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Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.
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Antígenos de Histocompatibilidad Clase I , Mycobacterium tuberculosis , Receptores de Antígenos de Linfocitos T , Linfocitos T , Mycobacterium tuberculosis/inmunología , Humanos , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Linfocitos T/inmunología , Antígenos HLA-E , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Tuberculosis/inmunologíaRESUMEN
IMPORTANCE: African swine fever virus (ASFV) causes a lethal disease of pigs with high economic impact in affected countries in Africa, Europe, and Asia. The virus encodes proteins that inhibit host antiviral defenses, including the type I interferon response. Host cells also activate cell death through a process called apoptosis to limit virus replication. We showed that the ASFV A179L protein, a BCL-2 family apoptosis inhibitor, is important in reducing apoptosis in infected cells since deletion of this gene increased cell death and reduced virus replication in cells infected with the A179L gene-deleted virus. Pigs immunized with the BeninΔA179L virus showed no clinical signs and a weak immune response but were not protected from infection with the deadly parental virus. The results show an important role for the A179L protein in virus replication in macrophages and virulence in pigs and suggest manipulation of apoptosis as a possible route to control infection.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Apoptosis , Eliminación de Gen , Macrófagos , Proteínas Proto-Oncogénicas c-bcl-2 , Porcinos , Proteínas Virales , Virulencia , Animales , Fiebre Porcina Africana/virología , Virus de la Fiebre Porcina Africana/genética , Macrófagos/virología , Proteínas Proto-Oncogénicas c-bcl-2/deficiencia , Proteínas Proto-Oncogénicas c-bcl-2/genética , Porcinos/virología , Virulencia/genética , Replicación Viral , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Virales/genéticaRESUMEN
OBJECTIVE: Given global shortages in the rheumatology workforce, the demand for rheumatology assessment often exceeds the capacity to provide timely access to care. Accurate triage of patient referrals is important to ensure appropriate utilization of finite resources. We assessed the feasibility of physiotherapist (PT)-led triage using a standardized protocol in identifying cases of inflammatory arthritis (IA), as compared to usual rheumatologist triage of referrals for joint pain, in a tertiary care rheumatology clinic. METHODS: We performed a single-center, prospective, nonblinded, randomized, parallel-group feasibility study with referrals randomized in a 1:1 ratio to either PT-led vs usual rheumatologist triage. Standardized information was collected at referral receipt, triage, and clinic visit. Rheumatologist diagnosis was considered the gold standard for diagnosis of IA. RESULTS: One hundred two referrals were randomized to the PT-led triage arm and 101 to the rheumatologist arm. In the PT-led arm, 65% of referrals triaged as urgent were confirmed to have IA vs 60% in the rheumatologist arm (P = 0.57), suggesting similar accuracy in identifying IA. More referrals were declined in the PT-led triage arm (24 vs 8, P = 0.002), resulting in fewer referrals triaged as semiurgent (6 vs 23, P = 0.003). One case of IA (rheumatologist arm) was incorrectly triaged, resulting in significant delay in time to first assessment. CONCLUSION: PT-led triage was feasible, appeared as reliable as rheumatologist triage of referrals for joint pain, and led to significantly fewer patients requiring in-clinic visits. This has implications for waitlist management and optimal rheumatology resource utilization.
