Daily Symptom Diary Research Articles

Rhinovirus Infections in the First 2 Years of Life

Rhinoviruses frequently cause respiratory infections in young children. We aimed to establish the burden of acute respiratory infections caused by rhinovirus during the first 2 years of life. In this prospective birth cohort study, we followed 923 children for acute respiratory infections from birth to 2 years of age. Data on respiratory infections were collected by daily symptom diaries, study clinic visits, and from electronic registries. Respiratory viruses were detected by reverse transcription-polymerase chain reaction and antigen assays during respiratory infections and at the age of 2, 13, and 24 months. The rates of rhinovirus infections and associated morbidities were determined. We documented 8847 episodes of acute respiratory infections, with an annual rate of 5.9 per child (95% confidence interval [CI], 5.7-6.1). Rhinovirus was detected in 59% of acute respiratory infections analyzed for viruses. Rhinovirus was associated with 50% of acute otitis media episodes, 41% of wheezing illnesses, 49% of antibiotic treatments, and 48% of outpatient office visits for acute respiratory infections. The estimated mean annual rate of rhinovirus infections was 3.5 per child (95% CI, 3.3-3.6), 47 per 100 children (95% CI, 42-52) for rhinovirus-associated acute otitis media, and 61 per 100 children (95% CI, 55-68) for rhinovirus-associated antibiotic treatment. The prevalence of rhinovirus at 2, 13, or 24 months of age was 14 to 24%, and 9% of asymptomatic children were positive for rhinovirus. Rhinovirus infections impose a major burden of acute respiratory illness and antibiotic use on young children.

Pain buddy: A novel use of m-health in the management of children's cancer pain

BackgroundOver 12,000 children are diagnosed with cancer every year in the United States. In addition to symptoms associated with their disease, children undergoing chemotherapy frequently experience significant pain, which is unfortunately often undertreated. The field of m-Health offers an innovative avenue for pain assessment and intervention in the home setting. The current study describes the development and initial evaluation of a tablet-based program, Pain Buddy, aimed to enhance pain management and foster improved quality of life in children ages 8–18 years undergoing cancer treatment. MethodsAn animated avatar-based tablet application was developed using state-of-the-art software. Key aspects of Pain Buddy include daily pain and symptom diaries completed by children, remote monitoring of symptoms by uploading patient's data through internet to a cloud server, cognitive and behavioral skills training, interactive three-dimensional avatars that guide children through the program, and an incentive system to motivate engagement. Twelve children between the ages of 8 and 18 participated in a pilot study of Pain Buddy. ResultsChildren were highly satisfied with the program. Pain and appetite disturbances were most frequently endorsed. Symptom trigger alerts to outside providers were largely related to clinically significant pain. Children infrequently used analgesics, and reported using some non-pharmacological pain management strategies. ConclusionPain Buddy appears to be a promising tool to improve pain and symptom management in children undergoing cancer treatment. Results from the current study will inform future improvements to Pain Buddy, in preparation for a randomized controlled trial to assess the efficacy of this innovative treatment.

Psychometric assessment of the IBS-D Daily Symptom Diary and Symptom Event Log.

PurposeDiarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients’ lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, “Event Log”) according to US regulatory recommendations.MethodsA US-based observational field study was conducted to understand cross-sectional psychometric properties of the IBS-D Daily Symptom Diary and Event Log. Analyses included item descriptive statistics, item-to-item correlations, reliability, and construct validity.ResultsThe IBS-D Daily Symptom Diary and Event Log had no items with excessive missing data. With the exception of two items (“frequency of gas” and “accidents”), moderate to high inter-item correlations were observed among all items of the IBS-D Daily Symptom Diary and Event Log (day 1 range 0.67–0.90). Item scores demonstrated reliability, with the exception of the “frequency of gas” and “accidents” items of the Diary and “incomplete evacuation” item of the Event Log. The pattern of correlations of the IBS-D Daily Symptom Diary and Event Log item scores with generic and disease-specific measures was as expected, moderate for similar constructs and low for dissimilar constructs, supporting construct validity. Known-groups methods showed statistically significant differences and monotonic trends in each of the IBS-D Daily Symptom Diary item scores among groups defined by patients’ IBS-D severity ratings (“none”/“mild,” “moderate,” or “severe”/“very severe”), supporting construct validity.ConclusionsInitial psychometric results support the reliability and validity of the items of the IBS-D Daily Symptom Diary and Event Log.

