Total Symptom Complex Research Articles

Montelukast: a better alternative than antihistaminics in allergic rhinitis

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Allergic rhinitis is associated with sleep disturbances, daytime somnolence, and fatigue. Hence, present study was undertaken to evaluate and compare the nocturnal symptoms such difficulty in going to sleep, night time awakening and nasal congestion/obstruction on awakening among allergic rhinitis patients after administration of montelukast, chlorpheniramine meleate, levocetrizine, desloratidine and fexofenadine and to find out anti-allergic drug with maximum improvement in total symptom complex score. </span></p><p class="abstract"><strong>Methods:</strong> <span lang="EN-IN">The present study comprised of 125 patients suffering from allergic rhinitis on the basis of characteristic history, corroborative physical findings and blood eosinophilia. Night times symptoms including difficulty in going to sleep, night time awakenings and nasal congestion on awakening were evaluated after patients were given oral treatment with chlorpheniramine maleate, levocetrizine, fexofenadine, desloratadine and montelukast for a period of 6 weeks in different 5 groups and the result interpreted on the basis of symptoms relieved. Symptoms were recorded on day 1, 2 weeks, 4 weeks and 6 weeks of treatment and analysed. All the patients were randomly divided into five groups of 25 each. The results were tabulated and analyzed by chi-square, Kruskal-Wallis test. </span></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">The present study found that levocetirizine provided immediate effect at 2 weeks which is significantly better than other drugs. But at 6 weeks, montelukast is best among the drugs which were compared; followed by levocetrizine, fexofenadine, and desloratadine and chlorpheniramine maleate. Montelukast was found to be a better drug as it has no significant side effects. Desloratadine group had dryness of mouth. Chlorpheniramine maleate has maximum side effects. 6 patients who took chlorpheniramine maleate complained of sedation, 1 patient complain of psychomotor disturbance. </span></p><p class="abstract"><strong>Conclusions:</strong> <span lang="EN-IN">The present study concludes that in terms of clinical efficacy, safety/tolerability and improvement in night time symptom scores at six weeks therapy in allergic rhinitis, montelukast is the better drug.</span></p>

Comparative Study of Apo-Cetirizine Single Therapy and Intermittent Sequential Therapy with Cetirizine, Loratadine and Chlorpheniramine in Allergic Rhinitis.

There are limited numbers of articles, studying combined use of antihistamines. In this study, we compare single therapy of Apo-Cetirizine with a new regimen of intermittent sequential therapy with cetirizine, loratadine and chlorpheniramine in treatment of seasonal allergic rhinitis. This randomized clinical trial was performed between April and September at the peak prevalence of seasonal allergic rhinitis. Fifty-four eligible patients diagnosed clinically to have seasonal allergic rhinitis were randomized in two groups: 24 cases in single therapy arm, received Apo-Cetirizine 10mg tablet daily and in other arm, 30 patients received sequential regimen of cetirizine 10mg tablet, loratadine 10mg tablet and chlorpheniramine 4mg tablet, one tablet each day. Major Symptom Complex Score (MSCS) and Total Symptom Complex Score (TSCS) of patients were recorded before treatment and after 30days of treatment in two groups. The average post-treatment MSCS and TSCS in combination therapy group showed better improvement than single therapy group but difference was not statistically significant (p value=0.053 and p value=0.104 respectively). Combination therapy regimen was better in improvement of nasal congestion (p value=0.006). There were no significant difference between two groups in efficacy, side effects and patient's satisfaction. Combination therapy would be effective on a wide spectrum of symptoms with lower price and theoretically offers lower chance of tolerance and re-appearance of complaints.

Efficacy of levocetirizine compared with montelukast in subjects with ragweed-induced seasonal allergic rhinitis in the Environmental Exposure Unit

Levocetirizine dihydrochloride, a potent H1-receptor antagonist, and montelukast sodium, a selective leukotriene receptor antagonist, have been approved for the treatment of seasonal allergic rhinitis (SAR), but target two different pathways that cause SAR symptoms. The study objective was to compare the efficacy of levocetirizine (LCTZ), 5 mg, and montelukast (MLKT), 10 mg, in reducing SAR symptoms in ragweed-sensitive adults exposed to ragweed pollen in the Environmental Exposure Unit (EEU). This randomized, double-blind, placebo-controlled, parallel-group study of 418 adult subjects with SAR to ragweed compared the efficacy of LCTZ, MLKT, and placebo administered once daily (11:00 A.M.) for 2 consecutive days in the EEU. There were three evaluation periods: period I, 0-5 hours after first dose; period II, 22.5-24 hours after first dose; and period III, 0-4.5 hours after second dose. The primary efficacy variable was the Major Symptom Complex (MSC) score (six symptoms) over period I. Both active drugs significantly improved the MSC score compared with placebo in all periods. The adjusted mean MSC score difference between LCTZ and MLKT was -0.93 (p = 0.100) in period I, -3.11 (p < 0.001) in period II, -2.42 (p < 0.001) in period III, and -1.88 (p < 0.001) over the total treatment period. The same trends were observed for the Total Symptom Complex score (10 symptoms) and most individual symptoms. Subject-reported global satisfaction was greater for LCTZ compared with MLKT and placebo. All treatments had a favorable safety profile. LCTZ, 5 mg, was more effective than MLKT, 10 mg, in subjects with SAR and had better subject-reported global satisfaction.

Onset of action of fexofenadine hydrochloride 60 mg/ pseudoephedrine hydrochloride 120 mg in subjects aged ⩾ 12 years with moderate to severe seasonal allergic Rhinitis: A pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies

Background: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR). Objective: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR. Methods: Subjects aged ⩾ 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol. Results: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2–1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo ( P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively). Conclusion: In this pooled analysis of 2 allergen exposure unit studies, FEX601PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

The relationship between lipodystrophy-associated body changes and measures of quality of life and mental health for HIV-positive adults

To investigate the relationship between lipodystrophy-specific symptom severity and wellbeing. HIV-positive adult patients with body fat redistribution (lipodystrophy syndrome) associated with antiretroviral therapy reported their total non-lipodystrophy symptoms and side effects and completed measures assessing body fat changes (yielding Atrophy, Hypertrophy and Total Lipodystrophy scores), mental health and quality of life. Effects of total symptom complex and lipodystrophy severity on quality of life and mental health were analyzed using Spearman's rho correlations. Logistic regression analyses were utilized to determine the relative-odds of depression produced by overall symptom count and lipodystrophy score increments. Mean ratings for Hypertrophy and Atrophy corresponded to 'very mild' and 'mild' degrees of severity, respectively. The total symptom complex was associated with ratings for most of the mental health and quality of life measures. Patient-perceived body image scores were the sole study variable responsive to lipodystrophy severity ratings. In comparison to reference norms, a pronounced degree of body image impairment was evident. Although responsive to the total symptom profile, psychosocial measures typically utilized for evaluating quality of life and mental health status in HIV disease lacked sensitivity and specificity for measuring the consequences of lipodystrophy-associated fat distribution changes alone. Lipodystrophy severity did impact negatively on body image.

The Environmental Exposure Unit: a system to test anti‐allergic treatment

SummaryBackground The Environmental Exposure Unit (EEU) is an indoor pollen exposure system designed to evaluate the efficacy and especially the onset of action of antiallergic medications. Some of the unpredictable factors that are associated with outdoor studies, which influence pollen levels are controlled using this system and antiallergic treatment can be assessed under conditions of predetermined uniform pollen levels sustained over designated time periods.Objective The aim of this study was to determine the onset of action and efficacy of cetirizine 10 mg OD, loratadine 10 mg OD and placebo in allergic subjects exposed to ragweed pollen in the EEU, using a study identical in design to a previously conducted EEU study and from the results to substantiate the EEU as an effective test system of antiallergic medication.Methods The onset of action and efficacy of cetirizine and loratadine on the symptoms of seasonal allergic rhinitis in subjects challenged with ragweed pollen in the EEU, were investigated in two separate randomized, placebo‐controlled, double‐blind, parallel‐group studies of identical design. In the first study (1995), a total of 202 subjects were randomized to cetirizine (n = 67), loratadine (n = 67) or placebo (n = 68). Subjects meeting inclusion/exclusion criteria were exposed to ragweed pollen in the EEU to activate allergic symptoms (priming phase) and those with qualifying symptoms returned for the treatment phase. Subjects attaining qualifying symptoms during the first 1.5 h of the baseline period of the treatment phase were randomized to receive a single daily dose of either cetirizine 10 mg, loratadine 10 mg or placebo on days 1 and 2. During the treatment phase, subjects were challenged to ragweed pollen (7 h on day 1, 6 h on day 2) and symptoms were recorded at half‐hourly time points. This study was repeated using a larger number of subjects (n = 360) in 1999 with an identical design.Results In both studies, cetirizine produced significant symptom improvement at 1 h compared with both loratadine and placebo. Cetirizine continued to reduce Total Symptom Complex (TSC) and Major Symptom Complex (MSC) scores at nearly all half‐hourly time points after onset of action for the 1995 study, and at all time points vs. placebo and at most time points vs. loratadine after onset of action during the 1999 study. The onset of action for loratadine was 3 h compared with placebo and loratadine significantly reduced symptoms postdosing on day 1 in both studies. The 24 h duration of effect of cetirizine was evident in both studies after 1.5 h of pollen exposure on day 2, which was not observed with loratadine. Cetirizine produced a significantly greater percentage change in MSC and TSC scores at 24 h compared with both loratadine and placebo in the 1995 study and in MSC scores in the 1999 study.Conclusion Cetirizine acted earlier and was more effective than loratadine and placebo in reducing symptoms of seasonal allergic rhinitis in subjects undergoing controlled ragweed pollen challenge in the EEU. The onset of action for cetirizine was 1 h compared with 3 h for loratadine. Similar results were observed in both studies that not only confirmed medication performance but validated the EEU as a test system for the determination of onset of action and short‐term efficacy of antiallergic medications.

Onset and Duration of Action of Ketotifen???0.025%???and???Emedastine???0.05% in Seasonal Allergic Conjunctivitis

To compare the efficacy, onset and duration of action, and the safety of ketotifen fumarate 0.025% ophthalmic solution and emedastine difumarate 0.05% ophthalmic solution in subjects with seasonal allergic conjunctivitis (SAC) induced by allergen exposure, using the Vienna Challenge Chamber model. This was a double-masked, randomised, comparative, crossover study conducted at an allergy outpatient clinic in Austria. Subjects with an allergy to grass pollen were exposed to the allergen in a pollen chamber for 4 hours, followed by a 3-hour break and then a second exposure for 3 hours. Study participants were randomised to a treatment sequence (ketotifen followed by emedastine or emedastine followed by ketotifen), receiving 1 drop per eye of ketotifen or emedastine 2 hours after the initial allergen exposure in the pollen chamber. Individual and composite ocular, individual and composite nasal, and total (ocular + nasal) symptom complex scores were determined by repeated exposure to allergen 0-2 hours and 5-8 hours after dosing. Onset of action was defined as the time to the first observation of a 20% reduction from baseline in the composite ocular symptom score. All 37 subjects enrolled completed the study. The median time to onset of action was 15 minutes for ketotifen and 30 minutes for emedastine. This difference was significant using the generalised linear model (p = 0.048), but not for the log-rank test analysis. In the initial 2 hours post dose, ketotifen provided significantly greater relief of both composite ocular symptoms (p = 0.026) and total symptom complex (p = 0.014). Both medications were effective in reducing symptoms 5 to 8 hours after dosing. No adverse events were reported for either treatment. In the Vienna Challenge Chamber model, ketotifen and emedastine both effectively alleviated ocular symptoms of SAC after single-dose administration. Ketotifen had a faster onset of action and provided better symptom relief than emedastine during the first 2 hours after dosing. The rapid onset of action and symptom control make ketotifen a valuable treatment for SAC.

Onset of action, efficacy, and safety of fexofenadine 60 mg/pseudoephedrine 120 mg versus placebo in the Atlanta allergen exposure unit

Second-generation antihistamine-decongestant combinations are often used to treat seasonal allergies. However, onset of action and efficacy data for these agents in a controlled setting are limited. Determine onset of action of fexofenadine-pseudoephedrine (Allegra-D, Aventis, Bridgewater, NJ) for treating moderate-to-severe seasonal allergies in an allergen exposure unit. This single-dose, double-blind, placebo-controlled study was conducted during the fall ragweed allergy season. Qualifying subjects attended one to two priming visits; those with sufficient symptom scores returned for treatment and were initially exposed to ragweed pollen for 90 minutes. Symptomatic subjects received fexofenadine-pseudoephedrine or placebo and recorded symptoms for 6 hours postdose. Efficacy variables were major symptom complex (MSC; sneezes, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, stuffy nose), total symptom complex (nose blows, sniffles, postnasal drip, cough, plus all MSC symptoms), and all individual symptoms as well as headache. Onset of action for each efficacy variable was calculated as the earliest time at which a consistent, significant decrease was seen for fexofenadine-pseudoephedrine versus placebo. Of 571 screened subjects, 298 were randomized. Onset of relief for fexofenadine-pseudoephedrine (n = 148) was 45 minutes postdose (MSC, P = 0.0127; total symptom complex, P = 0.0380). All individual symptoms were reduced to a greater extent with fexofenadine-pseudoephedrine than with placebo (P < 0.05, not adjusted for multiple comparisons). Decrease in headache with fexofenadine-pseudoephedrine versus placebo began 45 minutes postdose (P = 0.0425). Incidence of treatment-related adverse events was 1.4% for fexofenadine-pseudoephedrine and 3.3% for placebo. Fexofenadine-pseudoephedrine was safe and effective in treating a broad range of allergy symptoms, with a rapid onset of action at 45 minutes.

Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with seasonal allergic rhinitis: confirmation of a test system

The environmental exposure unit (EEU) is an instrument designed to determine onset of action of antiallergic treatment. Confirmation of test results would be useful in defining its role. This study was intended to confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU using an identical protocol design (randomized, double-blind, parallel-group comparison having the same symptom scoring system, endpoints, and statistical analyses), thus demonstrating reproducibility of studies conducted in the EEU. Onset of action and symptom relief with once-daily cetirizine 10 mg, loratadine 10 mg, and placebo (n = 120 each group) were evaluated replicating a previous study design. Subjects meeting inclusion and exclusion criteria and qualifying symptom scores were randomized to 2 days' exposure (6 to 7 hours daily) with treatment. Changes in total and major symptom complex (TSC, MSC) scores based on 14 symptoms evaluated at 30-minute intervals served as primary efficacy variables. Onset of action again was earlier with cetirizine (at 1 hour, P < or = 0.001) versus loratadine (at 3 hours, P < or = 0.01). Cetirizine produced a 25.4% least-square mean reduction in TSC scores overall versus an 11.2% decrease with loratadine (P = 0.006) and a 4.8% increase with placebo (P < 0.001); loratadine and placebo were also significantly different (P = 0.002). Similar changes were also noted in MSC scores. Cetirizine consistently reduced TSC and MSC scores after the first dose versus placebo (P < or = 0.001) and at most time points versus loratadine (P < or = 0.05). Adverse events were reported in 1.7% of patients in each active-treatment group and in 2.5% on placebo. Cetirizine acted earlier and was more effective than loratadine or placebo in reducing symptoms of seasonal allergic rhinitis in subjects undergoing a controlled pollen challenge, replicating results from an earlier, identically designed study, demonstrating reproducibility of these assessments by the EEU.

Controlled Comparison of the Efficacy and Safety of Cetirizine 10 mg o.d. and Fexofenadine 120 mg o.d. in Reducing Symptoms of Seasonal Allergic Rhinitis

Background: The efficacy, onset and duration of action and safety of cetirizine 10 mg o.d., fexofenadine 120 mg o.d., and placebo were compared in this investigator-blinded, crossover study involving the use of the Vienna Challenge Chamber. Methods: 40 volunteers with seasonal allergic rhinitis were exposed to a controlled grass pollen concentration for 6 h on 2 consecutive days. Subjective symptoms and objective measurements were recorded during the allergen exposure periods. Results: Both active medications were significantly more effective than placebo and had a comparable onset of action in alleviating the symptoms of seasonal allergic rhinitis. The efficacy of both active drugs was comparable for the first 4 h after administration of the drugs on day 1 and day 2. However from 22 to 24 h after the first dose cetirizine was significantly superior to fexofenadine for the major symptom complex score and for sneezing. Concerning the total symptom complex score at day 2 fexofenadine could not reach superiority to placebo. No serious adverse events were reported. Conclusions: Cetirizine and fexofenadine were significantly better than placebo, also in reducing the symptom of nasal congestion. However cetirizine appears to have a longer duration of action than fexofenadine.

Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: Effects after controlled ragweed pollen challenge in an environmental exposure unit

Background: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer once-daily selective H 1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. Objective: To better characterize the efficacy and onset of action of cetirizine in a more controlled but clinically relevant setting, this agent was compared with loratadine and placebo in patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an environmental exposure unit (EEU). Methods: This was a double-blind, randomized, parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six exposures), and those with qualifying symptom scores were randomized to controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg cetirizine ( n = 67), 10 mg loratadine ( n = 67), or placebo ( n = 68). The mean ragweed pollen level was 3480 ± 350 grains/m 3 (standard deviation). The primary efficacy variables were the total symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated every half hour in the EEU throughout the study. Results: Cetirizine produced a 36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo ( p ≤ 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7% with loratadine and 6.7% with placebo ( p ≤ 0.01). Onset of action as assessed by reductions in TSC and MSC scores versus placebo was evident within 1 hour with cetirizine ( p ≤ 0.02) and 3 hours with loratadine ( p ≤ 0.03). The incidence of treatment-related side effects was similar among groups, with headache reported most commonly in each group. Conclusion: Cetirizine is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing controlled pollen challenge.(J Allergy Clin Immunol 1998;101:638-45.)

Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis

BACKGROUND: Cetirizine, a new once-daily highly specific H 1-antagonist, has been shown in conventional studies to be efficacious in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy, duration and onset of action, and safety of cetirizine, 10 mg once daily, was compared with that of loratadine, 10 mg once daily, and placebo in a field study of patients with seasonal allergic rhinitis. METHODS: This was a randomized, double-blind, parallel, double-dummy study conducted over 2 days in spring allergy season at outdoor parks in San Diego and Iowa City. Study medication was administered at 10:00 AM on both days. After screening, eligible patients completed rhinitis symptom diaries in the park hourly from 7:30 to 9:30 AM (baseline); at 10:30 AM and hourly from 11:00 AM to 4:00 PM (period I); at 6:00, 8:00, and 10:00 PM at home (period II); and the next day in the park hourly from 8:00 to 10:00 AM (period III), and from 11:00 AM to 4:00 PM (period IV). Major and total symptom complex scores, global efficacy and overall satisfaction, and adverse events were assessed. RESULTS: Of the 279 patients (140 men and 139 women; mean age, 29 years) randomized to treatment, 278 were included in the efficacy analysis. Cetirizine produced significantly greater mean reductions than loratadine or placebo in major symptom complex severity scores at all periods ( p ≤ 0.05), except period I for placebo. Cetirizine also produced mean reductions in total symptom complex severity scores that were superior to loratadine at every evaluation period ( p < 0.05) and were statistically different from placebo at period II ( p < 0.01). A rapid onset of action was observed with cetirizine, as was a better response pattern in the patient global assessment of efficacy compared with loratadine. Study medications were well tolerated; no patient stopped treatment because of side effects. The incidence of somnolence with cetirizine was 13% versus 2% with placebo ( p < 0.05); headache occurred more frequently with loratadine (23%) than with cetirizine (11%, p = 0.03). CONCLUSION: Cetirizine relieved rhinitis symptoms more effectively and quickly than loratadine and placebo in this field study of seasonal allergic rhinitis. Both active agents were generally well tolerated. (J A LLERGY C LIN I MMUNOL 1996;97:617-26.)

A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis

Background: Azelastine solution is a topically (nasal) administered antiallergy drug with a preclinical profile suggestive of efficacy in patients with allergic rhinitis. Objectives: The study was designed to compare the effectiveness and safety of two dosages of azelastine nasal spray (2 sprays per nostril once daily and twice daily) with that of placebo in the treatment of patients with symptomatic seasonal allergic rhinitis. Methods: Two hundred fifty-one patients (12 years of age or older) were randomized to treatment in this 2-week, double-blind, parallel-group study. Primary efficacy variables were Major Symptom Complex (nose blows, sneezes, runny nose, itchy nose, watery eyes) and Total Symptoms Complex (Major Symptom Complex plus itchy eyes/ears/throat/palate, cough, postnasal drip). Results: Patients treated with azelastine had mean percent improvements in Total and Major Symptom Complex scores that were consistently superior to placebo at each evaluation point. Overall, improvements were statistically significant ( p ⩽ 0.05) in the Total Symptoms Complex for both azelastine groups and in the Major Symptom Complex for the twice daily group with a trend toward statistical significance for the once daily group. Azelastine was superior to placebo in improving all individual rhinitis symptoms. Adverse experiences in the azelastine groups were minor and infrequent. Conclusion: The results support the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis.

The Effectiveness of Oral Azelastine in the Management of Perennial Allergic Rhinitis

Azelastine, a phthalazinone derivative, is a chemically novel antiallergy compound that inhibits inflammatory responses in the upper and lower airway. Previous clinical trials demonstrated the effectiveness of azelastine in the treatment of allergic rhinitis. The objective of this double-blind trial was to further evaluate the efficacy and safety of oral azelastine compared with placebo in patients with perennial allergic rhinitis. A total of 192 patients (between 13 and 60 years of age) who satisfied a minimum symptom score during a single-blind placebo evaluation period were randomized to receive one of three treatments: 2 mg of azelastine b.i.d., 1.34 mg of clemastine fumarate b.i.d., or placebo b.i.d. for a 4-week double-blind treatment period. In the primary efficacy analysis, rhinitis symptoms were analyzed as a Total Symptom Complex severity score (nose blows, runny nose, sneezes, stuffy nose, itchy nose, and itchy eyes/ears/throat). After 2 and 4 weeks of therapy, the azelastine group had greater mean percent improvements than the placebo group in the Total Symptom Complex severity scores. The overall and endpoint improvements for the azelastine group were statistically significant (P ≤ .026) versus placebo. Improvements in individual rhinitis symptoms for the azelastine group were superior to placebo for nose blows, runny nose, sneezes, itchy nose, and itchy eyes/ears/throat. Azelastine was well tolerated. Clemastine was also significantly more effective than placebo and was well tolerated. The results support oral azelastine's safety and effectiveness in the treatment of perennial allergic rhinitis.

Effectiveness of Azelastine Nasal Solution in Seasonal Allergic Rhinitis

Azelastine is a novel antiallergy medication currently under investigation for the treatment of allergic rhinitis and asthma. Pharmacologic studies in laboratory animals and in vitro model systems indicate that azelastine exerts multiple actions including modulation of airways smooth muscle response, interference with inflammatory processes, and inhibition of allergic reactions. In a previous controlled clinical trial, azelastine nasal solution (ASTELIN N.S.) demonstrated effectiveness in controlling symptoms of seasonal allergic rhinitis (SAR). The objective of this 2-week double-blind, parallel-group study was to further assess the effectiveness of azelastine nasal solution in improving allergic rhinitis symptoms. Two hundred forty-seven patients (> or = 12 years) with symptomatic SAR who satisfied a minimum symptoms score during a 1-week, single-blind, baseline evaluation period were randomized to receive azelastine 2 sprays per nostril bid, azelastine 2 sprays per nostril qd, chlorpheniramine 12 mg bid, or placebo using a double-dummy technique to insure blinding. The primary efficacy variables were changes in Major Symptom Complex (nose blows, sneezes, runny nose/sniffles, itch nose, and watery eyes) and Total Symptom Complex (Major plus itchy eyes/ears/throat/palate, cough, and postnasal drip) severity scores. Patients treated with azelastine nasal solution qd and bid had mean percent improvements in the Total and Major Symptom Complex severity scores that were clinically significant (> or = 50% improvement over placebo) after both weeks, at endpoint, and overall. The improvements for the azelastine bid group were statistically significant (P < or = .05) at all evaluation points. Adverse experiences occurred infrequently, and none was considered serious or potentially limiting to the clinical utility of the nasal solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the efficacy of dicyclomine hydrochloride (‘Merbentyl’) syrup in the treatment of infant colic

SummaryA double-blind crossover trial was carried out in 25 babies with infant colic to compare the symptomatic relief provided by dicyclomine hydrochloride (5mg4-times daily) or placebo. Patients received each treatment, in random order, for 1 week. A scoring system was used to measure the total symptom complex as well as the individual parameters of post-prandial crying, post-prandial vomiting, and sleep disturbance. Dicyclomine hydrochloride syrup was found to be superior to placebo in relieving the total symptom complex (p < 0.025) and in reducing sleep disturbance (p < 0.05). Side-effects with both therapies were minimal.

Frequency of repetitive behaviors in early infantile autism and its variants.

EXTENSIVE clinical observations of children usually diagnosed as autistic, schizophrenic, symbiotic-psychotic, and with "atypical ego development" indicate that they manifest similar features and can be best understood as suffering from variants of a single disease¹. Their symptoms can be grouped into five subclusters which make their similarities clear: (1) disturbances of perception, (2) disturbances of motor behaviors, (3) disturbances in the ability to relate to others, (4) absent or pathologic language development, and (5) disturbances of developmental rate. The disturbances of perception appear to be fundamental to the other aspects of the disease. The total symptom complex suggests that there is an underlying neuropathology²which leads to periodic overloading and underloading of the central nervous system. These alternating states of excessive facilitation and inhibition vary the child's awareness and response to the same stimuli and causes what we have termed perceptual inconstancy.