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Estudios de Factibilidad , Fisioterapeutas , Derivación y Consulta , Reumatología , Triaje , Humanos , Triaje/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Reumatólogos , AncianoRESUMEN
OBJECTIVE: To explore the experiences and perspectives of patients and rheumatologists on decision aid-led tapering of advanced therapy in rheumatoid arthritis (RA). METHODS: Semi-structured interviews were completed with patients and rheumatologists, embedded within a pilot study of decision aid-led tapering (i.e. dose reduction) of biologic and targeted synthetic (b/ts) DMARDs in RA. All patients were in sustained (>= 6 months) remission and had chosen to reduce their therapy after a decision aid-led shared decision with their rheumatologist. The rheumatologists included those participating in the pilot (n=4), and those who were not. Reflexive thematic analysis of audiotaped and transcribed interviews identified themes in the group experiences. RESULTS: Patients (n=10; 6 female) unanimously found the decision aid easy to understand and felt confident in shared decision-making about treatment tapering and managing flares. Rheumatologists' (n=12; 5 female) perspectives on tapering b/ts DMARDs varied widely, from very supportive to completely opposed, and influenced their views on the decision aid. Rheumatologists expressed concerns about patient comprehension, destabilizing a stable situation, risks of flare, and extending appointment times. Despite their initial reservations about sending the decision aid to all eligible patients ahead of appointments, three of four participating rheumatologists adopted this approach during the pilot, which had the benefit of facilitating patient-led conversations. CONCLUSION: A decision aid-led strategy for tapering advanced therapy in RA was acceptable to patients and feasible in practice. Sending patients a decision aid ahead of their appointment facilitated patient-led conversations about tapering.
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OBJECTIVE: Patients may use emergency departments (EDs) to meet their health needs when ambulatory care systems are not sufficient. We aim to describe contributing factors to the decision made by persons with inflammatory arthritis (IA) to present to the ED, as well as their experiences of ED care and postdischarge follow-up. METHODS: An embedded mixed-methods approach was taken to contextualize quantitative data with associated free-text responses from an online survey distributed to residents of Alberta with a known IA condition and an ED visit. RESULTS: Eighty-two persons (63% aged 16-55 years, 48% female, 50% urban residents) with rheumatoid arthritis (48%), psoriatic arthritis (12%), spondyloarthritis (6%), or gout (34%) completed the survey. Presenting concerns were arthritis flare (37%), chest pain (15%), injury (12%), and infection (11%). Of all visits, 29% proceeded directly to the ED, 35% attempted accessing ambulatory care first, and 32% arrived for a return visit. In presentations for arthritis flare, patients were aware of the rheumatology service being contacted by the ED provider for advice in just 9% of events. Challenges in healthcare system coordination and system pressures resulted in patients requiring ED attendance to assess their concern. The quality of communication and relationality developed between patients with IA and healthcare providers informed experiences of ED care. CONCLUSION: Modifying rheumatology ambulatory care models could better meet patient needs and ultimately reduce avoidable ED use by patients with IA.
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We have updated the Canadian Rheumatology Association (CRA) guidelines for rheumatoid arthritis (RA) with 3 recommendations for the use of glucocorticoids (GCs). The recommendations address the use of short-term GCs for RA flares or as bridging therapy when disease-modifying antirheumatic drugs (DMARDs) are initiated or changed, and the use of long-term GCs as adjuncts to DMARDs.
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OBJECTIVE: Patient-initiated follow-up (PIFU) for rheumatoid arthritis (RA) is a model of care delivery wherein patients contact the clinic when needed instead of having regularly scheduled follow-up. Our objective was to investigate the influence of different patient eligibility characteristics on the number of potentially deferred visits to inform future implementation of a PIFU strategy. METHODS: We conducted a retrospective chart review of 7 rheumatologists' practices at 2 university-based clinics between March 1, 2021, and February 28, 2022. Data extracted included the type and frequency of visits, disease management, comorbidities, and care complexities. Stable disease was defined as remission or low disease activity with no medication changes at all visits. The influence of patient characteristics on the number of deferrable visits in patients with stable disease was explored in 4 criteria sets that were based on early disease duration, medication prescribed, presence of care complexity elements, and comorbidity burden. RESULTS: Records from 770 visits were reviewed from 365 patients with RA (71.5% female, 70% seropositive). Among all criteria sets, the proportion of visits that could be redirected varied between 2.5% and 20.9%. The highest proportion of deferrable visits was achieved when eligibility criteria included only stable disease activity and patients with RA on conventional synthetic disease-modifying antirheumatic drugs or no medications (n = 161, 20.9%). CONCLUSION: PIFU may result in a more efficient use of specialist healthcare resources. However, the applicability of such models of care and the number of deferred visits is highly dependent on patient characteristics used to establish eligibility criteria for that model. These findings should be considered when planning implementation trials.