Overuse of short-acting beta-agonist bronchodilators in COPD during periods of clinical stability

BackgroundOveruse of short-acting beta-agonists (SABA) is described in asthma, but little is known about overuse of SABA in chronic obstructive pulmonary disease (COPD). MethodsProspective 3-month cohort study of patients with moderate-to-severe COPD who were provided a portable electronic inhaler sensor to monitor daily SABA use. Subjects wore a pedometer for 3 seven-day periods and were asked to complete a daily diary of symptoms and inhaler use. Overuse was defined as >8 actuations of their SABA per day while clinically stable. ResultsAmong 32 participants, 15 overused their SABA inhaler at least once (mean 8.6 ± 5.0 puffs/day), and 6 overused their inhaler more than 50% of monitored days. Compared to those with no overuse, overusers had greater dyspnea (modified Medical Research Council Dyspnea Scale: 2.7 vs. 1.9, p = 0.02), were more likely to use home oxygen (67% vs. 29%, p = 0.04), and were more likely to be on maximal inhaled therapy (long-acting beta-agonist, long-acting antimuscarinic agent, and an inhaled steroid: 40% vs. 6%, p = 0.03), and most had completed pulmonary rehabilitation (67% vs. 0%, p < 0.001). However, 27% of overusers of SABA were not on guideline-concordant COPD therapy. ConclusionsOveruse of SABA was common and associated with increased disease severity and symptoms, even though overusers were on more COPD-related inhalers and more had completed pulmonary rehabilitation. More research is needed to understand factors associated with inhaler overuse and how to improve correct inhaler use.

Assessing Asthma Symptoms in Adolescents and Adults: Qualitative Research Supporting Development of the Asthma Daily Symptom Diary

BackgroundDespite the widespread availability of patient-reported asthma questionnaires, instruments developed in accordance with present regulatory expectations are lacking. To address this gap, the Patient-Reported Outcome (PRO) Consortium’s Asthma Working Group has developed a patient-reported asthma daily symptom diary (ADSD) for use in clinical research to assess outcomes and support medical product labeling claims in adults and adolescents with asthma. ObjectivesTo summarize the qualitative research conducted to inform the initial development of the ADSD and to provide evidence for content validity of the instrument in accordance with the Food and Drug Administration’s PRO Guidance. MethodsResearch informing the initial development and confirming the content validity of the ADSD is summarized. This comprised a review of published qualitative research, semi-structured concept elicitation interviews (n = 55), and cognitive interviews (n = 65) with a diverse and representative sample of adults and adolescents with a clinician-confirmed diagnosis of asthma in the United States to understand the asthma symptom experience and to assess the relevance and understanding of the newly developed ADSD. ResultsFrom the qualitative literature review and concept elicitation interviews, eight core asthma symptoms emerged. These were broadly categorized as breathing symptoms (difficulty breathing, shortness of breath, and wheezing), chest symptoms (chest tightness, chest pain, and pressure/weight on chest), and cough symptoms (cough and the presence of mucus/phlegm). Conceptual saturation was achieved and differences in the experience of participants according to socio-demographic or clinical characteristics were not observed. Subsequent testing of the ADSD confirmed participant relevance and understanding. ConclusionsThe ADSD is a new patient-reported asthma symptom diary developed in accordance with the Food and Drug Administration’s PRO Guidance. Evidence to date supports the content validity of the instrument. Item performance, reliability, and construct validity will be assessed in future quantitative research.

The Effect of Ramelteon on Heartburn Symptoms of Patients With Gastroesophageal Reflux Disease and Chronic Insomnia: A Pilot Study.

There is a bidirectional relationship between gastroesophageal reflux disease (GERD) and sleep. It has been demonstrated that antireflux treatment can improve sleep quality in GERD patients with nighttime reflux. Patients with heartburn and/or regurgitation ≥3 times/week and insomnia for ≥3 months were included. Patients were assessed at baseline with the demographic, GERD symptom assessment scale, Epworth sleepiness scale, Berlin sleep apnea, Pittsburgh sleep quality index, and the Insomnia severity index questionnaires. Subjects underwent an upper endoscopy followed by pH testing. Subsequently, subjects were randomized, in a double-blind, placebo-controlled trial, to receive either ramelteon 8 mg or placebo before bedtime for 4 weeks. During the last week of treatment, subjects completed a daily GERD symptom and sleep diary and underwent actigraphy. Sixteen patients completed the study, 8 in each arm (mean age and M/F were 48.5 vs. 57.8 y, and 8/0 vs. 6/2, respectively). Patients who received ramelteon demonstrated a statistically significant decrease in symptom score as compared with those who received placebo for daytime heartburn (-42% vs. -29%), nighttime heartburn (-42% vs. 78%), 24-hour heartburn (-42% vs. -3%), and 24-hour acid regurgitation (-26% vs. 19%) (all P<0.05). Insomnia severity index score was significantly reduced in patients receiving ramelteon as compared with placebo (-46% vs. -5%, P<0.05). Ramelteon group also demonstrated a significant improvement in sleep efficiency and sleep latency, as compared with placebo, P<0.05). No significant adverse events were observed with ramelteon. Ramelteon significantly improved symptoms in patients with GERD. In addition, ramelteon significantly improved patients' sleep experience. Further studies are needed in the future (NCT01128582).

A randomized, controlled, crossover study in patients with mild and moderate asthma undergoing treatment with traditional Chinese acupuncture

OBJECTIVES:This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma.METHODS:This was a randomized, controlled, crossover trial conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A total of 74 patients with mild/moderate, persistent asthma were randomized into two therapeutic groups: Group A – 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short- and long-acting β-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (α=0.05).RESULTS:In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation.CONCLUSION:Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma.

Comparative Burden of Influenza A/H1N1, A/H3N2 and B Infections in Children Treated as Outpatients.

Few studies have directly compared the clinical impact of different types and subtypes of influenza viruses in children. In a prospective study of respiratory infections in preenrolled cohorts of children ≤13 years of age, we compared the clinical features and the overall burden of illness between outpatient children with A/H1N1, A/H3N2 and B infections. The data were derived from structured medical records filled out by study physicians and from daily symptom diaries filled out by the parents throughout the follow-up period. Of 358 children included in the analyses, 203 (57%) had influenza A/H1N1, 96 (27%) had A/H3N2, and 59 (16%) had influenza B infection. Children with influenza A/H3N2 were significantly younger (median, 3.2 years) than those with A/H1N1 (median, 4.8 years) or B (median, 5.1 years) infections (P < 0.0001). When adjusted for age, children 3-6 years of age with A/H3N2 infection had a higher frequency of fever ≥39.0°C (67% vs. 38%; P = 0.002), longer duration of fever (median, 4 vs. 3 days; P = 0.02) and more antibiotic treatments (43% vs. 20%; P = 0.004) than did children with A/H1N1 infections. Overall, the clinical presentation, duration of illness, frequency of complications, children's absenteeism from day care or school and parental work absenteeism were comparable between children with A/H1N1, A/H3N2 and B infections. Adjusted for age, the clinical manifestations and the burden of illness are largely comparable between children with influenza A/H1N1, A/H3N2 and B infections.

Outcome measurement of refractory breathlessness: endpoints and important differences.

Standardized measurement of self-rated breathlessness using appropriate tools is essential for research and clinical care. The purpose was to review recent advances in the measurement of breathlessness and the minimal clinically important differences (MCIDs) in intensity of chronic breathlessness. Two tools have been validated in people with chronic obstructive pulmonary disease (COPD) to measure daily symptoms and breathlessness related to daily activities. Two multidimensional tools have been developed for different settings and aetiologies, which measure both the perceived intensity, unpleasantness, quality of breathlessness, and the person's emotional response to it. MCIDs have been reported for the intensity of chronic refractory breathlessness, the daily symptom diary, and breathlessness related to daily activities in COPD. There have been substantial developments in instruments able to provide reliable and valid unidimensional and multidimensional measurement of self-reported breathlessness and in the understanding of the MCID for chronic breathlessness. Routine use of agreed outcome measures in clinical practice and research are crucial steps to improve our understanding of the science of breathlessness and its impact on patients' outcomes.

Quality of life impacts from rotavirus gastroenteritis on children and their families in the UK

AimsRotavirus vaccines (RV) are safe and effective but demand significant investment of healthcare resource. In countries with low mortality due to rotavirus, a key component to assessing cost-effectiveness is quantifying the Health Related Quality of Life (HRQoL) lost due to rotavirus acute gastroenteritis (RVAGE). MethodsFamilies with children less than six years old with gastroenteritis were recruited from attendees to Bristol Children's Hospital Emergency Department. Stools were tested for viral causes of gastroenteritis. Children's HRQoL was assessed at presentation using Health Utilities Index 2 (HUI2) with visual analogue scale (VAS). The effect of the child's illness on the HRQoL of up to two adult carers was assessed using EQ-5D-5L. Families completed a daily symptom diary to assess time to recovery and within-family transmission. Results127 families consented to take part, 84(65%) had rotavirus as the cause of illness. At the time of attendance, mean paediatric HRQoL with RVAGE was 0.74(HUI2) and 0.42(VAS). Primary/secondary carer's HRQoL was 0.68/0.80 (EQ5D) or 0.70/0.79 (VAS). The mean number of QALYs lost due to RVAGE was 3.1–3.5 per thousand children and 7.7–8.7 per thousand family units.In 52% of RVAGE families at least one other member developed a secondary case of gastroenteritis. For working parents, 69% missed work, for a mean of 2.8 days (95% CI 2.3–3.4). ConclusionsWe have found the HRQoL loss associated with RVAGE in children and their carers to be significantly higher than estimates used for all RV medical attendances in UK cost-effectiveness calculations.

Effects of fosaprepitant (Fosa) administered as single dose versus two doses, on nausea/vomiting (N/V) in patients receiving multiday chemotherapy (CT) with a highly emetogenic regimen of doxorubicin and ifosafamide (AI): Randomized cross-over study.

9616 Background: AI is multi-day regimen of highly emetogenic chemotherapy, with high incidence of delayed N/V. Fosa, NK1 receptor antagonist (RA), administered IV as single dose (FDA-approved), with 5HT3RA and dexamethasone has improved the control of emesis. However, delayed N/V still remains problematic. Purpose of the study was to examine the effects of fosa administered IV on day 1 vs days 1 and 4 on N/V and the effect on ifosfamide (Ifex) and its active metabolites, due to potential drug interactions via CYP450. Methods: Sarcoma pts, planned to receive AI, were randomized 1:1 to Arm A (single- dose Fosa on day 1) or Arm B (2-doses, on days 1 and 4). Within each arm, patients were randomized to Group-1: Fosa in cycle-1 (C-1) and no Fosa in cycle-2 (C-2), and group-2: no Fosa in C-1 and Fosa in C-2. Blood samples were drawn for levels of Ifex/metabolites to be analyzed at the end of study. All pts could receive 2 doses of Fosa during cycles 3-6. Pts were monitored for N/V with daily symptom diary and ...

Measuring and quantifying acute exacerbations of COPD: pitfalls and practicalities

Pity the poor clinical researcher who is charged with identifying and quantifying chronic obstructive pulmonary disease (COPD) exacerbation events in clinical trials. An exacerbation of COPD is a clinical event that: 1) has no standard, consensus definition [1]; 2) often goes unreported and undetected if patients choose to stay at home instead of presenting to a healthcare provider [2]; 3) often occurs suddenly with little or no warning [3]; and 4) is subject to diagnostic uncertainty and is easily confused with pulmonary embolism, congestive heart failure or pneumonia [4–6]. Given these inherent difficulties, much-needed efforts have been made towards developing better measurement tools for quantifying COPD exacerbation events [7]. One such new measurement tool is the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item, patient-reported daily symptom diary that attempts to accurately capture the frequency, severity, and duration of exacerbations, and which is meant to be used in clinical trials and cohort studies of COPD patients [8]. A tool such as EXACT is desperately needed by COPD clinical researchers [9], assuming that it works. In this issue of the European Respiratory Journal , Mackay et al. [10] have attempted to test EXACT to see if it fulfils its expected functions. The investigators prospectively administered EXACT as well as their previously validated London COPD Cohort …

A Comprehensive Symptom Diary Intervention to Improve Outcomes in Patients With HF: A Pilot Study

BackgroundPatients with heart failure must monitor for and recognize escalating symptoms to take action to relieve symptoms and decrease hospitalizations. However, symptom monitoring is not commonly performed. One way to promote patients’ engagement in symptom monitoring is by providing a symptom diary. PurposeThe aim of this study was to test the effect of a comprehensive daily symptom diary intervention on event-free survival and health-related quality of life (HRQOL). MethodsPatients were randomized into either intervention (n = 23) or usual-care groups (n = 21). The intervention group received a symptom diary with self-care education and counseling at baseline with 5 follow-up calls for 3 months. All patients were interviewed to obtain survival data at 1 month and 3 months. HRQOL was measured at baseline, 1 month, and 3 months. Kaplan-Meier curves with the log-rank test were used to compare group differences in time to first event. Linear mixed models were conducted to examine the relationship between groups and changes in HRQOL over 3 months. ResultsThe intervention group had longer event-free survival than the usual-care group (P = .03). There were no differences in changes in HRQOL scores between the groups over 3 months. ConclusionsPositive effects of the intervention on survival were found. However, there was no significant difference in changes in HRQOL.

Detection of COPD Exacerbations and Compliance With Patient-Reported Daily Symptom Diaries Using a Smartphone-Based Information System

BackgroundPaper-based diaries and self-report of symptom worsening in COPD may lead to underdetection of exacerbations. Epidemiologically, COPD exacerbations exhibit seasonal patterns peaking at year-end. We examined whether the use of a BlackBerry-based daily symptom diary would detect 95% or more of exacerbations and enable characterization of seasonal differences among them.MethodsFifty participants with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I to IV COPD began a community-based study in December 2007. Another 30 began in December 2008. Participants transmitted daily symptom diaries using a BlackBerry. Alerts were triggered when symptom changes, missed diary transmissions, or medical care for a respiratory problem occurred. Participant encounters were initiated if COPD exacerbations were suspected. Participants used their BlackBerrys to report returns to normal breathing.ResultsParticipants transmitted 99.9% of 28,514 possible daily diaries. All 191 (2.5/participant-year) COPD exacerbations meeting Anthonisen criteria were detected. During 148 of the 191 exacerbations (78%, 1.97/participant-year), patients were hospitalized and/or ordered prednisone, an antibiotic, or both. Respiratory viruses were detected in 78 of the 191 exacerbations (41%). Those coinciding with a respiratory viral infection averaged 12.0 days, and those without averaged 8.9 days (P < .04), with no difference in Anthonisen score. Respiratory symptom scores before exacerbations and after normal breathing return showed no differences. Exacerbations were more frequent during the Christmas period than the rest of the year but were not more frequent than in the rest of winter alone.ConclusionsSmartphone-based collection of COPD symptom diaries enables near-complete identification of exacerbations at inception. Exacerbation rates in the Christmas season do not reach levels that necessitate changes in disease management.

A self-management approach using self-initiated action plans for symptoms with ongoing nurse support in patients with Chronic Obstructive Pulmonary Disease (COPD) and comorbidities: The COPE-III study protocol

BackgroundChronic Obstructive Pulmonary Disease (COPD) frequently coexists with other diseases. Whereas COPD action plans are currently part of usual care, they are less suitable and potentially unsafe for use in the presence of comorbidities. This study evaluates whether an innovative treatment approach directed towards COPD and frequently existing comorbidities can reduce COPD exacerbation days. We hypothesise that this approach, which combines self-initiated action plans and nurse support, will accelerate proper treatment actions and lead to better control of deteriorating symptoms. MethodsIn this multicenter randomised controlled trial we aim to include 300 patients with COPD (GOLD II-IV), and with at least one comorbidity (cardiovascular disease, diabetes, anxiety and/or depression). Patients will be recruited from hospitals in the Netherlands (n=150) and Australia (n=150) and will be assigned to an intervention or control group. All patients will learn to complete daily symptom diaries for 12-months. Intervention group patients will participate in self-management training sessions to learn the use of individualised action plans for COPD and comorbidities, linked to the diary. The primary outcome is the number of COPD exacerbation days. Secondary outcomes include hospitalisations, quality of life, self-efficacy, adherence, patient's satisfaction and confidence, health care use and cost data. AnalysesIntention-to-treat analyses (random effect negative binomial regression and random effect mixed models) and cost-effectiveness analyses will be performed. DiscussionPrudence should be employed before extrapolating the use of COPD specific action plans in patients with comorbidities. This study evaluates the efficacy of tailored action plans for both COPD and common comorbidities.

Short Term (14 Days) Consumption of Insoluble Wheat Bran Fibre-Containing Breakfast Cereals Improves Subjective Digestive Feelings, General Wellbeing and Bowel Function in a Dose Dependent Manner

This study investigated whether increasing insoluble (predominantly wheat bran) fibre over 14 days improves subjective digestive feelings, general wellbeing and bowel function. A single centre, multi-site, open, within subjects design with a 14 day non-intervention (baseline) monitoring period followed by a 14 day fibre consumption (intervention) period was performed. 153 low fibre consumers (<15 g/day AOAC 985.29) completed a daily symptom diary for 14 days after which they consumed one bowl of ready-to-eat breakfast cereal containing at least 5.4 g fibre (3.5 g from wheat bran) for 14 days and completed a daily symptom diary. Significant improvements were demonstrated in subjective perception of bowel function (e.g., ease of defecation) and digestive feelings (bloating, constipation, feeling sluggish and digestive discomfort). Significant improvements were also found in subjective perception of general wellbeing (feeling less fat, more mentally alert, slim, happy and energetic whilst experiencing less stress, mental and physical tiredness, difficulty concentrating and fewer headaches). In general, improvements in study outcomes increased with increasing cereal/fibre consumption. However, consuming an additional minimum 5.4 g of fibre (3.5 g wheat bran) per day was shown to deliver measurable and significant benefits for digestive health, comfort and wellbeing. Encouraging consumption of relatively small amounts of wheat bran could also provide an effective method of increasing overall fibre consumption.

Daily Diaries vs Retrospective Questionnaires to Assess Asthma Control and Therapeutic Responses in Asthma Clinical Trials: Is Participant Burden Worth the Effort?

Background Presently, there is insufficient information to compare the value of daily diaries vs retrospective questionnaires for assessing symptoms in relationship to asthma control in clinical trials. Daily symptom diaries are often burdensome to gather, incomplete, susceptible to fabrication, and of questionable reliability. There is also concern that retrospective symptom questionnaires may be subject to poor recall and may be insensitive. Methods To compare these two methods of assessing symptoms reporting, we analyzed data collected during the Best Add-on Therapy Giving Effective Responses (BADGER) trial. During the trial, asthma control in 182 children aged 6 to 17 years was assessed in two ways: (1) by asthma control days (ACDs) determined by manually recorded daily diary symptom and rescue medication use scores and (2) by monthly retrospective report of symptoms embedded within the age-appropriate version of the Asthma Control Test (ACT). Correlations between ACDs and ACT scores were analyzed, and the sensitivity of each method for measuring asthma control and determining the differential response among the three BADGER treatments was evaluated. Results Although validated using a 4-week recall period, ACT correlated better with daily diary information from the last 2 weeks of the 4-week recall (r = 0.46) than from the first 2 weeks (r = 0.34). In addition, clinically significant differential treatment responses were detected using ACDs but not ACT scores. Conclusions The results of this study indicate that daily diaries used to determine ACDs can be a more sensitive tool than ACT for assessing differential treatment responses with respect to asthma control. Presently, there is insufficient information to compare the value of daily diaries vs retrospective questionnaires for assessing symptoms in relationship to asthma control in clinical trials. Daily symptom diaries are often burdensome to gather, incomplete, susceptible to fabrication, and of questionable reliability. There is also concern that retrospective symptom questionnaires may be subject to poor recall and may be insensitive. To compare these two methods of assessing symptoms reporting, we analyzed data collected during the Best Add-on Therapy Giving Effective Responses (BADGER) trial. During the trial, asthma control in 182 children aged 6 to 17 years was assessed in two ways: (1) by asthma control days (ACDs) determined by manually recorded daily diary symptom and rescue medication use scores and (2) by monthly retrospective report of symptoms embedded within the age-appropriate version of the Asthma Control Test (ACT). Correlations between ACDs and ACT scores were analyzed, and the sensitivity of each method for measuring asthma control and determining the differential response among the three BADGER treatments was evaluated. Although validated using a 4-week recall period, ACT correlated better with daily diary information from the last 2 weeks of the 4-week recall (r = 0.46) than from the first 2 weeks (r = 0.34). In addition, clinically significant differential treatment responses were detected using ACDs but not ACT scores. The results of this study indicate that daily diaries used to determine ACDs can be a more sensitive tool than ACT for assessing differential treatment responses with respect to asthma control.

