Validation of the Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE): a new clinician reported outcome measure of CHE severity.

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711.

Development and Psychometric Validation of a Patient-Reported Outcome Measure to Assess the Signs and Symptoms of Chronic Hand Eczema: The Hand Eczema Symptom Diary (HESD).

INTRODUCTION: Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. METHODS: The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). RESULTS: Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (Intraclass Correlation Coefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53-0.64) and significant differences between severity groups (p < 0.001). Large effect sizes for mean change scores in participants that improved and significant differences between change groups indicated the ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 4-points for improvements in 7-day average HESD scores. CONCLUSION: The HESD is the first CHE-specific, patient-reported outcome measure of CHE signs/symptoms developed and validated in line with regulatory guidance. This article provides evidence of strong content validity and psychometric validity and shows improvements of ≥ 4 points on 7-day average HESD scores represent clinically meaningful, important changes. TRIAL REGISTRATION: NCT03683719, NCT04871711.

Multivariate Models to Diagnose Early Referral-Warranted Retinopathy of Prematurity With Handheld Optical Coherence Tomography.

Purpose: The purpose of this study was to create multivariate models predicting early referral-warranted retinopathy of prematurity (ROP) using non-contact handheld spectral-domain optical coherence tomography (OCT) and demographic data. Methods: Between July 2015 and February 2018, infants ≤1500 grams birth weight or ≤30 weeks gestational age from 2 academic neonatal intensive care units were eligible for this study. Infants were excluded if they were too unstable to participate in ophthalmologic examination (2), had inadequate image quality (20), or received prior ROP treatment (2). Multivariate models were created using demographic variables and imaging findings to identify early referral-warranted ROP (referral-warranted ROP and/or pre-plus disease) by routine indirect ophthalmoscopy. Results: A total of 167 imaging sessions of 71 infants (45% male infants, gestational age 28.2+/-2.8 weeks, and birth weight 995.6+/-292.0 grams) were included. Twelve of 71 infants (17%) developed early referral-warranted ROP. The area under the receiver operating characteristic curve (AUC) was 0.94 for the generalized linear mixed model (sensitivity = 95.5% and specificity = 80.7%) and 0.83 for the machine learning model (sensitivity = 91.7% and specificity = 77.8%). The strongest variables in both models were birth weight, image-based Vitreous Opacity Ratio (an estimate of opacity density), vessel elevation, and hyporeflective vessels. A model using only birth weight and gestational age yielded an AUC of 0.68 (sensitivity = 77.3% and specificity = 63.4%), and a model using only imaging biomarkers yielded 0.88 (sensitivity = 81.8% and specificity = 84.8%). Conclusions: A generalized linear mixed model containing handheld OCT biomarkers can identify early referral-warranted ROP. Machine learning produced a less optimal model. Translational Relevance: With further validation, this work may lead to a better-tolerated ROP screening tool.

Content validity of the EORTC quality of life questionnaire QLQ-C30 for use in cancer.

AIM: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) is among the most widely used patient-reported outcome measures in cancer research and practice. It was developed prior to guidance that content should be established directly from patients to confirm it measures concepts of interest and is appropriate and comprehensive for the intended population. This study evaluated the content validity of the QLQ-C30 for use with cancer patients. METHODS: Adults undergoing cancer treatment in Europe and the USA participated in open-ended concept elicitation interviews regarding their functional health, symptoms, side-effects and impacts on health-related quality of life. Thematic analysis was conducted, and similarities across cancer types, disease stages and countries or languages were explored. RESULTS: Interviews with 113 patients with cancer (85 European, 28 USA) including breast, lung, prostate, colorectal and other cancers were conducted between 2016 and 2020. Conceptual saturation was achieved. The most frequently reported concepts were included in the QLQ-C30 conceptual framework. QLQ-C30 items were widely understood across language versions and were relevant to patients across cancer types and disease stages. While several new concepts were elicited such as difficulty climbing steps or stairs, weight loss, skin problems and numbness, many were not widely experienced and/or could be considered sub-concepts of existing concepts. CONCLUSIONS: The QLQ-C30 demonstrates good evidence of content validity for the assessment of functional health, symptom burden and health-related quality of life in patients with localised-to-advanced cancer.

