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Background Accurate symptom monitoring is vital when managing pediatric asthma, providing an opportunity to improve control and relieve associated burden. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) has been validated for asthma control assessment in children; however, there are concerns that response option images used in the C-ACT are not culturally universal and could be misinterpreted. This cross-sectional, qualitative study developed and evaluated alternative response option images using interviews with children with asthma aged 4–11 years (and their parents/caregivers) in the United States, Spain, Poland, and Argentina. Interviews were conducted in two stages (with expert input) to evaluate the appropriateness, understanding and qualitative equivalence of the alternative images (both on paper and electronically). This included comparing the new images with the original C-ACT response scale, to provide context for equivalence results. Results Alternative response option images included scale A (simple faces), scale B (circles of decreasing size), and scale C (squares of decreasing quantity). In Stage 1, most children logically ranked images using scales A, B and C (66.7%, 79.0% and 70.6%, respectively). However, some children ranked the images in scales B (26.7%) and C (58.3%) in reverse order. Slightly more children could interpret the images within the context of their asthma in scale B (68.4%) than A (55.6%) and C (47.5%). Based on Stage 1 results, experts recommended scales A (with slight modifications) and B be investigated further. In Stage 2, similar proportions of children logically ranked the images used in modified scales A (69.7%) and B (75.7%). However, a majority of children ranked the images in scale B in the reverse order (60.0%). Slightly more children were able to interpret the images in the context of their asthma using scale B (57.6%) than modified scale A (48.5%). Children and parents/caregivers preferred modified scale A over scale B (78.8% and 90.9%, respectively). Compared with the original C-ACT, most children selected the same response option on items using both scales, supporting equivalency. Following review of Stage 2 results, all five experts agreed modified scale A was the optimal response scale. Conclusions This study developed alternative response option images for use in the C-ACT and provides qualitative evidence of the equivalency of these response options to the originals. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00390-2., Plain English summary Accurate monitoring of the symptoms associated with pediatric asthma is important when managing the condition. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) is a questionnaire widely used to measure asthma severity in young children (aged 4–11 years). Each question answered by the child in the C-ACT has four possible answer choices. To help children answer, each choice is presented alongside an image of a male child’s face ranging from sad to happy. However, there are concerns that the images used are not culturally universal and could be misinterpreted—due to difficulties translating to electronic formats and a lack of differentiation between the images used. Through interviewing children with asthma, we aimed to address these concerns by developing and testing new images. Alternative image options developed included simpler faces, circles of decreasing size and squares of decreasing quantity. Children aged 4–11 years old were interviewed to test whether they understood the response scale using the new images and if they answered in the same way as with the original images. Interviews were conducted in two stages, with expert guidance at key stages. Results showed that children can interpret and understand the newly developed images and that they answer the questions the same as they would using the original images. These new images have the advantages of being culturally neutral and easier to implement on an electronic device. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00390-2.

ObjectiveSLE and lupus nephritis (LN) have significant impacts on the health-related quality of life of patients living with the condition, which are important to capture from the patient’s perspective using patient-reported outcomes (PROs). The objectives of this study were to evaluate the content validity of PROs commonly used in SLE and LN (36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) and Lupus Quality of Life (LupusQoL), as well as novel PRO symptom severity items measuring skin rash, joint pain, joint stiffness and swelling of the legs and/or feet, in both populations.MethodsQualitative, semi-structured, cognitive interviews were conducted with 48 participants (SLE=28, LN=20). Understanding and relevance of symptom and impact PRO concepts from existing PROs were assessed, alongside novel PRO symptom severity items with different recall periods (24 hours vs 7 days) and response scales (Numerical Rating Scale (NRS) vs Verbal Rating Scale). Interviews were conducted in multiple rounds to allow for modifications to the novel PRO items. Analysis of verbatim interview transcripts was performed.ResultsSymptom and impact concepts assessed by the SF-36, FACIT-F, and LupusQoL were well understood by both participants with SLE and LN (≥90.0%), with most considered relevant by over half of the participants asked (≥51.9%). All participants asked (100%) understood the novel PRO symptom severity items, and the majority (≥90.0%) considered the symptoms relevant. Minor modifications to the novel PRO items were made between rounds to improve clarity based on participant feedback. The selected 7-day recall period and NRS in the final iteration of the PRO items were understood and relevant. No differences in interview findings between the SLE and LN samples were identified.ConclusionsFindings provide evidence of content validity for concepts assessed by the SF-36, FACIT-F, LupusQoL and the novel PRO symptom severity items, supporting use of these PROs to comprehensively assess disease impact in future SLE and LN clinical trials.