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Artritis Reumatoide , Reumatólogos , Humanos , Femenino , Masculino , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/terapia , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Antirreumáticos/uso terapéutico , Visita a Consultorio Médico/estadística & datos numéricos , Estudios de Seguimiento , Reumatología , Manejo de la Enfermedad , Determinación de la ElegibilidadRESUMEN
OBJECTIVE: To conduct an environmental scan and appraisal of online patient resources to support rheumatoid arthritis (RA) flare self-management. METHODS: We used the Google search engine (last search March 2023) using the terms "rheumatoid arthritis" and "flare management." Additional searches targeted major arthritis organizations, as well as regional, national, and international resources. Appraisal of the resources was conducted by 2 research team members and 1 patient partner to assess the understandability and actionability of the resource using the Patient Education Materials Assessment Tool (PEMAT). Resources rating ≥ 60% in both domains by either the research team or the patient partner were further considered for content review. During content review, resources were excluded if they contained product advertisements, inaccurate information, or use of noninclusive language. If content review criteria were met, resources were designated as "highly recommended" if both patient partners and researchers' PEMAT ratings were ≥ 60%. If PEMAT ratings were divergent and had a rating ≥ 60% from only 1 group of reviewers, the resource was designated "acceptable." RESULTS: We identified 44 resources; 12 were excluded as they did not pass the PEMAT assessment. Fourteen resources received ratings ≥ 60% on understandability and actionability from both researchers and patient partners; 10 of these were retained following content review as "highly recommended" flare resources. Of the 18 divergent PEMAT ratings, 8 resources were retained as "acceptable" following content review. CONCLUSION: There is high variability in the actionability and understandability of online RA flare materials; only 23% of resources were highly recommended by researchers and patient partners.
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Artritis Reumatoide , Educación del Paciente como Asunto , Brote de los Síntomas , Artritis Reumatoide/terapia , Humanos , Educación del Paciente como Asunto/métodos , Internet , Automanejo/métodosRESUMEN
BACKGROUND: Care complexity can occur when patients experience health challenges simultaneously with social barriers including food and/or housing insecurity, lack of transportation or other factors that impact care and patient outcomes. People with rheumatoid arthritis (RA) may experience care complexity due to the chronicity of their condition and other biopsychosocial factors. There are few standardised instruments that measure care complexity and none that measure care complexity specifically in people with RA. OBJECTIVES: We assessed the content validity of the INTERMEDS Self-Assessment (IMSA) instrument that measures care complexity with a sample of adults with RA and rheumatology healthcare providers (HCPs). Cognitive debriefing interviews utilising a reparative framework were conducted. METHODS: Patient participants were recruited through two existing studies where participants agreed to be contacted about future studies. Study information was also shared through email blasts, posters and brochures at rheumatology clinic sites and trusted arthritis websites. Various rheumatology HCPs were recruited through email blasts, and divisional emails and announcements. Interviews were conducted with nine patients living with RA and five rheumatology HCPs. RESULTS: Three main reparative themes were identified: (1) Lack of item clarity and standardisation including problems with item phrasing, inconsistency of the items and/or answer sets and noninclusive language; (2) item barrelling, where items asked about more than one issue, but only allowed a single answer choice; and (3) timeframes presented in the item or answer choices were either too long or too short, and did not fit the lived experiences of patients. Items predicting future healthcare needs were difficult to answer due to the episodic and fluctuating nature of RA. CONCLUSIONS: Despite international use of the IMSA to measure care complexity, patients with RA and rheumatology HCPs in our setting perceived that it did not have content validity for use in RA and that revision for use in this population under a reparative framework was unfeasible. Future instrument development requires an iterative cognitive debriefing and repair process with the population of interest in the early stages to ensure content validity and comprehension. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contributions included both patient partners on the study team and people with RA who participated in the study. Patient partners were involved in study design, analysis and interpretation of the findings and manuscript preparation. Data analysis was structured according to emergent themes of the data that were grounded in patient perspectives and experiences.