Japanese and French translation and linguistic validation of a patient-reported outcome tool to assess quality of life in patients with Immune Thrombocytopenia (ITP): the ITP Life Quality Index (ILQI).

OBJECTIVES: The Immune Thrombocytopenia (ITP) Life Quality Index (ILQI) is a 10-item patient-reported outcome (PRO) measure developed in US-English to assess health-related quality of life (HRQoL) of adults with ITP. Analysis of ILQI responses indicated differences between Western and non-Western countries. The objective of this study was to translate and linguistically validate the ILQI for Japan and France. METHODS: The ILQI underwent dual forwards/backwards translation with reconciliation and resolution. The translations were reviewed prior to conducting cognitive interviews with ITP patients (n = 5 Japan, n = 5 France). Analysis of interview transcripts highlighted required modifications to the ILQI translations. Japanese and French ITP experts reviewed the final translations for cultural relevance and appropriateness. RESULTS: Most of the Japanese and French forward/backwards translations were reconciled with no revision. The ILQI instructions and items were well understood by Japanese and French participants. Wording in one item of the Japanese version of the ILQI was revised to better align with the source instrument. Three terms/phrases in the French translation were revised due to misunderstanding, being deemed inaccurate or culturally inappropriate. Following review by ITP experts from Japan and France, minor modifications were made. CONCLUSION: Findings confirm the linguistic validity of the ILQI in Japanese and French.

Qualitative study to characterize patient experience and relevance of patient-reported outcome measures for patients with metastatic synovial sarcoma.

BACKGROUND: The outlook for patients with metastatic synovial sarcoma (mSS) is poor. Better understanding of patient experience in this setting, beyond clinical measures, may guide improvements in management. Validated patient-reported outcome (PRO) instruments specific to many types of cancer exist, but for rare cancers this is often not the case. METHODS: This study aimed to characterize patient experiences of symptoms and impacts of mSS and evaluate the content validity and relevance of the novel European Organization for Research and Treatment of Cancer Item Library 31 (EORTC IL31) Disease Symptoms PRO tool assessing synovial sarcoma symptoms. This tool comprises items from preexisting, validated cancer-specific PRO instruments from the EORTC Item Library. It was developed as an mSS-specific add-on to the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), which evaluates general cancer and treatment-related symptoms and functioning. This was a non-interventional, qualitative interview study involving semi-structured, concept elicitation (CE) and cognitive debriefing (CD) telephone interviews in adults with mSS. CE explored symptoms and their impact on functioning and quality of life; CD assessed participant understanding and relevance of the PRO tools. RESULTS: Among the 8 participants, the most common disease-related symptoms reported during CE were fatigue and pain, while shortness of breath was one of the most bothersome. The greatest negative impacts of mSS occurred in domains of physical functioning and sleep. Key treatment priorities for patients were to improve disrupted sleep and ability to undertake strenuous activities. CONCLUSIONS: The interviews showed that, when used together, the EORTC IL31 and EORTC QLQ-C30 covered symptoms and impacts of most relevance and importance to patients with mSS, with no notable gaps and good conceptual coverage. This study therefore supports the content validity of 2 tools in mSS, advocating their use in clinical trials to assess treatment impact on PRO measures of importance to these patients.

Development and content validity testing of patient-reported outcome (PRO) items to assess chest congestion associated with the common cold for use in children and adolescents.

BACKGROUND: This article describes qualitative interviews conducted with children (aged 6-11), adolescents (aged 12-17), and adults with the common cold as well as parents/caregivers of the 6-8-year-old children. The aim was to support the refinement and content validity testing of patient-reported outcome (PRO) items assessing chest congestion that could be used as pediatric clinical trial endpoints. Feasibility and acceptability of administering the PRO items electronically on a hand-held touch-screen device were also evaluated. The sample included children aged 6-8 years (n = 14), 9-11 years (n = 13), adolescents aged 12-17 years (n = 12), and adults (n = 10), all of who had current (n = 38) or recent (n = 11) cold. Both concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted with all of these participants, conducted over in two rounds. Ten parents/caregivers of participants aged 6-8 years were also interviewed (separately from their child) regarding how they thought their children would understand the items. The CE interviews explored the qualitative experience of having chest congestion and related symptoms of the common cold. Following their CE interview, participants completed draft items on an electronic patient-reported outcome (ePRO) device twice daily for 2-5 days prior to their CD interview. During the CD interview participants were asked about relevance, understanding and interpretation of the draft PRO items. Qualitative analysis of the interview data and descriptive analyses of the ePRO data were conducted following both rounds of interviews, with modifications to the items implemented following Round 1 and tested in Round 2. RESULTS: Eight symptoms were reported by children during concept elicitation. Findings from the child, adolescent, and adult/parent interviews supported revisions to the items and enabled the selection of the best performing items. The results provided evidence that the final items were well understood by participants and relevant to their experiences of chest congestion as part of a common cold. Findings also provide support for using the same items across age groups. CONCLUSIONS: The results of the CE and CD interviews provide evidence supporting the content validity of new PRO items assessing the experience of chest congestion symptoms associated with common cold experienced by children, adolescents, and adults.

Psychometric Evaluation of ITP Life Quality Index (ILQI) in a Global Survey of Patients with Immune Thrombocytopenia.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disorder caused by immunologic destruction of otherwise normal platelets. Patients and physicians differ in their views pertaining to the limitations imposed on patients' daily lives by ITP and its treatment. Poor understanding of ITP symptoms can result in misdiagnosis and complex treatment patterns, and affect patient health-related quality of life (HRQoL). The ITP Life Quality Index (ILQI) is a 10-item patient-reported outcome measure developed for clinical practice to aid discussions between patients and physicians. This research aimed to validate the psychometric properties of the ILQI using data collected in the ITP World Impact Survey (I-WISh). METHODS: I-WISh data containing responses to the ILQI from 1507 patients with ITP across 13 countries worldwide was subject to psychometric analysis to evaluate the structure, reliability and validity of the ILQI and assess scoring cut-offs. RESULTS: The ILQI has an overarching unidimensional structure, supporting a total score including all 10 items. Reliability was supported (Cronbach's alpha = 0.90). ILQI scores monotonically increased with ITP severity. ILQI scores correlated with measures of fatigue and emotional well-being, supporting construct validity. Differential item functioning (DIF) analyses showed that ILQI item responses were interpreted similarly between the USA and other Western countries. It was suggested that previous clinical cut-off score of 20 for "impaired HRQoL" was reduced to 17 and a cut-off of 23-25 (rather than 30) was suggested to assess "significantly impaired HRQoL". CONCLUSION: The validity and reliability of the ILQI to assess HRQoL of patients with ITP is supported. The revised cut-off scores for the ILQI will aid patient-centric decision-making.

Dome-shaped macula in premature infants visualized by handheld spectral-domain optical coherence tomography.

