were slightly lower in the hyoscyamine group (5.68 minutes/48%) compared with placebo (5.92 minutes/57.1%), although the differences were not statistically significant ( P = .57 and P = .36, respectively). Conclusions Procedural difficulty and colonic motility scores were significantly lower in subjects who received sublingual hyoscyamine before colonoscopy.

Isosorbide Dinitrate Spray as Therapeutic Strategy for Treatment of Chronic Venous Ulcers

Venous ulcers are the most common form of leg ulcers, which induce lesion because of the loss of substances deposited on the damaged skin. Isosorbide dinitrate is a vasodilator with effects on both arteries and veins and induces opening of vascular layers. The objective is to study the effects of isosorbide dinitrate-spray in patients with chronic venous ulcers. Forty-five patients of both sexes with chronic venous ulcers were randomized to receive isosorbide dinitrate or placebo sprays daily for 3 months. The ulcers were measured and clinical characteristics were taken every 15 days during the treatment. Patients treated with isosorbide dinitrate showed an improvement of the ulcerated area (71.29%) compared with patients treated with placebo (54.35%). The histopathological study indicated an increment in the number of hypertrophic and hyperplasic capillaries. Macroscopically, the isosorbide dinitrate-treatment showed the best results, but it was only during the first 6 weeks of treatment. Patients with chronic venous ulcer receiving isosorbide dinitrate spray showed improvement.

Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: Olopatadine hydrochloride versus mometasone furoate monohydrate

Rapid relief of symptoms should be one of the primary goals of treatment for allergic rhinitis (AR). The onset and duration of action of olopatadine hydrochloride nasal spray, 665 mcg (OLO; Patanese), for seasonal AR (SAR) was evaluated in this study. This study was performed to determine the onset and duration of action of OLO compared with placebo spray, with mometasone furoate monohydrate, 50 mcg (MM; Nasonex), as a reference standard. This was a single center, single-dose, randomized, double-blinded parallel-group environmental exposure chamber study. Patients were primed at two 2-hour priming visits. Eligible patients were randomized to OLO, placebo spray, or MM, 2 sprays/nostril. Allergy symptoms (sneezing, runny, itchy, and stuffy nose) were rated by patients at 16 time points during 12 hours after dosing and patient satisfaction was assessed at 4 and 12 hours postdose. Safety was assessed by a review of adverse events, cardiovascular and nasal examination parameters. Four hundred twenty-five adult patients were randomized. OLO was superior to placebo spray in reducing total nasal symptoms (TNSS) within 30 minutes after dosing and maintained superiority for at least 12 hours (p < 0.05). The onset of MM was not observed until 150 minutes postdose and was smaller in magnitude compared with OLO. OLO was superior to both placebo spray (p < 0.0001) and MM (p < 0.05) in patient satisfaction. Treatment was well-tolerated with no safety concerns. OLO is superior to placebo spray and MM in reducing allergy symptoms; OLO has a rapid onset of action and a duration of effect of at least 12 hours.

Onset of Action of Azelastine Nasal Spray Compared with Mometasone Nasal Spray and Placebo in Subjects with Seasonal Allergic Rhinitis Evaluated in an Environmental Exposure Chamber

The objective of this study was to determine the onset of action of azelastine hydrochloride nasal spray compared with placebo and an intranasal steroid, mometasone furoate, in subjects with seasonal allergic rhinitis (SAR). Subjects with a history of SAR and symptomatic while exposed to ragweed pollen in an environmental exposure chamber (EEC) were randomized to azelastine nasal spray (n=150), mometasone nasal spray (n=150), or placebo (n=150) and recorded total nasal symptom scores (TNSS), consisting of sneezing, nasal pruritus, rhinorrhea, and congestion, during an 8-hour study period. Azelastine nasal spray showed a statistically significant improvement in the TNSS at 15 minutes compared with placebo. The effect was durable at each time point during the 8-hour study. Azelastine nasal spray also was significantly more effective than mometasone at each time point. Azelastine nasal spray has a rapid (15 minute) onset of action. Azelastine nasal spray was superior to both placebo and imometasone nasal spray in reducing nasal symptoms of SAR occurring within 8 hours after an allergen challenge.

