Qualitative evaluation of the Autism Behavior Inventory: use of cognitive interviewing to establish validity of a caregiver report scale for autism spectrum disorder.

PURPOSE: The Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration's patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms. METHODS: Cognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the "think-aloud" and verbal probing approach to assess ABI's content validity and participant understanding of the instrument, including: item clarity and relevance; item interpretation; appropriateness of response scales; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12). RESULTS: In total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability. CONCLUSIONS: Cognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD.

Quantifying the importance of inhaler attributes corresponding to items in the patient satisfaction and preference questionnaire in patients using Combivent Respimat.

BACKGROUND: Physicians consider ease of use, satisfaction, and preferences when prescribing an inhaler device. These factors may impact appropriate usage and compliance. METHODS: The objectives were to quantify the relative importance of inhaler attributes in patients currently using Combivent Respimat by eliciting preferences for performance and convenience attributes assessed by items in the Patient Satisfaction and Preference Questionnaire (PASAPQ). Using a pharmacy database, 19,964 adults in the United States who filled ≥2 Combivent Respimat prescriptions were identified. Of those, 8150 patients were randomly selected to receive invitation letters. The online cross-sectional survey included the PASAPQ and best-worst scaling (BWS) questions. The PASAPQ measures satisfaction with medication attributes across two domains: performance and convenience. BWS questions asked participants to select the most and least important device attributes. A descriptive statistics analysis of the PASAPQ and a random-parameters logit model of BWS responses were conducted. RESULTS: The survey was completed by 503 participants. Most were female (57.3%), white (88.5%), and 51-70 years old (67.6%). Approximately 47% reported a chronic obstructive pulmonary disease diagnosis, 21.9% asthma, 8.2% other lung disease, and 23.1% more than one lung disease. PASAPQ scores indicated that the majority were satisfied or very satisfied; up to 20% reported being dissatisfied with Combivent Respimat. The three most important inhaler attributes were Feeling that your medicine gets into your lungs, Inhaler works reliably, and Inhaler makes inhaling your medicine easy. The most important attributes corresponded to six of seven items in the PASAPQ performance domain. CONCLUSIONS: Most participants reported satisfaction with Combivent Respimat. Performance attributes were more important than convenience attributes.

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

BACKGROUND AND OBJECTIVES: Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. METHODS: The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. RESULTS: The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. DISCUSSION AND CONCLUSIONS: MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. SCIENTIFIC SIGNIFICANCE: Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651).

Predicting Response to Subacromial Injections and Lidocaine/Tetracaine Patch from Pretreatment Pain Quality in Patients with Shoulder Impingement Syndrome.

OBJECTIVES: No existing pain treatment is effective for all pain problems, and response to pain treatment is highly variable. Knowledge regarding the patient factors that predict response to different treatments could benefit patients by providing an empirical foundation for patient-treatment matching. This study sought to test the hypothesis that improvements following two treatments thought to operate via similar mechanisms would be predicted by similar baseline pain qualities. DESIGN: Prospective prediction analysis using data from a previously published open label trial comparing a heated lidocaine/tetracaine patch versus subacromial corticosteroid injection for the treatment of pain in individuals with shoulder impingement syndrome. RESULTS: Consistent with the study hypothesis, the response to the two treatments were predicted by similar baseline pain qualities; specifically, higher baseline levels of unpleasant, electric, and sensitive pain predicted subsequent improvements in sleep interference, work/activity interference, and patient global ratings of improvement, respectively. CONCLUSIONS: The findings are consistent with the combined ideas that (1) those who have the most to gain (i.e., those reporting the highest levels of various pain qualities) can expect the best response to effective treatments and (2) different pain qualities may be associated with different types of outcomes. The findings support further research to examine how pain quality measures may be used to improve patient-treatment matching, and therefore, ultimately improve the efficiency, efficacy, and overall benefit-risk of pain treatment.

Development of a bedside pain assessment kit for the classification of patients with osteoarthritis.