Validation of the Daily Diary of Fatigue Symptoms—Fibromyalgia (DFS-Fibro)

Introduction: Fatigue is an important fibromyalgia (FM) symptom, but existing measures of fatigue are unlikely to meet regulatory standards for clinical trial use. We describe the development and validation of the Daily Diary of Fatigue Symptoms—Fibromyalgia (DFS-Fibro), a 24-hour recall, patient-reported outcome (PRO) measure of fatigue in FM that is administered electronically (ePRO). Methods: There were 3 phases of work: 1) item generation based on concept elicitation interviews with FM patients, with clinical relevance confirmed by expert clinician review; 2) pilot testing/cognitive debriefing interviews with FM patients; and 3) psychometric validation using data from a methodology study with 145 FM patients. The measure was finalised based on both qualitative and quantitative findings. Results: Twenty-three items were generated in phase 1, some minor revisions were made following the pilot testing and cognitive debriefing (phase 2) but none were deleted. All patients found the measure easy to understand and use. Item reduction was conducted taking into account both the initial psychometric data and the earlier qualitative research, resulting in a final 5 item measure of the “symptom” of fatigue. The 5-item DFS-Fibro had very high internal consistency (alpha = 0.99), and strong test-re-test reliability (r > 0.84), convergent validity and known-groups validity. Conclusion: The DFS-Fibro has strong psychometric properties and strong face and content validity for the measurement of fatigue in FM.

A Randomized Trial of the Efficacy of Hand Disinfection for Prevention of Rhinovirus Infection

Hand disinfection is frequently recommended for prevention of rhinovirus (RV) infection and RV-associated common colds. The effectiveness of this intervention has not been established in a natural setting. The purpose of this study was to determine the effect of hand disinfection on RV infection and RV-associated common cold illness in a natural setting. A controlled clinical trial was done in young adult volunteers during 9 weeks of the fall 2009 RV season. Volunteers were randomized to either an antiviral hand treatment containing 2% citric acid and 2% malic acid in 62% ethanol (n = 116) or to a no-treatment control group (n = 96). The hand treatment was applied every 3 hours while the subjects were awake. All volunteers kept a daily diary of symptoms and had a nasal lavage for polymerase chain reaction once each week and 2 additional lavages around the time of each common cold illness. The primary endpoint was the number of RV-associated illnesses. The incidence of RV infection and of common cold illnesses were evaluated as secondary endpoints. The hand treatment did not significantly reduce RV infection or RV-related common cold illnesses. The total number of common cold illnesses was significantly reduced in the intent-to-treat analysis, but this effect was not seen in the per protocol analysis. In this study, hand disinfection did not reduce RV infection or RV-related common cold illnesses. NCT00993759.

Clinical Subtypes of Premenstrual Syndrome and Responses to Sertraline Treatment

To estimate response of diagnosis and symptom-based subtypes to sertraline treatment. This was a secondary data analysis for women who were diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder and treated in three National Institutes of Health-supported clinical trials (N=447). Three PMS subtypes were identified based on predominance of psychological, physical, or both symptom types. Scores for each symptom and a total premenstrual score at baseline and endpoint were calculated from daily symptom diaries. Change from baseline after three treated menstrual cycles (or endpoint if sooner) was estimated using linear regression models adjusted for baseline severity. The PMS and premenstrual dysphoric disorder diagnoses improved similarly with sertraline relative to placebo, whereas symptom-based subtypes had differential responses to treatment. The mixed symptom subtype had the strongest response to sertraline relative to placebo (Daily Symptom Rating difference 33.80; 95% confidence interval [CI] 17.16-50.44; P<.001), and the physical symptom subtype had the poorest response to sertraline (Daily Symptom Rating difference 9.50; 95% CI -16.29 to 35.28; P=.470). Results based on clinical improvement (50% decrease from baseline) indicated that 8.3 participants in the mixed symptom subtype, 3.9 in the psychological subtype, and 7.1 in the physical subtype are needed to observe one woman in the subtype who would achieve clinical improvement. The PMS and premenstrual dysphoric disorder diagnoses have similar response to sertraline treatment, but symptom-based subtypes have significantly different responses to this treatment. Mixed and psychological symptom subtypes improved whereas the physical symptom subtype did not improve significantly. Identifying the patient's predominant symptoms and their severity is important for individualized treatment and a possible response to a selective serotonin reuptake inhibitor. II.