Evaluation of symptoms in respiratory syncytial virus infection in adults: psychometric evaluation of the Respiratory Infection Intensity and Impact Questionnaire™ symptom scores.

BACKGROUND: The Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) is a patient-reported outcome measure designed to assess symptoms and impacts of respiratory syncytial virus (RSV) infection. This study evaluated the construct validity, reliability, and responsiveness of the RiiQ™ Respiratory and Systemic Symptoms Scale scores. METHODS: Prospective data were analyzed from a total of 1795 participants, including from non-hospitalized patients with acute respiratory infection (ARI) and no coinfections enrolled in a Phase 2b RSV vaccine study (RSV-positive: n = 60; RSV-negative: n = 1615), and two observational studies of patients hospitalized with RSV (n = 20; n = 100). Descriptive statistics, confirmatory factor analysis (CFA), test-retest intraclass correlation coefficients (ICCs), construct validity correlations (between a clinician-assessed clinical questionnaire and the RiiQ™ symptoms scale), known-groups validity, and responsiveness (correlations of change scores) were evaluated. RESULTS: Mean patient age ranged from 66.5 to 71.5 years and the majority of patients were female. Initial assessments in the vaccine trial (ARI Day 1) were suggestive of less severe illness than in the observational studies with hospitalized patients. CFA loadings (> 0.40) supported summary scores. ICCs exceeding the recommended threshold of 0.70 supported test-retest reliability for Respiratory and Systemic Symptoms, except in the small observational study. At the scale level, correlations were moderate to strong (|r| ≥ 0.3) and positive between the Respiratory Symptoms Scale and the related clinical questionnaire scores, reflecting measurement of similar symptoms in support of convergent validity. Correlations with change in Patient Global Impression of Severity > 0.30 supported responsiveness. CONCLUSIONS: Psychometric tests applied to the RiiQ™ Symptoms scales provide evidence of its reliability, construct validity, discriminating ability, and responsiveness for use in clinical studies to assess the onset and severity of RSV symptoms.

Development and evaluation of the Acromegaly Symptom Diary.

BACKGROUND: Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD. METHODS: Semistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants' experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n = 13) and ACROBAT Edge (NCT03789656; n = 47) clinical trials. RESULTS: The 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n = 13) and fatigue (n = 12), followed by swelling (n = 8), headache (n = 7), and mood swings (n = 6), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91 - 0.80), test-retest reliability with item-level and total ASD scores (> 0.70), baseline construct validity (r ≥ |0.38|) across scales, and responsiveness to change (r = 0.52-0.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients' perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70. CONCLUSION: These findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.

The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire: Development and Psychometric Validation.

OBJECTIVES: To facilitate the development of new therapies for Prader-Willi syndrome (PWS), we sought to develop a reliable and valid assessment of anxiousness and distress, common characteristics that have a significant negative impact on individuals with PWS and their families. METHODS: The PWS Anxiousness and Distress Behaviors Questionnaire (PADQ) was developed with extensive input from clinical experts, as well as caregivers of individuals with PWS, who participated in iterative sets of qualitative interviews. The psychometric properties of the PADQ were subsequently demonstrated in a cross-sectional evaluation using data from the Global PWS Registry provided by > 400 caregivers and confirmed using data from a phase 3 clinical trial of an oxytocin analogue (intranasal carbetocin, LV-101). RESULTS: Qualitative interview participants consistently endorsed the content of the PADQ and were confident they could accurately respond to each item based on their observations of their child's behavior. Analysis of cross-sectional data supported the computation of a total PADQ score, as well as the reliability and validity of the measure. The results of analyses using longitudinal clinical trial data confirmed these properties and provided evidence for the responsiveness of the PADQ, further supporting its appropriateness for the evaluation of new treatments targeting anxiousness and distress in PWS. CONCLUSIONS: The current body of evidence supports the conclusion that the PADQ measures observable behaviors that are meaningful to patients and their families and provides a valid and reliable method to assess beneficial treatment effects for some of the most challenging behaviors associated with PWS.

Development and Validation Clinician and Patient Reported Photonumeric Scales to Assess Buttocks Cellulite Severity.

BACKGROUND: The Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported PCSS (PR-PCSS) are newly developed tools for assessing cellulite severity. OBJECTIVE: To report on the reliability, validity, and ability to detect a change in cellulite severity on the buttocks of adult women with the CR-PCSS and PR-PCSS. MATERIALS AND METHODS: Content validity of both scales was established through concept elicitation and cognitive interviews. Test-retest reliability was evaluated, and intra-rater (both scales) and inter-rater (CR-PCSS only) reliability were estimated using intraclass correlation coefficients (ICCs) for agreement and consistency. Ability to detect a change was determined using the Subject-Global Aesthetic Improvement Scale (GAIS) or Investigator-GAIS as anchors. RESULTS: For the CR-PCSS (n = 6) at baseline and Day 2, the mean interrater ICCs were ≥0.70 and mean intrarater ICCs (95% confidence interval [CI]) were ≥0.81 (0.72-0.90) for both buttocks. For the PR-PCSS (n = 99) at baseline and Day 14, the mean test-retest reliability ICCs (95% CI) were ≥0.86 (0.79-0.91) for both buttocks. A clinically meaningful change was 1.0 point on the PR-PCSS and 1.0 on the CR-PCSS. CONCLUSION: The CR-PCSS and PR-PCSS reliably assess cellulite severity of the buttocks and can detect a clinically meaningful change after treatment for cellulite.

Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). OBJECTIVES: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. METHODS: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. RESULTS: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values < 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). CONCLUSIONS: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum.

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI).

Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic). Results: A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3 years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE = 0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.

A Scale to Assess Activities of Daily Living in Pantothenate Kinase-Associated Neurodegeneration.

OBJECTIVE: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive, neurodegenerative disorder with a mixed-motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient-reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. METHODS: A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12-item Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL). The PKAN-ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro-QoL) measures, selected attributes of the Health Utilities Index (HUI)-2/3, and the Stroke Aphasia Depression Questionnaire (SADQ-10) to assess construct validity. RESULTS: Internal consistency was 0.93, with excellent test-retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31-54) and 42% (n = 5) showed a floor effect >30% (range, 31-46), reflecting disease heterogeneity. Convergent validity was shown with Neuro-QoL measures (rs > 0.90) and HUI-2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ-10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0-10 scale) ranged from 7.0 to 9.9. CONCLUSION: The PKAN-ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN-ADL scale in clinical trials.

Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17ß-estradiol/progesterone.

OBJECTIVE: To characterize the impact of TX-001HR on the relationship between vasomotor symptom (VMS) improvement and quality of life and sleep. METHODS: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial, which evaluated four daily doses of 17ß-estradiol and progesterone (E2/P4) combined in a single, oral, softgel capsule in postmenopausal women (40-65 years) with a uterus and moderate to severe VMS (≥7/day or ≥50/week). In post hoc analyses, growth models were used to examine relationships between linear changes in VMS frequency and severity over 12 weeks and changes from baseline in the Menopause-Specific Quality of Life (MENQOL; total score and VMS domain) and the Medical Outcomes Study-Sleep (total score, sleep problems indices I and II) questionnaire outcomes at 12 weeks with treatment compared with placebo. RESULTS: Outcomes with all four E2/P4 doses were combined (n = 591) and compared with placebo (n = 135). In all 5 growth models, the effects of TX-001HR on MENQOL total score and vasomotor domain were significantly associated with changes in VMS frequency and severity observed over 12 weeks (all, P < 0.001). Treatment-mediated effects on MENQOL via VMS frequency and severity models were significant. Similar results were found with Medical Outcomes Study-Sleep total score and sleep problems indices. CONCLUSIONS: TX-001HR improvements in quality of life and sleep outcomes are associated with and may be mediated through improvements in VMS frequency and severity.

Adoption of cardiovascular risk reduction guidelines: a cluster-randomized trial.

BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) and underlying atherosclerosis begin in childhood and are related to CVD risk factors. This study evaluates tools and strategies to enhance adoption of new CVD risk reduction guidelines for children. METHODS: Thirty-two practices, recruited and supported by 2 primary care research networks, were cluster randomized to a multifaceted controlled intervention. Practices were compared with guideline-based individual and composite measures for BMI, blood pressure (BP), and tobacco. Composite measures were constructed by summing the numerators and denominators of individual measures. Preintervention and postintervention measures were assessed by medical record review of children ages 3 to 11 years. Changes in measures (pre-post and intervention versus control) were compared. RESULTS: The intervention group BP composite improved by 29.5%, increasing from 49.7% to 79.2%, compared with the control group (49.5% to 49.6%; P < .001). Intervention group BP interpretation improved by 61.1% (from 0.2% to 61.3%), compared with the control group (0.4% to 0.6%; P < .001). The assessment of tobacco exposure or use for 5- to 11-year-olds in the intervention group improved by 30.3% (from 3.4% to 49.1%) versus the control group (0.6% to 21.4%) (P = .042). No significant change was seen in the BMI or tobacco composites measures. The overall composite of 9 measures improved by 13.4% (from 48.2% to 69.8%) for the intervention group versus the control group (47.4% to 55.2%) (P = .01). CONCLUSIONS: Significant improvement was demonstrated in the overall composite measure, the composite measure of BP, and tobacco assessment and advice for children aged 5 to 11 years.

