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Objective: This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models. Methods: The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4©), which was used to define adherence. Results: A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant associations, the adherence prediction models included type of treatment, age, race (RA and AS) or disease duration (PsA) and medication beliefs (RA and PsA, BMQ-General Harm score; AS, BMQ-Specific Concerns score). The models had cross-validated areas under the receiver operating characteristic curve of 0.637 (RA), 0.641 (PsA) and 0.724 (AS). Predicted probabilities of full adherence (MMAS-4©=4) ranged from 5% to 96%. Adherence was highest for tumour necrosis factor inhibitors versus other treatments, older patients and those with low treatment harm beliefs or concerns. Adherence was higher in white patients with RA and AS and in patients with PsA with duration of disease <9 years. Conclusions: For the first time, simple medication adherence prediction models for patients with RA, PsA and AS are available, which may help identify patients at high risk of non-adherence to systemic therapies. Trial registration number: ACTRN12612000977875.
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Artritis Psoriásica/epidemiología , Artritis Psoriásica/terapia , Artritis Reumatoide/epidemiología , Artritis Reumatoide/terapia , Cumplimiento de la Medicación/estadística & datos numéricos , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/terapia , Adulto , Anciano , Antirreumáticos/uso terapéutico , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Vigilancia en Salud Pública , Autoinforme , Encuestas y CuestionariosRESUMEN
The non-integrin 37/67-kDa laminin receptor (LAMR1) is a complex protein with diverse functions. LAMR1 is widely expressed in epithelial cells and recently it was reported on neutrophils and a subset of activated T cells. Ligation of LAMR1 on peripheral blood mononuclear cells (PBMC) downregulated LPS-induced TNFα production, suggesting immune functions. However, its expression on primary monocytes remain unknown. Interestingly, LAMR1 mRNA is downregulated in PBMC of patients with early rheumatoid arthritis (RA), and low gene expression is an independent predictor of poor response to anti-TNFα treatment, suggesting a role in RA pathogenesis. We found LAMR1 was constitutively expressed on all peripheral blood monocytes and a subset of B cells from healthy individuals and patients with RA and it was abundantly present in synovial tissue of patients with RA. On monocytes and synovial tissue lower levels of LAMR1 expression tended to correlate with increased disease activity scores. In vitro treatment of monocytes with IFNγ or IL-10 up-regulated surface LAMR1 in healthy individuals and patients with RA with greater effects observed in healthy individuals. Importantly, treatment with IFNγ significantly increased specific binding of monocytes to laminin-1. TNFα and IL-1ß caused marginal downregulation of LAMR1 in patients but effects in controls were variable. Taken together, constitutively expressed LAMR1 on monocytes is differentially regulated by pro-inflammatory and immune-regulatory cytokines suggesting LAMR1 may regulate the threshold and amplitude of their activation and migration. Decreased levels in patients with RA may indicate loss of this potentially critical homeostatic regulation thereby contributing to the excessive inflammation.
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Artritis Reumatoide/inmunología , Subgrupos de Linfocitos B/inmunología , Leucocitos Mononucleares/inmunología , Receptores de Laminina/sangre , Proteínas Ribosómicas/sangre , Líquido Sinovial/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Subgrupos de Linfocitos B/patología , Citocinas/inmunología , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, 'smartphone' application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT. METHODS AND ANALYSIS: Setting and designPrimary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial. PARTICIPANTS: GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster. INTERVENTION: The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary. PRIMARY AND SECONDARY OUTCOMES: The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed 'dropout' rate 20%. ETHICS AND DISSEMINATION: This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferences and peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12616000455460.