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Artritis Reumatoide , Reumatología , Adulto , Humanos , Autoevaluación (Psicología) , Personal de Salud , Artritis Reumatoide/psicologíaRESUMEN
Some emergency department (ED) visits by persons with rheumatoid arthritis (RA) may be avoidable. This study aims to describe ED use by persons with RA in Alberta, Canada over a 10-year period. Using linked population-based administrative datasets, the annual frequency of ED visits, timing of visits, acuity at presentation assessed (Canadian Triage Acuity Scale (CTAS)), return visits within 72 h, and final disposition were assessed. Most responsible diagnoses assessed by the ED provider were categorized. Between 2008 and 2017, a total of 48,633 persons with RA had 416,964 unique ED visits. There was a 41% relative increase in visits over the study period and within a fiscal year 37% of persons with RA on average attended an ED. Half of the visits were assessed as CTAS 4 'Less Urgent' (31%) and CTAS 5 'Non-Urgent' (19%). No specific diagnosis could be assigned in 36% of visits and RA was listed as the most responsible diagnosis in 2.5% of all visits. Hospital admissions, occurring on average for 14% of ED visits, increased by 15% over the 10 years, and were rare for CTAS 4 (6.4%) and CTAS 5 (1.4%) presentations. Male patients (difference to female 1.2%, 95%CI 0.6, 1.7) and urban patients (difference to rural 8.4%, 95%CI 7.7, 9.2) were more frequently admitted to hospital. Persons with RA have increased ED utilization over time, with a significant volume of less urgent and non-urgent visits. Opportunities for appropriate ambulatory care provision to reduce acute care use should be identified.
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Artritis Reumatoide , Servicio de Urgencia en Hospital , Humanos , Artritis Reumatoide/epidemiología , Artritis Reumatoide/terapia , Artritis Reumatoide/diagnóstico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Alberta/epidemiología , Anciano , Adulto , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios de CohortesRESUMEN
BACKGROUND: The Dixon-Woods et al. Candidacy Framework, a valuable tool since its 2006 introduction, has been widely utilized to analyze access to various services in diverse contexts, including healthcare. This social constructionist approach examines micro, meso, and macro influences on access, offering concrete explanations for access challenges rooted in socially patterned influences. This study employed the Candidacy Framework to explore the experiences of individuals living with rheumatoid arthritis (RA) and their formal care providers. The investigation extended to assessing supports and innovations in RA diagnosis and management, particularly in primary care. METHODS: This systematic review is a Critical Interpretive Synthesis (CIS) of qualitative and mixed methods literature. The CIS aimed to generate theory from identified constructs across the reviewed literature. The study found alignment between the seven dimensions of the Candidacy Framework and key themes emerging from the data. Notably absent from the framework was an eighth dimension, identified as the "embodied relational self." This dimension, central to the model, prompted the proposal of a revised framework specific to healthcare for chronic conditions. RESULTS: The CIS revealed that the eight dimensions, including the embodied relational self, provided a comprehensive understanding of the experiences and perspectives of individuals with RA and their care providers. The proposed Candidacy 2.0 (Chronic Condition (CC)) model demonstrated how integrating approaches like Intersectionality, concordance, and recursivity enhanced the framework when the embodied self was central. CONCLUSIONS: The study concludes that while the original Candidacy Framework serves as a robust foundation, a revised version, Candidacy 2.0 (CC), is warranted for chronic conditions. The addition of the embodied relational self dimension enriches the model, accommodating the complexities of accessing healthcare for chronic conditions. TRIAL REGISTRATION: This study did not involve a health care intervention on human participants, and as such, trial registration is not applicable. However, our review is registered with the Open Science Framework at https://doi.org/10.17605/OSF.IO/ASX5C .
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Artritis Reumatoide , Accesibilidad a los Servicios de Salud , Humanos , Artritis Reumatoide/terapia , Artritis Reumatoide/psicología , Enfermedad Crónica/terapia , Enfermedad Crónica/psicología , Investigación Cualitativa , Atención Primaria de SaludRESUMEN
The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.
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Aminoácidos , Antígenos HLA , Antígenos de Histocompatibilidad Clase I , Péptidos , Receptores de Antígenos de Linfocitos T , Antígenos HLA-ERESUMEN
OBJECTIVES: To understand the perspectives of patients and rheumatologists for tapering DMARDs in RA. METHODS: Using semi-structured interview guides, we conducted individual interviews and focus groups with RA patients and rheumatologists, which were audiotaped and transcribed. We conducted a pragmatic thematic analysis to identify major themes, comparing and contrasting different views on DMARD tapering between patients and rheumatologists. RESULTS: We recruited 28 adult patients with RA (64% women; disease duration 1-54 y) and 23 rheumatologists (52% women). Attitudes across both groups towards tapering DMARDs were ambivalent, ranging from wary to enthusiastic. Both groups expressed concerns, particularly the inability to 'recapture' the same level of disease control, while also acknowledging potential positive outcomes such as reduced drug harms. Patient tapering perspectives (whether to and when) changed over time and commonly included non-biologic DMARDs. Patient preferences were influenced by lived experiences, side effects, previous tapering experiences, disease trajectory, remission duration and current life roles. Rheumatologists' perspectives varied on timing and patient profile to initiate tapering, and were informed by both data and clinical experience. Patients expressed interest in shared decision-making (SDM) and close monitoring during tapering, with ready access to their health-care team if problems arose. Rheumatologists were generally open to tapering (not stopping), though sometimes only when requested by their patients. CONCLUSION: The perspectives of patients and rheumatologists on tapering DMARDs in RA vary and evolve over time. Rheumatologists should periodically discuss DMARD tapering with patients as part of SDM, and ensure monitoring and flare management plans are in place.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Reducción Gradual de Medicamentos/métodos , Conocimientos, Actitudes y Práctica en Salud , Pautas de la Práctica en Medicina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , ReumatólogosRESUMEN
BACKGROUND AND AIMS: Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBV-specific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinity-enhanced T Cell receptor with an anti-CD3 T Cell-activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus-derived peptides presented by human leukocyte antigen (HLA). APPROACH AND RESULTS: ImmTAV molecules specific for HLA-A*02:01-restricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAV-Env to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imaging-based killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAV-Env can redirect T cells from healthy and HBV-infected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAV-Env redirection of T cells induced cytolysis of antigen-positive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA. CONCLUSIONS: The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous non-HBV-specific T cells, bypassing exhausted HBV-specific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials.
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Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Receptores de Antígenos de Linfocitos T/uso terapéutico , Proteínas Recombinantes de Fusión/farmacología , Linfocitos T/efectos de los fármacos , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Complejo CD3/antagonistas & inhibidores , Línea Celular Tumoral , Epítopos/inmunología , Antígeno HLA-A2/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Hepatocitos , Humanos , Inmunoconjugados/genética , Inmunoconjugados/inmunología , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Activación de Linfocitos/efectos de los fármacos , Cultivo Primario de Células , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: Patients with rheumatic diseases often have multiple comorbidities which may impact well-being leading to high psychosocial complexity. This scoping review was undertaken to identify complexity measures/tools used in rheumatology that could help in planning and coordinating care. METHODS: MEDLINE, EMBASE and CINAHL were searched from database inception to 14 December 2019 using keywords and Medical Subject Headings for "care coordination", "complexity" and selected rheumatic diseases and known complexity measures/tools. Articles describing the development or use of complexity measures/tools in patients with adult rheumatologic diagnoses were included regardless of study design. Included articles were evaluated for risk of bias where applicable. RESULTS: The search yielded 407 articles, 37 underwent full-text review and 2 were identified during a hand search with 9 included articles. Only 2 complexity tools used in populations of adult patients with rheumatic disease were identified: the SLENQ and the INTERMED. The SLENQ is a 97-item patient needs questionnaire developed for patients with systemic lupus (n = 1 study describing tool development) and applied in 5 cross-sectional studies. Three studies (a practice article, trial and a cross-sectional study) applied the INTERMED, a clinical interview to ascertain complexity and support coordinated care, in patients with rheumatologic diagnoses. CONCLUSIONS: There is limited information on the use of patient complexity measures/tools in rheumatology. Such tools could be applied to coordinate multidisciplinary care and improve patient experience and outcomes. PATIENT CONTRIBUTION: This scoping review will be presented to patient research partners involved in co-designing a future study on patient complexity in rheumatic disease.
