Daily Symptom Severity Research Articles

The Impact of Ambient Air Pollution on Allergic Rhinitis Symptoms: A Prospective Follow-Up Study.

Air pollution has become a serious public health problem and there is evidence that air pollution affects the incidence of allergic rhinitis. To further investigate the effect of ambient air pollutants on the severity of allergic rhinitis symptoms, a prospective follow-up study in patients with allergic rhinitis was conducted. A total of 167 allergic rhinitis patients with a mean age of 35.4 years, who were visiting the hospital, were enrolled. The daily symptom severity of allergic rhinitis and the concentrations of six air pollutants, including PM2.5, PM10, SO2, CO, O3 and NO2, were collected through follow-up investigations. The impact of ambient air pollutants on symptom severity was assessed via multi-pollutant models. Among several typical ambient air pollutants, we observed correlations of allergic rhinitis symptoms with PM2.5, PM10, CO, SO2 and NO2, whereas O3 showed no such correlation. Specifically, PM2.5 and PM10 were significantly associated with sneezing and nasal blockage. NO2 was significantly correlated with symptoms of rhinorrhea, itchy nose and itchy eyes. CO was significantly linked to sneezing and nasal blockage symptoms. These air pollutants not only had a direct impact on allergic rhinitis symptoms but also exhibited a lagging effect. This study indicates that short-term exposure to air pollutants is associated with exacerbation of nasal symptoms in patients with allergic rhinitis, leading to a decline in their quality of life.

Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is associated with abdominal pain and stool frequency/character alterations that are linked to changes in microbiome composition. We tested whether taxa differentially abundant between females with IBS vs healthy control females (HC) are associated with daily gastrointestinal and psychological symptom severity. Participants (age 18-50 year) completed a 3-day food record and collected a stool sample during the follicular phase. They also completed a 28-day diary rating symptom intensity; analysis focused on the three days after the stool sample collection. 16S rRNA gene sequencing was used for bacterial identification. Taxon abundance was compared between IBS and HC using zero-inflated quantile analysis (ZINQ). We found that females with IBS (n= 67) had greater Bacteroides abundance (q= 0.003) and lower odds of Bifidobacterium presence (q= 0.036) compared to HC (n= 46) after adjusting for age, race, body mass index, fibre intake, and hormonal contraception use. Intestimonas, Oscillibacter, and Phascolarctobacterium were more often present and Christensenellaceae R-7 group, Collinsella, Coprococcus 2, Moryella, Prevotella 9, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, and Ruminococcaceae UCG-014 were less commonly present in IBS compared to HC. Despite multiple taxon differences in IBS vs HC, we found no significant associations between taxon presence or abundance and average daily symptom severity within the IBS group. This may indicate the need to account for interactions between microbiome, dietary intake, metabolites, and host factors.

Traditional Vietnamese Medicine Containing Garlic Extract for Patients With Non-severe COVID-19: A Phase-II, Double-Blind, Randomized Controlled Trial.

Background Coronavirus disease 2019 (COVID-19) is still ongoing with the omicron variant. Low-cost, effective treatments are still needed, particularly in low-to-middle-income countries. This study assessed the safety and efficacy of TD0068, an herbal medicine developed from mainly garlic, for patients with non-severe COVID-19. Methods This is a phase-II, double-blind, randomized controlled trial to compare oral capsule TD0068 and placebo in adults aged 18-65 years with non-severe COVID-19 between September and October 2021. The efficacy outcomes measured included daily cycle threshold (Ct) value from the time of the initial reverse transcription-polymerase chain reaction (RT-PCR) test, time to viral clearance, daily symptom severity score from 15 symptoms of interest, time to symptom resolution, and progression to severe/critical COVID-19. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Results Sixty patients were randomized (31 received TD0068, and 29 received a placebo). The two groups were balanced in baseline characteristics: mean age was 39 years, and female was predominant (66%). Daily Ct value (median on days 3, 5, 7, and 9 was 25.7, 30.8, 35.4, and 37.6 in the TD0068 group, and 26.4, 31.2, 36.0, and 37.4 in the placebo group, respectively) and time to viral clearance (median: 10 vs. 11 days in TD0068 and placebo groups) were similar between groups. Daily symptom severity score (median on days 3, 5, 7, and 9 was 2, 2, 1, and 0 in the TD0068 group, and 3, 2, 1, and 1 in the placebo group), and time to symptom resolution (median: seven vs. nine days, respectively) were also comparable between groups. No SAE occurred in the study. Conclusions TD0068 is safe but does not show an effect for non-severe COVID-19 patients. Further research is needed to explore the potential benefits of garlic in other forms or dosages for the treatment of COVID-19.