Planning in middle childhood: early predictors and later outcomes.

Data from 1,364 children and families who participated in the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development were analyzed to track the early correlates and later academic outcomes of planning during middle childhood. Maternal education, through its effect on parenting quality when children were 54 months old, predicts their concurrent performance on sustained attention, inhibition, and short-term verbal memory tests. This performance predicts planning in first grade, which predicts third-grade reading and mathematics attainment, but not the rate of growth in academic skills from first to fifth grades. This path was also found when the same parenting, cognitive, and academic constructs were measured at later time points.

Implementation of the NHLBI integrated guidelines for cardiovascular health and risk reduction in children and adolescents: rationale and study design for young hearts, strong starts, a cluster-randomized trial targeting body mass index, blood pressure, and tobacco.

BACKGROUND: Cardiovascular disease (CVD) and the underlying atherosclerosis begin in childhood, and their presence and intensity are related to known cardiovascular disease risk factors. Attention to risk factor control in childhood has the potential to reduce subsequent risk of CVD. OBJECTIVE: The Young Hearts Strong Starts Study was designed to test strategies facilitating adoption of the National, Heart, Lung and Blood Institute supported Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. This study compares guideline-based quality measures for body mass index, blood pressure, and tobacco using two strategies: a multifaceted, practice-directed intervention versus standard dissemination. STUDY DESIGN: Two primary care research networks recruited practices and provided support for the intervention and outcome evaluations. Individual practices were randomly assigned to the intervention or control groups using a cluster randomized design based on network affiliation, number of clinicians per practice, urban versus nonurban location, and practice type. The units of observation are individual children because measure adherence is abstracted from individual patient's medical records. The units of randomization are physician practices. This results in a multilevel design in which patients are nested within practices. The intervention practices received toolkits and supported guideline implementation including academic detailing, an ongoing e-learning group. This project is aligned with the American Board of Pediatrics Maintenance of Certification requirements including monthly physician self-abstraction, webinars, and other elements of the trial. SIGNIFICANCE: This trial will provide an opportunity to demonstrate tools and strategies to enhance CV prevention in children by guideline-based interventions.

Longitudinal study of resilience and mental health in Marines leaving military service.

BACKGROUND: Despite a growing emphasis on psychological outcomes following military combat, few longitudinal studies have examined the combined role of risk and protective factors in the mental health of combat-exposed military personnel. This study characterizes the impact of resilience scale scores and combat exposure on mental health outcomes among Marines after separating from military service, along with intra-individual changes in mental health status. METHODS: Data were collected from longitudinal surveys of 475 active duty Marines attending a random sample of mandatory Transition Assistance Program workshops before leaving the military and responding to follow-up mail or web surveys an average of 6 months after returning to civilian life. RESULTS: Results revealed distinct risk and protective factors for those meeting screening criteria for mental health problems (depression, anxiety, and PTSD) and functional impairment at follow-up. Primary risk factors included experiencing higher levels of pre-separation combat exposure; post-separation stress across multiple life domains; and experiencing multiple areas of pain post-separation. Protective factors include having higher scores on pre-separation resilience and perceived social support at follow-up indices. We also identified a number of factors associated with change in mental health status from baseline to follow-up. LIMITATIONS: Generality is limited by a lower than expected follow-up response rate and an exclusively Marine sample. CONCLUSION: The role of resilience appeared to have a greater impact on functional impairment than on mental health symptoms per se. Findings provide important input for enhancing training programs and services intended to promote adjustment from military to civilian life. Additional emphasis on social support and coping with stress-related issues are needed in support of combat veterans.

Patterns of developmental change in infants' nighttime sleep awakenings from 6 through 36 months of age.

Nighttime sleep awakenings and infant and family characteristics were measured longitudinally in more than 1,200 infants when the infants were 6, 15, 24, and 36 months old. By 6 months of age, the majority of children slept through the night, awakening their mothers only about once or twice per week. However, not all children followed this predominant developmental pattern. Using growth mixture modeling, we identified 2 distinct developmental patterns. One group, labeled Sleepers, included 66% of the children. These children showed a flat trajectory of sleep awakenings from 6 through 36 months, with mothers reporting their infant awakening from sleep about 1 night per week. The second group, labeled Transitional Sleepers, included 34% of the infants. These children had 7 reported nights of awakenings per week at 6 months, dropping to 2 nights per week at 15 months and to 1 night per week by 24 months. Compared with Sleepers, Transitional Sleepers were more likely to be boys, score higher on the 6-month difficult temperament assessment, be breastfed at 6 and 15 months old, and have more depressed mothers at 6 months old. Using 2-group structural equation modeling, we examined individual differences at different points on the individual infants' sleep trajectories. For infants in both groups, reported sleep awakenings were associated with difficult temperament measured at 6 months, breastfeeding, infant illness, maternal depression, and greater maternal sensitivity. Infant-mother attachment measures were not related to these sleep awakenings.