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Enfermedades Reumáticas , Adulto , Comorbilidad , Estudios Transversales , Humanos , Proyectos de Investigación , Enfermedades Reumáticas/terapiaRESUMEN
There are now multiple targeted and immunotherapies available for the treatment of metastatic melanoma. Although these agents have dramatically improved the survival of patients, the appropriate sequencing and the safety during the transition between these drugs remains unknown. Recently two cases of cytokine release syndrome (CRS) following transition from immune-checkpoint inhibitors to BRAF and MEK inhibitors (BRAFi/MEKi) in patients with metastatic melanoma have been reported. CRS is a systemic cytokine-driven inflammatory reaction, previously well reported in chimeric antigen receptor T-cell therapies for hematologic malignancies. Here, we report a third case in which severe CRS resistant to glucocorticoid therapy following transition to a MEKi/BRAFi was treated successfully with tocilizumab, an interleukin-6 (IL-6) inhibitor. CRS should be on the differential diagnosis of immune-related adverse events of immunotherapies or targeted cancer therapies for metastatic melanoma, and clinicians in multiple disciplines should be aware of this rare complication and the potential benefits of IL-6 blockade.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Síndrome de Liberación de Citoquinas , Humanos , Interleucina-6 , Melanoma/tratamiento farmacológico , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
OBJECTIVES: To develop a web-based tool (Rheum4U) to capture clinically meaningful data to direct treatment. Rheum4U integrates longitudinal clinical data capture of rheumatoid arthritis (RA) disease activity measures and patient-reported outcomes measures (PROMs). This study tests the feasibility, acceptability and efficiency of Rheum4U among patients and healthcare providers. METHODS: Rheum4U was developed in two phases: P1 design and development; and P2 pilot testing. P1: A working group of rheumatologists and researchers (n=13) performed a prioritisation exercise to determine data elements to be included in the platform. The specifications were finalised and supplied to the platform developer. Alpha testing was performed to correct initial software bugs. 18 testers (physicians, nurses and recruited non-patient lay-testers) beta tested Rheum4U for usability. P2: Rheum4U was piloted in 2 rheumatology clinics and evaluated for feasibility, efficiency and acceptability using interviews, observation and questionnaires with patients and healthcare providers. RESULTS: 110 RA patients, 9 rheumatologists and 9 allied health providers participated in the pilot. Mean patient age was 53 years and 74% were female. The majority (86%) were satisfied or very satisfied with online data entry and 79% preferred it to paper entry. Healthcare providers found Rheum4U easy and clear to use (90%), and they perceived that it improved their job performance (91%). Completeness and easy availability of the patient information improved clinic efficiency. CONCLUSIONS: Rheum4U highlights the benefits of a web-based tool for clinical care, quality improvement and research in the clinic and this study provides valuable information to inform full platform implementation.
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Artritis Reumatoide , Atención a la Salud/métodos , Internet , Medición de Resultados Informados por el Paciente , Artritis Reumatoide/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de la Atención de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: The published literature demands examples of health-care systems designed with the active engagement of patients to explore the application of this complex phenomenon in practice. METHODS: This case study explored how the voice of patients was incorporated into the process of redesigning an element of the health-care system, a centralized system for intake of referrals from primary care to rheumatologists for patients with suspected rheumatoid arthritis (RA)-centralized intake. The phenomenon of patient engagement using "patient and community engagement researchers" (PaCERs) in research and the process of redesigning centralized intake were selected as the case. In-depth evaluation of the case was undertaken through the triangulation of findings from the document review and participants' reflection on the case. RESULTS: In this case, patients and PaCERs participated in multiple activities including an initial meeting of key stakeholders to develop the project vision; a patient-to-patient PaCERs study to gather perspectives of patients with RA on the challenges they face in accessing and navigating the health-care system, and what they see as key elements of an effective system that would be responsive to their needs; the development of an evaluation framework for future centralized intake; and the choice of candidate centralized intake strategies to be evaluated. CONCLUSIONS: The described feasible multistep approach to active patient engagement in health-care system redesign contributes to an understanding of the application of this complex phenomenon in practice. Therefore, the manuscript serves as one more step towards a patient-centred health-care system that is redesigned with active patient engagement.
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Artritis Reumatoide/terapia , Participación del Paciente , Derivación y Consulta/organización & administración , Adulto , Colombia Británica , Femenino , Grupos Focales , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos Organizacionales , Atención Primaria de Salud , Garantía de la Calidad de Atención de Salud , Reumatología , Participación de los InteresadosRESUMEN
BACKGROUND: To describe the process of patient engagement to co-design a patient experience survey for people with arthritis referred to central intake. METHODS: We used a participatory design to engage with patients to co-design a patient experience survey that comprised three connected phases: 1) Identifying the needs of patients with arthritis, 2) Developing a set of key performance indicators, and 3) Determining the survey items for the patient experience survey. RESULTS: Patient recommendations for high quality healthcare care means support to manage arthritis, to live a meaningful life by providing the right knowledge, professional support, and professional relationship. The concept of integrated care was a core requirement from the patients' perspective for the delivery of high quality arthritis care. Patients experience with care was ranked in the top 10 of 28 Key Performance Indicators for the evaluation of central intake, with 95% of stakeholders rating it as 9/10 for importance. A stakeholder team, including Patient and Community Engagement Researchers (PaCER), mapped and rated 41 survey items from four validated surveys. The final patient experience survey had 23 items. CONCLUSION: The process of patient engagement to co-design a patient experience survey, for people with arthritis, identified aspects of care that had not been previously recognized. The linear organization of frameworks used to report patient engagement in research does not always capture the complexity of reality. Additional resources of cost, time and expertise for patient engagement in co-design activity are recognized and should be included, where possible, to ensure high quality data is captured.
Asunto(s)
Artritis/terapia , Investigación sobre Servicios de Salud , Participación del Paciente/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Calidad de la Atención de Salud/normas , Humanos , Proyectos de InvestigaciónRESUMEN
BACKGROUND: The study evaluates Performance Measures (PMs) for Juvenile Idiopathic Arthritis (JIA): The percentage of patients with new onset JIA with at least one visit to a pediatric rheumatologist in the first year of diagnosis (PM1); and the percentage of patients with JIA under rheumatology care seen in follow-up at least once per year (PM2). METHODS: Validated JIA case ascertainment algorithms were used to identify cases from provincial health administrative databases in Manitoba, Canada in patients < 16 years between 01/04/2005 and 31/03/2015. PM1: Using a 3-year washout period, the percentage of incident JIA patients with ≥1 visit to a pediatric rheumatologist in the first year was calculated. For each fiscal year, the proportion of patients expected to be seen in follow-up who had a visit were calculated (PM2). The proportion of patients with gaps in care of > 12 and > 14 months between consecutive visits were also calculated. RESULTS: One hundred ninety-four incident JIA cases were diagnosed between 01/04/2008 and 03/31/2015. The median age at diagnosis was 9.1 years and 71% were female. PM1: Across the years, 51-81% of JIA cases saw a pediatric rheumatologist within 1 year. PM2: Between 58 and 78% of patients were seen in yearly follow-up. Gaps > 12, and > 14, months were observed once during follow-up in 52, and 34%, of cases, and ≥ twice in 11, and 5%, respectively. CONCLUSIONS: Suboptimal access to pediatric rheumatologist care was observed which could lead to diagnostic and treatment delays and lack of consistent follow-up, potentially negatively impacting patient outcomes.