Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Evaluating the Appropriateness of Existing Health-Related Quality of Life Measures in Lichen Planus.

INTRODUCTION: Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]) and mucosal regions (mucosal LP [MLP]). Several existing patient-reported outcome measures (PROMs) were identified for potential use in LP clinical development programs. This study aimed to assess the content validity and psychometric measurement properties of the Dermatology Life Quality Index (DLQI), Epworth Sleepiness Scale (ESS), Scalpdex and Oral Lichen Planus Symptom Severity Measure (OLPSSM) in an LP population. METHODS: Patients completed the PROs at various time points as part of an international Phase 2 clinical study in adults with MLP (n = 37), LPP (n = 37) and CLP (n = 37). Test-retest reliability, construct validity and sensitivity to change were assessed. In addition, qualitative cognitive debriefing interviews were conducted with adults with MLP (n = 20), LPP (n = 19) and CLP (n = 19) in the USA and Germany to examine the PROM content validity. RESULTS: The DLQI demonstrated adequate reliability and validity, although its ability to detect change was modest and most items were considered not relevant in qualitative interviews. The ESS had good reliability but limited evidence of validity and ability to detect change. Conceptual relevance varied according to the qualitative interview data. The Scalpdex was miscellaneous across domains, but the 'Symptoms' domain performed well overall. Overall, Scalpdex concepts were reported as relevant by most LPP patients interviewed. The OLPSSM demonstrated good psychometric properties and strong evidence of content validity. CONCLUSIONS: The psychometric and qualitative findings support the use of the OLPSSM and Scalpdex within specific LP subtypes but cautioned use of the DLQI. Administration of the ESS is not recommended in LP because of its poor psychometric performance. Given these limitations, further validation of non-specific disease measures is needed and/or the development of additional LP-specific PROMs. TRIAL REGISTRATION: NCT04300296.

An App to Support Fathers' Mental Health and Well-Being: User-Centered Development Study.

BACKGROUND: Numerous studies describe the popularity and usefulness of parenting programs. In particular, parenting programs are generally viewed as effective for supporting parents' mental well-being during key transition periods. However, the evidence base for fathers is limited owing to their lack of involvement in parenting programs and scarcity of tailored support. OBJECTIVE: This paper aimed to describe the co-design process for a universal digital intervention for fathers (fatherli) and the outline of a logic model with its expected outcomes. METHODS: Following established guidelines for co-designing and developing complex interventions, we conducted a nonsystematic review of the available literature to gather key information, developed market surveys to assess fathers' needs and interests, consulted with key stakeholders to obtain expert opinions, and engaged in a rapid iterative prototyping process with app developers. Each step was summarized, and the information was collated and integrated to inform a logic model and the features of the resulting intervention. RESULTS: The steps in the co-design process confirmed a need for and interest in a digital intervention for fathers. In response to this finding, fatherli was developed, consisting of 5 key features: a discussion forum for anyone to post information about various topics (the forum), a socializing platform for fathers to create and engage with others in small groups about topics or points of shared interest (dad hub), a tool for fathers to find other fathers with shared interests or within the same geographic location (dad finder), a resource for fathers to access up-to-date information about topics that interest them (dad wiki), and a portal to book sessions with coaches who specialize in different topics (dad coaching space). The evidence-based logic model proposes that if fatherli is successfully implemented, important outcomes such as increased parental efficacy and mental health help-seeking behaviors may be observed. CONCLUSIONS: We documented the co-design and development process of fatherli, which confirmed that it is possible to use input from end users and experts, integrated with theory and research evidence, to create suitable digital well-being interventions for fathers. In general, the key findings suggest that an app that facilitates connection, communication, and psychoeducation may appeal to fathers. Further studies will now focus on acceptability, feasibility, and effectiveness. Feedback gathered during pilot-testing will inform any further developments in the app to increase its applicability to fathers and its usability.

Patient Experience of Lichen Planus: A Qualitative Exploration of Signs, Symptoms, and Health-Related Quality of Life Impacts.

INTRODUCTION: Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]), and mucosal regions (mucosal LP [MLP]). Qualitative exploration of the patient experience of LP, notably symptoms and impacts on health-related quality of life (HRQoL), is limited. A scarcity of research was also identified relating to emotional wellbeing impacts of CLP patients. Two qualitative studies were conducted with LP patients to address these gaps. METHODS: Study 1 consisted of exit interviews conducted with a subset of adult patients with MLP (n = 5), CLP (n = 4), and LPP (n = 4) enrolled in an LP clinical study in the United States (US) to explore the patient experience. Study 2 consisted of independent qualitative interviews conducted with adult CLP patients (n = 13) from the US and Germany to further explore impacts on emotional wellbeing. RESULTS: Exit interviews found that itch , pain, and skin lesions were most frequently reported as signs/symptoms of LP. Itch and skin lesions were experienced across all LP subtypes, while pain was only reported by CLP and MLP patients. These signs/symptoms impacted HRQoL including emotional wellbeing (frustration, embarrassment), daily activities (oral hygiene, clothing options), social functioning (intimacy, social activities), and physical functioning (chewing/swallowing, opening/moving mouth). Impacts on activities of daily living (ADL) and physical functioning were mostly experienced by MLP patients. Independent qualitative interviews, which further explored impacts of CLP on patients' emotional wellbeing, identified frustration, worry, sadness, embarrassment, and depression as the most frequently experienced. CONCLUSION: The findings contribute to the literature by providing qualitative insights into signs/symptoms and HRQoL impacts of LP, from the adult patient perspective. The findings also highlight the importance of considering assessment of HRQoL impacts in future clinical LP research, particularly impacts on emotional wellbeing when selecting instruments for assessment of HRQoL in the CLP population. TRIAL REGISTRATION: NCT04300296.

