How strong should my anchor be for estimating group and individual level meaningful change? A simulation study assessing anchor correlation strength and the impact of sample size, distribution of change scores and methodology on establishing a true meaningful change threshold.

PURPOSE: Treatment benefit as assessed using clinical outcome assessments (COAs), is a key endpoint in many clinical trials at both the individual and group level. Anchor-based methods can aid interpretation of COA change scores beyond statistical significance, and help derive a meaningful change threshold (MCT). However, evidence-based guidance on the selection of appropriately related anchors is lacking. METHODS: A simulation was conducted which varied sample size, change score variability and anchor correlation strength to assess the impact of these variables on recovering the simulated MCT for interpreting individual and group-level results. To assess MCTs derived at the individual-level (i.e. responder definitions; RDs), Receiver Operating Characteristic (ROC) curves and Predictive Modelling (PM) analyses were conducted. To assess MCTs for interpreting change at the group-level, the mean change method was conducted. RESULTS: Sample sizes, change score variability and magnitude of anchor correlation affected accuracy of the estimated MCT. For individual-level RDs, ROC curves were less accurate than PM methods at recovering the true MCT. For both methods, smaller samples led to higher variability in the returned MCT, but higher variability still using ROC. Anchors with weaker correlations with COA change scores had increased variability in the estimated MCT. An anchor correlation of around 0.50-0.60 identified a true MCT cut-point under certain conditions using ROC. However, anchor correlations as low as 0.30 were appropriate when using PM under certain conditions. For interpreting group-level results, the MCT derived using the mean change method was consistently underestimated regardless of the anchor correlation. CONCLUSION: Sample size and change score variability influence the necessary anchor correlation strength when recovering individual-level RDs. Often, this needs to be higher than the commonly accepted threshold of 0.30. Stronger correlations than 0.30 are required when using the mean change method. Results can assist researchers selecting and assessing the quality of anchors.

Psychometric evaluation of a patient-reported outcome measure in pancreatic exocrine insufficiency (PEI).

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is commonly caused by chronic pancreatitis (CP) or cystic fibrosis (CF). There are no PEI-specific patient-reported assessments of symptoms and impacts. The PEI Questionnaire (PEI-Q) was developed through qualitative research with PEI patients and expert clinical input. This study evaluated the psychometric properties of the PEI-Q. METHODS: 162 PEI patients (CF = 71 and CP = 91), 62 diarrhoea-specific irritable bowel syndrome (IBS-D) patients and 60 healthy controls completed the 26-item PEI-Q and the Gastrointestinal Quality of Life Index (GIQLI) at baseline. PEI patients completed the measures again two weeks later to assess the test-retest reliability of the PEI-Q. Analyses supported item reduction and scoring algorithm development, followed by psychometric evaluation. RESULTS: Over 90% of PEI patients completed at least 23 of the 26 items at baseline. Item responses and clinical relevance supported retention of 18 items. Factor analysis supported a three-factor solution (abdominal symptoms, bowel movements, impacts) with adequate model fit. PEI-Q scores had good internal consistency (Cronbach's alpha: 0.77-0.82) and test-retest reliability (ICC: 0.73-0.87). Correlations between PEI-Q and GIQLI supported convergent validity. Known-groups and receiver operating characteristic analyses demonstrated that PEI-Q scores discriminated (p < 0.001) between differing PEI severities, and PEI patients and controls. CONCLUSIONS: The PEI-Q has good validity and reliability. Results indicate that the PEI-Q could be used to aid identification and diagnosis of PEI, assist in the management of patients already diagnosed with PEI, ensuring correct and optimum treatment as well as enhance patient-clinician communication.

Perception of impact of Dravet syndrome on children and caregivers in multiple countries: looking beyond seizures.

AIM: To assess the relevance and generalizability across countries of concepts of the impact of Dravet syndrome beyond seizures, as recognized by families. METHOD: Caregivers of children with Dravet syndrome in four countries (Australia [n=8]; USA, UK, and Italy [all n=4]) participated in 1-hour qualitative telephone interviews, identifying key Dravet syndrome concepts. Interviews were recorded, transcribed, and, where necessary, translated into English for thematic analysis. Conceptual saturation was assessed and findings compared to the previously developed French conceptual disease model. RESULTS: The most common seizure types reported by caregivers were tonic-clonic, absence, or focal-impaired awareness (localized/partial). Fever and physical activity were the most commonly reported triggers. Patient-relevant impacts included impairment in cognition, motor skills, communication, social skills, and behavioural functioning. Caregivers consistently reported negative social, physical, and family impacts. Concepts identified in the interviews showed similarity with the French conceptual model. Minor differences between countries are likely to reflect variations in health care systems. INTERPRETATION: Findings in Italy, Australia, UK, and USA confirm that the key impacts of Dravet syndrome on children and caregivers identified in France are generalizable across countries. Key symptom and impact concepts relevant to children and parents should be targeted as critical outcomes in new therapy evaluations. WHAT THIS PAPER ADDS: Relevance of the impact of Dravet syndrome on children and caregivers was confirmed across countries. Patient and caregiver-relevant Dravet syndrome impacts contribute to poorer health-related quality of life. Indirect seizure impacts were reported to be as important as direct impacts. Country-specific differences in concepts probably reflect differences in health care systems.

PERCEPCIÓN DEL IMPACTO DEL SÍNDROME DE DRAVET EN NIÑOS Y CUIDADORES EN MÚLTIPLES PAÍSES: UNA OBSERVACIÓN MÁS ALLÁ DE LAS CONVULSIONES: OBJETIVO: Evaluar la relevancia y la generalización de los conceptos del impacto del síndrome de Dravet, más allá de las convulsiones, en distintos países y como lo reconocen las familias. METODO: Cuidadores de niños con síndrome de Dravet en cuatro países (Australia [n=8], EEUU, Reino Unido e Italia [todos n=4]) participaron de una entrevista cualitativa de una hora de duración, identificando conceptos claves en el síndrome de Dravet. Las entrevistas fueron grabadas, transcriptas, y si era necesario, traducidas al inglés para análisis temáticos. Se evaluó la saturación conceptual y los resultados se compararon con el modelo conceptual de enfermedad francés, desarrollado previamente. RESULTADOS: Los tipos más comunes de convulsión reportados por los cuidadores fueron la tónico-clónica, las ausencias o las focales con alteración de la conciencia (localizadas/parciales). La fiebre y las actividades físicas fueron los desencadenantes más comúnmente reportados. Los impactos reportados en los pacientes fueron alteraciones en la cognición, habilidades motrices, comunicación, habilidades sociales y funcionamiento conductual. Los cuidadores informaron sistemáticamente sobre los impactos negativos a nivel social, físico y familiar. Los conceptos identificados en las entrevistas mostraron similitud con el modelo conceptual francés. Es probable que las diferencias menores entre países reflejen variaciones en los sistemas de atención de salud. INTERPRETACIÓN: Los hallazgos en Italia, Australia, Reino Unido y EEUU confirman que las alteraciones claves del síndrome de Dravet en niños y cuidadores identificados en Francia son generalizables en todos los países. Los síntomas claves y las alteraciones relevantes para los niños y los padres deben ser considerados como objetivos críticos de evolución cuando se evalúan el diseño de nuevas terapias.

PERCEPÇÃO DO IMPACTO DA SÍNDROME DE DRAVET EM CRIANÇAS E CUIDADORES EM MÚLTIPLOS PAÍSES: OLHANDO PARA ALÉM DAS CONVULSÕES: OBJETIVO: Avaliar a relevância e generalizabilidade entre países dos conceitos sobre o impacto da síndrome de Dravet para além das convulsões, com base no reconhecimento das famílias. MÉTODO: Cuidadores de crianças com síndrome de Dravet em quatro países (Australia [n=8]; EUA, Reino Unido, e Itália [all n=4]) participaram de entrevistas qualitativas por telefone com duração de 1 hora, identificando conceitos chave da síndrome de Dravet. As entrevistas foram gravadas, transcritas, e quando necessário, traduzidas para o inglês para análise temática. A saturação conceitual foi avaliada e os resultados comparados com o modelo conceitual francês da doença desenvolvido previamente. RESULTADOS: Os tipos mais comuns de convulsões reportados pelos cuidadores eram tônico-clônico, ausência, ou redução focal da consciência (localizada/parcial). Febre e atividade física foram os gatilhos mais comumente reportados. Os impactos relevantes para os pacientes incluíram deficiências na cognição, habilidades motoras, comunicação, habilidades sociais, e funcionamento comportamental. Os cuidadores reportaram impactos negativos sociais, físicos e familares. Os conceitos identificados nas entrevistas mostraram similaridades com o modelo conceitural francês. Diferenças pequenas entre países provavelmente refletem variações nos sistemas de cuidado à saúde. INTERPRETAÇÃO: Achados na Itália, Austrália, Reino unido e EUA confirmam que os impactos principais da síndrome de Dravet em crianças e cuidadores identificados na Franca são generalizáveis entre países. Os principais sintomas e conceitos de impacto relevantes para crianças e pais devem ser visados como desfechos críticos na avaliação de novas terapias.

