Challenges of developing a district child welfare plan in South Africa: Lessons from a community-engaged HIV/AIDS research project

The Amajuba Child Health and Wellbeing Research Project measured the impact of orphaning due to HIV/AIDS on South African households between 2004 and 2007. Community engagement was a central component of the project and extended through 2010. We describe researcher engagement with the community to recruit participants, build local buy-in, stimulate interest in study findings, and promote integration of government social welfare services for families and children affected by HIV/AIDS. This narrative documents the experience of researchers, drawing also on project reports, public documents, and published articles, with the objective of documenting lessons learned in this collaboration between researchers from two universities and a community in South Africa during a period that spanned seven years. This experience is then analyzed within the context of an applied research, community-engagement framework

Psychometric validation of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI)

Background: Generalized pustular psoriasis (GPP) is a rare and life-threatening skin disease often accompanied by systemic inflammation. There are currently no standardized or validated GPP-specific measures for assessing severity. Objective: To evaluate the reliability, validity, and responder definitions of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI). Methods: The GPPGA and GPPASI were validated using outcome data from Week 1 of the Effisayil™ 1 study. The psychometric analyses performed included confirmatory factor analysis, item-to-item/item-to-total correlations, internal consistency reliability, test-retest reliability, convergent validity, known-groups validity, responsiveness analysis, and responder definition analysis. Results: Using data from this patient cohort (N=53), confirmatory factor analysis demonstrated unidimensionality of the GPPGA total score (root mean square error of approximation <0.08), and GPPGA item-to-item and item-to-total correlations ranged from 0.58–0.90. The GPPGA total score, pustulation subscore, and GPPASI total score all demonstrated good test-retest reliability (intraclass correlation coefficient: 0.70, 0.91, and 0.95, respectively), and good evidence of convergent validity. In anchor-based analyses, all three scores were able to detect changes in symptom and disease severity over time; reductions of -1.4, -2.2, and -12.0 were suggested as clinically meaningful improvement thresholds for the GPPGA total score, GPPGA pustulation subscore, and GPPASI total score, respectively. Anchor-based analyses also supported the GPPASI 50 as a clinically meaningful threshold for improvement. Conclusions: Overall, our findings indicate that the GPPGA and GPPASI are valid, reliable, and responsive measures for the assessment of GPP disease severity, and support their use in informing clinical endpoints in trials in GPP

Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy–Fatigue and pain‐Visual Analogue Scale in patients with generalized pustular psoriasis

Background: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. Objectives: To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. Methods: Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test–retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. Results: Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75–0.94; FACIT-Fatigue range, 0.11–0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test–retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001–0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001–0.0002). Conclusions: Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP

Local Cooperativity in an Amyloidogenic State of Human Lysozyme Observed at Atomic Resolution

The partial unfolding of human lysozyme underlies its conversion from the soluble state into amyloid fibrils observed in a fatal hereditary form of systemic amyloidosis. To understand the molecular origins of the disease, it is critical to characterize the structural and physicochemical properties of the amyloidogenic states of the protein. Here we provide a high-resolution view of the unfolding process at low pH for three different lysozyme variants, the wild-type protein and the mutants I56T and I59T, which show variable stabilities and propensities to aggregate in vitro. Using a range of biophysical techniques that includes differential scanning calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate that thermal unfolding under amyloidogenic solution conditions involves a cooperative loss of native tertiary structure, followed by progressive unfolding of a compact, molten globule-like denatured state ensemble as the temperature is increased. The width of the temperature window over which the denatured ensemble progressively unfolds correlates with the relative amyloidogenicity and stability of these variants, and the region of lysozyme that unfolds first maps to that which forms the core of the amyloid fibrils formed under similar conditions. Together, these results present a coherent picture at atomic resolution of the initial events underlying amyloid formation by a globular protein

Exploring the implementation of patient-reported outcome measures in cancer care: need for more real-world evidence results in the peer reviewed literature

Abstract Background To explore the existing evidence of the real-world implementation of patient-reported outcomes (PROs) in oncology clinical practice and address two aims: (1) summarize available evidence of PRO use in clinical practice using a framework based on the International Society for Quality of Life Research (ISOQOL) PRO Implementation Guide; and (2) describe reports of real-world, standardized PRO administration in oncology conducted outside of scope of a research study. Methods A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was developed to guide the systematic literature review (SLR) that was conducted in MEDLINE and Embase databases. A two step search strategy was implemented including two searches based on previously completed reviews. Studies published from 2006 to 2017 were synthesized using a framework based on the ISOQOL PRO Implementation Guide. Results After screening 4427 abstracts, 36 studies met the eligibility criteria. Most elements of the ISOQOL PRO Implementation Guide were followed. Two notable exceptions were found: 1) providing PRO score interpretation guidelines (39% of studies); and 2) providing patient-management guidance for addressing issues identified by PROs (25% of studies). Of the 22 studies with an intervention component, 19 (86%) reported intervention effects on study outcomes. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) was the most commonly used PRO (n = 10, 28%); use of 38 other PRO measures was also reported. Only three studies (8%) reported real-world PRO implementation. Conclusion Reports of real-world PRO implementation are limited. Reports from studies conducted in clinical settings suggest gaps in information on PRO score interpretation and the use of PRO results to inform patient management. Before the promise of practice-based PRO assessment in oncology can be truly realized, investigators need to advance the state-of-the-art of real-time PRO score interpretation as well as developing guidance on how to use PRO insights to drive clinically-meaningful patient-management strategies

Symptom experience and content validity of the Psoriasis Symptom Scale (PSS) in patients with generalized pustular psoriasis (GPP)

Introduction: We sought to understand key symptoms of generalized pustular psoriasis (GPP) and to confirm the relevance to patients and content validity of the Psoriasis Symptom Scale (PSS) in GPP. Methods: A targeted literature review and clinical expert interviews were conducted as background research. Patients were interviewed individually (involving concept elicitation and cognitive interviews), and a separate patient workshop was conducted to determine disease-specific symptoms of importance. Results: Seven participants with moderate (n = 4), severe (n = 2), and mild (n = 1) GPP and clinician diagnosis were interviewed. During concept elicitation, all participants indicated that pustules may underlie other symptoms. Symptoms reported by all patients were pain, redness, itch, burning, and discomfort. The PSS symptoms of pain, itching, burning, and redness were reported by ≥ 86% of patients as most frequently experienced. Upon debriefing, the PSS was well understood. Relevance and importance of these symptoms was confirmed in the GPP patient workshop. Conclusion: Participant feedback found the PSS measure to be relevant and easy to understand. The symptoms included in the instrument, pain, redness, itch, and burning, were most frequently reported, important, and well understood by patients. Study results provided support for the content validity of the PSS for use as endpoints in GPP clinical trials

Burden of renal angiomyolipomas associated with tuberous sclerosis complex: results of a patient and caregiver survey

Abstract Background Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors in multiple organs, including non-cancerous kidney lesions known as renal angiomyolipomas. This study’s objective is to describe the age-stratified morbidity, treatment patterns, and health-related quality of life of TSC patients with renal angiomyolipomas in the United States. A cross-sectional, anonymous web-based survey was conducted with a convenience sample of TSC patients and caregivers identified through a patient advocacy organization. Results Out of the total sample of 676, 182 respondents reported having kidney complications with 33% of the pediatric group and 25% of the adult group with TSC reporting them. Of those with kidney complications, 110 (60%) reported a diagnosis of renal angiomyolipomas, of which 79 (72%) were adult patients and 31 (28%) were pediatric age patients. Eighty-four percent of the pediatric group and 76% of the adult group reported lesions on both kidneys. Of the patients experiencing involvement of only one kidney, 60% of the pediatric group and 21% of the adult group reported having multiple tumors within the affected kidney. Almost all of the sample (99%) reported seeing a physician and having a procedure or test for TSC in the past year. Less than half the respondents (44%) reported being hospitalized in the past year. Thirty-nine percent reported an emergency room visit as well. Compared to scores for patients with kidney disease, the angiomyolipoma adult patients reported significantly lower Mental Component Summary scores on the SF-12. Conclusions Renal angiomyolipomas burden leads to frequent healthcare resource use including hospitalization, invasive treatments, and surgical procedures, which result in an impaired mental health related quality of life

Content validity and ePRO usability of the BPI-sf and “worst pain” item with pleural and peritoneal mesothelioma

Abstract Background The Brief Pain Inventory-short form (BPI-sf) is widely used in self-reported pain assessment, incorporates pain numeric rating scales (NRS) and is commonly utilized in electronic format in clinical trials, however, there is no published information about its usability as an electronic patient-reported outcome (ePRO) measure. The objective of this qualitative study was threefold: 1) to better understand pain experiences among patients with pleural or peritoneal mesothelioma; 2) to assess the interpretability of the instructions, item stem, recall period, and response option of the “worst pain” item of the BPI-sf; and 3) to examine the usability of the TrialMax Touch™ (CRF Health, Inc., Plymouth Meeting, PA) screen-based handheld device and the electronic format of the BPI-sf in a sub-sample of pleural mesothelioma patients. Methods A cross-sectional qualitative study was conducted among participants with pleural and peritoneal mesothelioma recruited from 4 clinical sites in the US. Semi-structured telephone or in-person interviews were conducted consisting of concept elicitation, cognitive interviewing of the 11-item BPI-sf, and in-person interview evaluation of ePRO assessment usability in pleural mesothelioma patients. Results Twenty-one participants recruited from 4 clinical sites in the US were interviewed in-person (n = 9) and by telephone (n = 12); 71% male; mean age 68.7 ± 13.6 years. Pleural and peritoneal patients described pain as ranging from discomfort to intense pain and reported being able to distinguish tumor pain from treatment pain. The BPI-sf “worst pain” item was relevant to, and easily understood by, study participants with pleural and peritoneal mesothelioma. The ePRO version was found to be easy to use, but readability of small font may be an issue. Participants reported minimal differences between their responses on the paper and ePRO version for all of the pain severity and pain interference items. Conclusions Results support the relevance and ease of understanding of the “worst pain” item and provide support for its content validity in patients with pleural and peritoneal mesothelioma. Usability of the ePRO format of the BPI-sf was confirmed for use in clinical trials among patients with pleural mesothelioma

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease : a multi-country Delphi-panel approach

Background: Lack of a global consensus on the definition of advanced Parkinson’s disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care. Objectives: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms. Methods: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus. Results: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor—moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h “off” symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor—mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment—repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS. Conclusion: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes