Individual Symptom Scores Research Articles

A six‐month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia

A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, as evidenced by low serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms. FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill). A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated. Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.

Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5–grass pollen tablet for seasonal allergic rhinitis

Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition. To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis. In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5-grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments. Both the 300-index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 +/- 3.0, P = .0001; and 3.74 +/- 3.1, P = .0006, respectively) compared with placebo (4.93 +/- 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 +/- 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported. In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo. The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.

Acupuncture for persistent allergic rhinitis: a randomised, sham‐controlled trial

To investigate the effectiveness and safety of acupuncture in persistent allergic rhinitis (PAR) DESIGN: Randomised, single-blind, sham-controlled trial conducted from May 2004 to February 2005. 80 patients with PAR (age, 16-70 years) were randomly assigned to receive real or sham acupuncture. After a 1-week baseline period, participants were treated twice weekly for 8 weeks and followed up for another 12 weeks. Nasal obstruction, sneezing, rhinorrhoea and nasal itch were each self-assessed daily on a 5-point scale, and scores were aggregated weekly. The sum of the symptom scores (total nasal symptom score, TNSS) was also determined. A secondary outcome was use of PAR relief medication. After 8 weeks' treatment, the weekly mean difference in TNSS from baseline was greater with real (-17.2; 95% CI, -24.6 to -9.8) than with sham acupuncture (-4.2; 95% CI, -11.0 to 2.7) (P = 0.01). The decrease in individual symptom score was also greater with real acupuncture for rhinorrhoea (P < 0.01) but not the other symptoms. At the end of follow-up, the greater difference in TNSS from baseline in the real acupuncture group was still apparent: real, -21.0 (95% CI, -29.1 to -12.9) versus sham, - 2.3 (95% CI, -10.2 to 5.6) (P = 0.001). Moreover, the differences from baseline in all four individual symptom scores were greater for the real than for the sham group (P < 0.05). Real and sham acupuncture were both well tolerated. Our findings suggest that acupuncture is effective in the symptomatic treatment of PAR. Australian Government Therapeutic Goods Administration CTN 034/2004.

Rhinosinusitis Task Force Symptoms versus the Sinonasal Outcomes Test in Patients Evaluated for Chronic Rhinosinusitis

The aim of this study was to compare Rhinosinusitis Task Force (RSTF) symptom scores with Sinonasal Outcome Test 20 (SNOT-20) in patients with chronic rhinosinusitis (CRS) and controls. An analysis was performed of prospectively collected data in patients with CRS (n=201) and controls (n=100). The severity of individual RSTF major and minor symptom scores graded on a visual analog scale and total symptom scores were compared between the two groups. Correlation of the RSTF symptoms with the SNOT-20 was performed using data collected from the CRS group at baseline and at 1 year postoperatively. CRS patients had higher RSTF symptom scores compared with control patients when asked to rate the severity of nasal obstruction, facial pain/pressure, facial congestion, alteration of smell, nasal discharge, postnasal drip, headache, halitosis, fatigue, cough, and ear pain (p < 0.005). No statistically significant difference was seen for the symptoms of dental pain and fever. Total RSTF scores were 54.5 +/- 1.9 in CRS patients versus 23.4 +/- 3.0 in controls. Total SNOT-20 scores were 28.7 +/- 0.8 in CRS patients versus 15.2 +/- 0.6 in controls. In CRS patients, total RSTF scores correlated with total SNOT-20 scores at baseline (r = 0.36; p < 0.0001) and 1-year postoperatively (r = 0.37; p < 0.0001). Total RSTF symptom scores are significantly different in patients with chronic rhinosinusitis compared with those without this disease. The total RSTF symptom scores also correlate with a validated outcome measures instrument.