Development and content validation of a preliminary core set of patient- and caregiver-relevant outcomes for inclusion in a potential composite endpoint for Dravet Syndrome.

BACKGROUND: Dravet Syndrome (DS) is a rare developmental and epileptic encephalopathy characterized by multiple seizures, frequently prolonged and treatment refractory, with significant developmental disabilities and behavioral and psychiatric disorders. Patients with DS require intensive support and supervision from a caregiver, impacting significantly on both patients' and caregivers' lives. This study aimed to identify core concepts to measure the impact on both patients and caregivers in future DS clinical trials. METHODS: Qualitative concept elicitation interviews were conducted with caregivers and healthcare professionals involved in caring for children with DS (aged 2-18years) in France to identify important concepts related to the global impact of DS. Interviews explored a range of concepts, including triggers, symptoms, impacts, and coping strategies, from which a conceptual model was developed. A Delphi consensus panel with eight international clinical experts aimed to identify important and relevant endpoints. RESULTS: Seizure was the most commonly reported symptom with DS further impacting children's cognitive and behavioral functioning. Caregivers identified impact concepts not reported by healthcare professionals. Both groups described additional impacts on wider family members and home modifications. Clinical experts agreed on the inclusion of five patient- and caregiver-relevant concepts for measurement in future DS clinical trials in a composite endpoint. The five concepts for inclusion were; seizures, expressive communication of the child, receptive communication of the child, impact on daily activities, and social functioning of the caregiver. CONCLUSIONS: This study showed the wider potential impact of DS to extend beyond that of seizures, demonstrating that there is a need for additional patient- and caregiver-relevant concepts to be measured in clinical trials to fully identify the value of therapeutic interventions.

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 .

Development and validation of a quality of life and treatment satisfaction measure in canine osteoarthritis.

Introduction: Canine osteoarthritis (OA) causes pain and mobility impairment. This can reduce dog quality of life (QoL), owner QoL and owners' satisfaction with, and adherence to, treatments. No existing canine OA-specific instrument assesses all three impacts. This study aimed to develop and psychometrically evaluate an owner-completed canine OA-specific measure of dog QoL, owner QoL and owner treatment satisfaction; the "Canine OA Quality of Life and Treatment Satisfaction Questionnaire" (CaOA-QoL-TS). Methods: The CaOA-QoL-TS was developed using a conceptual model derived from a meta-synthesis of published literature followed by cognitive interviews with ten owners of dogs with OA, to evaluate content validity. Results: Based on interview findings, ten items were reworded, four removed, and two added; resulting in 26 items that all owners understood and considered relevant. The recall period and response options were well understood and appropriate to almost all owners. To evaluate its psychometric properties, the CaOA-QoL-TS (draft 26-item version) was administered, across six timepoints in a phase 4 field study, to owners of OA treated dogs, recruited from veterinary practices (N = 93). Inter-item correlations suggested items clustered into three distinct domains: Dog QoL, Owner QoL and Treatment Satisfaction, as hypothesized. Confirmatory factor analysis supported deletion of two items and calculation of the three domain scores, with acceptable model fit. The resulting 24-item CaOA-QoL-TS instrument demonstrated strong internal consistency and good to excellent test-retest reliability. Convergent validity was supported by moderate to strong correlations with concurrent measures. Known groups validity was supported by statistically significant differences between groups categorized by owner global impression of QoL. Ability to detect change was demonstrated through statistically significant improvements over time in Owner and Dog QoL, with larger within-group effect sizes reported for the mean of 'improved' dogs compared to the mean of 'stable' dogs. Only a small sample of dogs worsened throughout the study. Anchor-based analyses supported-0.9 and-1.0-point within-group responder definitions for dog and owner QoL domains, respectively. Discussion: Findings support the content validity of the CaOA-QoL-TS in canine OA. The 24-item CaOA-QoL-TS is a reliable and valid instrument to measure owner and canine QoL and TS and is sensitive to improvements following OA treatment.