Combined effects of cumulative stress and daily stressors on daily health.

It has been proposed that cumulative stress, one's experience of chronic stressors across multiple domains, worsens health by altering the extent to which daily stressors impact daily affect and physical symptoms. Recent work confirms that high cumulative stress exacerbates the association between daily stressor exposure and increased daily negative affect, though it remains untested the extent to which cumulative stress and daily stressor exposure interact to predict daily symptoms. We employed data from the second wave of the midlife in the U.S. Survey (N = 2,022; Mage = 56.2; 57.2% female) to examine whether levels of cumulative stress compound daily symptoms on days with (vs. without) stressful events. Experiences of life stressors across eight domains, occurrence of daily stressors, and occurrence, number, and severity of daily physical symptoms were analyzed using multilevel modeling. Greater cumulative stress and experiencing (vs. not experiencing) a daily stressor independently increased the odds of occurrence, number, and severity of daily symptoms (ps ≤ .016). Moreover, after adjusting for covariates (e.g., sociodemographic characteristics, chronic health conditions, percent of days with reported stressors, and health behaviors), the associations between daily stressor exposure and odds of occurrence, number, and severity of daily symptoms were potentiated as levels of cumulative stress increased (ps ≤ .009). The negative implications of daily stressor exposure for daily health may be most pronounced in those who report higher levels of cumulative stress across multiple life domains and across time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Symptom Free Days In Patients With Severe Chronic Rhinosinusitis with Nasal Polyps Treated with Dupilumab

Dupilumab demonstrated improvements in patient-reported daily symptom severity scores in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This post hoc analysis assessed the proportion of patients with symptom-free days (SFD) in the Phase 3 SINUS-24/SINUS-52 studies.

Relationship between symptoms during a gastric emptying study, daily symptoms and quality of life in patients with diabetes mellitus.

Gastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a 13 C-spirulina-based gastric emptying breath test (GEBT) or scintigraphy predicting the severity of daily symptoms in diabetes mellitus. Gastric emptying, symptoms during a gastric emptying study, either scintigraphy (n=38) or GEBT (n=111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms. Gastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P<0.0001). Symptoms during the GEBT (46%) and emptying thalf (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the thalf was insignificant. Patients who reported that one or more symptoms were more severe than the others during the GE study were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary. Symptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.

Evaluation of Patient Reported Gastroesophageal Reflux Severity at Baseline and at 1-year After Bariatric Surgery.

To assess patient-reported gastroesophageal reflux disease (GERD) severity before and after SG and Roux-en-Y gastric bypass (RYGB). Development of new-onset or worsening GERD symptoms after bariatric surgery varies by procedure, but there is a lack of patient-reported data to help guide decision-making. Methods: Retrospective cohort study of patients undergoing bariatric surgery in a statewide quality collaborative between 2013 and 2017. We used a validated GERD survey with symptom scores ranging from 0 (no symptoms) to 5 (severe daily symptoms) and included patients who completed surveys both at baseline and 1-year after surgery (n = 10,451). We compared the rates of improved and worsened GERD symptoms after SG and RYGB. Within our study cohort, 8680 (83%) underwent SG and 1771 (17%) underwent RYGB. Mean baseline score for all patients was 0.94. Patients undergoing SG experienced similar improvement in GERD symptoms when compared to RYGB (30.4% vs 30.8%, P = 0.7015). However, SG patients also reported higher rates of worsening symptoms (17.8% vs 7.5%, P < 0.0001) even though they were more likely to undergo concurrent hiatal hernia repair (35.1% vs 20.0%, P<0.0001). More than half of patients (53.5%) did not report a change in their score. Although SG patients reported higher rates of worsening GERD symptoms when compared to RYGB, the majority of patients (>80%) in this study experienced improvement or no change in GERD regardless of procedure. Using clinically relevant patient-reported outcomes can help guide decisions about procedure choice in bariatric surgery for patients with GERD.

A-49 To Nap or Not to Nap? The Influence of Napping on Recovery Outcomes Following Concussion

Abstract Objective To determine the influence of nap frequency on daily symptom severity and recovery time following concussion in college students. Method A prospective study of college students within 72 hours of a diagnosed concussion was performed. Participants reported nap occurrence (yes/no) and daily concussion symptoms using the Post-Concussion Symptom Scale (PCSS) for six days. Participants were categorized into frequent (&amp;gt;2 naps) and infrequent (&amp;lt;3 naps) nap groups. Recovery time was defined as total days from injury to unrestricted medical clearance. A mixed between-within ANOVA evaluated changes in daily symptom severity between nap groups, while Spearman’s Rank Correlation assessed the relationship between the number of days napping and recovery time. Results Thirty-four participants (23 female, 11 male; age = 19.91 ± 1.38 years) were included, with 22 in the infrequent nap group and 12 in the frequent nap group. Average recovery time for the infrequent nap group was 13.85 days compared to 18.8 days in the frequent nap group. There was no significant group x time interaction for daily symptom severity (Wilks’ λ = 0.85, F(5,24) = 0.85, p = 0.53, η2 = 0.15). There was a significant main effect for time, with daily symptom severity improving following concussion (Wilks’ λ = 0.31, F(5,24) = 10.66, p &amp;lt; 0.001, η2 = 0.69), but there was no significant group effect (F(1,28) = 0.79, p = 0.38, η2 = 0.03). Overall, the more naps taken, the longer the recovery time (Rs = 0.46, p = 0.01). Conclusions Findings from the present study suggest that frequent napping does not affect symptom severity following concussion. Further research is needed to elucidate the association between the number of naps and recovery time.

Relationship between symptoms during a gastric emptying study and intestinal chemosensitivity with daily symptoms.

Non-ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon-like peptide-1 (GLP-1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP-1 mediates symptoms during duodenal lipid infusion in NUD. Gastric emptying of solids, symptoms during the GE study and duodenal lipid infusion, and daily gastrointestinal symptoms (2week diary) were measured in 24 healthy controls and 40 NUD patients. During duodenal lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo. In controls and patients, GE of solids was normal in 75% and 75%, delayed in 8% and 12.5%, or rapid in 17% and 12.5%, respectively. No controls but 26 patients (65%) had severe symptoms during the GE study. During lipid infusion, gastrointestinal symptoms were greater (P=.001) in patients and not affected by exendin. Symptoms during GE study and lipid infusion accounted for respectively 62% and 37% of variance in daily symptom severity. In NUD, symptoms during a GE study and to a lesser extent during lipid infusion explain the variance in daily symptoms. Intestinal chemosensitivity is not reduced by GLP-1 antagonist. Assessment of symptoms during a GE study may provide a useful biomarker for NUD in research and clinical practice.

Patient-Reported Burden of Illness in a Prevalent COPD Population Treated with Long-Acting Muscarinic Antagonist Monotherapy: A Claims-Linked Patient Survey Study.

IntroductionSymptom burden in inadequately controlled chronic obstructive pulmonary disease (COPD) considerably impacts quality of life, healthcare resource utilization (HCRU) and associated costs. This claims-linked cross-sectional survey study assessed symptom burden and HCRU among a prevalent population of COPD patients prescribed long-acting muscarinic antagonist (LAMA) monotherapy.MethodsPatients were identified using claims data from the Optum Research Database. Eligible patients were aged ≥ 40 years with 12 months’ continuous enrollment in a US health plan, ≥ 2 medical claims containing COPD diagnosis codes ≥ 30 days apart, and ≥ 2 claims for LAMA monotherapy in the latter half of the 12-month sample identification period. Patients were mailed a cross-sectional survey assessing patient-reported outcomes (PROs) [COPD assessment test (CAT) and modified medical research council dyspnea scale (mMRC)], clinical characteristics, smoking history, and demographics. Patients also completed the Exacerbations of Chronic Pulmonary Disease Tool (EXACT-PRO) daily diary for 7 days. HCRU was assessed from claims data.ResultsThe study included 433 patients with a self-reported healthcare provider COPD diagnosis, and both claims-based and self-reported LAMA monotherapy treatment (mean age 71.0 years; 59.8% female). Most patients (85.5%) reported a high symptom burden (CAT score ≥ 10), 45.5% had high levels of dyspnea (mMRC grade ≥ 2), and 64.4% reported more severe daily symptoms by the EXACT-PRO. Most patients (71.6%) reported high scores on ≥ 2 PROs. More patients with high symptom burden had COPD-related emergency department visits than those with lower disease burden (27.6% vs 12.7%, P = 0.012).ConclusionsIn conclusion, a large proportion of patients with COPD receiving LAMA monotherapy experienced a high symptom burden and may benefit from therapy escalation. Healthcare professionals can use validated PROs to help them assess symptom burden.FundingGlaxoSmithKline (GSK study number: 205862)Electronic supplementary materialThe online version of this article (10.1007/s41030-019-0091-0) contains supplementary material, which is available to authorized users.

Journal Club - Bronchiectasis/COPD Overlap: Syndrome Versus Treatable Trait?

Journal Club - Bronchiectasis/COPD Overlap: Syndrome Versus Treatable Trait?

Chronic Obstructive Pulmonary Disease in Older Adults: Part I: Case Study.

Chronic obstructive pulmonary disease (COPD) is a distressing respiratory disease that may greatly impact a patient's quality of life. Although many treatment options exist, the Global Initiative for Chronic Obstructive Lung Disease Guidelines outline management strategies based on severity of daily symptoms and exacerbations. Although it is important to weigh the risks and benefits of medication use, involvement of patients in their overall care plan is imperative to optimal outcomes. According to recent studies, the prevalence of COPD in older adults is increasing, along with the complexity of care due to comorbidities, drug interactions, and side effects. A thorough evaluation of a patient case provides insight into the everyday challenges of COPD management. [Journal of Gerontological Nursing, 44(7), 10-14.].

Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study.

In the double-blind (DB) ELECT study, lanreotide depot/autogel significantly reduced versus placebo the need for short-acting octreotide for symptomatic carcinoid syndrome (CS) control in neuroendocrine tumor (NET) patients. Here we present patient-reported symptom data during DB and initial open-label (IOL) treatment. Adults with NETs and CS history, with/without prior somatostatin analog use, were randomized to 16 weeks' DB lanreotide 120 mg subcutaneous or placebo every 4 weeks, followed by 32 weeks' IOL lanreotide. Patients recorded diarrhea and/or flushing frequency and severity daily by Interactive Voice (Web) Response System for 1 month prior to randomization and throughout the study. Of 115 patients randomized (n = 59 lanreotide, n = 56 placebo), 56 lanreotide and 45 placebo patients enrolled in the IOL phase. During DB treatment, least square (LS) mean percentages of days with moderate/severe diarrhea and/or flushing were significantly lower for lanreotide (23.4%) versus placebo (35.8%; LS mean difference [95% confidence interval]: -12.4 [-20.73 to -4.07]; p = .004). For DB lanreotide patients, average daily composite (frequency × severity) diarrhea scores improved significantly between DB and IOL treatment (mean difference: -0.71 [-1.20 to -0.22]; p = .005), and remained stable for diarrhea and/or flushing. For DB placebo patients, composite scores for diarrhea, flushing, and diarrhea and/or flushing improved significantly between DB and IOL treatment (mean differences: -1.07 [-1.65 to -0.49]; -1.06 [-1.93 to -0.19]; and -2.13 [-3.35 to -0.91]; all p ≤ .018). Improved diarrhea and flushing control in CS patients during 16-week lanreotide treatment was sustained during maintenance of lanreotide treatment for the 32-week IOL phase (48 weeks total). This study prospectively collected daily patient-reported data on diarrhea and flushing from the ELECT trial to evaluate the direct impact of lanreotide depot on patients' relief of carcinoid syndrome symptoms. Treatment with lanreotide depot was associated with significant reductions in the percentages of days patients reported symptoms of diarrhea and flushing, as well as reductions in the frequency and severity of daily symptoms compared with placebo during 16 weeks of double-blind treatment. These improvements were sustained for 32 additional weeks of open-label lanreotide treatment (i.e., through week 48 of treatment), resulting in clinically meaningful, long-term symptom reduction.

Increased nutrient sensitivity and plasma concentrations of enteral hormones during duodenal nutrient infusion in functional dyspepsia.

Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in patients with functional dyspepsia vs. healthy controls. Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 min each, with a 120-min washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagon-like peptide 1 (GLP1), and peptide YY were measured during infusions. Moderate or more severe symptoms during lipid (4 controls vs. 14 patients) and dextrose (1 control vs. 12 patients) infusions were more prevalent in patients than controls (P≤0.01), associated with higher dyspepsia symptom score (P=0.01), worse QOL (P=0.01), and greater plasma hormone concentrations (e.g., GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia.

A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis.

BackgroundPrevious studies have not addressed rheumatoid arthritis (RA) patients’ help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients’ experiences of daily life on current treatments, and their help-seeking behaviours for RA flares.MethodsUsing Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis.ResultsDaily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact.Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist’s time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms.ConclusionsPatients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-364) contains supplementary material, which is available to authorized users.

Responsiveness of a Tri-Component Endpoint in Non-Constipation Irritable Bowel Syndrome: Pooled Results from Two Phase 3 Trials, TARGET 1 and TARGET 2

Purpose: Current FDA guidance suggests the use of a composite endpoint that includes two primary symptoms of IBS with diarrhea (IBS-D): abdominal pain and stool consistency. Because this endpoint may not capture otherwise unmeasured GI symptoms such as urgency and bloating, which may be important to patients with IBS-D, we sought to evaluate the responsiveness of a tri-component endpoint that includes daily assessment of abdominal pain and stool consistency as recommended by the FDA guidance as well as daily assessment of global IBS symptoms. Methods: Patients with mild-to-moderate non-constipation IBS (N=1260) were randomized to rifaximin 550 mg three times daily (TID) or placebo for two weeks and evaluated for 10 weeks post treatment. The primary results of these trials have been previously published. Patients rated daily IBS symptom severity for global IBS symptoms and IBS-related abdominal pain using a 7-point scale (0=not at all - 6=a very great deal). Stool consistency was rated using a 5-point scale (1=very hard-5=watery). The proposed tri-component endpoint defines the weekly responders as patients who reported ≥30% improvement from baseline in abdominal pain, had ≥50% improvement in the number of days in a week with stool consistency of loose or watery compared with baseline, and had ≥1 point improvement in weekly average score of daily global IBS symptoms. Responsiveness (ability to detect change) was assessed (Wilcoxon rank-sum test) by comparing the change from baseline in each daily question between weekly responder and non-responder. Spearman rank correlation coefficients were calculated to assess the correlations among weekly responders and daily measures of efficacy. Results: For each study and the combined data, the responders defined by the tri-component endpoint had significantly greater improvements in all daily IBS symptom severity measures than non-responders at each week during the course of the study, demonstrating it was a responsive endpoint. The tricomponent endpoint also demonstrated evidence for convergent validity as it consistently correlated with all daily IBS symptom severity measures at each week during the course of the study based on a Spearman's correlation of 0.40 or greater with other daily symptom severity measures. Conclusion: The tri-component endpoint, which adds a global assessment of IBS symptoms to the FDA's guidance endpoint, is a responsive endpoint that correlates with all daily IBS symptoms. Further study with this endpoint is warranted in patients with IBS-D. Disclosure: Salix Pharmaceuticals, Inc. provided all study drug and research funding for these studies. Dr. Lembo - Consultant and Speaker: Salix Pharmaceuticals, Inc.; Dr. Pimentel - Consultant, Speaker, and Investigator: Salix Pharmaceuticals, Inc.; Dr. Yu - Employee and Stockholder: Salix Pharmaceuticals, Inc.; Dr. Paterson - Employee and Stockholder: Salix Pharmaceuticals, Inc.; Dr. Bortey - Employee and Stockholder: Salix Pharmaceuticals, Inc.; and Dr. Forbes - Employee and Stockholder: Salix Pharmaceuticals, Inc. This research was supported by an industry grant from Salix Pharmaceuticals, Inc.

Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management.

Crohn's disease is a serious and debilitating gastrointestinal disorder with a high, unmet need for new treatments. Biologic agents have the potential to alter the natural course of Crohn's disease but present known risks of potential serious adverse events (SAEs). Previous studies have shown that patients are willing to accept elevated SAE risks in exchange for clinical efficacy. Gastroenterologists and patients may have similar goals of maximizing treatment benefit while minimizing risk; however, gastroenterologists may assess the relative importance of risk differently than patients. To (a) understand how gastroenterologists caring for patients with Crohn's disease balance benefits and risks in their treatment decisions and (b) compare their treatment preferences with those of adult patients with Crohn's disease. Both patient and gastroenterologist treatment preferences were elicited using a web-based, choice-format conjoint survey instrument. The conjoint questions required subjects to choose between 2 hypothetical treatment options with differing levels of treatment attributes. Patients evaluated the treatment options for themselves, and gastroenterologists evaluated the treatment options for each of 3 hypothetical patient types: (a) female aged 25 years with no history of Crohn's disease surgery (young), (b) male aged 45 years with 1 Crohn's disease surgery (middleaged), and (c) female older than 70 years with 4 Crohn's disease surgeries (older). Treatment attributes represented the expected outcomes of treatment: severity of daily symptoms, frequency of flare-ups, serious disease complications, oral steroid use, and the risks of 3 potentially fatal SAEs - lymphoma, serious or opportunistic infections, and progressive multifocal leukoencephalopathy (PML) - during 10 years of treatment. Maximum acceptable risk (MAR), defined as the highest level of SAE risk that subjects would accept in return for a given improvement in efficacy (i.e., the increase in treatment risk that exactly offsets the hypothetical increase in treatment benefit), was calculated using preference weights (parameter marginal log odds ratios) that were estimated with conjoint analysis (random parameters logit models). Gastroenterologists' and patients' mean MARs for 3 SAE risks were calculated for 6 improvements in Crohn's disease symptoms, and gastroenterologists' preference weights for each of the 3 patient profiles were compared. Gastroenterologists' MARs for a hypothetical middle-aged patient were then compared with predicted MARs derived using data from the patient study for male patients aged 40 to 50 years with 1 surgery. After exclusion of nonrespondents (n = 4,021 of 4,422 gastroenterologists; n = 681 of 1,285 patients) and nonevaluable respondents (n = 86 gastroenterologists; n = 24 patients), 315 gastroenterologists and 580 patients were included in the final analytic samples. There were no statistically significant differences in gastroenterologists' preference weights for the middle-aged versus young patient profiles. However, preference weights indicated that gastroenterologists are more concerned about 5% side-effect risks for the older patient profile than for the middle-aged patient profile. For symptomatic improvements from severe symptoms to remission, gastroenterologists' highest MARs were for lymphoma: 6.21%, 8.99%, and 25.00% for the young, middle-aged, and older patient types, respectively. In analyses of improvements from severe to moderate symptoms and from moderate symptoms to remission for hypothetical middle-aged patients, gastroenterologists' 10-year risk tolerance ranged between 1.96% lymphoma risk in return for an improvement from moderate symptoms to remission and 4.93% lymphoma risk for an improvement from severe to moderate symptoms; patients' 10-year risk tolerance for middle-aged patients ranged between 1.52% PML risk in return for an improvement from severe to moderate symptoms and 5.86% infection risk for an improvement from moderate symptoms to remission. On average, gastroenterologists and patients disagreed about how much risk is tolerable for improvements in efficacy. In exchange for improvements from severe to moderate symptoms for the middle-aged patient profile, gastroenterologists were significantly more tolerant than patients of treatment risks of PML (P < 0.001) and serious infection (P = 0.001) but not lymphoma (P = 0.230). In contrast, in exchange for improvements from moderate symptoms to remission for the same patient profile, patients were significantly more tolerant than gastroenterologists of treatment risks for serious infection (P < 0.001) and lymphoma (P < 0.001) but not PML (P = 0.158). Gastroenterologists and patients have well-defined preferences among treatment attributes and are willing to accept tradeoffs between efficacy and treatment risks. However, risk tolerance varies depending on the type of patient for whom gastroenterologists are being asked to consider treatment. In rating treatment preferences for patients with a middle-aged profile, gastroenterologists are less tolerant of SAE risks than patients in exchange for improvement from moderate symptoms to remission.

The Responsiveness and Validity of a Binary Weekly Recall Question and the Proposed FDA Composite Endpoint as Measures of Daily Symptom Severity in Non-Constipation Irritable Bowel Syndrome: Results of TARGET 1 and TARGET 2

The Responsiveness and Validity of a Binary Weekly Recall Question and the Proposed FDA Composite Endpoint as Measures of Daily Symptom Severity in Non-Constipation Irritable Bowel Syndrome: Results of TARGET 1 and TARGET 2

Exploratory Study of Tegaserod for Dyspepsia in Women Receiving PPIs for Heartburn

Background and AimsTegaserod is a selective serotonin receptor (5-HT4) agonist that relieves dysmotility symptoms associated with constipation. Here we explore its effects on functional dyspepsia symptoms and heartburn during continued proton pump inhibitor (PPI) treatment.MethodsIn this multicenter pilot study, following a 2-week screening/baseline period, women with functional dyspepsia and persisting heartburn treated with PPIs received add-on open-label tegaserod 6 mg twice daily (bid) for 4 weeks. Treatment responders were then randomized 1:1 to continue double-blind tegaserod or placebo therapy for 6 weeks. Efficacy variables included the proportion of days with satisfactory relief of dyspepsia symptoms (early satiety, postprandial fullness and bloating) as well as the change in individual symptom severity scores for these three cardinal dyspepsia symptoms. Health-related quality of life was evaluated using a validated questionnaire, the Nepean Dyspepsia Index. Adverse events (AEs) were monitored.ResultsOf 101 women enrolled, 71 completed open-label treatment, and 70 responders were randomized to double-blind treatment. The proportion of days with satisfactory relief of dyspepsia symptoms (least squares mean, LSM) increased with tegaserod and placebo, to 0.69 and 0.62, respectively at study end (P = 0.366). Similarly, both groups showed improvements in the composite daily symptom severity score (overall LSM change from baseline of 1.55 and 1.57, P = 0.934), and the Nepean Dyspepsia Index (overall LSM change of −39.0 and −37.8, P = 0.537). Tegaserod was well tolerated. Diarrhea was the most common AE (8.1% tegaserod, 0% placebo). There were no serious AEs or deaths.ConclusionsA significant treatment effect was not demonstrated in this study using a treatment-withdrawal methodology. In future studies of functional dyspepsia patients with heartburn, a more rigorous parallel-group study design should be considered.

Asimadoline, a kappa‐opioid agonist, and satiation in functional dyspepsia

Asimadoline, a kappa-opioid agonist, reduces visceral sensitivity in experimental animal models and may decrease satiation and postprandial fullness in healthy individuals. However, its effect on satiation in functional dyspepsia is unclear, and any symptom benefit has not been explored. To evaluate the effects of asimadoline on satiation volume and postchallenge symptoms in functional dyspepsia. A randomized, double-blind trial evaluated gastric satiation and symptoms before and after 8 weeks of asimadoline 0.5 mg (n = 13) or 1.0 mg (n = 13) or placebo (n = 14) b.d. in patients with functional dyspepsia (Rome II). Gastrointestinal Symptom Rating Scale and Nepean Dyspepsia Index were used to assess symptoms during the 8-week treatment. Over 8 weeks of treatment, asimadoline had no significant effect on maximum-tolerated volume or aggregate symptom score with nutrient drink challenge, and on the mean of the total daily symptom severity score compared to placebo. In a post hoc analysis, asimadoline 0.5 mg significantly increased the maximum-tolerated volume (1217 mL +/- 90.2) compared to placebo (807 mL +/- 111.8) in patients with higher postprandial fullness scores (P = 0.01). Asimadoline overall did not significantly alter maximum-tolerated volume, symptoms postnutrient challenge or symptoms over 8 weeks in functional dyspepsia.