Donepezil in Alzheimer's disease: a clinical observational study evaluating individual treatment response

ABSTRACTObjective: A post-marketing surveillance study evaluating the sensitivity of the Individual Symptom Score (IndiSS) in assessing the treatment benefits of donepezil in patients with Alzheimer's disease (AD) under everyday conditions.Research design and methods: For each patient, up to three ‘especially relevant’ individual symptoms were defined and evaluated during donepezil treatment. Changes were scored on a five-point Likert-type scale, ranging from ‘markedly improved’ (+2) to ‘markedly worsened’ (–2). The mean score for all IndiSS items was calculated after 3 and 6 months. Positive values represented treatment success. In addition, patients with concomitant parkinsonian symptoms (PS+) or cerebrovascular disease (CVD+) were compared with those with neither condition.Results: A total of 2046 patients with AD enrolled. The most frequent IndiSS items were (% patients): memory (24%), disorientation (14%) and loss of initiative/apathy (9%). The mean IndiSS for the overall patient population was +0.7 ± 0.7 points after 3 months and +0.9 ± 0.8 after 6 months. Patients with concomitant PS+ or CVD+ showed similar improvements in IndiSS.Conclusion: Identification and follow-up of individual symptoms is a useful tool for evaluating therapy response to donepezil in everyday practice. Patients with concomitant PS+ or CVD+ benefit from donepezil therapy and show a similar side-effect profile.

Efficacy of an oncology palliative care clinic for improving symptom management and patient satisfaction

19552 Background: Previous studies to assess symptom control in a palliative care clinic setting have largely been retrospective. This study prospectively assesses the efficacy of an Oncology Palliative Care Clinic (OPCC) for improving symptom management and satisfaction with cancer care. Methods: All consenting patients newly referred to the OPCC completed the Edmonton Symptom Assessment System (ESAS) and the FAMCARE Scale (modified for patient use) at baseline, one week, and one month. The primary outcomes were the ESAS distress and FAMCARE total scores, for which one-week analyses are presented (paired t-test). Individual ESAS symptom scores were also assessed in an exploratory analysis, with the p-value set at 0.01 to provide some protection from multiple comparisons. Results: 118 patients, all with metastatic cancer, have completed the one-week assessment. The mean ESAS symptom distress score at baseline was 38.31±18.34. One week after the initial OPCC assessment there was a mean decrease in the distress score of 7.94 units (95%CI 5.11–10.76, p&lt;0.0001). The mean baseline score for patient satisfaction was 66.31±13.23, with a mean increase of 7.22 points at one week (95%CI 4.51–9.94, p&lt;0.0001). Individual symptom scores that showed the greatest improvement were anxiety (improved 1.40 units; p&lt;0.0001), nausea (1.16 units, p = 0.0001), dyspnea (1.08 units; p = 0.0003), insomnia (0.97 units, p = 0.0003), pain (1.01 units, p = 0.0018), drowsiness (0.93 units, p = 0.0083), appetite (0.86 units, p = 0.0023) and fatigue (0.77 units p = 0.0039). The only symptoms that did not reach statistical significance were constipation (improved by 0.71, p = 0.053) and depression (0.6 units, p = 0.018). Conclusions: One week after assessment in an OPCC, there were significant improvements in symptom distress and satisfaction with care. It remains to be determined whether or not these results will be sustained at one month. Randomized controlled trials of the effectiveness of an OPCC are needed. No significant financial relationships to disclose.

Association of physical and psychological symptom burden with time to death among palliative cancer outpatients

19523 Background: Patients with terminal cancer have a high symptom burden, which tends to increase as death approaches. Previous studies have assessed the association of symptom burden with time to death (TTD) among inpatients or using baseline data for patients enrolled in a trial. Our purpose was to determine the association of symptom burden with TTD in patients who were followed by an outpatient palliative oncology clinic (OPOC). Methods: Cancer patients seen in the OPOC between January 2005 to June 2006 and who subsequently died were identified from the palliative care database. The last outpatient Edmonton Symptom Assessment Scale (ESAS) score completed in clinic was compared among patients in the last 4 months of life. Multiple linear regression was used to determine the association of ESAS total symptom distress score (SDS), physical subscore (PHS), psychological subscore (PSS) and individual symptom scores with demographic parameters, disease characteristics and TTD. Results: In total, 198 patients were identified. All patients had stage IV cancer, the mean age was 63.8 years (SD 12.9) and 55% were male. Median survival time from initial assessment was 6.6 weeks (range 0.3 to 16.7) and mean SDS was 46.0 (SD 18.0). Sites of cancer included gastrointestinal (36%), lung (12%), genitourinary (10%), hematological (8%), gynecological (8%), breast (7%) and others (19%). There was no significant association between symptom burden and gender, age or cancer site. TTD was significantly associated with SDS (p&lt;0.001) and PHS (p&lt;0.001), but not with PSS (p=0.19). Individual symptoms most strongly associated with TTD were fatigue (p=0.001), appetite (p=0.001), drowsiness (p=0.0005) and shortness of breath (p=0.0008). There was no significant association between TTD and depression (p=0.24) or anxiety (p=0.20). Conclusions: In this outpatient palliative cancer population, the association between TTD and symptoms held true only for physical symptoms, particularly constitutional symptoms and shortness of breath which are amenable to therapy. Symptoms in palliative patients should be rigorously assessed and treated, regardless of prognosis and especially at end-of-life. No significant financial relationships to disclose.

Important Clinical Symptoms in Patients Undergoing Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis

To evaluate the prevalence and severity of individual Rhinosinusitis Task Force (RSTF) symptoms in patients with chronic rhinosinusitis (CRS) undergoing functional endoscopic sinus surgery (FESS). Retrospective analysis of prospectively collected data in 201 patients treated with FESS. The prevalence and severity of individual RSTF major and minor symptom scores graded on a visual analogue scale (VAS) were compared. Correlation between absolute improvement in individual symptom scores at 1-year postoperative was performed. One-hundred fifty-eight of 201 patients met inclusion criteria giving a response rate of 78%. The average age was 49.4 (range 18-80) with a male-to-female ratio of 1.1:1. The preoperative leading mean symptom scores were postnasal drip (5.8 +/- 0.3), nasal obstruction (5.7 +/- 0.3), and facial congestion (5.1 +/- 0.3). These symptoms were also the most prevalent with 82%, 84%, and 79% of patients reporting these symptoms, respectively. Postoperative symptom improvements were significant (P < .0001) across all RSTF domains except fever. The highest percentage improvement was seen with facial congestion (93%), nasal obstruction (92%), and postnasal drip (85%). Multivariate analysis revealed significant (P < .0001) high correlation between improvements of facial pain/pressure with facial congestion (R = 0.72), facial congestion with nasal obstruction (R = 0.65), and facial pain/pressure with headache (R = 0.72). The top three RSTF symptoms were postnasal drip, nasal obstruction, and facial congestion in terms of prevalence and severity. Symptom scores improved after FESS. Of these symptoms, the degree of improvement of facial pain/pressure, facial congestion, nasal obstruction, and headache are highly correlated.

Efficacy of a single evening dose of a syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple common cold symptoms

The aim of this study was to evaluate the efficacy of a single night-time dose of a syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple cold symptoms. A syrup containing 15 mg dextromethorphan hydrobromide, 7.5 mg doxylamine succinate, 600 mg paracetamol and 8 mg ephedrine sulfate (Wick MediNait produced by WICK Pharma, Germany, a subsidiary of Procter & Gamble GmbH; test syrup) or placebo (placebo syrup) for oral administration. This was a randomized, double-blind, placebo-controlled, multi-center, parallel design study. At enrollment, eligible subjects had to have at least moderate nasal congestion and a runny nose, at least mild cough and at least mild pain with one or more of the following: sore throat, sore chest, headache or body pain/aches. Subjects were randomized into either Group T (test syrup) or Group P (placebo syrup). On the evening of enrollment, subjects rated baseline symptoms, ingested the assigned study product and completed symptom-relief assessments at 3 hours post-dosing. Within one hour of awakening the following morning, subjects completed night-time symptom relief and sleep satisfaction assessments. All symptoms were recorded using an Interactive Voice Response system. Treatment comparisons were made after adjusting for the severity of baseline symptom using analysis of covariance. Of 485 subjects who took the study product, 432 (224 in Group T; 208 in Group P) were evaluable for analysis. For the primary endpoint (composite of nasal congestion/runny nose/cough/pain relief scores 3 hours post-dosing), subjects in Group T had clinically and statistically significantly greater relief than Group P (p = 0.0002). Each individual symptom score also showed statistically significant improvement at this time point (p < or = 0.017). The next morning, Group T continued to show clinically and statistically significant benefits over Group P on the composite score and each of the individual symptoms (p < or = 0.003). Evidence of benefit with the test syrup was also seen in the higher score for overall night-time relief (p < 0.0001) and greater satisfaction on sleep (p = 0.002) compared to placebo syrup. Improvement in individual symptoms after 3 hours was obtained in 16-42% more subjects in Group T than in Group P, whereas the percentage of subjects in Group T having Good or Very Good relief the morning after dosing increased by 25-68% compared to subjects in Group P. 14 subjects (5 in Group T; 9 in Group P) reported AEs but none of these occurred with an incidence greater than 1%. There were no serious AEs. The results confirm the multisymptom benefit of a single dose of the test syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate and support its role as an effective and convenient therapy for symptoms of nasal congestion, runny nose, cough and pain/body aches associated with the common cold and for increasing sleep quality disturbed by the common cold.

Effectiveness of desloratadine 5 mg once daily in patients with symptoms of seasonal allergic rhinitis: Results of a Canadian multicenter, open-label trial

Background: Seasonal allergic rhinitis (SAR) is an inflammatory response to seasonal allergens. Desloratadine, a once-daily selective histamine H 1-receptor antagonist, has been reported to be efficacious in relieving symptoms of SAR in controlled clinical trials. However, to assess the actual effectiveness of a drug, it is important to examine information about its use in routine clinical practice. Objective: The Partners in Allergy Control and Therapy (PACT) study examined the effectiveness of desloratadine in patients with SAR symptoms receiving treatment in a community setting of primary care physicians in Canada. Methods: Patients with symptoms of SAR received desloratadine 5 mg once daily for 7 days during the spring-summer allergy season (April–July 2002). Patients rated their SAR symptoms along with their physicians by completing a questionnaire at baseline and day 7. Nasal, ocular, respiratory, and overall symptoms were rated on a scale of 0 (no symptoms evident) to 3 (severe/interfere with activities of daily living and/or sleeping). Physicians were asked to keep a record of adverse events reported by patients. The Wilcoxon signed-rank test was used to evaluate symptom severity scores. A 2-way (time x treatment), repeated measures, mixed analysis of variance (ANOVA) model was constructed to assess differences in variables over time. Results: A total of 6829 patients participated in the study. Patients reported nasal stuffiness/congestion as their most severe symptom. Just over half (50.1%) of patients were receiving another medication for SAR at study entry; 29.7% were receiving an intranasal corticosteroid. After 7 days of treatment with desloratadine, individual symptom scores and overall symptom scores were significantly reduced compared with baseline (all scores, P < 0.001). An improvement in nasal/stuffiness/ congestion was reported by 88.0% of patients. The ANOVA detected a statistically significant incremental benefit with desloratadine and an intranasal corticosteroid compared with desloratadine monotherapy ( P < 0.001). No severe adverse events were reported. Conclusion: Desloratadine 5 mg once daily was associated with significant improvement in symptoms of SAR, and appeared to provide additional benefit in relieving moderate to severe nasal stuffiness/congestion in 6786 patients receiving 7-day treatment in an actual practice setting of primary care physicians in Canada.