Psychometric Validation of the ViSIO-PRO and ViSIO-ObsRO in Retinitis Pigmentosa and Leber Congenital Amaurosis.

INTRODUCTION: Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) are rare inherited retinal degenerative disorders. The Visual Symptom and Impact Outcomes patient-reported outcome (ViSIO-PRO) and observer-reported outcome (ViSIO-ObsRO) instruments were developed in this population to assess visual function symptoms and impacts on vision-dependent activities of daily living (ADL) and distal health-related quality of life (HRQoL). This study aimed to explore the psychometric properties of the ViSIO-PRO and ViSIO-ObsRO in RP/LCA. METHODS: The 49-item ViSIO-PRO and 27-item ViSIO-ObsRO instruments were completed by 83 adult and adolescent patients and 22 caregivers of child patients aged 3-11 years with RP/LCA, respectively, at baseline and 12-16-day follow-up. Concurrent measures were also administered at baseline. Psychometric analyses assessed item (question) properties, dimensionality, scoring, reliability, validity, and score interpretation. RESULTS: Item responses were mainly evenly distributed across the response scale, and inter-item correlations were mostly moderate to strong (> 0.30) at baseline within hypothesized domains. Item deletion was informed by item properties, qualitative data, and clinical input and supported retention of 35 ViSIO-PRO items and 25 ViSIO-ObsRO items. Confirmatory factor analysis in line with pre-hypothesized domains supported a four-factor model assessing visual function symptoms, mobility, vision-dependent ADL, and distal HRQoL. A bifactor model supported calculation of total scores and four domain scores. Internal consistency was high for domain and total scores (Cronbach's alpha > 0.70) and test-retest reliability for total scores was strong between baseline and 12-16-day follow-up (intraclass correlation coefficients 0.66-0.98). Convergent validity was supported by strong correlations in a logical pattern with concurrent measures. Mean baseline scores differed significantly between severity groups. Distribution-based methods provided initial insights to guide interpretation of scores. CONCLUSIONS: Findings supported item reduction and established scoring of the instruments. Evidence of reliability and validity as outcome measures in RP/LCA was also reported. Further research is ongoing to explore responsiveness of the ViSIO-PRO and ViSIO-ObsRO instruments and interpretation of change scores.

Qualitative exploration of the visual function impairments and impacts on vision-dependent activities of daily living in Retinitis Pigmentosa and Leber Congenital Amaurosis: content validation of the ViSIO-PRO and ViSIO-ObsRO measures.

BACKGROUND: Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) are rare inherited retinal degenerative disorders. The associated visual impairments have significant impacts on patients' vision-dependent activities of daily living (ADL), mobility, and distal health-related quality of life (HRQoL). To adequately capture patient and caregiver perspectives in clinical trials, patient and observer-reported outcome instruments must demonstrate sufficient evidence of content validity in the target population. This study aimed to explore the patient experience of RP/LCA and assess the content validity of the Visual Symptom and Impact Outcomes PRO (ViSIO-PRO) and ObsRO (ViSIO-ObsRO) instruments in RP/LCA. METHODS: A total of 66 qualitative, combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted (33 adults, 10 adolescents, 8 children and 15 caregivers of children) in the US, France, Germany, and Canada. Patients had a clinical and genetic diagnosis of RP/LCA from a range of genotypes. CE results were used to further inform the development of a conceptual model and CD interviews assessed the relevance and understanding of the 44-item ViSIO-PRO and 26-item ViSIO-ObsRO instruments. Interviews were conducted across two iterative rounds to allow item modifications. RESULTS: Findings were consistent across RP/LCA genotypes. Night blindness, reduced peripheral vision, vision in very bright lighting and light/dark adaptation were the most frequently reported visual function symptoms impacting vision-dependent ADL and mobility. Impacts on distal HRQoL domains were also reported. The ViSIO-PRO and ObsRO items were well understood by participants and relevant across genotypes. The instructions, 7-day recall period and response scales were well understood and endorsed. Participant and expert clinician feedback supported modifications to item wording, the addition of six new ViSIO-PRO items and one new ViSIO-ObsRO item, and the removal of one ViSIO-PRO item due to lack of relevance. CONCLUSIONS: Findings support the content validity of the ViSIO-PRO and ViSIO-ObsRO instruments for use across RP/LCA genotypes. Ongoing research to evaluate the psychometric validity of the instruments will support future use of the instruments as efficacy endpoints in clinical trials and in general clinical practice to track disease severity and impact of disease on functioning.

