Patient Experience of Living With Hemophilia A: A Conceptual Model of Humanistic and Symptomatic Experience in Adolescents, Adults, and Children.

People living with hemophilia A face challenges impacting their daily lives despite treatment innovations. Previous studies have explored perceptions and treatment experiences; however, there is a lack of an evidence-based, comprehensive model to identify concepts (clinical, physical, and psychological functioning) relevant for people with hemophilia A (PwHA). The aim of this qualitative study was to address the question: What is the humanistic and symptomatic experience of adolescents, adults, and children living with hemophilia A and what is the impact of hemophilia A on their quality of life? Participants, identified through patient associations in the UK, were male PwHA and caregivers of male PwHA receiving prophylactic treatment.

Highly variable hearing loss due to POU4F3 (c.37del) is revealed by longitudinal, frequency specific analyses.

Genotype-phenotype correlations add value to the management of families with hereditary hearing loss (HL), where age-related typical audiograms (ARTAs) are generated from cross-sectional regression equations and used to predict the audiogram phenotype across the lifespan. A seven-generation kindred with autosomal dominant sensorineural HL (ADSNHL) was recruited and a novel pathogenic variant in POU4F3 (c.37del) was identified by combining linkage analysis with whole exome sequencing (WES).

Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.

Development and Preliminary Validation of an Instrument to Measure Symptoms and Impacts in Patients with Proliferative Diabetic Retinopathy.

Introduction: Following a review of patient-reported outcome (PRO) instruments in the literature, existing PRO instruments may not adequately capture the experience of receiving treatment for proliferative diabetic retinopathy (PDR). Therefore, this study aimed to develop a de novo instrument to comprehensively assess the patient experience of PDR.

Methods: This qualitative, mixed-methods study comprised item generation for the Diabetic Retinopathy-Patient Experience Questionnaire (DR-PEQ), content validation in patients with PDR, and preliminary Rasch measurement theory (RMT) analyses.

Development of a Conceptual Model of the Patient Experience in Small Cell Lung Cancer: A Qualitative Interview Study.

Introduction: Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves.

Methods: This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit.

The Patient Experience with Diabetic Retinopathy: Qualitative Analysis of Patients with Proliferative Diabetic Retinopathy.

Introduction: Few qualitative studies have explored the patient experience of daily life with proliferative diabetic retinopathy (PDR) and associated treatments. Herein, a conceptual model was developed to comprehensively examine symptoms, functional impacts, and treatment experiences in PDR.

Methods: A qualitative, mixed-methods study comprising a literature search and semi-structured interviews with clinicians and patients was conducted.

Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention.

Patient experience of symptoms and impacts of COVID-19: a qualitative investigation with symptomatic outpatients.

Objectives: There is little in-depth qualitative evidence of how symptoms manifest themselves in outpatients with COVID-19 and how these in turn impact outpatients' daily lives. The objective of the study was therefore to explore the experience of outpatients with COVID-19 qualitatively, concerning the symptomatic experience and its subsequent impact on daily life.

Setting: Qualitative research study comprising virtual in-depth, open-ended interviews with outpatients and clinicians.

"I Can't Take off My Shirt or Do My Own Hair"-A Qualitative Investigation of the Symptoms and Impact Experience of Children and Adolescents with Fibrodysplasia Ossificans Progressiva (FOP).

Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents' perspectives.

Measuring the Patient Experience in Rare Disorders: Benefit of Pragmatic Mixed-Methods Research in NUT Carcinoma.

Introduction: Patient-centered outcome measurement (PCOM) is essential to capture the outcomes important to patients. However, it presents unique challenges in rare diseases, particularly those that are "young" (not diagnosed before the twenty-first century), with limited literature, lack of disease-specific patient-reported outcome (PRO) measures, and difficult sampling and data collection. One example of this is NUT (nuclear protein in testis) carcinoma (NUTca), a rare and rapidly progressing cancer, with tumors preliminary in the head, neck, and lungs.

Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene.

Sequencing exomes/genomes have been successful for identifying recessive genes; however, discovery of dominant genes including deafness genes (DFNA) remains challenging. We report a new DFNA gene, ATP11A, in a Newfoundland family with a variable form of bilateral sensorineural hearing loss (SNHL). Genome-wide SNP genotyping linked SNHL to DFNA33 (LOD = 4.

Understanding the Patient Experience in NUT Carcinoma: Qualitative Interviews with Patients and Caregivers to Develop a Conceptual Framework.

Introduction: NUT (nuclear protein of the testis) carcinoma (NUTca) is a rare and aggressive cancer that is genetically hallmarked by a chromosomal abnormality in the NUT gene, and presents with tumors in the head, neck, and lungs. Currently there is no standard of care, but patients may undergo surgery, radiation, and/or chemotherapy. There is a lack of published research describing the patient experience of NUTca.

Measuring patient-reported physical functioning and fatigue in myelodysplastic syndromes using a modular approach based on EORTC QLQ-C30.

Purpose: Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library.

Methods: The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%).

Psychometric Analysis from EMBODY1 and 2 Clinical Trials to Help Select Suitable Fatigue PRO Scales for Future Systemic Lupus Erythematosus Studies.

Introduction: Fatigue is one of the most important symptoms reported by patients with systemic lupus erythematosus (SLE) and a key concept of interest in SLE clinical trials. Despite this, fatigue remains poorly understood and sub-optimally measured by existing patient-reported outcome (PRO) instruments and scales. Here, we psychometrically evaluated the measurement properties of three PRO scales that purport to measure fatigue, using data from two SLE clinical trials.

First Documentation of Persistent SARS-Cov-2 Infection Presenting With Late Acute Severe Myocarditis.

A 64-year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.

Asymmetric sampling in human auditory cortex reveals spectral processing hierarchy.

Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC).

Rhythmic Training Improves Temporal Anticipation and Adaptation Abilities in Children With Hearing Loss During Verbal Interaction.

Purpose In this study, we investigate temporal adaptation capacities of children with normal hearing and children with cochlear implants and/or hearing aids during verbal exchange. We also address the question of the efficiency of a rhythmic training on temporal adaptation during speech interaction in children with hearing loss. Method We recorded electroencephalogram data in children while they named pictures delivered on a screen, in alternation with a virtual partner.

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

Background: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.

Methods: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.

Expired Drugs in the Remote Environment.

Introduction: The British Antarctic Survey Medical Unit works in a very remote area of the world, with several Antarctic bases receiving only a single annual resupply of consumable goods. Pharmaceuticals supplied in this manner will often be approaching or past the end of their nominal shelf life before the following year's resupply. Drugs are transported from the UK via ship; the hold is not temperature controlled, and the ship crosses through the tropics (air temperature 25-30°C for approximately 3 wk).

Association of catastrophic condylar fracture with bony changes of the third metacarpal bone identified by use of standing magnetic resonance imaging in forelimbs from cadavers of Thoroughbred racehorses in the United States.

OBJECTIVE To compare bony changes of the third metacarpal bone (MC3) of Thoroughbred racehorse cadavers with (cases) or without (controls) catastrophic condylar fracture by use of standing MRI. SAMPLE 140 forelimbs from 26 case horses (both forelimbs) and 88 control horses (single forelimb). PROCEDURES Bone marrow lesions (BMLs), identified as a decrease in T1-weighted (T1W) signal and increases in T2*-weighted (T2*W) and short tau inversion recovery (STIR) signals, and dense bone volume percentage (DBVP), identified as decreases in T1W, T2*W, and STIR signals, in the distopalmar aspect of MC3 were recorded.

Development of a gait module to complement the 12-item Multiple Sclerosis Walking Scale: a mixed methods study.

Background And Objective: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population.