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Gota/terapia , Internet , Proyectos de Investigación , Automanejo/métodos , Alopurinol/uso terapéutico , Supresores de la Gota/uso terapéutico , Humanos , Cooperación del Paciente , Estudios Prospectivos , Calidad de Vida , Ácido Úrico/sangreRESUMEN
PURPOSE: The medical education community is rapidly accepting the use of entrustable professional activities (EPAs) as a means of assessing residents. Stakeholder engagement is advised in developing EPAs, but no studies have investigated the role of patient input. In this qualitative study, the authors investigated what patient input may add to designing a patient-centered EPA. METHOD: The authors chose "management of acute low back pain (LBP)" as a common, important clinical task on which to base the patient-centered EPA. In 2015, 14 patients who presented to a teaching hospital with acute LBP participated in semistructured interviews exploring their illness experience and expectations of doctors. Clinicians representing multiple disciplines participated in a focus group. The authors used the Framework Method to analyze data, identifying and developing themes, similarities, and differences between patient and clinician input. They used the findings to develop the EPA. Through an iterative procedure of data review and tracking data sources, they determined how patient and clinician input informed each EPA descriptor. RESULTS: Drawing from their firsthand experience of LBP, patients described unique expectations of trainees which directly informed EPA descriptors. For example, the authors primarily used patients' detailed descriptions of desirable and observable trainee behaviors to inform the required attitudes descriptor. CONCLUSIONS: Patients can provide unique contributions, complementary to those of clinicians, to EPAs. Consultations with patients led to the development of a patient-centered EPA, which aligned best clinical practice with patient expectations. Educators seeking to apply patient-centered care to EPA development could adopt a similar approach.
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Competencia Clínica/normas , Educación de Postgrado en Medicina/normas , Internado y Residencia/normas , Dolor de la Región Lumbar/terapia , Participación del Paciente , Atención Dirigida al Paciente/normas , Competencia Profesional/normas , Adulto , Evaluación Educacional/métodos , Femenino , Grupos Focales , Humanos , Masculino , Satisfacción del Paciente , Evaluación de Programas y Proyectos de Salud , Estudiantes de Medicina , Estados Unidos , Adulto JovenRESUMEN
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC-CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralis-infected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis of mMCP-5 from the MCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wild-type mice in two disease models.
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Artritis Experimental/patología , Quimasas/efectos adversos , Mastocitos/enzimología , Animales , Artritis Experimental/enzimología , Artritis Experimental/etiología , Carboxipeptidasas A/análisis , Carboxipeptidasas A/deficiencia , Carboxipeptidasas A/metabolismo , Quimasas/deficiencia , Quimasas/fisiología , Humanos , Mastocitos/metabolismo , Mastocitos/patología , Ratones , Ratones Endogámicos C57BL , Vesículas Secretoras/metabolismoRESUMEN
BACKGROUND: We hypothesised that vertebroplasty provides effective analgesia for patients with poorly controlled pain and osteoporotic spinal fractures of less than 6 weeks' duration. The effectiveness of vertebroplasty, using an adequate vertebral fill technique, in fractures of less than 6 weeks' duration has not been specifically assessed by previously published masked trials. METHODS: This was a multicentre, randomised, double-blind, placebo-controlled trial of vertebroplasty in four hospitals in Sydney, Australia. We recruited patients with one or two osteoporotic vertebral fractures of less than 6 weeks' duration and Numeric Rated Scale (NRS) back pain greater than or equal to 7 out of 10. We used an automated telephone randomisation service provided by the National Health and Medical Research Council to assign patients (1:1; stratified according to age, degree of vertebral compression, trauma, corticosteroid use, and hospital) to either vertebroplasty or placebo, immediately before the procedure. Patients received conscious sedation. Vertebroplasty was done with the adequate vertebral fill technique and the placebo procedure with simulated vertebroplasty. Follow-up was for 6 months. Outcome assessors and patients were masked to treatment allocation. The primary outcome was the proportion of patients with NRS pain below 4 out of 10 at 14 days post-intervention in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01482793. FINDINGS: Between Nov 4, 2011, and Dec 5, 2014, 120 patients were enrolled. 61 patients were randomly assigned to vertebroplasty and 59 to placebo. 24 (44%) patients in the vertebroplasty group and 12 (21%) in the control group had an NRS pain score below 4 out of 10 at 14 days (between-group difference 23 percentage points, 95% CI 6-39; p=0·011). Three patients in each group died from causes judged unrelated to the procedure. There were two serious adverse events in each group, related to the procedure (vertebroplasty group) and the fracture (control group). INTERPRETATION: Vertebroplasty is superior to placebo intervention for pain reduction in patients with acute osteoporotic spinal fractures of less than 6 weeks' in duration. These findings will allow patients with acute painful fractures to have an additional means of pain management that is known to be effective. FUNDING: Education grant from CareFusion Corporation.