Facial EMG as an index of affective response to nicotine.

Negative affect reduction has been postulated to be a key feature of cigarette smoking. In the present study, facial electromyography (EMG), heart rate (HR), and skin conductance response (SCR) were used to evaluate the affective significance of acute nicotine administration and overnight withdrawal. Smokers (N = 115) attended four 90-min laboratory assessment sessions scheduled approximately 3 days apart. The sessions provided a complete crossing of 2 prelaboratory deprivation conditions (12-hr deprived vs. nondeprived) with 2 drug conditions (nicotine vs. placebo nasal spray). During each session, smokers viewed affective slides while facial EMG, HR, and SCR were recorded. Results indicated that for women, nicotine nasal spray resulted in lower corrugator EMG activity during both smoking-deprived and nondeprived sessions, compared with placebo. However, nondeprived women also showed an increase in zygomaticus EMG when given nicotine compared with placebo spray, whereas smoking-deprived women demonstrated a decrease in the zygomaticus response to nicotine compared with placebo. With men, nicotine also appeared to lower corrugator during deprivation, but not nondeprivation, compared with placebo spray, though the contrast only approached significance. With zygomaticus EMG, nicotine spray decreased men's zygomaticus responding during nondeprivation but not during deprivation, compared with placebo spray. The HR results reflected the stimulatory properties of the drug rather than nicotine's affective properties, whereas SCR was unresponsive to our experimental manipulations. The corrugator EMG results support negative reinforcement models of smoking that postulate that acute nicotine use reduces withdrawal-driven negative affect.

Once-daily Fluticasone Furoate∗ Nasal Spray (FF) Provides 24-hour Symptom Relief In Subjects With Seasonal Allergic Rhinitis (SAR) Caused By Mountain Cedar Pollen ∗USAN approved name

RATIONALE: FF is a novel enhanced-affinity steroid being developed for the treatment of rhinitis.METHODS: Three hundred two subjects (≥12 years) with active SAR to mountain cedar pollen were randomized to once-daily FF 110mcg or placebo spray administered in a unique, side-actuated device. Primary endpoint: Mean change from baseline (MCFB) over the entire 2-week treatment period in daily reflective total nasal symptoms scores (rTNSS), which was the sum of 4 symptoms: nasal congestion, itching, rhinorrhea, and sneezing. Key secondary endpoints were MCFB in AM pre-dose instantaneous total nasal symptoms scores (iTNSS), overall response to therapy (ORT), and MCFB in daily reflective total ocular symptoms scores (rTOSS). Total ocular scores were the sum of 3 symptoms: eye itching/burning; tearing/watering; and redness. Nasal and ocular symptom data were analyzed using ANCOVA. ORT was analyzed using logistic regression.RESULTS: For the primary endpoint, MCFB in rTNSS, FF 110mcg was significantly more effective at improving the nasal symptoms of SAR compared with placebo (p = 0.003). FF 110mcg also was significantly more effective for the key secondary endpoints: MCFB in AM pre-dose iTNSS (p <0.001), ORT (p <0.001), and MCFB in rTOSS (p =0.008). The incidence of epistaxis was 7% and 5% in the placebo and FF groups, respectively, but in each group, only 3% were considered drug-related. There were no serious AEs.CONCLUSIONS: The results of this study support the use of once-daily FF 110 mcg for the symptoms of seasonal allergic rhinitis caused by mountain cedar pollen in subjects 12 years of age and older. RATIONALE: FF is a novel enhanced-affinity steroid being developed for the treatment of rhinitis. METHODS: Three hundred two subjects (≥12 years) with active SAR to mountain cedar pollen were randomized to once-daily FF 110mcg or placebo spray administered in a unique, side-actuated device. Primary endpoint: Mean change from baseline (MCFB) over the entire 2-week treatment period in daily reflective total nasal symptoms scores (rTNSS), which was the sum of 4 symptoms: nasal congestion, itching, rhinorrhea, and sneezing. Key secondary endpoints were MCFB in AM pre-dose instantaneous total nasal symptoms scores (iTNSS), overall response to therapy (ORT), and MCFB in daily reflective total ocular symptoms scores (rTOSS). Total ocular scores were the sum of 3 symptoms: eye itching/burning; tearing/watering; and redness. Nasal and ocular symptom data were analyzed using ANCOVA. ORT was analyzed using logistic regression. RESULTS: For the primary endpoint, MCFB in rTNSS, FF 110mcg was significantly more effective at improving the nasal symptoms of SAR compared with placebo (p = 0.003). FF 110mcg also was significantly more effective for the key secondary endpoints: MCFB in AM pre-dose iTNSS (p <0.001), ORT (p <0.001), and MCFB in rTOSS (p =0.008). The incidence of epistaxis was 7% and 5% in the placebo and FF groups, respectively, but in each group, only 3% were considered drug-related. There were no serious AEs. CONCLUSIONS: The results of this study support the use of once-daily FF 110 mcg for the symptoms of seasonal allergic rhinitis caused by mountain cedar pollen in subjects 12 years of age and older.

Effectiveness and Acceptability of Lidocaine Spray in Reducing Perineal Pain During Spontaneous Vaginal Delivery: Randomized Controlled Trial

Women planning spontaneous vaginal delivery often are not offered analgesia for perineal pain while in the second stage of labor. Midwives, however, sometimes apply various substances, including lidocaine, in an attempt to limit postpartum perineal pain. This study was a randomized, controlled trial comparing a topically applied local anesthetic spray with a placebo spray in 185 women having spontaneous vaginal delivery without epidural analgesia. The active and placebo solutions looked and smelled alike. The anesthetic solution was formulated to be equivalent to Xylocaine spray. Midwives were asked to apply 5 0.1-mL sprays to the perineum and the inside of the labia when birth appeared imminent but preferably at least 3 minutes beforehand. The actively treated and placebo-treated women were similar in most obstetric and sociodemographic characteristics. Women in both groups received 4.8 sprays on average. The intervals between treatment and delivery also were similar, approximating 11 to 12 minutes. Approximately 80% of women in each group delivered within 15 minutes of spraying. Pain scores, estimated using a 0 to 100 scale, were high and similar in the 2 groups. There was no evidence that the lidocaine spray lessened perineal pain, and it may even have increased it slightly. Fewer women in the active treatment group incurred second-degree perineal injuries. There were no third- or fourth-degree injuries. Women sprayed with lidocaine less often described dyspareunia when resuming sexual activity. Although acceptable to parturients, spraying the perineal region with a local anesthetic solution did not decrease postpartum pain. Further studies are needed to explore the reductions in second-degree perineal trauma and dyspareunia observed in women sprayed with lidocaine solution.

Intranasal lidocaine 8% spray for second-division trigeminal neuralgia

Trigeminal nerve block has been widely used for trigeminal neuralgia. This may induce paraesthesia. The second division of the trigeminal nerve passes through the sphenopalatine ganglion, which is located posterior to the middle turbinate and is covered by a mucous membrane. We examined the effectiveness of intranasal lidocaine 8% spray on paroxysmal pain in second-division trigeminal neuralgia. Twenty-five patients with second-division trigeminal neuralgia were randomized to receive two sprays (0.2 ml) of either lidocaine 8% or saline placebo in the affected nostril using a metered-dose spray. After a 7 day period, patients were crossed over to receive the alternative treatment. The paroxysmal pain triggered by touching or moving face was assessed with a 10 cm visual analogue scale (VAS) before and 15 min after treatment. Patients used a descriptive scale to grade pain outcome, and were asked to note whether the pain returned and how long after therapy it recurred. Intranasal lidocaine 8% spray significantly decreased VAS [baseline: 8.0 (2.0) cm, 15 min postspray: 1.5 (1.9) cm, mean (SD)], whereas the placebo spray did not [7.9 (2.0) cm, 7.6 (2.0) cm]. Moreover, pain was described as moderate or better by 23 patients of the lidocaine spray and 1 of the placebo group. The effect of treatment persisted for 4.3 h (range 0.5-24 h). Intranasal lidocaine 8% administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia.