Management of refractory disease and persistent symptoms in inflammatory arthritis: qualitative framework analysis of interviews with patients and healthcare professionals.

Objectives: This study aims to explore patients' and clinicians' experiences in managing and living with refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with RA or polyarticular JIA from their perspectives through interviews and/or focus groups. Methods: A qualitative exploration with 25 patients and 32 multidisciplinary rheumatology healthcare professionals (HCPs) was conducted to obtain participants respective understanding and experiences of managing RD/PPES and its impact on the patient-professional relationship. A pragmatic epistemology approach with framework analysis was employed. Results: Four key themes were identified from both patients and professionals in the management of RD/PPES: risk/perpetuating factors/triggers; need for a patient-centred holistic approach to care, diagnosis and treatment; discordance and impact on the patient-practitioner relationship and current problems in managing RD/PPES. These themes covered 22 subthemes, with none being patient specific and seven being HCP specific. Suggestions for potential management strategies were highlighted throughout, such as involving other specialties or a multidisciplinary team, assessing/treating patient-reported outcome measures and psychosocial factors, patient (re)education, need for adjustments/aids or adaptations, checking the diagnosis and further investigations/imaging and optimizing medications. Conclusion: Management strategies need to be developed that enable appropriate treatment plans for those with RD/PPES that account for wider biopsychosocial factors beyond inflammation and reduce discordance in the patient-practitioner relationship.

Refractory inflammatory arthritis definition and model generated through patient and multi-disciplinary professional modified Delphi process.

OBJECTIVE: Various definitions have been proposed for Refractory Disease in people with Rheumatoid Arthritis; however, none were generated for Polyarticular Juvenile Idiopathic Arthritis or involving adult and paediatric multidisciplinary healthcare professionals and patients. The study aim is to redefine Refractory Disease, using Delphi methodology. METHODS: Three rounds of surveys (one nominal group and two online (2019-2020)) to achieve consensus using a predetermined cut-off were conducted voting on: a) name, b) treatment and inflammation, c) symptoms and impact domains, and d) rating of individual components within domains. Theoretical application of the definition was conducted through a scoping exercise. RESULTS: Votes were collected across three rounds from Patients, Researchers and nine multi-disciplinary healthcare professional groups (n = 106). Refractory Inflammatory Arthritis was the most popular name. Regarding treatment and inflammation, these were voted to be kept broad rather than specifying numbers/cut-offs. From 10 domains identified to capture symptoms and disease impact, six domains reached consensus for inclusion: 1) Disease Activity, 2) Joint Involvement, 3) Pain, 4) Fatigue, 5) Functioning and Quality of Life, and 6) Disease-Modifying Anti-Rheumatic Drug Experiences. Within these domains, 18 components, from an initial pool (n = 73), were identified as related and important to capture multi-faceted presentation of Refractory Inflammatory Arthritis, specifically in Rheumatoid Arthritis and Polyarticular Juvenile Idiopathic Arthritis. Feasibility of the revised definition was established (2022-2023) with good utility as was applied to 82% of datasets (n = 61) incorporating 20 outcome measures, with two further measures added to increase its utility and coverage of Pain and Fatigue. CONCLUSION: Refractory Inflammatory Arthritis has been found to be broader than not achieving low disease activity, with wider biopsychosocial components and factors incorporating Persistent Inflammation or Symptoms identified as important. This definition needs further refinement to assess utility as a classification tool to identify patients with unmet needs.

Strategies for Success in Regulatory Readiness.

This article describes the formation of a Regulatory Advisory Council to address regulatory preparedness. The council used quality improvement methods to address data and findings from previous mock surveys and created 2 categories of work, an environment of care and clinical standards group, with checklists and work streams to improve organizational success with regulatory readiness.

Efficacy of brief personcentered cognitive behavioral therapy to facilitate self-management for patients with Rheumatoid Arthritis: A mixed methods case series feasibility study / Eficacia de la terapia cognitivo conductual breve centrada en la persona para facilitar la autogestión de pacientes con artritis reumatoide: un estudio de la viabilidad de métodos mixtos para una serie de casos

The psychological consequences of living with rheumatoid arthritis (RA) are common. The objectives of this study were: (I) to investigate views of patients with RA about the provision of psychological support; (II) to study the efficacy of a person-centred cognitive behavioural therapy (CBT) self-management approach, including a health economic investigation. A mixed methods was applied: a formative qualitative interview study and a quantitative CBT intervention formed the case series feasibility study design, and a health economic investigation. The qualitative study highlighted that patients welcome emotional support. The CBT intervention from a small sample suggested that participants may have benefitted from the intervention until to the point of the follow-up. The results of the economic component need to be interpreted with caution in relation to service gaps. A broad approach in the delivery of a psychological intervention may benefit patients with long-term conditions. The practice implications are that RA patients may benefit from psychological interventions to cope better with their condition through personal intervention, and flexible appointment system. Intervention studies need to test this question in detail in the future

Las consecuencias psicológicas de vivir con artritis reumatoide (AR) son frecuentes. Los objetivos de este estudio fueron: (I) investigar las opiniones de los pacientes con AR acerca de la provisión de apoyo psicológico, (II) estudiar la eficacia de un enfoque de autogestión basado en la terapia cognitivo conductual (TCC) centrada en la persona, incluyendo una investigación económica de la salud. Se utilizaron métodos mixtos. Un estudio formativo de entrevista cualitativa y una intervención cuantitativa de TCC formaron el diseño del estudio de viabilidad de la serie de casos y una investigación económica de la salud. El estudio cualitativo destacó que los pacientes agradecen el apoyo emocional. La intervención de TCC con una pequeña muestra sugirió que los participantes podrían haberse beneficiado de la intervención hasta el seguimiento. Los resultados del componente económico deben interpretarse con precaución respecto a las carencias de los servicios. Un enfoque amplio en la prestación de una intervención psicológica puede beneficiar a los pacientes con dolencias a largo plazo. Las implicaciones prácticas son que los pacientes con AR pueden beneficiarse de intervenciones psicológicas para afrontar de mejor manera su enfermedad a través de una intervención personal y un sistema flexible de citas. Los estudios de intervención necesitan comprobar con detalle esta cuestión en el futuro

Patient involvement in rheumatology outpatient service design and delivery: a case study.

BACKGROUND: Patient involvement is increasingly recognized as important within the UK National Health Service to ensure that services delivered are relevant to users' needs. Organizations are encouraged to work with service users to achieve excellence in care. Patient education can improve health outcomes and reduce health-care costs. Mobile technologies could play a vital role in this. AIM: Patient-centred development of innovative strategies to improve the experience of rheumatology outpatients. CASE STUDY: The Group Rheumatology Initiative Involving Patients (GRIIP) project was set up in 2013 as a joint venture between patients, clinicians, academics and management at a London hospital. The project saw (i) the formation of an independent patient group which provided suggestions for service improvement - outcomes included clearer signs in the outpatient waiting area, extended phlebotomy opening hours and better access to podiatry; (ii) a rolling patient educational evening programme initiated in 2014 with topics chosen by patient experts - feedback has been positive and attendance continues to grow; and (iii) a mobile application (app) co-designed with patients launched in 2015 which provides relevant information for outpatient clinic attendees and data capture for clinicians - downloads have steadily increased as users adopt this new technology. CONCLUSION: Patients can effectively contribute to service improvement provided they are supported, respected as equals, and the organization is willing to undergo a cultural change.

Sleep and neurocognitive functioning in children with eczema.

Sleep disruption in childhood is associated with clearly defined deficits in neurocognition and behaviour. Childhood eczema is also a potent cause of sleep disruption though it is unknown whether it too results in neurocognitive deficits. To test this hypothesis, neurocognitive (WISC-IV), parental-reported sleep quality (Sleep Disturbance Scale of Children (SDSC)) and overnight polysomnographic (PSG) data were collected in 21 children with eczema and 20 healthy controls (age range 6-16 years). Children with eczema had worse sleep quality on both PSG (notably increased nocturnal wakefulness, a higher number of stage shifts and a longer latency to REM onset) and parental report. In addition, they demonstrated significant neurocognitive deficits (especially verbal comprehension, perceptual reasoning and to a lesser extent working memory) with a composite Full Scale IQ 16 points lower than controls. Parental reported sleep problems but not PSG parameters were correlated with reduced neurocognitive performance. However, hierarchical regression analyses revealed that eczema status was predictive while sleep fragmentation (parental or PSG) was not predictive of neurocognitive performance. As this is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition. The unanswered question is whether these cognitive deficits normalise with effective eczema treatment and if this is mediated by improvements in sleep architecture.

Incudomalleal joint formation: the roles of apoptosis, migration and downregulation.

BACKGROUND: The middle ear of mammals is composed of three endochondrial ossicles, the stapes, incus and malleus. Joints link the malleus to the incus and the incus to the stapes. In the mouse the first arch derived malleus and incus are formed from a single Sox9 and Type II collagen expressing condensation that later subdivides to give rise to two separate ossicles. In contrast the stapes forms from a separate condensation derived from the second branchial arch. Fusion of the malleus and incus is observed in a number of human syndromes and results in conductive hearing loss. Understanding how this joint forms during normal development is thus an important step in furthering our understanding of such defects. RESULTS: We show that the developing incudomalleal joint is characterised by a lack of proliferation and discrete areas of apoptosis. Apoptosis has been suggested to aid in the removal of pre-cartilaginous cells from the joint region, allowing for the physical separation of the cartilaginous elements, however, we show that joint initiation is unaffected by blocking apoptosis. There is also no evidence of cell migration out of the presumptive joint region, as observed by labelling of joint and ossicle cells in culture. Using Type II collagen lacZ reporter mice, however, it is evident that cells in the presumptive joint region remain in place and downregulate cartilage markers. CONCLUSION: The malleus and incus first appear as a single united condensation expressing early cartilage markers. The incudomalleal joint region forms by cells in the presumptive joint region switching off cartilage markers and turning on joint markers. Failure in this process may result in fusion of this joint, as observed in human syndromes such as Branchio-Oto-Renal Syndrome or Treacher Collins Syndrome.