Improving kidney care for people with severe mental health difficulties: a thematic analysis of twenty-two healthcare providers' perspectives.

Introduction: People with severe mental health difficulties (SMHDs) and concurrent kidney disease have less access to quality kidney care and worse clinical outcomes. Our research investigates the barriers and facilitators to effective kidney care for people with SMHDs, and how care might be improved for this underserved population. Methods: We conducted semi-structured interviews with twenty-two physical (n = 14) and mental (n = 8) healthcare professionals with experience working with people with SMHDs and concurrent kidney disease. Interview data were analysed and interpreted using reflexive thematic analysis. Results: Four themes were generated from the data: 1. "It's about understanding their limitations and challenges, without limiting their rights" describes how some people with SMHDs need additional support when accessing kidney care due to challenges with their mental state, motivation, cognitive difficulties, or mistrust of the healthcare system. 2. "There are people falling through the cracks" describes how the separation of physical and mental healthcare, combined with under-resourcing and understaffing, results in poorer outcomes for people with SMHDs. 3. "Psychiatry is a black spot in our continuing medical education" describes how many renal healthcare providers have limited confidence in their understanding of mental health and their ability to provide care for people with SMHDs. 4. "When they present to a busy emergency department with a problem, the staff tend to go '…psych patient"" describes how stigma towards people with SMHDs can negatively impact quality of care. Conclusion: Healthcare professionals accounts' describe how people with SMHDs and kidney disease can have favourable outcomes if they have appropriate hospital, community and social supports. Findings indicate that effective management of kidney disease for people with SMHDs requires integrated physical and mental health care, which takes an individualised "whole person" approach to addressing the interaction between kidney disease and mental health.

High rates of psychological distress, mental health diagnoses and suicide attempts in people with chronic kidney disease in Ireland.

BACKGROUND: People with chronic kidney disease (CKD) experience high levels of psychological distress, which is associated with higher mortality and adverse health outcomes. Little is known about the rates of a range of mental health difficulties or rates of suicide attempts in people with CKD. METHODS: Individuals with CKD (n = 268; age range 18-94 years, mean = 49.96 years) on haemodialysis (n = 79), peritoneal dialysis (n = 46), transplant recipients (n = 84) and who were not on renal replacement therapy (RRT; n = 59) were recruited through the Irish Kidney Association social media pages and three Irish hospitals. Participants completed surveys to gather demographics and mental health histories, the Hospital Anxiety and Depression Scale (HADS) and the 12-item Short Form Health Survey (SF-12) to measure health-related quality of life (HRQoL). RESULTS: A total of 23.5% of participants self-reported they had received a mental health diagnosis, with depression (14.5%) and anxiety (14.2%) being the most common, while 26.4% of participants had experienced suicidal ideation and 9.3% had attempted suicide. Using a clinical cut-off ≥8 on the HADS subscales, current levels of clinically significant anxiety and depression were 50.7% and 35.4%, respectively. Depression levels were slightly higher for those on haemodialysis compared with those with a transplant and those not on RRT. Depression, anxiety and having a mental health diagnosis were all associated with lower HRQoL. CONCLUSIONS: People with CKD in Ireland experience high levels of psychological distress, mental health difficulties, suicidal ideation and suicide attempts. The identification of and intervention for mental health difficulties in CKD should be prioritised in clinical care.

Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the gastrointestinal tract, associated with high levels of inflammatory cytokine production. Human caspases-4 and -5, and their murine ortholog caspase-11, are essential components of the innate immune pathway, capable of sensing and responding to intracellular lipopolysaccharide (LPS), a component of Gram-negative bacteria. Following their activation by LPS, these caspases initiate potent inflammation by causing pyroptosis, a lytic form of cell death. While this pathway is essential for host defence against bacterial infection, it is also negatively associated with inflammatory pathologies. Caspases-4/-5/-11 display increased intestinal expression during IBD and have been implicated in chronic IBD inflammation. This review discusses the current literature in this area, identifying links between inflammatory caspase activity and IBD in both human and murine models. Differences in the expression and functions of caspases-4, -5 and -11 are discussed, in addition to mechanisms of their activation, function and regulation, and how these mechanisms may contribute to the pathogenesis of IBD.

The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

Synthesis and antimicrobial evaluation of carbohydrate and polyhydroxylated non-carbohydrate fatty acid ester and ether derivatives.

A series of fatty acid ester and ether derivatives have been chemically synthesised based on carbohydrate and non-carbohydrate polyhydroxylated scaffolds. The synthesised compounds, along with their corresponding fatty acid monoglyceride antimicrobials, were evaluated for antimicrobial activity against Staphylococcus aureus and Escherichia coli. Of the derivatives synthesised, several of the carbohydrate-based compounds have antimicrobial efficacy comparable with commercially available antimicrobials. The results suggest that the nature of the carbohydrate core plays a role in the efficacy of carbohydrate fatty acid derivatives as antimicrobials.