PURPOSE: To describe dome-shaped macula and associated clinical findings in premature infants. METHODS: This prospective, observational cohort study included a consecutive sample of premature infants screened for retinopathy of prematurity (ROP) with 9-month follow-up. Handheld spectral domain optical coherence tomography (SD-OCT) was performed at the time of ROP screening. Images were assessed for dome-shaped macula, cystoid macular edema, epiretinal membrane, vitreous bands, and punctate hyperreflective vitreous opacities. Dome height measurements were performed in a subset of images. Teller visual acuity and cycloplegic refraction were performed at an adjusted age of 8-10 months. RESULTS: Of 37 infants (74 eyes; 49% male; mean gestational age 27.8 ± 3.2 weeks; mean birth weight 949 ± 284 g), 24/37 (65%) demonstrated dome-shaped macula in at least one eye (13 both eyes, 5 right eye only, and 6 left eye only). Of the 74 eyes, 26 (35%) could be reliably measured, with a mean dome height of 139.0 ± 72.3 µm (range, 54-369 µm). Presence of dome-shaped macula was associated with a diagnosis of ROP (P = 0.02; OR, 3.03; 95% CI, 1.18-7.82) and pre-plus or plus disease (P = 0.02; OR, 4.20; 95% CI, 1.05-16.78). Infants with dome-shaped macula had lower birth weight compared with those without (877 vs 1081 g; P = 0.04). No associations with other demographics, OCT findings, and 9-month refractive outcomes were found. CONCLUSIONS: Dome-shaped macula was frequently identified by handheld SD-OCT in premature infants, especially those with lower birth weight and severe ROP. The long-term clinical significance of this finding is unknown.

EXUDATIVE RETINAL DETACHMENT DOCUMENTED BY HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AFTER RETINAL LASER PHOTOCOAGULATION FOR RETINOPATHY OF PREMATURITY.

BACKGROUND: Few cases of exudative retinal detachments have been reported in the literature after laser treatment for retinopathy of prematurity, and none of the cases include optical coherence tomography images. METHODS: Case report. RESULTS: A 469-g birth weight, 25-week gestational age baby girl at 35-week postmenstrual age received a retinal laser (1,724 spots in the right eye and 1,287 spots in the left eye) for bilateral Stage 3 Zone II plus disease retinopathy of prematurity. The patient developed a large macular exudative retinal detachment seen in the right eye at the first follow-up, 5 days after the laser. Serial handheld optical coherence tomography demonstrated resolution of retinal detachment and intraretinal fluid over the course of 4 weeks with only topical tobramycin/dexamethasone ophthalmic ointment 3 to 4 times daily for 2 weeks. The patient was left with a residual subretinal scar and outer retinal loss on optical coherence tomography, with a later appearance of a dragged macula on funduscopic examination noted at 52-week postmenstrual age. It is unclear whether systemic steroid therapy, intravitreal bevacizumab, or surgery would hasten resolution of exudative retinal detachment after the retinopathy of prematurity laser and avoid photoreceptor damage seen on optical coherence tomography in this case. CONCLUSION: This case suggests that post-retinopathy of prematurity laser exudative retinal detachments can resolve without aggressive intervention, but may cause permanent retinal sequelae.

Vitreous Findings by Handheld Spectral-Domain OCT Correlate with Retinopathy of Prematurity Severity.

PURPOSE: To evaluate the association between retinopathy of prematurity (ROP) and vitreous findings in premature infants detected by handheld spectral-domain (SD) OCT. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Consecutive sample of 92 premature infants requiring ROP screening at 2 academic neonatal intensive care units between July 2015 and March 2018. METHODS: Infants underwent handheld SD OCT at the time of routine ROP examinations. Two masked, trained graders analyzed right-eye vitreoretinal findings, including semiautomated quantification of punctate hyperreflective vitreous opacities within 5 foveal or parafoveal B-scans (vitreous opacity ratio). MAIN OUTCOME MEASURES: Excluding posttreatment data, vitreous findings were compared with clinical ROP diagnoses. RESULTS: Agreement between image graders for all vitreoretinal findings was 91% (κ = 0.86; 95% confidence interval, 0.82-0.90; P < 0.001). Among 92 infants undergoing 280 imaging sessions (52% male; mean gestational age, 28.3 ± 2.8 weeks; mean birthweight, 1014.5 ± 285.0 g), 36 of 92 (39%) demonstrated ROP. Punctate hyperreflective vitreous opacities were identified in 61 of 92 infants (66%). The presence of punctate hyperreflective vitreous opacities at least once was associated with a diagnosis of ROP (62% vs. 29% without opacities; P = 0.003), maximum ROP stage (P = 0.001), preplus or plus disease (24% vs. 5%; P = 0.005), and type 1 disease (14% vs. 2%; P = 0.03). Among 29 infants (45 imaging sessions) with right-eye punctate hyperreflective vitreous opacities, the vitreous opacity ratio from 2 graders (F1 score, 0.82 ± 0.36; Dice coefficient, 0.97 ± 0.04) correlated with ROP stage (P = 0.02). Tractional vitreous bands on imaging correlated with plus disease status (29% vs. 5% without bands; P = 0.05). CONCLUSIONS: Punctate hyperreflective vitreous opacities and tractional vitreous bands predict the presence and severity of ROP. Further studies should explore handheld OCT as a noninvasive ROP screening tool.

Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists.

INTRODUCTION: Chronic hand eczema (CHE) is a relapsing inflammatory dermatologic disease. Signs and symptoms can have a significant impact on patients' health-related quality of life (HRQoL). The aim of this study is to characterize the core signs, symptoms and impacts of CHE to develop a conceptual model. METHODS: A structured literature search and qualitative interviews with 20 adult CHE patients in the US and 5 expert dermatologists were conducted to explore the patient experience of CHE signs, symptoms and impacts. Findings were used to support the development of a conceptual model. RESULTS: There was a paucity of CHE qualitative research in the literature, supporting the need for the prospective qualitative research. The primary signs and symptoms identified from the literature review and interviews included itch, dryness, cracking, pain, thickened skin and bleeding. The most salient impacts included embarrassment and appearance concerns, frustration, impacts on work and sleep disturbance. Saturation was achieved for all signs, symptoms and impact concepts. CONCLUSIONS: Findings from this literature review and in-depth qualitative interviews supported the development of a comprehensive conceptual model documenting the signs, symptoms and impacts relevant to CHE patients. Such a model is of considerable value given the lack of existing studies in the literature focused on the qualitative exploration of the CHE patient experience. Limitations included the patient sample being only from the US and not including some CHE subtypes.

Conceptual Model to Illustrate the Symptom Experience and Humanistic Burden Associated With Atopic Dermatitis in Adults and Adolescents.

Atopic dermatitis (AD) is a pruritic or painful dermatologic disease characterized by xerosis and eczema lesions. The symptoms/signs of AD can significantly impact patients' health-related quality of life (HRQoL). This study aimed to qualitatively explore the adult and adolescent experience of AD. A targeted literature review and qualitative concept elicitation interviews with clinicians (n = 5), adult AD patients (n = 28), and adolescent AD patients (n = 20) were conducted to elicit AD signs/symptoms and HRQoL impacts experienced. Verbatim transcripts were analyzed using thematic analysis. Twenty-nine symptoms/signs of AD were reported, including pruritus, pain, erythema, and xerosis. Atopic dermatitis symptoms/signs were reported to substantially impact HRQoL. Scratching was reported to influence the experience of symptoms and HRQoL impacts. Four proximal impacts (including discomfort and sleep disturbance) were reported. Ten domains of distal impact were reported, including impacts on psychological and social functioning and activities of daily living. A conceptual model was developed to summarize these findings. This study highlights the range of symptoms and HRQoL impacts experienced by adults and adolescents with AD. To our knowledge, this study was first to explore the lived experience of AD in both adult and adolescent patients, providing valuable insight into the relatively unexplored adolescent experience of AD.

Health utilities and quality of life in individuals with tuberous sclerosis complex (TSC) who experience epileptic seizures: A web-based survey.