Objectives To qualitatively explore patient experiences of severe, recurrent, bilateral nasal polyps (NP). Methods A targeted literature review of published qualitative studies and online blogs describing patient experiences of NP was conducted. Semistructured concept elicitation interviews were conducted in the United States and Germany with participants ≥18 years with severe, recurrent, bilateral NP to explore their symptom experience and impacts on health-related quality of life (HRQoL; NCT03221192 ). A subset of 10 participants reported symptoms and impacts using a smartphone or tablet application (app) over a 10-day period. Results A paucity of qualitative evidence regarding patient experience of NP was identified from the literature or blog review. Twenty-seven participant interviews were conducted. Thirty-six symptoms were identified, including 7 primary symptoms (nasal congestion [n = 27 of 27], breathing difficulties [n = 27 of 27], postnasal drip [n = 25 of 27], runny nose [n = 24 of 27], head/facial pressure [n = 23 of 27], loss of smell [n = 23 of 27], loss of taste [n = 22 of 27]) and 29 secondary symptoms (the most common were mucus/catarrh and nose bleeds [both n = 20 of 27]). Most symptoms were reported to vary both within and between days. Sixty impacts of severe NP were reported, including impacts on sleep (n = 22 of 27), physical functioning (n = 21 of 27), activities of daily living (n = 21 of 27), emotional well-being (n = 27 of 27), treatment (n = 23 of 27), social life (n = 26 of 27), and work (n = 19 of 27). Symptoms/impacts reported using the app were consistent with interview findings, although new symptoms were identified (ear pain, throat pain, nasal scabs, and nasal burning). These results supported the development of a conceptual model outlining concepts related to symptoms, impacts, and treatment of NP. Conclusions Severe, recurrent, bilateral NP are associated with a range of symptoms that have significant detrimental impact on HRQoL.

Background:Lupus nephritis (LN) is an autoimmune disease characterized by inflammation of the kidneys as a result of systemic lupus erythematosus (SLE). Approximately 50% of SLE patients will develop LN, which is considered to be one of the most severe manifestations of SLE and the leading cause of morbidity and mortality in SLE. While there is ample existing evidence on disease experience and PROs used in extra-renal SLE, little research has been done in LN. Qualitative interviews with patients can help identify concepts that are both important and relevant to the patient. In order to effectively evaluate treatment benefit, it is critical that PRO measures used to assess such concepts and define clinical trial endpoints are fit for purpose and have strong evidence of content validity in the specific context of use.Objectives:The objective of this study was to understand the patient experience of LN and to identify and characterize the signs and symptoms of LN and their impact on health-related quality of life (HRQoL) through the development of a disease-specific conceptual model. This model was then used to evaluate the content validity of existing PRO measures available for use in LN.Methods:A structured literature search was conducted in Medline, Embase and PsycINFO to identify qualitative research articles documenting the patient experience of LN. PRO measures developed or commonly used to assess patient experiences of LN were also identified. Semi-structured concept elicitation interviews were conducted with 15 adult patients in the US with a clinician-confirmed diagnosis of LN (defined in accordance with established clinical guidelines). Supplementary qualitative data were also collected from a review of publicly available online blogs/forums. Findings were used to inform the development of a conceptual model detailing the impact of LN signs, symptoms and HRQoL and evaluate the validity of existing measures used within LN.Results:Searches revealed a paucity of qualitative research conducted with LN patients, supporting the need for prospective research in LN. Consistent with existing literature in SLE, the core signs and symptoms identified from the qualitative literature review, interviews and blog/forum review included joint pain, fatigue, joint stiffness, swelling (particularly in the extremities) and skin rashes. LN patients also reported urinary frequency, urgency, foamy urine and blood in their urine. Disease impact on physical functioning, activities of daily living, emotions, social life, work/finances and sleep were reported. PRO measures commonly used to evaluate patient experiences in LN included the SF-36, LupusQOL, LupusPRO, SLE Symptom Checklist, KDQoL and KSQ. Conceptual mapping of instruments against the newly developed conceptual model (Figure 1) highlighted that no single measure provides a comprehensive assessment of all symptoms/impact important to LN patients. Furthermore, items are largely focused on impact of symptoms with few items on symptom severity.Figure 1.Conceptual model of lupus nephritis symptoms and associated impactsConclusion:The presentation of signs and symptoms in LN patients appears similar to those reported in extra-renal SLE populations, with the addition of swelling and urinary symptoms. Qualitative research with LN patients guided the development of a comprehensive LN conceptual model outlining the disease experience from the patients’ perspective. These insights can be useful to inform PRO measurement strategies for clinical trials in LN.Acknowledgments:With thanks to Dr. Betty Diamond and Dr. David Wofsy for their collaboration and helpful insightsDisclosure of Interests:Pamela Berry Employee of: Janssen, Kate Burrows Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Rebecca Hall Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract., Adam Gater Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Helena Bradley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Amy Ward Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Chloe Tolley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Patricia Delong Employee of: Janssen, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC

During Ebola virus (EBOV) infection, secreted glycoprotein (sGP) and viral protein 40 (VP40) are found in large quantities in the serum of infected animals. Studies suggest that sGP only provides passive immunity by serving as a decoy to anti-EBOV antibodies, and no role for soluble VP40 has been determined. Using an in vitro model incorporating treatment of THP-1 macrophages with recombinant EBOV sGP and recombinant VP40, we examined the impact of the viral proteins upon key macrophage functions. Treatment with sGP inhibited macrophage production of pro-inflammatory cytokines (TNFα and IL-6) while the yield of anti-inflammatory cytokine (IL-10) remains unaltered. In contrast, VP40 seems to increase the production of pro-inflammatory cytokines. Furthermore, sGP affected only the function of activated macrophages and not the polarization. Phagocytic capacity was unaffected by sGP. Interestingly, the migratory ability of macrophages was diminished by sGP, and cell viability was increased, potentially due to a decrease in expression of CD11b, a vital macrophage integrin. Thus, the results suggests that while EBOV VP40 increases anti-viral immunity, EBOV sGP may operate to diminish functional contributions of non-infected macrophages for the purpose of increasing the potential viral dissemination between macrophages. Previously macrophages were activated utilizing a TLR4 agonist, LPS. TLR2 agonist zymosan, TLR3 agonist HMW Poly (I:C), TLR7 agonist imiquimod, and TLR9 agonist Class C CpG were examined. Further directions include determining the mechanism behind the inhibition and the specific TLR pathway molecules that are affected by sGP treatment.

[reaction: see text]. The Ugi reaction has been used to prepare divalent galactose derivatives. NMR analysis shows that a divalent neoglycoconjugate, where the glycopeptides are bridged by a terephthaloyl group, is an 83:17 mixture of two conformers; the amide groups of the major isomer have E-anti conformations. The spatial relationship and the relative orientation of the sugars are restricted, which may have consequences for the recognition of this and related structures in biological systems.

Compounds that alter endothelial cell growth are of interest in the development of angiogenesis modulators. A structurally diverse series of saccharide derivatives (glycosylamide conjugates) have been synthesized and evaluated for their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin (HA) reduced BAEC growth by 32% at 10 microg/mL and a number of the novel saccharide conjugates from the library were found to mimic the effect of HA as they also inhibit endothelial cell survival under identical conditions. Two thiophene conjugates, thioglucamide (24% inhibition at 35 microM) and a related glucuronide (26% inhibition at 33 microM) were the most potent inhibitors of BAEC growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects of thioglucamide and HA on absolute cell number were also studied using cell counting experiments; thioglucamide (47% after 24 h) was more potent than indicated by the MTT assay and initially reduced the BAEC number to a greater extent than HA (30% after 24 h); however, its actions were over more rapidly than were HA's as cell growth had returned to levels of the control after 72 h where HA still caused 25% inhibition. The binding of the monosaccharide conjugates to fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was investigated to establish the possible mechanism by which glycoconjugates could alter growth but there was no general correlation between reduction in viable cell population and binding to FGF-2. No glycoconjugate reduced the proliferation of mouse mammary epithelial cells, nor did any alter gross cell morphology, supporting a proposal that the reduction in BAEC survival by monosaccharide conjugates such as thioglucamide is a result of the inhibition of cell proliferation rather than being an induction of cytotoxicity. These studies indicate that cell biological studies to determine the mechanism of action of the simple monosaccharide conjugates may be worthwhile.

The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein-protein or other receptor-receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein-protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.