A concept elicitation study to understand the relationship between sleep and pain in rheumatoid arthritis and axial spondyloarthritis.

PURPOSE: This qualitative study (GSK study: 213635) was designed to better understand sleep disturbance as experienced by individuals with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA), and the relationship between sleep disturbance and pain and other aspects of the disease and disease activity. METHODS: Sixty-minute, one-on-one, concept elicitation interviews were conducted with 30 participants (15 with RA and 15 with axSpA) from the US. Interviews were audio-recorded and transcribed verbatim. Interview transcripts were coded and analyzed to explore themes related to pain and sleep disturbance, and relationships among those themes. RESULTS: Pain was a prominent driver of sleep disturbance; 12 participants with RA (80%) and 14 with axSpA (93%) reported that pain impacted their ability to fall asleep, while all 15 with RA (100%) and 14 with axSpA (93%) reported that pain impacted their ability to stay asleep. Two-thirds of participants with RA (67%) or axSpA (60%) described a bi-directional relationship, whereby pain worsened sleep disturbance and sleep disturbance further aggravated pain. Factors other than pain, such as fatigue and emotional health, were also reported as important contributors to sleep disturbance (RA: n = 12/15, 80%; axSpA: n = 14/15, 93%). Participants with RA or axSpA described complex interconnections between fatigue, emotional health, pain, and sleep, often labeling these relationships as "vicious cycles". Notably, half of all participants reported sleep disturbance occurring without pain or other understood causes. CONCLUSION: These perspectives collected from people with RA or axSpA suggest that reducing sleep disruption directly may offer clinically relevant benefits.

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups.

BACKGROUND: Schizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I. METHODS: Six 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable. RESULTS: Among participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem. CONCLUSIONS: People living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients' experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

Content validity and psychometric properties of the inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus©) instrument in patients with COVID-19.

PURPOSE: A well-defined and reliable patient-reported outcome instrument for COVID-19 is important for assessing symptom severity and supporting research studies. The InFLUenza Patient-Reported Outcome (FLU-PRO) instrument has been expanded to include loss of taste and smell in the FLU-PRO Plus, to comprehensively cover COVID-19 symptoms. Our studies were designed to evaluate and validate the FLU-PRO Plus among patients with COVID-19. METHODS: Two studies were conducted: (1) a qualitative, non-interventional, cross-sectional study of patients with COVID-19 involving hybrid concept elicitation and cognitive debriefing interviews; (2) a psychometric evaluation of the measurement properties of FLU-PRO Plus, using data from COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early). RESULTS: In the qualitative interviews (n = 30), all 34 items of the FLU-PRO Plus were considered relevant to COVID-19, and participants determined the questionnaire was easily understood, well written, and comprehensive. In the psychometric evaluation (n = 845), the internal consistency reliability of FLU-PRO Plus total score was 0.94, ranging from 0.71 to 0.90 for domain scores. Reproducibility (Day 20-21) was 0.83 for total score, with domain scores of 0.67-0.89. Confirmatory factor analysis with the novel smell/taste domain demonstrated an acceptable fit to the data. CONCLUSION: The content, reliability, validity, and responsiveness of the FLU-PRO Plus in the COVID-19 population were supported. Our results suggest that FLU-PRO Plus is a content- and psychometrically-valid, fit-for-purpose measure which is easily understood by patients. FLU-PRO Plus is a suitable PRO measure for evaluating symptoms of COVID-19 and treatment benefit directly from the patient perspective. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04545060, September 10, 2020; retrospectively registered.

Validation of the PROFAD-SSI-SF in Patients with Primary Sjögren's Syndrome with Organ Involvement: Results of Qualitative Interviews and Psychometric Analyses.

INTRODUCTION: The Profile of Fatigue and Discomfort-Sicca Symptoms Inventory-Short Form (PROFAD-SSI-SF) is a 19-item patient-reported outcome (PRO) measure to assess pain, fatigue, and dryness in patients with primary Sjögren's syndrome (pSS). This analysis identified concepts important to measure, and evaluated the content validity and measurement properties of the PROFAD-SSI-SF, in patients with pSS. METHODS: Qualitative analyses (GSK Study 208396) used transcripts from an online concept elicitation (CE) discussion forum with patients with pSS and interviews with key opinion leaders (KOLs) to finalize a disease model depicting important concepts for patients with pSS. Cognitive debriefing (CD) interviews with patients with pSS were conducted to further evaluate the content validity of the PROFAD-SSI-SF. Quantitative analyses (GSK Study 213253) used post hoc analyses of blinded data from a phase 2 trial to assess PROFAD-SSI-SF measurement properties. RESULTS: The CE discussion forum (N = 46) revealed dryness (oral 87.0%, ocular 73.9%, cutaneous 37.0%, vaginal 23.9%, nasal 15.2%, otic 6.5%), pain (89.1%), and fatigue (87.0%) as the most reported symptoms. KOLs (N = 5) found the concepts identified in the disease model accurate and understandable, and confirmed that PROs used in pSS studies should focus on dryness, joint pain, and fatigue. In the CD interviews (N = 20), of the 19 participants asked, all found the PROFAD-SSI-SF easy to understand, and 14/19 items were considered relevant by ≥ 18/20 participants. The quantitative analyses found an acceptable fit of the PROFAD-SSI-SF factor structure, with adequate internal consistency, test-retest reliability, convergent validity with other PRO measures, known-groups validity with Patient Global Assessment, and ability to detect change in patients with pSS. CONCLUSION: The final disease model confirmed that the PROFAD-SSI-SF assesses concepts that are relevant and important to patients with pSS. Our findings support the content validity and measurement properties of the PROFAD-SSI-SF as a fit-for-purpose PRO measure appropriate for use in clinical trials in patients with pSS. CLINICAL TRIAL REGISTRATION NUMBER FOR THE PHASE 2 TRIAL: Clinicaltrials.gov NCT02631538.

Primary Sjögren's syndrome (pSS) is a disease where the immune system attacks the body, causing a number of symptoms, most notably dryness (sicca) of the eyes and mouth. The Profile of Fatigue and Discomfort­Sicca Symptoms Inventory­Short Form (PROFAD-SSI-SF) is a questionnaire for patients with pSS that asks about their symptoms. This paper evaluates how relevant the PROFAD-SSI-SF questions are to patients with pSS, and how consistently and accurately the questionnaire can measure changes in their symptoms. We reviewed information about the symptoms and impacts of pSS from an online discussion forum for patients with pSS. Patients said that dryness, fatigue, and pain were the symptoms that most affected their day-to-day lives and well-being. We combined this information with previous research on pSS to design a diagram explaining the key symptoms and day-to-day impacts of pSS, which was reviewed by five experts in pSS. In doing so, we aimed to confirm whether the most important things to patients about living with pSS are asked in the PROFAD-SSI-SF questionnaire. Next, we asked 20 patients with pSS how easy they found the PROFAD-SSI-SF to complete and if any important concepts were missing; they reported that the PROFAD-SSI-SF was easy to fill in and that the important questions were included. Finally, we looked at data from a clinical trial that used the PROFAD-SSI-SF and found it accurately measures changes in symptoms of patients with pSS. This means that the PROFAD-SSI-SF could be used in clinical trials to help assess new medicines for pSS.

Qualitative research with patients and caregivers of patients with PIK3CA related overgrowth spectrum: content validity of clinical outcome assessments.

BACKGROUND: PIK3CA-Related Overgrowth Spectrum (PROS) are rare syndromes caused by a mutation in the PIK3CA gene, including fibroadipose hyperplasia or overgrowth; congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES); megalencephaly-capillary malformation (MCAP or M-CM); fibro-adipose vascular anomaly (FAVA); Klippel-Trenaunay syndrome (KT; also known as, Klippel-Trenaunay-Weber syndrome); capillary, lymphatic, and venous malformations (CLVM); and lymphatic malformation (LM). Characterized by malformations and tissue overgrowth, PROS manifests at birth or in early childhood. Pain and functional limitations associated with these conditions may greatly impact the health-related quality of life (HRQoL) of persons with PROS including physical functioning, work/school, social functioning, and emotional well-being. RESULTS: Selected clinical outcome assessments (COAs), identified during a literature review, were tested with adults with PROS, and children with PROS and their caregivers to determine comprehensibility, relevance, and appropriateness for measuring symptom severity and HRQoL. Tested were the Patient Global Impression of Symptom Severity (PGI-S), Brief Pain Inventory (BPI), Wong-Baker FACES, Patient-Reported Outcomes Measurement Information System (PROMIS) Profile, PROMIS Pediatric Short Form Sleep Disturbance, and PROMIS Dyspnea Severity. Qualitative interviews tested the self-report adult, self-report pediatric, and observer-report COAs with adults with PROS, and children with PROS and their caregivers. Ten adults (≥ 18 years old) with PROS, and 20 children (6-17 years old) with PROS and their caregivers, participated. All reported positive feedback on item relevance. Adults and children over the age of 12 comprehended and responded to self-reported items. Secondary objectives examined the age children could self-report their conditions using pediatric versions and assessed available observer-report versions of the COAs with caregivers. Some participants under the age of 12 had trouble understanding some terminology. Further, adults and children with cognitive impairment associated with MCAP/M-CM sometimes had difficulty with self-report. Caregivers were able to report their child's symptoms and impacts using observer-report COAs. Participant feedback prompted further consideration of the measurement of pain in this population, including variability of pain over time, location of pain, and type. CONCLUSIONS: This study provided valuable information from patients about PROS, supporting the content validity of the COAs, with recommended revisions. COAs are easily understood by persons with PROS and caregivers and are appropriate for measuring symptoms and disease-related impacts across diverse PROS syndromes in clinical trials.

Content validation of observer-reported sickle cell pain diaries (SCPD-CS and SCPD-CN): results from interviews with caregivers.

BACKGROUND: Patients with sickle cell disease (SCD) experience daily pain and acute episodes known as sickle cell pain crises (SCPCs). The Sickle Cell Pain Diary-Caregiver Report (SCPD-C) is an observer-reported diary for use by caregivers of children ages < 12 years with SCD. This study reports on the content validity of the SCPD-C. METHODS: The SCPD-C was developed based on a literature review, measurement expert input, and a patient advisory board including clinicians. Three rounds of interviews (including both concept elicitation and cognitive debriefing methodologies) were conducted with caregivers of children with SCD aged < 12 to evaluate the content validity of the SCPD-C. RESULTS: Across three rounds of interviews, caregivers confirmed concepts in the SCPD-C and described observed impacts that were important and were added. Overall, caregivers evaluated the SCPD-C as easy to understand, with some minor adaptations for clarity. Additionally, the diary was split into two versions based on the child's age and school enrollment status (SCPD-CS for school-aged and SCPD-CN for non-school age children). CONCLUSIONS: Caregivers provided valuable input that led to important additions and changes to the measures. The SCPD-CS and SCPD-CN are appropriate and fit-for-purpose observer-reported outcome measures of SCPC-related pain frequency and severity, and impacts on health-related quality of life.

Qualitative and psychometric approaches to evaluate the PROMIS pain interference and sleep disturbance item banks for use in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) commonly experience pain despite the availability of disease-modifying treatments. Sleep disturbances are frequently reported in RA, with pain often a contributing factor. The Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Sleep Disturbance item banks were initially developed to provide insights into the patient experience of pain and sleep, respectively, though they were not specifically intended for use in RA populations. This study evaluated the content validity of the PROMIS Pain Interference and Sleep Disturbance item banks in RA and identified relevant content for short forms for patients with RA that achieved high measurement precision across a broad range of health. METHODS: A qualitative approach consisting of hybrid concept elicitation and cognitive debriefing interviews was used to evaluate the content validity of the item banks in RA. Interviews were semi-structured and open-ended, allowing a range of concepts and responses to be captured. Findings from the qualitative interviews were used to select the most relevant items for the short forms, and psychometric evaluation, using existing item-response theory (IRT) item parameters, was used to evaluate the marginal reliability and measurement precision of the short forms across the range of the latent variables (i.e. pain interference and sleep disturbance). RESULTS: Thirty-two participants were interviewed. Participants reported that RA-related pain and sleep disturbances have substantial impacts on their daily lives, particularly with physical functioning. The PROMIS Pain Interference and Sleep Disturbance item banks were easy to understand and mostly relevant to their RA experiences, and the 7-day recall period was deemed appropriate. Qualitative and IRT-based approaches identified short forms for Pain Interference (11 items) and Sleep Disturbance (7 items) that had high relevance and measurement precision, with good coverage of the concepts identified by participants during concept elicitation. CONCLUSION: Pain and sleep disturbances affect many aspects of daily life in patients with RA and should be considered when novel treatments are developed. This study supports the use of the PROMIS Pain Interference and Sleep Disturbance item banks in RA, and the short forms developed herein have the potential to be used in clinical studies of RA.

Content validation of a self-report daily diary in patients with sickle cell disease.

BACKGROUND: Sickle Cell Disease (SCD) is a genetic progressive vascular disease that impacts patients overall health and quality of life. Sickle-cell pain crises (SCPCs) are a hallmark clinical presentation of SCD and have been associated with increased morbidity and mortality. The Sickle Cell Pain Diary- Self Report (SCPD-S) was developed as a daily patient-reported outcome (PRO) measure primarily intended to capture the frequency and severity of SCD-related pain during and outside of a SCPC. The SCPD-S also examines the impact of the pain associated with an SCPC on other health-related quality of life concepts. The objective of this study was to investigate the content validity of the SCPD-S. METHODS: The content validation testing included 18 in-depth hybrid concept elicitation and cognitive debriefing interviews conducted with SCD patients in the US aged 12 years and older. Interviewers used a semi-structured interview guide and a think-aloud approach for the cognitive debriefing portion. All interviews were recorded, transcribed, coded and analyzed. RESULTS: Eighteen interviews across two rounds were conducted. Round 1 hybrid interviews (n = 12) resulted in the expansion of the SCPD-S from 13 to 19 items. Items on the impact of an SCPC on social and recreational activities, sleep, and emotional well-being were added. Five items were significantly revised, as were three response choice sets. Round 2 hybrid interviews (n = 6) confirmed the comprehensiveness of the revised diary, understandability of the wording, and appropriateness of the recall period and response sets. Saturation analyses specific to concept elicitation revealed that no additional interviews were needed. CONCLUSIONS: This study provided evidence to support the content validity of the SCPD-S, a self-report daily diary. Data gathered during patient interviews indicated that the SCPD-S is a fit for purpose measure of SCD and SCPC-related pain frequency and severity and the impact of this pain on other health-related quality of life concepts including fatigue and emotional health. The numerous changes to the SCPD-S as a result of the study findings highlight the importance of the content validation process when developing a PRO measure.