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Método Doble Ciego , Fracturas Osteoporóticas , Fracturas por Compresión , Humanos , Dimensión del Dolor , Resultado del Tratamiento , VertebroplastiaRESUMEN
Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity. A prospective, cross-sectional cohort study was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM. Urine samples were collected from patients with RA (n = 60), SM (n = 17) and healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing elevated levels. One third of patients with RA had elevated T-PGDM excretion, and the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo MC activity and elevated levels in 33% of patients with RA provides evidence of MC activation in this disease.
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BACKGROUND: The UNSW Australia Medicine program explicitly structures peer learning in program wide mixing of students where students from two adjoining cohorts complete the same course together, including all learning activities and assessment. The purpose of this evaluation is to explore the student experience of peer learning and determine benefits and concerns for junior and senior students. METHODS: All medical students at UNSW Australia in 2012 (n = 1608) were invited to complete the Peer Learning Questionnaire consisting of 26 fixed-response items and 2 open-ended items exploring vertical integration and near-peer teaching. Assessment data from vertically integrated and non-vertically integrated courses were compared for the period 2011-2013. RESULTS: We received valid responses from 20 % of medical students (n = 328). Eighty percent of respondents were positive about their experience of vertical integration. Year 1 students reported that second year students provided guidance and reassurance (87.8 %), whilst year 2 students reported that the senior role helped them to improve their own understanding, communication and confidence (84 %). Vertical integration had little effect on examination performance and failure rates. CONCLUSIONS: This evaluation demonstrates that vertical integration of students who are one year apart and completing the same course leads to positive outcomes for the student experience of learning. Students benefit through deeper learning and the development of leadership qualities within teams. These results are relevant not only for medical education, but also for other professional higher education programs.
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Medicina Clínica/educación , Educación de Pregrado en Medicina/métodos , Evaluación Educacional , Grupo Paritario , Aprendizaje Basado en Problemas/organización & administración , Encuestas y Cuestionarios , Competencia Clínica , Curriculum , Femenino , Humanos , Masculino , Nueva Gales del Sur , Satisfacción Personal , Evaluación de Programas y Proyectos de Salud , Facultades de Medicina/organización & administración , Estudiantes de Medicina/estadística & datos numéricos , Adulto JovenRESUMEN
The ideal immune response is rapid, proportionate and effective. Crucially, it must also be finite. An inflammatory response which is disproportionate or lasts too long risks injury to the host; chronic un-regulated inflammation in autoimmune diseases is one example of this. Thus, mechanisms to regulate and ultimately terminate immune responses are central to a healthy immune system. Despite extensive knowledge of what drives immune responses, our understanding of mechanisms of immune termination remains relatively sparse. It is clear that such processes are more complex than a one-dimensional homeostatic balance. Recent discoveries have revealed ever more nuanced mechanisms of signal termination, such as intrinsically self-limiting signals, multiple inhibitory mechanisms acting in tandem and activating proteins behaving differently in a variety of contexts. This review will summarise some important mechanisms, including termination by immunoreceptor tyrosine-based inhibitory motifs (ITIM), inhibition by soluble antagonists, receptor endocytosis or ubiquitination, and auto-inhibition by newly synthesised intracellular inhibitory molecules. Several recent discoveries showing immunoreceptor tyrosine-based activation motifs transducing inhibitory signals, ITIM mediating activating responses and the possible roles of immunoreceptor tyrosine-based switch motifs will also be explored.
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Endocitosis/inmunología , Sistema Inmunológico/fisiología , Motivo de Inhibición del Inmunorreceptor Basado en Tirosina/inmunología , Ubiquitinación/inmunología , Animales , Humanos , Transducción de SeñalRESUMEN
BACKGROUND: This paper is an evaluation of an integrated selection process utilising previous academic achievement [Universities Admission Index (UAI)], a skills test [Undergraduate Medicine and Health Sciences Admission Test (UMAT)], and a structured interview, introduced (in its entirety) in 2004 as part of curriculum reform of the undergraduate Medicine Program at the University of New South Wales (UNSW), Australia. Demographic measures of gender, country of birth, educational background and rurality are considered. METHOD: Admission scores and program outcomes of 318 students enrolled in 2004 and 2005 were studied. Regression analyses were undertaken to determine whether selection scores predicted overall, knowledge-based and clinical-based learning outcomes after controlling for demographics. RESULTS: UAI attained the highest values in predicting overall and knowledge-based outcomes. The communication dimension of the interview achieved similar predictive values as UAI for clinical-based outcomes, although predictive values were relatively low. The UMAT did not predict any performance outcome. Female gender, European/European-derived country of birth and non-rurality were significant predictors independent of UAI scores. CONCLUSION: Results indicate promising validity for an integrated selection process introduced for the Medicine Program at UNSW, with UAI and interview predictive of learning outcomes. Although not predictive, UMAT may have other useful roles in an integrated selection process. Further longitudinal research is proposed to monitor and improve the validity of the integrated student selection process.