Mometasone Furoate Nasal Spray Improves Nasal and Ocular Symptoms of Seasonal Allergic Rhinitis in Adolescent Patients

Symptoms of Seasonal Allergic Rhinitis in Adolescent Patients R. Anolik, D. Pearlman, M. Danzig, D. Gates; Allergy & Asthma Specialists, PC, Blue Bell, PA, Colorado Allergy and Asthma Centers, PC, Denver, CO, Schering-Plough Research Institute, Kenilworth, NJ. RATIONALE: In a population of adolescents, a demographic with a high incidence of seasonal allergic rhinitis (SAR), data for mometasone furoate nasal spray (MFNS) was examined. METHODS: Data from patients aged 12 to 17 years with symptomatic SAR enrolled in a phase III study were analyzed. These patients, who were part of a larger trial, were randomized to treatment with MFNS 200 mcg qd (n586) or placebo (n582) for 15 days. Symptom severity scores (05none; 35severe) were recorded in patient diaries twice daily. Endpoints included changes from baseline in total nasal symptom score (TNSS), as well as individual symptom scores and total ocular sign/symptom scores (TOSS). The endpoints were the same as those for the total study population. RESULTS: Over the 15 days of treatment, a significantly greater decrease from baseline in mean TNSS was observed with MFNS (-2.47; 28.8% decrease) compared with placebo (-0.9; 9.6% decrease) (P<0.001). In addition, MFNS demonstrated statistically significant improvements over placebo for each full day of the treatment period. Over the 15 days, improvements were seen with MFNS for each individual symptom: congestion (-0.66 vs -0.16; P<0.001); rhinorrhea (-0.63 vs -0.19; P<0.001); sneezing (-0.66 vs -0.26; P<0.001); and nasal itching (-0.52 vs -0.28; P50.03). The MFNS group demonstrated greater improvement in mean TOSS compared with the placebo group (-1.31 vs -0.55; P50.011). No serious adverse events were reported. CONCLUSIONS: In adolescents with symptomatic SAR, MFNS 200 mcg qd was shown to provide significant improvement in nasal and ocular J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 1 Abstracts S61

Montelukast in the Treatment of Allergic Rhinitis

Cysteinyl-leukotrienes (CysLTs) are endogenous mediators of inflammation and play an important role in allergic airway disease by stimulating bronchoconstriction, mucus production, mucosal oedema and inflammation, airway infiltration by eosinophils, and dendritic cell maturation that prepares for future allergic response. Montelukast inhibits these actions by blocking type 1 CysLT receptors found on immunocytes, smooth muscle and endothelium in the respiratory mucosa. Initially developed as a treatment for asthma, montelukast has more recently found use in the treatment of allergic rhinitis (AR). We conducted a systematic review of studies that have evaluated montelukast in the treatment of seasonal AR (SAR) and perennial AR (PAR), with and without concomitant asthma. Primary consideration was given to large, randomised, placebo-controlled, double-blind clinical trials in which AR endpoints were assessed and the use of concurrent treatments for AR was excluded. Eight such studies were found in the literature. The primary endpoint in these was daytime nasal symptom severity represented by a composite score derived from individual self-ratings of nasal congestion, rhinorrhoea, nasal pruritus and sneezing. Secondary endpoints have included these individual nasal symptom scores, additional scores for eye, ear and throat symptoms, the impact of rhinitis on quality of sleep, global evaluations of outcome by patients and physicians, and measures of the severity of concomitant asthma. A general outcome was that patients treated with montelukast had significantly greater improvements in their symptoms of SAR and PAR than did patients who were given a placebo. As monotherapy, montelukast exhibited efficacy similar to that of loratadine, but less than that of the intranasally administered corticosteroid fluticasone propionate. The use of montelukast in combination with antihistamines such as loratadine or cetirizine has generally resulted in greater efficacy than when these agents were used alone, and in some studies has produced results comparable with intranasally applied corticosteroids. In patients with AR comorbid with asthma, montelukast treatment has resulted in significant improvements in both, compared with placebo. Montelukast is well tolerated and has a favourable safety profile; adverse events have occurred at similar frequencies in patients taking either montelukast or placebo. Montelukast provides an effective and well tolerated oral treatment for allergic airway inflammation in patients with SAR or PAR without asthma, and in patients in whom AR is comorbid with asthma.