OBJECTIVES: Individuals with tuberous sclerosis complex (TSC) experience a wide range of health impacts, including epileptic seizures, negatively impacting their health-related quality of life (HRQoL). Health state utility values (HSUVs) are index values representing HRQoL and are used as key inputs for health economic analyses. Such data are currently very limited in the TSC population. The objective of this study was to generate HSUVs for TSC health states, defined by the number and type of seizures experienced in the previous week, and to compare with UK normative values. METHODS: This cross-sectional study involved 186 participants (individuals with TSC = 61, caregivers reporting for individuals with TSC = 125) from Europe and North America who completed a web-based survey. Participants completed the [EuroQol - 5 dimensions - 3 levels] (self-report version for individuals with TSC or proxy version 1 for caregivers). RESULTS: The mean age of individuals with TSC was 27.3 years (self-reported: 41.3 years, caregiver-reported: 20.5 years); 56% were males. Most individuals with TSC (71%) reported experiencing between one and ten seizures in the week prior to participating in the study. The most frequently reported type of seizure was focal: simple partial (50%). Across all participants (combined self-report and caregiver-report), the mean HSUV was 0.474 (95% confidence interval [CI]: 0.424-0.524), significantly lower than the UK norm (0.856, 95%CI: 0.848-0.864) [1]. Mean HSUV and HRQoL scores were consistently lower when reported by caregivers than when self-reported by individuals with TSC (HSUV = 0.351 vs. 0.727). This is in part because caregivers reported for individuals with TSC who experienced more frequent and severe seizures than those who were able to self-report. HSUVs incrementally decreased with the experience of more frequent (1-5 per week: HSUV = 0.666 vs. >20: HSUV = 0.290) and more severe seizures (focal: simple partial: HSUV = 0.450 vs. generalized: convulsive: HSUV = 0.194). CONCLUSIONS: The HRQoL and HSUV index scores indicate substantial impairment among individuals with TSC; HSUVs were shown to decrease considerably with increases in seizure frequency or seizure severity, indicating that more burdensome seizure health states are associated with poorer HRQoL.

Fatigue, treatment satisfaction and health-related quality of life among patients receiving novel drugs suppressing androgen signalling for the treatment of metastatic castrate-resistant prostate cancer.

Clinical studies have demonstrated the benefits of abiraterone acetate + prednisone (AAP) and enzalutamide (ENZ) in significantly improving survival among metastatic castration-resistant prostate cancer (mCRPC) patients. However, evidence regarding patient's real-world experience, particularly with respect to fatigue, treatment satisfaction and health-related quality of life (HRQoL) is limited. Interviews were initially conducted with patients (n = 38) and carers (n = 12) to elicit qualitative data regarding their experiences. Findings informed the design of a quantitative, multinational online survey of mCRPC patients (n = 152) receiving AAP or ENZ. Participants completed validated questionnaires assessing fatigue (Brief Fatigue Inventory), treatment satisfaction (Cancer Therapy Satisfaction Questionnaire) and HRQoL (EuroQol-5-Dimensions). Results indicated that patients were generally satisfied with these therapies, more specifically with reductions in prostate-specific antigen levels and extended survival. Fatigue was commonly linked to poor HRQoL and responses indicated that significantly fewer patients in the AAP group reported feeling usually tired or fatigued in the last week compared to the ENZ group (33% vs. 55%, p = 0.006 respectively). Findings highlight the benefit of AAP and ENZ in promoting the "quality" of extended survival. That fatigue was lower among patients receiving AAP may be important for informing treatment decisions. Further research is needed to gain deeper insights.

Private provision of public goods by environmental groups.

Many environmental nonprofit groups are assumed to provide public goods. While an extensive literature examines why donors join and give to nonprofits, none directly tests whether donations actually provide public goods. We seek such a test by using a common form of environmental organization: watershed groups. We find their increased presence resulted in lower dissolved oxygen deficiency and higher proportions of swimmable and fishable water bodies. Increased donations to and expenditures by the groups also improved water quality. Thus, private groups likely played a role in mitigating environmental problems. Overall, our results indicate private provision of a public good by nonprofit organizations.