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Criterios de Admisión Escolar , Facultades de Medicina/normas , Adolescente , Adulto , Prueba de Admisión Académica , Escolaridad , Femenino , Humanos , Masculino , Nueva Gales del Sur , Reproducibilidad de los Resultados , Criterios de Admisión Escolar/estadística & datos numéricos , Facultades de Medicina/organización & administración , Adulto JovenRESUMEN
BACKGROUND: This study evaluates the impact of a new 'Preparation for Internship' (PRINT) course, which was developed to facilitate the transition of University of New South Wales (UNSW) medical graduates from Medical School to Internship. METHODS: During a period of major curricular reform, the 2007 (old program) and 2009 (new program) cohorts of UNSW final year students completed the Clinical Capability Questionnaire (CCQ) prior to and after undertaking the PRINT course. Clinical supervisors' ratings and self-ratings of UNSW 2009 medical graduates were obtained from the Hospital-based Prevocational Progress Review Form. RESULTS: Prior to PRINT, students from both cohorts perceived they had good clinical skills, with lower ratings for capability in procedural skills, operational management, and administrative tasks. After completing PRINT, students from both cohorts perceived significant improvement in their capability in procedural skills, operational management, and administrative tasks. Although PRINT also improved student-perceived capability in confidence, interpersonal skills and collaboration in both cohorts, curriculum reform to a new outcomes-based program was far more influential in improving self-perceptions in these facets of preparedness for hospital practice than PRINT. CONCLUSIONS: The PRINT course was most effective in improving students' perceptions of their capability in procedural skills, operational management and administrative tasks, indicating that student-to-intern transition courses should be clinically orientated, address relevant skills, use experiential learning, and focus on practical tasks. Other aspects that are important in preparation of medical students for hospital practice cannot be addressed in a PRINT course, but major improvements are achievable by program-wide curriculum reform.
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Educación de Pregrado en Medicina , Internado y Residencia , Competencia Clínica , Curriculum , Evaluación Educacional , Nueva Gales del Sur , Evaluación de Programas y Proyectos de Salud , Facultades de Medicina , Encuestas y CuestionariosAsunto(s)
Articulación del Tobillo/microbiología , Antirreumáticos/efectos adversos , Artritis Infecciosa/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Histoplasmosis/diagnóstico , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Anciano , Antirreumáticos/uso terapéutico , Artritis Infecciosa/etiología , Artritis Infecciosa/inmunología , Artritis Reumatoide/complicaciones , Australia , Histoplasmosis/etiología , Histoplasmosis/inmunología , Humanos , Inmunosupresores/uso terapéutico , Laos , Masculino , ViajeRESUMEN
The S1A serine proteases function in many key biological processes such as development, immunity, and blood coagulation. S1A proteases contain a highly conserved disulfide bond (Cys(191)-Cys(220) in chymotrypsin numbering) that links two ß-loop structures that define the rim of the active site pocket. Mast cell ßII-tryptase is a S1A protease that is associated with pathological inflammation. In this study, we have found that the conserved disulfide bond (Cys(220)-Cys(248) in ßII-tryptase) exists in oxidized and reduced states in the enzyme stored and secreted by mast cells. The disulfide bond has a standard redox potential of -301 mV and is stoichiometrically reduced by the inflammatory mediator, thioredoxin, with a rate constant of 350 m(-1) s(-1). The oxidized and reduced enzymes have different substrate specificity and catalytic efficiency for hydrolysis of both small and macromolecular substrates. These observations indicate that ßII-tryptase activity is post-translationally regulated by an allosteric disulfide bond. It is likely that other S1A serine proteases are similarly regulated.
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Cisteína/química , Mastocitos/enzimología , Oxidación-Reducción , Triptasas/química , Regulación Alostérica , Animales , Sitios de Unión , Catálisis , Dominio Catalítico , Línea Celular Tumoral , Cisteína/metabolismo , Disulfuros/química , Disulfuros/metabolismo , Humanos , Mastocitos/metabolismo , Ratones , Relación Estructura-Actividad , Especificidad por Sustrato , Triptasas/metabolismoRESUMEN
Mouse mast cell protease (mMCP)-6-null C57BL/6 mice lost less aggrecan proteoglycan from the extracellular matrix of their articular cartilage during inflammatory arthritis than wild-type (WT) C57BL/6 mice, suggesting that this mast cell (MC)-specific mouse tryptase plays prominent roles in articular cartilage catabolism. We used ex vivo mouse femoral head explants to determine how mMCP-6 and its human ortholog hTryptase-ß mediate aggrecanolysis. Exposure of the explants to recombinant hTryptase-ß, recombinant mMCP-6, or lysates harvested from WT mouse peritoneal MCs (PMCs) significantly increased the levels of enzymatically active matrix metalloproteinases (MMP) in cartilage and significantly induced aggrecan loss into the conditioned media, relative to replicate explants exposed to medium alone or lysates collected from mMCP-6-null PMCs. Treatment of cartilage explants with tetramer-forming tryptases generated aggrecan fragments that contained C-terminal DIPEN and N-terminal FFGVG neoepitopes, consistent with MMP-dependent aggrecanolysis. In support of these data, hTryptase-ß was unable to induce aggrecan release from the femoral head explants obtained from Chloe mice that resist MMP cleavage at the DIPEN↓FFGVG site in the interglobular domain of aggrecan. In addition, the abilities of mMCP-6-containing lysates from WT PMCs to induce aggrecanolysis were prevented by inhibitors of MMP-3 and MMP-13. Finally, recombinant hTryptase-ß was able to activate latent pro-MMP-3 and pro-MMP-13 in vitro. The accumulated data suggest that human and mouse tetramer-forming tryptases are MMP convertases that mediate cartilage damage and the proteolytic loss of aggrecan proteoglycans in arthritis, in part, by activating the zymogen forms of MMP-3 and MMP-13, which are constitutively present in articular cartilage.
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Agrecanos/metabolismo , Cartílago Articular/metabolismo , Mastocitos/inmunología , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Animales , Artritis/metabolismo , Células Cultivadas , Precursores Enzimáticos/metabolismo , Matriz Extracelular/metabolismo , Inflamación , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Triptasas/deficiencia , Triptasas/genética , Triptasas/metabolismoRESUMEN
OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that significantly impairs patients' quality of life and can be life threatening. This study aimed to describe the experiences and perspectives of adults living with SLE. METHODS: We conducted a systematic review and thematic synthesis of qualitative studies that explored the experiences of adults living with SLE. We searched MEDLINE, Embase, PsycINFO, CINAHL (to November week 1, 2012), Google Scholar, a thesis database, and reference lists of relevant articles. RESULTS: Forty-six studies involving 1,385 participants were included. Five themes were identified: restricted lifestyle(including subthemes of pervasive pain, debilitating fatigue, mental deterioration, disruptive episodic symptoms, and postponing parenthood), disrupted identity (gaining diagnostic closure, prognostic uncertainty, being a burden, hopelessness, heightened self-consciousness, fearing rejection, and guilt and punishment), societal stigma and indifference(illness trivialization, socially ostracized, and averse to differential treatment), gaining resilience (optimism, control and empowerment, being informed and involved, and valuing mutual understanding), and treatment adherence (preserving health, rapport with clinicians, negotiating medication regimens, and financial burden). CONCLUSION: SLE has a severe and pervasive impact on patients' self-esteem and independence. Their physical and social functioning is limited and they feel anxious about their future. Patients perceive that SLE is trivialized, misunderstood,and stigmatized by their family, friends, and physicians, which intensifies their sense of isolation. Educational, psychosocial, and self-care interventions are needed to promote mental resilience, positive coping strategies, self-advocacy, and capacities for social participation, and thereby to achieve better treatment and health outcomes in patients with SLE.