Neostigmine-Induced Postprandial Phasic Contractility in the Proximal Stomach and Dyspepsia-Like Symptoms in Healthy Volunteers

In a subset of functional dyspepsia patients, we have recently described the association between unsuppressed postprandial phasic contractions of the proximal stomach and a specific symptom pattern. To better elucidate the role of phasic contractility of the proximal stomach in symptom generation, we aimed at inducing this motility pattern in healthy volunteers and we carefully monitored symptom onset. Eleven healthy volunteers underwent gastric barostat on two separate days. Gastric tone and phasic contractility were evaluated for a 90-minute period. In particular, after 30 min of basal recording, a caloric liquid meal and neostigmine 0.5 mg IV or saline in a double-blind, randomized, crossover protocol were administered. During the measurement, severity of 9 dyspeptic symptoms was evaluated on a visual analog scale. Computer-aided baseline reconstruction allowed us to quantify phasic contractions as a motility index (MI), reflecting the area between signal and baseline normalized over time. Perception of contractions after placebo or neostigmine was evaluated. Moreover, we tested for influence of gastric tone and phasic contractility on symptoms. After neostigmine, gastric accommodation was not different than after placebo (225 +/- 36 vs 206 +/- 76 mL, P= NS). During the first 30-min postprandial period, the MI was significantly higher after neostigmine than after placebo (26.4 +/- 3 vs 21.4 +/- 3, P < 0.001), confirming the induction of unsuppressed postprandial phasic contractions. The postprandial total symptom score was significantly higher after neostigmine compared to saline; several individual postprandial symptom scores were also significantly higher after neostigmine-compared placebo. After neostigmine, a higher percentage of postprandial contractions was perceived compared to placebo. Unsuppressed postprandial phasic contractility of the proximal stomach is a mechanism potentially involved in the pathogenesis of dyspeptic symptoms.

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.

Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis

In fall 2004, the first Azelastine Cetirizine Trial demonstrated statistically significant improvements in the total nasal symptom score (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores with the use of azelastine nasal spray vs oral cetirizine in patients with seasonal allergic rhinitis (SAR). To compare the effects of azelastine nasal spray vs cetirizine on the TNSS and RQLQ scores in patients with SAR. This 2-week, double-blind, multicenter trial randomized 360 patients with moderate-to-severe SAR to azelastine, 2 sprays per nostril twice daily, or cetirizine, 10-mg tablets once daily. The primary efficacy variable was the 12-hour reflective TNSS (rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were individual symptom scores and the RQLQ score. Azelastine nasal spray and cetirizine significantly improved the TNSS and individual symptoms compared with baseline (P < .001). The TNSS improved by a mean of 4.6 (23.9%) with azelastine nasal spray compared with 3.9 (19.6%) with cetirizine. Significant differences favoring azelastine nasal spray were seen for the individual symptoms of sneezing and nasal congestion. Improvements in the RQLQ overall (P = .002) and individual domain (P < or = .02) scores were greater with azelastine nasal spray. Both treatments were well tolerated. Azelastine nasal spray and cetirizine effectively treated nasal symptoms in patients with SAR. Improvements in the TNSS and individual symptoms favored azelastine over cetirizine, with significant differences for nasal congestion and sneezing. Azelastine nasal spray significantly improved the RQLQ overall and domain scores compared with cetirizine.

A Prospective, Randomized, Double-blind, Placebo-Controlled Multi-centre Study on the Efficacy and Safety of Sublingual Immunotherapy (SLIT) in Children With Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

Purpose of the Study. Subcutaneous immunotherapy (SCIT) for seasonal allergic rhinitis is a well-established, effective, and potentially curative therapy. This study evaluated an alternate route for immunotherapy: the oral mucosa and gastrointestinal tract. Study Population. Ninety-seven children, aged 3 to 14 years, with seasonal allergic rhinitis and proven sensitivity to grass pollen were studied. Methods. Sensitivity to grass pollen was confirmed by positive skin-prick test, grass pollen–specific immunoglobulin E, and conjunctival provocation test. Patients were enrolled in a prospective, double-blind trial comparing sublingual immunotherapy (SLIT) to placebo. The treatment duration was 32 months. The primary outcome measure was the change in a multiple-symptom/medication score (which measured eye, nasal, and lung symptoms and rescue-medication use) after treatment. Data collected included patient-reported symptom scores and medication use, total and antigen-specific immunoglobulin E, skin-prick test, conjunctival provocation test, nasal provocation test, spirometry, exhaled nitric-oxide concentration, atopic dermatitis score, and eosinophilic cationic protein in nasal lavage fluid. Results. The multiple-symptom/medication score was significantly reduced by SLIT to 77.3% of the placebo group (P = .049). This overall score was affected mainly by a large reduction in rescue-medication usage among those in the treatment group (67% of placebo; P = .0025). There was no significant difference in any individual-symptom score. Conclusion. SLIT had a positive effect on rescue-medication usage but no significant effect on symptoms alone. Reviewer Comments. SLIT represents an alternative therapy with multiple potential advantages to SCIT, including the elimination of injections and improved safety profile. Several studies in adults and children have found improvement in symptom scores as well as reductions in medication use to the point where this is now being used in clinical practice in place of SCIT in many European countries. Additional studies, including investigation of optimal dosing and the potential to use multiple allergens, are needed to further define the future role of SLIT in the United States.

Treatment of Diarrhea-Predominant Irritable Bowel Syndrome with Traditional Chinese Herbal Medicine: A Randomized Placebo-Controlled Trial

As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS. This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patient's global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36). One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points. The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the treatment of seasonal allergic rhinitis symptoms

Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms. Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment. Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Functional bowel disorders in rotating shift nurses may be related to sleep disturbances

To compare the frequency and severity of bowel disturbances between rotating shift and regular day nurses and to determine whether functional bowel disorders (FBD) were related to sleep disturbances. Sixty regular day and 58 rotating shift nurses answered three standardized questionnaires: the Gastrointestinal Symptom Questionnaire; the Hospital Anxiety and Depression Scale; and the Irritable Bowel Syndrome Symptoms Evaluation Questionnaire, which included the Sleep Questionnaire, on the frequency and severity of gastrointestinal symptoms, sleep disturbances and psychological distress. Responses to these questions were numerically rated and the sums of individual symptom scores under the respective categories were computed and analysed using statistical tests, as appropriate. Although 22 out of 58 rotating shift nurses (38%) had FBD, only 12 out of 60 regular day nurses (20%) had it (P=0.04). The mean FBD symptom score (P<0.002), sleep disturbance score (P<0.0001) and anxiety score (P<0.002) were all significantly higher among the rotating shift nurses. FBD symptom scores were positively correlated with the sleep disturbance (P=0.0001), anxiety (P=0.0001), depression (P=0.0001), well-being (P=0.0001), fatigue (P=0.0001), and somatic pain scores (P=0.0001). Sleep disturbance (P=0.04), decreased well-being (P=0.04), anxiety (P=0.02), and somatic pain (P=0.03) were independent predictors of FBD symptoms. FBD were more common and severe among rotating shift nurses. The FBD symptom score was positively and independently correlated with the sleep disturbance score, suggesting that poor sleep might be associated with increased FBD symptoms in rotating shift nurses.

Efficacy of desloratadine, 5 mg, compared with fexofenadine, 180 mg, in patients with symptomatic seasonal allergic rhinitis

This is the first U.S.-based study to compare efficacy and safety of desloratadine with fexofenadine in subjects with symptomatic seasonal allergic rhinitis (SAR). In this double-blind study, subjects were randomized to desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n = 144) once daily for 15 days. Primary end point was mean change from baseline to study end in morning instantaneous total symptom score (AM NOW TSS) excluding congestion. Secondary measures included change from baseline in the morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR ISS including congestion. Subjects self-evaluated their symptoms on a five-point scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo. Desloratadine and fexofenadine were not statistically different (p = 0.491); the upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS excluding congestion was comparable between desloratadine and fexofenadine (p = 0.405; CI = 0.221) but was significantly greater with both active treatments versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS (both including congestion) versus placebo; reductions were comparable between active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and fexofenadine, 180 mg, provide comparable efficacy and tolerability in the treatment of SAR. Both treatments are significantly more effective than placebo.