RESUMO
BACKGROUND: In the absence of clinical trials evidence, Juvenile-onset Systemic Lupus Erythematosus (JSLE) treatment plans vary. AIM: To explore 'real world' treatment utilising longitudinal UK JSLE Cohort Study data. METHODS: Data collected between 07/2009-05/2020 was used to explore the choice/sequence of immunomodulating drugs from diagnosis. Multivariate logistic regression determined how organ-domain involvement (pBILAG-2004) impacted treatment choice. RESULT: 349 patients met inclusion criteria, median follow-up 4-years (IQR:2,6). Mycophenolate mofetil (MMF) was most commonly used for the majority of organ-domains, and significantly associated with renal involvement (OR:1.99, 95% CI:1.65-2.41, pc < 0.01). Analyses assessing the sequence of immunomodulators focused on 197/349 patients (meeting relevant inclusion/exclusion criteria). 10/197 (5%) solely recieved hydroxychloroquine/prednisolone, 62/197 (31%) received a single-immunomodulator, 69/197 (36%) received two, and 36/197 patients (28%) received ≥three immunomodulators. The most common first and second line immunomodulator was MMF. Rituximab was the most common third-line immunomodulator. CONCLUSIONS: Most UK JSLE patients required ≥two immunomodulators, with MMF used most commonly.
Assuntos
Lúpus Eritematoso Sistêmico , Estudos de Coortes , Humanos , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Ácido Micofenólico/uso terapêutico , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE). METHODS: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage. RESULTS: LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (>1 year), significantly reduced the hazard of severe flare (P < 0.001). As cumulative time in each target increased, hazard of severe flare progressively reduced. LLDAS attainment reduced the hazard of severe flare more than LA or Toronto-LDA (P < 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (P > 0.05). Attainment of all targets reduced the hazards of new damage (P < 0.05). CONCLUSIONS: This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical remission.
Assuntos
Lúpus Eritematoso Sistêmico , Adulto , Estudos de Coortes , Progressão da Doença , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Indução de Remissão , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. METHODS: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. RESULTS: At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). CONCLUSION: In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Idade de Início , Criança , Estudos de Coortes , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: 'Rapid balance reaction' or 'perturbation' training is an emerging paradigm in elderly back pain rehabilitation due to its connection to postural stability. OBJECTIVE: This study aimed to inform the feasibility and practicality of perturbation-based balance training (PBT) using a stratification approach and to determine the effectiveness of land versus water-based PBT in elderly individuals with chronic low back pain (CLBP). METHODS: Elderly CLBP participants (n=24) received exercise interventions as per treatmentbased classification (TBC) and were randomly allotted into water-based perturbation exercises (WBPE, Mean age=63.0±2.6years, n=12) and land-based perturbation exercise group (LBPE, 62.3±2.6 years, n=12). Pain intensity, disability, scores of fear-avoidance beliefs, fall efficacy, and rate of perceived exertion (RPE) were assessed before and at the end of 6 weeks. RESULTS: WBPE group reported a significant reduction in pain score (median difference(MD)):2, p<0.03), fear avoidance behaviour for work (MD:9, p<0.01) and fear avoidance behaviour for physical activity (MD:10, p< 0.05), improved straight leg raise right (SLR) (MD:37.5°, p<0.05), and improved modified fall efficacy scores (MFES, MD:25, p<0.05) compared to the LBPE group at post-intervention. Within-group analysis in both groups revealed significant improvement in clinical outcomes except for fear-avoidance beliefs related to physical activity in the LBPE group. Subgroup analysis revealed that the high BMI elderly CLBP group of LBPE had significant improvements similar to the WBPE group except for scores of FABQ physical activity scores and SLR. CONCLUSION: Possible key factors for future research are discussed in the realms of perturbation exercise in the elderly with CLBP.