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Adaptación Psicológica , Emociones , Lupus Eritematoso Sistémico/psicología , Investigación Cualitativa , Calidad de Vida , Adulto , Enfermedad Crónica , HumanosRESUMEN
AIM: To determine whether implementation of a protocol to manage in-hospital acute gout has improved the care of patients by non-rheumatologists. METHOD: Two systematic case-file reviews were performed to determine the management of acute gout in all episodes occurring in hospitalized patients before (April 2005-December 2006) and after (November 2008-September 2009) introduction of a protocol for acute gout management in a tertiary referral hospital. The protocol targeted non-rheumatologists with primary intentions to continue baseline anti-gout medications on admission, prevent inappropriate prescriptions of colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and allopurinol in the hospital, encourage invitations for assistance by rheumatology, and promote combination therapy in cases of severe gout. RESULTS: Excluding patients under the primary care of a rheumatologist, 118 cases of acute gout occurring during hospitalization were reviewed before and 89 cases after introduction of the gout protocol. Post-protocol, there was a significant increase in continuation of baseline allopurinol (P = 0.01), significantly less inappropriate prescriptions of colchicine (P < 0.001) and allopurinol (P = 0.02), and a fall in the occurrence of overall adverse events (P = 0.01). After protocol introduction, when monotherapy was prescribed, NSAID usage declined and prednisone usage increased (P = 0.04), but there was no significant shift toward combination therapy use. Delays from symptom recognition to treatment were significantly reduced (P < 0.001), and rheumatology involvement significantly increased from 33.9% pre-protocol to 51.7% post-protocol. CONCLUSION: Following introduction of a hospital-wide protocol for acute gout management, there have been significant improvements in the management of acute gout by non-rheumatologist clinicians.
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Protocolos Clínicos , Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Hospitalización , Evaluación de Procesos y Resultados en Atención de Salud , Mejoramiento de la Calidad , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Estudios Transversales , Diagnóstico Tardío , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Gota/diagnóstico , Supresores de la Gota/efectos adversos , Adhesión a Directriz , Humanos , Prescripción Inadecuada/prevención & control , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Evaluación de Programas y Proyectos de Salud , Derivación y Consulta , Centros de Atención Terciaria , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The University of New South Wales (UNSW) Faculty of Medicine replaced its old content-based curriculum with an innovative new 6-year undergraduate entry outcomes-based integrated program in 2004. This paper is an initial evaluation of the perceived and assessed clinical capabilities of recent graduates of the new outcomes-based integrated medical program compared to benchmarks from traditional content-based or process-based programs. METHOD: Self-perceived capability in a range of clinical tasks and assessment of medical education as preparation for hospital practice were evaluated in recent graduates after 3 months working as junior doctors. Responses of the 2009 graduates of the UNSW's new outcomes-based integrated medical education program were compared to those of the 2007 graduates of UNSW's previous content-based program, to published data from other Australian medical schools, and to hospital-based supervisor evaluations of their clinical competence. RESULTS: Three months into internship, graduates from UNSW's new outcomes-based integrated program rated themselves to have good clinical and procedural skills, with ratings that indicated significantly greater capability than graduates of the previous UNSW content-based program. New program graduates rated themselves significantly more prepared for hospital practice in the confidence (reflective practice), prevention (social aspects of health), interpersonal skills (communication), and collaboration (teamwork) subscales than old program students, and significantly better or equivalent to published benchmarks of graduates from other Australian medical schools. Clinical supervisors rated new program graduates highly capable for teamwork, reflective practice and communication. CONCLUSIONS: Medical students from an outcomes-based integrated program graduate with excellent self-rated and supervisor-evaluated capabilities in a range of clinically-relevant outcomes. The program-wide curriculum reform at UNSW has had a major impact in developing capabilities in new graduates that are important for 21st century medical practice.
Asunto(s)
Benchmarking/métodos , Competencia Clínica/estadística & datos numéricos , Curriculum , Internado y Residencia/estadística & datos numéricos , Facultades de Medicina/normas , Benchmarking/normas , Competencia Clínica/normas , Femenino , Humanos , Internado y Residencia/normas , Masculino , Nueva Gales del Sur , Calidad de la Atención de Salud/normas , Calidad de la Atención de Salud/estadística & datos numéricos , Facultades de Medicina/estadística & datos numéricos , Autoimagen , Autoinforme , Encuestas y Cuestionarios , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Rheumatoid arthritis (RA) is a heterogeneous chronic inflammatory joint disease characterized by excessive activation of inflammatory cells of which the underlying mechanisms are not fully elucidated. Perturbed expression and function of immune regulatory molecules called leukocyte immunoglobulin-like receptors (LILRs) may contribute to uncontrolled inflammation. LILRs primarily expressed on the surface of leukocytes are emerging as critical regulators of the threshold and amplitude of leukocyte activation. Inhibitory LILRs (LILRBs) contain cytoplasmic tails with immunoreceptor tyrosine-based inhibitory motifs that provide negative signals. Activating LILRs (LILRAs) have short cytoplasmic domains lacking signaling motifs but transmit activating signals by linking to immunoreceptor tyrosine-based activation motifs of the FcR γ-chain. Here we show that activating LILRA2, A5 and inhibitory LILRB2, B3 were abundantly expressed in synovial tissue of > 75% RA patients. Expression of LILRA2, A5, and B3 significantly correlated to disease activity. In contrast, LILRA1 and B4 were expressed in a subset of patients and no B1 or B5 expression was detected. LILRA2 and A5 were mainly expressed by synovial macrophages and endothelial cells but not lymphocytes, whereas B2 and B3 were expressed by macrophages and lymphocytes. Increase in the number of macrophages expressing activating LILRs and macrophages and lymphocytes expressing inhibitory LILRs suggest a crosstalk between these cells that may regulate the levels of cellular activation and disease severity, while differences in expression pattern may contribute to disease heterogeneity.
Asunto(s)
Artritis Reumatoide/metabolismo , Regulación de la Expresión Génica , Linfocitos/metabolismo , Macrófagos/metabolismo , Receptores Inmunológicos/biosíntesis , Membrana Sinovial/metabolismo , Adulto , Anciano , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Femenino , Humanos , Linfocitos/inmunología , Linfocitos/patología , Macrófagos/inmunología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Receptores Inmunológicos/inmunología , Membrana Sinovial/inmunología , Membrana Sinovial/patologíaRESUMEN
Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is an important regulator of cytokine-mediated inflammatory responses in both in vitro and in vivo models of rheumatoid arthritis (RA). However, treatment of RA patients with sPLA(2)-IIA inhibitors shows only transient benefit. Using an activity-impaired sPLA(2)-IIA mutant protein (H48Q), we show that up-regulation of TNF-dependent PGE(2) production and cyclooxygenase-2 (COX-2) induction by exogenous sPLA(2)-IIA in RA fibroblast-like synoviocytes (FLSs) is independent of its enzyme function. Selective cytosolic phospholipase A(2)-α (cPLA(2)-α) inhibitors abrogate TNF/sPLA(2)-IIA-mediated PGE(2) production without affecting COX-2 levels, indicating arachidonic acid (AA) flux to COX-2 occurs exclusively through TNF-mediated activation of cPLA(2)-α. Nonetheless, exogenous sPLA(2)-IIA, but not H48Q, stimulates both AA mobilization from FLSs and microparticle-derived AA release that is not used for COX-2-dependent PGE(2) production. sPLA(2)-IIA-mediated AA production is inhibited by pharmacological blockade of sPLA(2)-IIA but not cPLA(2)-α. Exogenous H48Q alone, like sPLA(2)-IIA, increases COX-2 protein levels without inducing PGE(2) production. Unlike TNF, sPLA(2)-IIA alone does not rapidly mobilize NF-κB or activate phosphorylation of p38 MAPK, two key regulators of COX-2 protein expression, but does activate the ERK1/2 pathway. Thus, sPLA(2)-IIA regulates AA flux through the cPLA(2)-α/COX-2 pathway in RA FLSs by up-regulating steady state levels of these biosynthetic enzymes through an indirect mechanism, rather than direct provision of substrate to the pathway. Inhibitors that have been optimized for their potency in enzyme activity inhibition alone may not adequately block the activity-independent function of sPLA(2)-IIA.