21st century neontology and the comparative development of the vertebrate skull.

Classic neontology (comparative embryology and anatomy), through the application of the concept of homology, has demonstrated that the development of the gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the gnathostome bauplan and the exquisite elaboration of final structural design. Just as homology is an old concept amended for modern purposes, so are many of the questions regarding the development of the skull. With due deference to Geoffroy-St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How are bauplan fidelity and elaboration of design maintained, coordinated, and modified to generate the amazing diversity seen in cranial morphologies? What establishes and maintains pattern in the skull? Are there universal developmental mechanisms underlying gnathostome autapomorphic structural traits? Can we detect and identify the etiologies of heterotopic (change in the topology of a developmental event), heterochronic (change in the timing of a developmental event), and heterofacient (change in the active capacetence, or the elaboration of capacity, of a developmental event) changes in craniofacial development within and between taxa? To address whether jaws are all made in a like manner (and if not, then how not), one needs a starting point for the sake of comparison. To this end, we present here a "hinge and caps" model that places the articulation, and subsequently the polarity and modularity, of the upper and lower jaws in the context of cranial neural crest competence to respond to positionally located epithelial signals. This model expands on an evolving model of polarity within the mandibular arch and seeks to explain a developmental patterning system that apparently keeps gnathostome jaws in functional registration yet tractable to potential changes in functional demands over time. It relies upon a system for the establishment of positional information where pattern and placement of the "hinge" is driven by factors common to the junction of the maxillary and mandibular branches of the first arch and of the "caps" by the signals emanating from the distal-most first arch midline and the lamboidal junction (where the maxillary branch meets the frontonasal processes). In this particular model, the functional registration of jaws is achieved by the integration of "hinge" and "caps" signaling, with the "caps" sharing at some critical level a developmental history that potentiates their own coordination. We examine the evidential foundation for this model in mice, examine the robustness with which it can be applied to other taxa, and examine potential proximate sources of the signaling centers. Lastly, as developmental biologists have long held that the anterior-most mesendoderm (anterior archenteron roof or prechordal plate) is in some way integral to the normal formation of the head, including the cranial skeletal midlines, we review evidence that the seminal patterning influences on the early anterior ectoderm extend well beyond the neural plate and are just as important to establishing pattern within the cephalic ectoderm, in particular for the "caps" that will yield medial signaling centers known to coordinate jaw development.

Reassessing the Dlx code: the genetic regulation of branchial arch skeletal pattern and development.

The branchial arches are meristic vertebrate structures, being metameric both between each other within the rostrocaudal series along the ventrocephalic surface of the embryonic head and within each individual arch: thus, just as each branchial arch must acquire a unique identity along the rostrocaudal axis, each structure within the proximodistal axis of an arch must also acquire a unique identity. It is believed that regional specification of metameric structures is controlled by the nested expression of related genes resulting in a regional code, a principal that is though to be demonstrated by the regulation of rostrocaudal axis development in animals exerted by the nested HOM-C/Hox homeobox genes. The nested expression pattern of the Dlx genes within the murine branchial arch ectomesenchyme has more recently led to the proposal of a Dlx code for the regional specification along the proximodistal axis of the branchial arches (i.e. it establishes intra-arch identity). This review re-examines this hypothesis, and presents new work on an allelic series of Dlx loss-of-function mouse mutants that includes various combinations of Dlx1, Dlx2, Dlx3, Dlx5 and Dlx6. Although we confirm fundamental aspects of the hypothesis, we further report a number of novel findings. First, contrary to initial reports, Dlx1, Dlx2 and Dlx1/2 heterozygotes exhibit alterations of branchial arch structures and Dlx2-/- and Dlx1/2-/- mutants have slight alterations of structures derived from the distal portions of their branchial arches. Second, we present evidence for a role for murine Dlx3 in the development of the branchial arches. Third, analysis of compound Dlx mutants reveals four grades of mandibular arch transformations and that the genetic interactions of cis first-order (e.g. Dlx5 and Dlx6), trans second-order (e.g. Dlx5 and Dlx2) and trans third-order paralogues (e.g. Dlx5 and Dlx1) result in significant and distinct morphological differences in mandibular arch development. We conclude by integrating functions of the Dlx genes within the context of a hypothesized general mechanism for the establishment of pattern and polarity in the first branchial arch of gnathostomes that includes regionally secreted growth factors such as Fgf8 and Bmp and other transcription factors such as Msx1, and is consistent both with the structure of the conserved gnathostome jaw bauplan and the elaboration of this bauplan to meet organismal end-point designs.