Development of Novel Patient-Reported Outcome (PRO) and Observer-Reported Outcome (ObsRO) Instruments in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA): ViSIO-PRO and ViSIO-ObsRO.

INTRODUCTION: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are rare inherited retinal degenerative disorders resulting in visual impairments and impacts on patients' vision-dependent activities of daily living (ADL), mobility and distal health-related quality of life (HRQoL). This study aimed to conduct qualitative research to understand the patient experience of RP/LCA across genotypes and inform development of patient- and observer-reported outcome (PRO/ObsRO) instruments in RP/LCA. METHODS: Research activities included a qualitative literature review and review of existing visual function PRO instruments in RLBP1 RP, and concept elicitation (CE) and cognitive debriefing (CD) interviews of existing PRO instruments with patients with RLBP1 RP, expert clinicians, and payers. In wider RP/LCA, a social media listening (SML) study and a qualitative literature review was conducted, while psychometric evaluation of a PRO instrument in LCA was performed. Input from expert clinicians was sought at key stages. RESULTS: Findings from the qualitative literature reviews identified a range of visual function symptoms which had significant impacts on patients' vision-related ADL and distal HRQoL. Patient interviews identified additional visual function symptoms and impacts not previously reported in published literature. These sources informed development and refinement of a conceptual model displaying the patient experience of RP/LCA. Review of existing visual function PRO instruments, and CD interviews evaluating their content validity, confirmed that no existing instrument provides a comprehensive assessment of all concepts relevant to patients with RP/LCA. This highlighted the need for development of the Visual Symptom and Impact Outcomes PRO and ObsRO instruments to adequately assess the patient experience of RP/LCA. CONCLUSIONS: Results informed and supported development of the instruments to assess visual functioning symptoms and vision-dependent ADL, mobility and distal HRQoL in RP/LCA, in accordance with regulatory standards. Next steps to further support use in RP/LCA clinical trials/practice includes content and psychometric validation of the instruments in this population.

Generation of evidence supporting the content validity of SF-36, FACIT-F, and LupusQoL, and novel patient-reported symptom items for use in patients with systemic lupus erythematosus (SLE) and SLE with lupus nephritis (LN).

OBJECTIVE: SLE 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. METHODS: Qualitative, 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. RESULTS: Symptom 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. CONCLUSIONS: Findings 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.

Development and preliminary psychometric evaluation of an owner-completed measure of feline quality of life.

Due to improved healthcare and pet longevity, measurement of health-related quality of life (HRQoL) is increasingly important in companion animal medicine. The aim of this study was to develop and evaluate the content and psychometric properties of an owner-completed assessment of health and quality of life (QoL) in cats for use in general veterinary clinical practice. A 23-item feline QoL measure, drafted based on findings from an online survey completed by 45 pet owners, was revised following qualitative interviews with 10 pet owners of healthy cats to assess content validity. The resulting 22-item measure was completed twice by 199 owners of healthy cats to assess the reliability and validity of the measure via psychometric evaluation, including assessment of missing data, item response distributions, item correlations, factor analysis, internal consistency, test-retest reliability, multi-trait analysis, known groups analyses and estimation of minimally important differences. There were no missing data. Responses for all items were heavily skewed due to the sample being healthy. Analysis of items and factor analysis supported deletion of six items and calculation of two domain scores and a total score. Internal consistency and test-retest reliability were strong for all domains (0.70-0.80), indicating good reliability. All but three items demonstrated strong item convergent validity (item-scale correlation>0.40) and correlated highest with their respective domain (item discriminant validity). Significant between-group differences in scores differing according to a global impression of feline health item provided evidence of discriminative validity. Findings provide evidence that the final 16-item feline QoL measure has strong cross-sectional psychometric properties.

Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency (PEI) to Inform the Development of a Patient-Reported Outcome (PRO) Instrument.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) affects patients with chronic pancreatitis (CP) and cystic fibrosis (CF) who produce insufficient digestive pancreatic enzymes. Common symptoms include steatorrhoea, diarrhea, and abdominal pain. OBJECTIVE: The objective of the study was to develop and test the content validity of a patient-reported outcome (PRO) instrument assessing PEI symptoms and their impact on health-related quality of life. METHODS: Instrument development was supported by a literature review, expert physician interviews (n = 10: Germany 4, UK 3, France 3), and exploratory, qualitative, concept-elicitation interviews with patients with CF and CP with PEI (n = 61: UK 29, Germany 18, France 14) and expert physicians (n = 10). Cognitive debriefing of the draft instrument was then performed with patients with PEI (n = 37: UK 24, Germany 8, France 5), and feasibility was assessed with physicians (n = 3). For all interviews, verbatim transcripts were qualitatively analysed using thematic analysis methods and Atlas.ti computerized qualitative software. All themes were data driven rather than a priori. RESULTS: Patient interviews elicited symptoms and impacts not reported in the literature. Six symptom concepts emerged: pain, bloating, bowel symptoms, nausea/vomiting, eating problems, and tiredness/fatigue. Six impact domains were also identified. A 45-item instrument was developed in English, French, and German for testing in cognitive debriefing patient interviews. Following cognitive debriefing, 18 items were deleted. CONCLUSION: Rigorous qualitative patient research and expert clinical input supported development of a PEI-specific PRO with the potential to aid management and monitoring of unmet needs among patients with PEI. The next step is to perform psychometric evaluation of the resulting instrument.

Development of a Consensus Statement for the Definition, Diagnosis, and Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis Using the Delphi Technique.

INTRODUCTION: There is a lack of agreed and established guidelines for the treatment of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This reflects, in part, the limited evidence-base underpinning the management of AE-IPF. In the absence of high-quality evidence, the aim of this research was to develop a clinician-led consensus statement for the definition, diagnosis and treatment of AE-IPF. METHODS: A literature review was conducted to obtain published material on the definition and treatment of AE-IPF. The results of this review were circulated to an online panel of clinicians for review. Statements were then shared with ten expert respiratory clinicians who regularly treat patients with IPF. A Delphi technique was then used to develop a consensus statement for the definition, diagnosis and treatment of AE-IPF. During the first round of review, clinicians rated the clarity of each statement, the extent to which the statement should be included and provided comments. In two subsequent rounds of review, clinicians were provided with the group median inclusion rating for each statement, and any revised wording of statements to aid clarity. Clinicians were asked to repeat the clarity and inclusion ratings for the revised statements. RESULTS: The literature review, online panel discussion, and face-to-face meeting generated 65 statements covering the definition, diagnosis, and management of AE-IPF. Following three rounds of blind review, 90% of clinicians agreed 39 final statements. These final statements included a definition of AE-IPF, approach to diagnosis, and treatment options, specifically: supportive measures, use of anti-microbials, immunosuppressants, anti-coagulants, anti-fibrotic therapy, escalation, transplant management, and long-term management including discharge planning. CONCLUSION: This clinician-led consensus statement establishes the 'best practice' for the management and treatment of AE-IPF based on current knowledge, evidence, and available treatments.

Methicillin resistance of staphylococci isolated from the skin of dogs with pyoderma.

OBJECTIVE: To determine the methicillin-resistant profile of staphylococcal isolates from the skin of dogs with pyoderma. ANIMALS: 90 dogs with pyoderma. PROCEDURE: Staphylococci isolated from dogs with pyoderma were tested for susceptibility to methicillin by use of a standard disk diffusion test with oxacillin disks. The DNA extracted from the isolates was tested for the mecA gene that encodes the penicillin-binding protein 2a (PBP2a) by use of a polymerase chain reaction (PCR) assay. The expression of PBP2a was determined with a commercial latex agglutination assay. Species of staphylococcal isolates were identified by use of morphologic, biochemical, and enzymatic tests. RESULTS: Most of the isolated staphylococci were methicillin-susceptible, coagulase-positive Staphylococcus intermedius isolates. Whereas only 2 of 57 S. intermedius isolates were resistant to methicillin, approximately half of the isolates had the mecA gene and produced PBP2a. Staphylococcus schleiferi was the second most common isolate. Widespread resistance to methicillin was found among S. schleiferi isolates. More coagulase-negative S. schleiferi isolates were identified with mecA gene-mediated resistance to methicillin, compared with coagulase-positive S. schleiferi isolates. CONCLUSIONS AND CLINICAL RELEVANCE: The latex agglutination assay for the detection of PBP2a expression coupled with the PCR assay for the mecA gene may provide new information about emerging antimicrobial resistance among staphylococcal isolates.

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs.

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.