Cost-effectiveness analysis of motivational interviewing with feedback to reduce drinking among a sample of college students.

OBJECTIVE: This study evaluated the costs and cost-effectiveness of combining motivational interviewing with feedback to address heavy drinking among university freshmen. METHOD: Microcosting methods were used in a prospective cost and cost-effectiveness study of a randomized trial of assessment only (AO), motivational interviewing (MI), feedback only (FB), and motivational interviewing with feedback (MIFB) at a large public university in the southeastern United States. Students were recruited and screened into the study during freshman classes based on recent heavy drinking. A total of 727 students (60% female) were randomized, and 656 had sufficient data at 3-months' follow-up to be included in the cost-effectiveness analysis. Effectiveness outcomes were changes in average drinks per drinking occasion and number of heavy drinking occasions. RESULTS: Mean intervention costs per student were $16.51 for MI, $17.33 for FB, and $36.03 for MIFB. Cost-effectiveness analysis showed two cost-effective interventions for both outcomes: AO ($0 per student) and MIFB ($36 per student). CONCLUSIONS: This is the first prospective cost-effectiveness study to our knowledge to examine MI for heavy drinking among students in a university setting. Despite being the most expensive intervention, MIFB was the most effective intervention and may be a cost-effective intervention, depending on a university's willingness to pay for changes in the considered outcomes.

Suicidal or self-harming ideation in military personnel transitioning to civilian life.

Suicides have markedly increased among military personnel in recent years. We used path analysis to examine factors associated with suicidal/self-harming ideation among male Navy and Marine Corps personnel transitioning to civilian life. Roughly 7% of men (Sailors = 5.3%, Marines = 9.0%) reported ideation during the previous 30 days. Results suggest that combat exposure, substance abuse, and resilience are associated with suicidal ideation/self-harming thoughts through the mediation of posttraumatic stress disorder symptoms and/or depression symptoms. Substance abuse plays a moderating role. Resilience had a direct effect only among the Marines. Implications for improving the transition to civilian life are discussed.

Diagnostic validity of two instruments for assessing anxiety and depression among pregnant women in Hyderabad, Pakistan.

The objective of this study was to compare the diagnostic validity of two measures, the Aga Khan University Anxiety and Depression Scale (AKUADS) and the How I Feel scale, for assessing anxiety and depression among pregnant women in Pakistan. The sample included 200 pregnant women in Hyderabad, Pakistan. Using psychiatrist-administered Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria, 71 (36%) of the women were diagnosed with depression or anxiety or both. Receiver operating characteristic (ROC) analyses indicated that the two scales had similar levels of discrimination. This study represents an important initial step in developing measures to assess the psychological well-being of Pakistani pregnant women. Additional research is needed, however, to improve the sensitivity and specificity of these scales by removing items that do not function well in this population.

Teachers' education, classroom quality, and young children's academic skills: results from seven studies of preschool programs.

In an effort to provide high-quality preschool education, policymakers are increasingly requiring public preschool teachers to have at least a Bachelor's degree, preferably in early childhood education. Seven major studies of early care and education were used to predict classroom quality and children's academic outcomes from the educational attainment and major of teachers of 4-year-olds. The findings indicate largely null or contradictory associations, indicating that policies focused solely on increasing teachers' education will not suffice for improving classroom quality or maximizing children's academic gains. Instead, raising the effectiveness of early childhood education likely will require a broad range of professional development activities and supports targeted toward teachers' interactions with children.

Including disenrollees in CAHPS managed care health plan assessment reporting.

This study addresses the question whether basing plan quality ratings on the data of both enrollees and disenrollees provides more accurate reporting. We test whether including disenrollee data in calculating the CAHPS scores, reported in health plan assessments, will result in lower scores indicating lower plan quality. Adding disenrollees results in statistically significant score decreases. Factors likely to result in larger score changes when disenrollees are included are explored. The study concludes that though final determinations should rest on more extensive data, that there is evidence to suggest that including disenrollee feedback improves accuracy.