Achieving the BpTRUth: emergency department hypertension screening and the Centers for Medicare & Medicaid Services quality measure.

In 2012, the Centers for Medicare & Medicaid Services (CMS) instituted a Physician Quality Reporting System measure for screening and referring patients with elevated blood pressure (BP). The aims of this study were to (1) assess the reliability of ED triage BP as a metric to establish when the CMS threshold (≥120/80 mm Hg), and other clinically relevant BP thresholds (≥140/90 and ≥160/100 mm Hg) have been met, using BP measured with a highly accurate device (BpTRU) in the emergency department as the gold standard; and (2) determine whether correct identification varies by gender, race, or triage acuity. Using the BpTRU, we calculated the proportion of patients whose triage BP accurately indicated a need for further referral and treatment for hypertension according to three suggested BP thresholds (≥120/80, ≥140/90, and ≥160/100 mm Hg). Of 354 patients, the median age was 39 years, 48.9% were women, and 66.4% were White. At the three suggested BP thresholds (≥120/80, ≥140/90, and ≥160/100 mm Hg), 66.1%, 74.0%, and 88.8% of patients were confirmed to meet the CMS threshold, respectively. There were no differences by gender, race, or triage acuity. Emergency department triage BP would reliably identify elevated BP using the CMS threshold in up to two-thirds of those without known hypertension.

An Initial evaluation of law enforcement overdose training in Rhode Island.

OBJECTIVES: To assess initial change in knowledge, self-efficacy, and anticipated behaviors among Rhode Island law enforcement officers on drug overdose response and prevention. METHODS: Law enforcement officers (N=316) voluntarily completed a pre-post evaluation immediately before and after taking part in overdose prevention and response trainings. Assessment items included measures of knowledge (Brief Overdose Recognition and Response Assessment (BORRA)), self-efficacy, attitudes toward drugs and overdose prevention, awareness of the Good Samaritan Law, and open-ended items pertaining to overdose knowledge and response behaviors. Non-parametric tests measured within-group and between-group differences. Wilcoxon Signed Rank tests and Kruskal-Wallis tests evaluated changes in BORRA scores and self-efficacy items. McNemar's tests assessed changes regarding the Good Samaritan law and open-ended items. Wilcoxon Signed Rank tests measured post-training change in attitudes. RESULTS: Law enforcement officers demonstrated statistically significant improvements in self-efficacy (identifying signs of opioid overdose, naloxone indication, counseling witnesses in overdose prevention, and referring witnesses for more information), overdose identification knowledge (BORRA mean increased from 7.00 to 10.39), naloxone administration knowledge (BORRA mean increased from 10.15 to 12.59), Good Samaritan Law awareness (17.9% increase after training), and anticipated behaviors in response to future observed overdose (65.7% changed from passive to active response post training). CONCLUSIONS: Harm reduction programs can provide law enforcement officers with the knowledge and skills necessary to intervene and reduce overdose mortality. Given the statistically significant improvements in self-efficacy, attitudinal changes, and Good Samaritan law awareness, law enforcement officers are more prepared to actively interact with drug users during a drug-involved emergency.

Could Blood Pressure Phobia Go Beyond the White Coat Effect?

BACKGROUND: While it is known that excessive anxiety surrounding the measuring of blood pressure may preclude an accurate measurement, it is not known whether it could also lead to phobic avoidance behavior. METHODS: Self-reported information was collected on 125 individuals who made postings on 5 internet-based medical forums. RESULTS: Qualitative thematic analysis revealed that these individuals reported experiencing intense fear associated with the measuring of blood pressure, that was excessive or irrational and which contributed to avoidance of medical treatment and interference with life decisions. CONCLUSIONS: Based on these preliminary observations, we are speculating that these symptoms could be considered consistent with a diagnosis of a Specific Phobia. Investigations using quantitative methods, representative samples, and standardized clinical instruments need to be conducted before definitive conclusions can be reached.