There are no standardized bedside assessments for subtyping patients with osteoarthritis (OA) based on pain mechanisms. Thus, we developed a bedside sensory testing kit (BSTK) to classify OA patients based on sensory profiles potentially indicative of pain mechanism. After usability and informal reliability testing (n = 22), the kit was tested in a formal reliability study (n = 20). Patients completed questionnaires and sensory testing: pressure algometry to detect hyperalgesia; repeat algometry after heterotopic noxious conditioning stimulation to measure diffuse noxious inhibitory control (DNIC); light touch using Von Frey filaments; and cold allodynia using a brass rod. The procedure was brief and well tolerated. Algometry and filament testing were highly reliable [intra-class correlation coefficients (ICCs) 0.71-0.91]; DNIC was acceptably reliable (ICCs 0.53-0.91); brass rod reliability was inconclusive. Patients were classified empirically into four groups: "All abnormal findings" (primary and secondary hyperalgesia and dysfunctional DNIC); "all normal findings"; and two intermediate groups. The "all abnormal findings" group had more neuropathic pain symptoms, and lower WOMAC total, stiffness, and activity scores than the "all normal findings" group. Simple BSTK procedures, consolidated in a kit, reliably classified OA patients into subgroups based on sensory profile, suggesting that OA patients differ in underlying pain mechanisms. Further research is needed to confirm these subgroups and determine their validity in predicting response to treatment.

Social Influence on Adolescent Polysubstance Use: The Escalation to Opioid Use.

BACKGROUND: Fewer than 9% of 12-17 year olds in need (∼146,000 of 1.7 million) receive inpatient or outpatient substance abuse recovery services or other mental health services (SAMHSA, 2012). The literature on adolescent addiction is sparse, however, as most published addiction recovery efforts involve adult populations-often college students. OBJECTIVES: The present study examined social influences on escalating substance use (from tobacco, alcohol, and marijuana use to polysubstance use involving opioids) for students enrolled in recovery high schools. METHODS: A sample of 31 adolescents enrolled in substance use recovery high schools were surveyed on their patterns of substance use leading to their abuse of opioids. RESULTS: Youth who begin their substance use as young as age 8 are often pressured by peer culture to do so and come from substance-using families. Their escalation in polysubstance use to a pattern including opioids was also most often attributed to peer influence over several years. Conclusions/Importance: This paper is one of scant few that address patterns of use in high school students. Perhaps most salient from this study are the tertiary prevention implications: similar to their adult counterparts, students enrolled in recovery high school programs are likely from substance-using families and have combined complex constellations of substances including opioids by dint of their relationships with substance-using peers.

Assessment of pain and activity using an electronic pain diary and actigraphy device in a randomized, placebo-controlled crossover trial of celecoxib in osteoarthritis of the knee.

OBJECTIVE: The primary goal was to determine whether a composite measure of pain and activity is a more responsive assessment of analgesic effect than pain alone or activity alone in patients with osteoarthritis (OA) of the knee. DESIGN: We conducted a randomized, double-blind, placebo-controlled, 2-period, crossover study of celecoxib vs. placebo in subjects with chronic pain due to knee OA. Patients with knee OA and baseline pain intensity score ≥4 on a 0-10 numerical rating scale (NRS) before each period were randomized. Pain endpoints included in-clinic pain score (24-hour and 1-week recall), daily paper diary pain score, current pain on an electronic pain diary (each on NRS), and WOMAC pain subscale. Activity measures included WOMAC function subscale and actigraphy using a device. Three composite pain-activity measures were prespecified. RESULTS: Sixty-three patients were randomized and 47 completed the study. The WOMAC pain subscale was the most responsive of all five pain measures. Pain-activity composites resulted in a statistically significant difference between celecoxib and placebo but were not more responsive than pain measures alone. However, a composite responder defined as having 20% improvement in pain or 10% improvement in activity yielded much larger differences between celecoxib and placebo than with pain scores alone. Actigraphy was more responsive than the WOMAC function scale, possibly due to lower placebo responsiveness. CONCLUSION: We have identified composite pain-activity measures that are similarly or more responsive than pain-alone measures in patients with OA. Further research is warranted to determine the optimal method for computing these composites.

Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations.

PURPOSE: This study determined how the magnitude of change in positive subjective responses predicts clinical outcome in a treatment setting. Specifically, we attempted to define what constitutes a clinically important difference (CID) in subjective responses. METHODS: A 100-mm visual analog scale (VAS) measured subjective ratings of drug "high," calculated via an anchor-based method with published data from participants receiving sustained-release naltrexone (NTX) and heroin in a laboratory setting. The data were then compared to clinical outcomes in a treatment trial with sustained-release naltrexone. A distribution-based method subsequently analyzed data from participants who received ALO-01 (extended-release morphine with sequestered NTX) to predict its abuse liability. RESULTS: Differences in ratings of drug high of approximately 10 mm on a 100-mm line were clinically significant. By extrapolation, CIDs were also found between crushed or intact ALO-01 and immediate-release morphine sulfate (IRMS). No CIDs were found between intact and crushed ALO-01. CONCLUSIONS: From laboratory and treatment trial data involving naltrexone, calculation of CIDs in subjective ratings of high is possible. Consequently, crushing/swallowing or injecting ALO-01 produces clinically significantly less drug high than oral or intravenous morphine alone, suggesting that ALO-01 has lower abuse liability by those routes than morphine formulations.

A brief survey to characterize oxycodone abuse patterns in adolescents enrolled in two substance abuse recovery high schools.

BACKGROUND: Although oxycodone is one of the most widely available and abused opioids, little published information exists on the abuse of immediate-release oxycodone. OBJECTIVE: To obtain information on abuse of oxycodone and the effectiveness of abuse-deterrent strategies, especially for immediate-release oxycodone, we surveyed oxycodone abuse patterns in a population of experienced opioid abusers. METHODS: Students or recent graduates of two substance abuse recovery high schools in Massachusetts were surveyed on abuse behaviors with short-acting single-entity oxycodone (e.g., Roxicodone), short-acting combination oxycodone (e.g., Percocet), and extended-release oxycodone. RESULTS: Twenty-four students completed surveys. Mean age was 17.7 years (range 16-19), and mean age at first abuse of oxycodone was 15 (range 13-18). Overall, 56% of students reported oxycodone as their favorite prescription opioid to abuse. The primary preferred method of abuse of all oxycodone formulations was intranasal administration: 83% of single-entity oxycodone abusers preferred intranasal administration compared with 67% of combination oxycodone abusers and 69% of extended-release oxycodone abusers. Approximately half of our respondents preferred to ingest oxycodone orally, 25-38% of respondents swallowed the pill intact, and another 13-17% chewed the pill before swallowing. Maximum dose ever abused at one time ranged from 15 to 400 mg. Most respondents had abused ≥60 mg of oxycodone at a time. CONCLUSIONS: In this small study, adolescent oxycodone abusers use high quantities of oxycodone at a time, alter routes of administration for not only extended-release but also immediate-release products, and commonly abuse single-entity oxycodone products. Abuse-deterrent formulations may be one strategy for addressing such behaviors.

Health-related quality of life and treatment satisfaction in Chronic Lymphocytic Leukemia (CLL) patients on ibrutinib compared to other CLL treatments in a real-world US cross sectional study.

The objective of this study was to describe real-world health-related quality of life (HRQoL) and treatment satisfaction of ibrutinib-treated patients with CLL compared to a reference group. This study was completed in two parts. The first portion (Norming Study) was a US online survey conducted to serve as a reference population. The Norming Study included a total of 139 patients with CLL, excluding those treated with ibrutinib: 64 were treatment naive (Tx naive), 36 were 1st line (1L), and 38 were in or had completed ≥2 lines (2L+) patients with CLL. The second portion (CLL Ibrutinib Study) included 1L and 2L+ ibrutinib patients with CLL treated for ≥6 months in which 118 patients (1L n = 88 and 2L+ n = 30) completed the study. Respondents completed demographic and clinical information and the following HRQoL surveys: (Short Form-12v2® Health Survey [SF-12v2], Functional Assessment of Cancer Therapy-General [FACT-G], FACT-Leukemia [FACT-Leu] Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, and Cancer Therapy Satisfaction Questionnaire [CTSQ]). Higher scores indicate better HRQoL/treatment satisfaction. Differences in effect sizes between the two samples at the group level were calculated using Hedges' g. Medium to large positive effects were seen in the CLL Ibrutinib group on several measures compared to the Reference Study groups. The FACT-G total score was 89.2±11.1 for CLL Ibrutinib Study patients compared to 75.8±22.6 CLL Norming Tx naïve patients, 61.3±21.8 in 1L, and 61.7±20.7 in 2L+. Similar trends were seen with FACT-Leu total score and FACIT-Fatigue. CLL Ibrutinib Study patients scored higher on all CTSQ domain scores compared to the CLL Norming patients treated with other CLL therapies. We found that Ibrutinib-treatment had better HRQoL and treatment satisfaction compared to patients receiving other therapies, irrespective of line of therapy.

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy.

BACKGROUND: In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo. OBJECTIVE: We evaluated health-related quality of life (HRQoL) at the final analysis of the SPARTAN study. INTERVENTION: Patients received apalutamide (240 mg/d) or placebo in 28-d cycles. All patients continued androgen deprivation therapy (ADT). DESIGN, SETTING, AND PARTICIPANTS: A total of 1207 patients with nmCRPC were randomized 2:1 to apalutamide or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HRQoL was assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires at day 1 of cycle 1 (predose/baseline), cycles 2-6, every two cycles during cycles 7-13, every four cycles thereafter, at the end of treatment, and every 4 mo after progression to 1 yr. Results are presented using descriptive statistics. A mixed model for repeated measures was fitted to estimate the mean scores at each scheduled visit during treatment. RESULTS: At final analysis, with 52 mo follow-up for survival, the median treatment duration was 32.9 mo for apalutamide and 11.5 mo for placebo. Patients had good baseline HRQoL. At each scheduled collection during treatment, >90% per group completed the questionnaires. The change in FACT-P total score from baseline to cycles 21 and 25 significantly favored apalutamide over placebo (p = 0.0138 and 0.0009, respectively). The apalutamide group generally maintained favorable FACT-P (total and subscales) and EQ-5D-3L scores, while placebo scores tended to decline over time (starting in cycles 11-13 and pronounced by cycles 21-25). Notably, patient-reported fatigue did not worsen with apalutamide. Most patients reported being "not at all bothered" by side effects, and bother did not increase over time with apalutamide or placebo. Patients receiving apalutamide had minimal change in side-effect bother following symptomatic adverse events. CONCLUSIONS: Final analysis of SPARTAN confirms that HRQoL is preserved in patients with nmCRPC receiving apalutamide plus ADT, but declines in patients receiving placebo plus ADT after approximately 1 yr. PATIENT SUMMARY: Responses from patients with prostate cancer who were included in the SPARTAN study indicated that treatment with apalutamide, even after the most extensive follow-up time possible, did not reduce their quality of life. These results, along with improved survival and longer time to the development of metastases (reported separately), confirm the benefits of apalutamide for patients with nonmetastatic castration-resistant prostate cancer.

Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study.

BACKGROUND: CARTITUDE-1 is a phase 1b-2 study evaluating ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma. Primary efficacy outcomes have previously been reported. Here, we report health-related quality of life (HRQOL) secondary outcomes evaluated using patient-reported outcomes. METHODS: This single-arm, open-label, phwase 1b-2 study was done at 16 centres in the USA. Patients were aged 18 years or older with diagnosis of multiple myeloma and Eastern Cooperative Oncology Group performance status of 1 or less with three or more previous lines of therapy, or were double refractory to a proteasome inhibitor and immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR+ T cells per kg) was administered 5-7 days after lymphodepletion. Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30-item, pre-specified items from the EORTC myeloma module, and EuroQol five-dimensional descriptive system questionnaire. Clinically meaningful changes in patient-reported outcomes were defined by anchor-based minimally important differences. This trial is registered with ClinicalTrials.gov, NCT03548207. This trial is completed but feeding into a long-term follow-up study. FINDINGS: Between July 16, 2018, and Oct 7, 2019, 78 patients were enrolled and underwent apheresis in phase 2 of the study. 68 patients were treated (43 [63%] male, 49 [72%] White), and their patient-reported outcomes assessed (median follow-up 16·9 months, IQR 15·7-17·5). After infusion, a transient decline was observed, followed by improvements in global health status (mean change from baseline to day 464 +8·0 points, SD 20·9), physical (+4·6 points, 21·1), and emotional functional scales (+1·9 points, 23·7) over time, and declines for symptom-based scores (-14·1 pain, SD 31·5 and -15·4 fatigue; SD 29·5), indicating improved patient HRQOL following treatment with cilta-cel. INTERPRETATION: These durable HRQOL improvements are consistent with clinical findings, in which a single cilta-cel infusion led to substantial and durable responses in heavily pre-treated patients with relapsed or refractory multiple myeloma. These results support the use of cilta-cel in patients with relapsed or refractory multiple myeloma. FUNDING: Janssen Research & Development and Legend Biotech USA.

Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions.

BACKGROUND: Transdermal and solid oral prescription opioid (PO) formulations can be abused by ingesting (with or without tampering), snorting, or injection (both requiring tampering). OBJECTIVE: To determine the patterns of tampering with POs for abuse. METHODS: Information was collected from published studies and databases. RESULTS: Tampering with POs for abuse is common practice. Ingestion is the most prevalent method of abuse, followed by snorting and injection. From 1992 to 2002, injecting POs has decreased in favor of ingesting and snorting. Methods of abuse vary widely by product. Abuse methods with the highest morbidity are injection and inhalation. CONCLUSIONS: The seriousness of health outcomes associated with tampering with POs warrants the development of PO formulations that prevent or deter tampering.

Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes.

BACKGROUND: The lower-risk (low and intermediate-1 risk based on IPSS) myelodysplastic syndrome (MDS) has a negative impact on patients' health-related quality of life (HRQoL). Patient Reported Outcomes (PROs) instruments, which are used to collect patients' HRQoL data, should have established content validity in the target population to ensure that the instrument is comprehensive and comprehensible. The present study was conducted to evaluate the content validity of the Quality of Life in Myelodysplasia Scale (QUALMS) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An) PRO instruments in patients with lower-risk MDS. METHODS: In this cross-sectional, qualitative study, 16 patients aged ≥18 years with lower-risk MDS, who were RBC transfusion dependent, literate and fluent in US-English were interviewed. Interviews were semi-structured comprising of two parts: concept elicitation (CE) explored symptoms and impacts important to patients, and cognitive debriefing (CD) assessed understanding and relevance of the QUALMS and FACT-An. A conceptual model was developed, which was used to map the concepts that emerged during CE onto the QUALMS and FACT-An to assess concept coverage and suitability of the instruments. RESULTS: The median age of participants was 67.5 years (range: 51-91), with half being female (n = 8). Nine (56.2%) participants had intermediate-1-risk MDS and 10 (62.5%) were relapsed or refractory to erythropoiesis-stimulating agent treatment. Fatigue/tiredness (100.0%), shortness of breath (87.5%), weakness (81.2%), and low energy (75.0%) were reported most commonly and were the most bothersome symptoms as well. Of seven high-level HRQoL domains identified, activities of daily living (n = 16, 100.0%), physical functioning (n = 15, 93.8%), emotional wellbeing (n = 13, 81.3%), social functioning (n = 12, 75.0%), sleep disturbance (n = 9, 56.3%), and impact on work (n = 9, 56.3%) were the most commonly reported. For CD, the QUALMS and FACT-An were found to be mostly relevant and very well understood; response options were easy to use, and recall period was appropriate. CONCLUSION: Both QUALMS and FACT-An demonstrated a strong face and content validity in patients with lower-risk MDS, suggesting that these instruments are appropriate for assessing HRQoL in this population.

Patient-reported symptom burden of chronic graft versus host disease: a systematic literature review.

INTRODUCTION: Chronic graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic stem cell transplantation (HSCT) leading to high morbidity and quality of life issues. We conducted a systematic literature review on the patient reported symptom burden of chronic GVHD. AREAS COVERED: English-language articles published between 2005 and November 2018 were searched using CENTRAL, EMBASE and MEDLINE. Studies that used the 2005 or 2015 National Institute of Health consensus criteria for the diagnosis and staging of chronic GVHD were included. EXPERT OPINION: Patient reported symptom burden was widely assessed in the literature (n = 38). The Lee Chronic GVHD Symptom Scale was the most frequently used instrument (n = 28), followed by the NIH Patient-reported Symptom scores (n = 11). Association of symptom burden with clinical outcome assessment endpoints (e.g. mortality) and with quality of life measures was investigated by fairly low number of studies with limited generalizability. By systematically investigating the influencing factors of symptom burden this review helps to better understand patients' perceptions and may help improving the management and care of chronic GVHD. However, data on influencing factors was quite diverse, which indicates that specific questions identified as research gaps need to be incorporated in randomized clinical trials in a more systematic way.

Humanistic burden of patients with chronic graft-versus-host disease - systematic literature review of health-related quality of life and functional status.

INTRODUCTION: Chronic graft-versus-host disease (GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to provide a systematic overview of evidence on the health-related quality of life (HRQoL) and functional capacity of HSCT patients with National Institutes of Health (NIH)-defined chronic GVHD. Areas covered: English-language articles published between 2007 and 2017 were searched using PubMed. Studies that used the 2005 or 2015 NIH consensus criteria for the diagnosis and staging of chronic GVHD and had a cohort size of at least 100 patients were included. Expert opinion: Disease severity and organ involvement were the most important predictors of HRQoL and functionality in chronic GVHD patients. Further, identified predictors of HRQoL were nutrition status and functional capacity, while functional status was also associated with disease symptoms, nutrition status, age, and survival. Data regarding the effect of symptom bother on HRQoL were limited. Our findings confirm that the management of chronic GVHD should focus on improving not only clinical outcomes but also on HRQoL and functional capacity. Therefore, to evaluate new treatment options it is recommended to include patient relevant endpoints into prospective studies. This study also highlights the importance of nonpharmacological aspects in the management of chronic GVHD.