Assuntos
Dor Crônica , Terapia por Exercício , Medo , Dor Lombar , Equilíbrio Postural , Humanos , Dor Lombar/fisiopatologia , Dor Lombar/terapia , Dor Lombar/diagnóstico , Dor Lombar/reabilitação , Masculino , Feminino , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Idoso , Dor Crônica/fisiopatologia , Dor Crônica/terapia , Dor Crônica/reabilitação , Dor Crônica/diagnóstico , Dor Crônica/psicologia , Resultado do Tratamento , Medição da Dor , Água , Estudos de Viabilidade , Fatores de Tempo , Avaliação da Deficiência , Fatores Etários , Recuperação de Função Fisiológica , Acidentes por Quedas/prevenção & controleRESUMO
UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.
Assuntos
Pérnio , Lúpus Eritematoso Sistêmico , Receptor 7 Toll-Like , Feminino , Humanos , Masculino , Pérnio/genética , Mutação com Ganho de Função , Células HEK293 , Lúpus Eritematoso Cutâneo/genética , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Sistêmico/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Mutação de Sentido Incorreto , Linhagem , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/genética , Receptor 8 Toll-Like/metabolismo , Pré-Escolar , Criança , Adulto Jovem , AdultoRESUMO
PURPOSE: The purpose of this trial was to compare the effectiveness of standardized outpatient cardiac rehabilitation combined with treadmill power walking versus standardized outpatient cardiac rehabilitation alone on health-related quality of life (HQoL), functional exercise capacity (FEC), left ventricular ejection fraction (LVEF) and metabolic equivalent of tasks (METs) in patients who went post coronary angioplasty (CA). Further this study evaluated the association between average numbers of steps taken with above clinical outcomes. METHODS: In a pragmatic sequential randomized clinical trial, 24 patients were randomized into two groups (n = 12) and participated in a standardized outpatient cardiac rehabilitation program (SOCRP) with treadmill power walking as an intervention group and SOCRP alone in control group. Scores obtained before and after 4 weeks of intervention, that is, after 12 treatment sessions were assessed using a HQoL questionnaire and 6-min walk test (6 MWT). Average number of steps taken throughout the 4 weeks, METs and LVEF values were obtained by pedometer, exercise stress testing and echocardiogram respectively. RESULTS: Significant improvements were found in intergroup and intragroup comparison after 4 weeks of cardiac rehabilitation (p < 0.05). Scores of 6 MWT and LVEF significantly improved in the intervention group (p < 0.003) compared to the control group (p < 0.032). HQoL components that is, global and physical, MET values and average number of steps were significantly higher in the intervention group compared to the control group (p < 0.001). CONCLUSION: SOCRP with power walking was more effective in improving HQoL, FEC, LVEF, METs and average numbers of steps than SOCRP alone although both interventions were significant after 4 weeks in patients underwent CA and completed cardiac rehabilitation program. Positive significant associations were found between the average number of steps taken with scores of METs and scores of global and physical domains of HQoL.
Assuntos
Reabilitação Cardíaca , Angioplastia , Terapia por Exercício , Humanos , Pacientes Ambulatoriais , Qualidade de Vida , Volume Sistólico , Função Ventricular Esquerda , CaminhadaRESUMO
Measurements of exhaled nitric oxide (FE(NO)) may be useful in the diagnosis and management of asthma in children. A new hand-held device (MINO, Aerocrine) for measuring FE(NO) has been marketed but has not been validated in a pediatric population. The objective is to validate the MINO against the NIOX analyzer. This was a randomized cross-over study where FE(NO) was measured in a single assessment using the MINO and NIOX. Children were recruited from a respiratory clinic and had six attempts to provide a FE(NO) measurement with each analyzer. Fifty-five children were enrolled, 33 boys, median age 9 years. A mean FE(NO) value was obtained in 39 children with MINO and 44 with NIOX. Paired mean FE(NO) values were obtained in 34 children and the values were higher for the NIOX (mean difference 3.9 ppb limits of agreement -1.1, 8.9). The differences between analyzers became greater at higher FE(NO) values. The first FE(NO) value using the MINO was 24 ppb and the mean of all FE(NO) values using the MINO was 27 ppb (difference not significant). Exhaled NO values were comparable between the two analyzers although there was greater consistency at lower values. The findings of the study do not contradict the manufacturer's recommendation that only one FE(NO) value is required with the MINO, however, we suggest that the mean of at least two values should be reported in children.