Qualitative and Quantitative Assessment of Patient and Carer Experience of Chemotherapy (Docetaxel) in Combination with Androgen Deprivation Therapy (ADT) for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

INTRODUCTION: Recent studies suggest that docetaxel plus androgen deprivation therapy can prolong survival among men with metastatic hormone-sensitive prostate cancer (mHSPC). However, as a cytotoxic therapy, there is a need to understand the experiences of men with mHSPC receiving docetaxel and their carers in a real-world setting. METHODS: During phase 1, semi-structured qualitative interviews were conducted with men with mHSPC (n = 31) and their carers (n = 14) in Europe to elicit in-depth data concerning their experiences with docetaxel. Eighteen men were also asked to record their experiences in a diary for 7 days. During phase 2, men with mHSPC (n = 161) and carers of men with mHSPC (n = 135) completed an online survey comprising self-report questionnaires including the Cancer Therapy Satisfaction Questionnaire, Brief Fatigue Inventory, Functional Assessment of Cancer Therapy-Prostate, EuroQol-5-Dimensions and the Burden Scale for Family Caregivers (carers only). RESULTS: At the outset of therapy, men reported a willingness to take docetaxel to prolong their life, despite being fearful of the potential side effects and impacts on their daily lives. Patient and carer experiences were generally consistent with pre-treatment expectations. However, variations in individual experiences and their ability to tolerate side effects were evident. Fatigue emerged as a prominent symptom with the majority (n = 98, 60.9%) of men reporting experiencing moderate-severe fatigue in the past 24 h. Participant ratings of fatigue were strongly correlated with health-related quality of life (r = - 0.82). Nausea, diarrhoea and sore mouth were also among the most bothersome symptoms for participants. CONCLUSIONS: Findings from this study highlight that real-world experience of docetaxel may differ from that observed in clinical trials and that care must be taken to ensure that treatment options are tailored to the needs of individual patients to promote not only how long patients survive but also the quality of that survival. FUNDING: Janssen.

Noradrenergic receptor modulation influences the acoustic parameters of pro-social rat ultrasonic vocalizations.

Rats produce high rates of ultrasonic vocalizations (USVs) in social situations; these vocalizations are influenced by multiple neurotransmitter systems. Norepinephrine (NE) plays a significant role in vocalization biology; however, the contribution of NE to normal, prosocial vocal control has not been well established in the rat. To address this, we used NE adrenoceptor agonists (Cirazoline, Clonidine) and antagonists (Prozasin, Atipamezole, Propranolol) to quantify the contribution of specific alpha-1, alpha-2, and beta NE receptors to USV parameters in male Long Evans rats during seminaturalistic calling. We found that multiple USV acoustic variables (intensity, bandwidth, duration, peak frequency, and call profile) are modified by alterations in NE signaling. Very generally, agents that increased NE neurotransmission (Atipamezole) or activated alpha-1 receptors (Cirazoline), led to an increase in intensity and duration, respectively. Agents that decreased NE neurotransmission (Clonidine) or blocked alpha-1 receptors (Prazosin) reduced call rate, intensity, and bandwidth. However, the beta-receptor antagonist, Propranolol, was associated with increased call rate, duration, and intensity. Limb motor behaviors were largely unaffected by any drug, with the exception of Clonidine. Higher doses of Clonidine significantly reduced gross motor, grooming, and feeding behavior. These results confirm the involvement of NE transmission in vocal control in the rat, and suggest that this USV model is useful for studying the neuropharmacology of behavioral measures that may have implications for disease states, such as Parkinson's disease. (PsycINFO Database Record

Pink1 -/- Rats Show Early-Onset Swallowing Deficits and Correlative Brainstem Pathology.

Parkinson disease (PD) compromises oropharyngeal swallowing, which negatively affects quality of life and contributes to aspiration pneumonia. Dysphagia often begins early in the disease process, and does not improve with standard therapies. As a result, swallowing deficits are undertreated in the PD population. The Pink1 -/- rat is used to model PD, and demonstrates widespread brainstem neuropathology in combination with early-onset sensorimotor dysfunction; however, to date, swallowing behaviors have not been evaluated. To test the hypothesis that Pink1 -/- rats demonstrate early-onset differences in swallowing, we analyzed within-subject oropharyngeal swallowing using videofluoroscopy. Pink1 -/- and wildtype (WT) controls at 4 (Pink1 -/- n = 16, WT = 16) and 8 (Pink1 -/- n = 12, WT = 12) months of age were tested. The average and maximum bolus size was significantly increased in Pink1 -/- rats at both 4 and 8 months. Bolus average velocity was increased at 8 months for all animals; yet, Pink1 -/- animals had significantly increased velocities compared to WT at 8 months. The data show a significant reduction in mastication rate for Pink1 -/- rats at 8 months suggesting the onset of oromotor dysfunction begins at this time point. Relationships among swallowing variables and neuropathological findings, such as increased alpha-synuclein protein in the nucleus ambiguus and reductions in noradrenergic cells in the locus coeruleus in the Pink1 -/- rats, were determined. The presence of early oropharyngeal swallowing deficits and relationships to brainstem pathology in Pink1-/- rat models of PD indicate that this may be a useful model of early swallowing deficits and their mechanisms. These findings suggest clinical implications for early detection and management of dysphagia in PD.

Vitreous Bands Identified by Handheld Spectral-Domain Optical Coherence Tomography Among Premature Infants.

Importance: Handheld spectral-domain optical coherence tomography (SD-OCT) can provide insights into the complex interactions occurring at the vitreoretinal interface in retinopathy of prematurity (ROP) to enhance our understanding of ROP pathology. Objective: To characterize vitreous bands in premature infants with use of handheld SD-OCT. Design, Setting, and Participants: Prospective cohort study conducted from July 7, 2015, to February 28, 2017, at 2 university-based neonatal intensive care units. Seventy-three premature infants who required routine ROP screening examination were recruited. Informed consent was obtained from all legal guardians. Trained graders who were masked to the clinical assessment analyzed each SD-OCT scan of the right eye for vitreoretinal findings. A third trained grader mediated disagreements. Main Outcomes and Measures: Associations between the presence of vitreous bands in premature infants with ROP diagnoses and the presence of other vitreoretinal SD-OCT findings were investigated. Results: Of the 73 infants recruited, 6 infants' parents withdrew their children from the study, and 2 infants were too hemodynamically unstable for imaging, leaving a total of 65 participants. Of these, 32 (49%) were female, 36 (55%) were white, 10 (15%) were Hispanic, 3 (5%) were Native American, 4 (6%) were African American, 4 (7%) were Asian/Pacific Islander, and 8 (12%) were other. The mean (SD) gestational age was 28 (2.7) weeks, the mean (SD) birth weight was 997 g (286 g), and the mean (SD) postmenstrual age at imaging was 34 (3) weeks (mean [SD] total of 3 [2] imaging sessions). Comparing the 24 infants (37%) who had a right eye vitreous band at any time with the 41 (63%) who did not, no difference in mean birth weight, gestational age, postmenstrual age at imaging, sex, or race/ethnicity was identified. No associations with ROP stage (eg, in 6 [25%] infants with vitreous bands vs 4 [9.8%] in those without; P = .23), presence of plus disease (2 [8%] vs 2 [5%]; P = .84), or type 1 ROP (3 [12%] vs 3 [7%]; P = .66) were identified. Vitreous bands were associated with epiretinal membrane detected on SD-OCT (P = .001) with an odds ratio of 9.4 (95% CI, 2.8-31.3) in 15 [62%] infants with vitreous bands vs 6 [15%] in those without. Vitreous bands were also associated with cystoid macular edema (in 15 [62%] infants with vitreous bands vs 1 [27%] in those without; P = .005) with an odds ratio of 4.5 (95% CI, 1.5-13.3). Conclusions and Relevance: In this study, the development of vitreous bands was associated with both cystoid macular edema and epiretinal membrane. These findings suggest a tractional pathogenesis to these entities among premature infants. This study did not find a direct association between vitreous bands and severe ROP. Additional study is needed to determine whether vitreous bands represent subclinical hyaloidal organization leading to retinal detachment in advanced ROP.