Embodiment and abstraction: actions create relational representations.

Theories of embodied, modal representation propose that concepts are grounded in the sensorimotor system. According to these theories, action (or the potential for action) creates meaning. An apparent challenge for these theories is the fact that higher-order relations (i.e., relations among relations), such as monotonic increase or alternation, have no straightforward sensorimotor analog. A single action can increase or alternate only relative to another action. Therefore, if embodied theories are to handle concepts more generally, patterns of action must provide meaning to the system. Previous research suggested that as participants simulated the motion of gear problems they discovered a higher-order relation, alternation, based on the episodic traces of their own alternating actions. The present study showed that the number of alternating actions in episodic memory prior to discovery of the alternation relation predicted its generalization to new problem types. Actions can function as the representational substrate of higher-order relations.

Development and preliminary validation of the focused analgesia selection test to identify accurate pain reporters.

Clinical trials of analgesics have been plagued with poor assay sensitivity due, in part, to variability in subjects' pain reporting. Herein, we develop and evaluate the focused analgesia selection test (FAST), a method to measure patients' pain reporting skills. Subjects with osteoarthritis of the hip, knee, and/or ankle with pain intensity of ≥3/10 on a 0-10 numerical rating scale were enrolled. Subjects underwent the FAST procedure, which consists of recording subjects' pain reports in response to repeated administration of thermal noxious stimuli of various intensities applied on the arm with the Medoc® Thermal Sensory Analyzer II. Subjects also rated non-noxious stimuli consisting of visual contrast rating. After performing an exercise task, subjects also rated clinical pain and were asked to report whether their pain had increased, decreased, or stayed the same. Overall, 88 subjects were enrolled, and 83 were included in the analyses. FAST's outcomes including the R2, intraclass correlation coefficient (ICC), and coefficient of variation (CoV) indicated that subjects' pain reporting skills were widely distributed. Higher FAST ICC significantly predicted greater changes in clinical pain following exercise (p=0.017), whereas the visual contrast test did not predict postexercise pain. FAST is the first method that measures subjects' pain reporting skills. Using FAST to enrich clinical trials with "good" pain reporters (with high FAST ICC) could increase assay sensitivity. Further evaluation of FAST is ongoing.

Initial development of a patient-reported outcome measure of experience with cognitive impairment associated with schizophrenia.

Cognitive impairment is a serious, often distressing aspect of schizophrenia that affects patients' day-to-day lives. Although several interview-based instruments exist to assess cognitive functioning, a reliable measure developed based on the experiences of patients facing cognitive difficulties is needed to complement the objective performance-based assessments. The present article describes the initial development of a patient-reported outcome (PRO) measure to assess the subjective experience of cognitive impairment among patients with schizophrenia, the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS). The phases of development included the construction of a conceptual model based on the existing knowledge and two sets of qualitative interviews with patients: 1) concept elicitation interviews to ensure face and content validity from the perspective of people with schizophrenia and 2) cognitive debriefing of the initial item pool. Input from experts was elicited throughout the process. The initial conceptual model included seven domains. The results from concept elicitation interviews (n=80) supported these domains but yielded substantive changes to concepts within domains and to terminology. Based on these results, an initial pool of 53 items was developed to reflect the most common descriptions and languages used by the study participants. Cognitive debriefing interviews (n=22) resulted in the removal of 18 items and modification of 22 other items. The remaining 35 items represented 23 concepts within six domains plus two items assessing bother. The draft PRO measure is currently undergoing psychometric testing as a precursor to broad-based clinical and research use.

Response scale selection in adult pain measures: results from a literature review.

BACKGROUND: The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population. METHODS: The search strategy involved a comprehensive, structured, literature review with multiple search objectives and search terms. RESULTS: The searched yielded 6918 abstracts which were reviewed against study criteria for eligibility across the adult pain objective. The review included 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles providing insights into optimal response scale selection for pain assessment in the adult population. Based on the extensive and varied literature on pain assessments, the adult pain studies typically use simple response scales with single-item measures of pain-a numeric rating scale, visual analog scale, or verbal rating scale. Across 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles, the NRS response scale was most often recommended in these guidance documents. When reviewing the empirical basis for these recommendations, we found that the NRS had slightly superior measurement properties (e.g., reliability, validity, responsiveness) across a wide variety of contexts of use as compared to other response scales. CONCLUSIONS: Both empirical studies and review articles provide evidence that the 11-point NRS is likely the optimal response scale to evaluate pain among adult patients without cognitive impairment.