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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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OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of culture-positive neonatal sepsis with or without meningitis.
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Antibacterianos , Sepsis Neonatal , Humanos , Recién Nacido , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Esquema de Medicación , Sepsis Neonatal/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Revisiones Sistemáticas como AsuntoRESUMEN
OBJECTIVES: Frailty is a risk factor for adverse health in systemic lupus erythematosus (SLE). The Fried phenotype (FP) and the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) are common frailty metrics reflecting distinct approaches to frailty assessment. We aimed to 1) compare frailty prevalence according to both metrics in women with SLE and describe differences between frail and non-frail participants using each method and 2) evaluate for cross-sectional associations between each metric and self-report disability. METHODS: Women aged 18-70 years with SLE were enrolled. FP and SLICC-FI were measured, and agreement calculated using a kappa statistic. Physician-reported disease activity and damage, Patient Reported Outcome Measurement Information System (PROMIS) computerized adaptive tests, and Valued Life Activities (VLA) self-report disability were assessed. Differences between frail and non-frail participants were evaluated cross-sectionally, and the association of frailty with disability was determined for both metrics. RESULTS: Of 67 participants, 17.9% (FP) and 26.9% (SLICC-FI) were frail according to each metric (kappa = 0.41, p< 0.01). Compared with non-frail women, frail women had greater disease damage, worse PROMIS scores, and greater disability (all p< 0.01 for FP and SLICC-FI). After age adjustment, frailty remained associated with a greater odds of disability (FP: odds ratio [OR] 4.7, 95% confidence interval [CI] 1.2-18.8; SLICC-FI: OR 4.6, 95% CI 1.3-15.8). CONCLUSION: Frailty is present in 17.9-26.9% of women with SLE. These metrics identified a similar, but non-identical group of women as frail. Further studies are needed to explore which metric is most informative in this population.
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OBJECTIVE: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE. METHODS: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls. RESULTS: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC. CONCLUSION: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment.
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Disfunción Cognitiva , Lupus Eritematoso Sistémico , Humanos , Barrera Hematoencefálica/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Cognición/fisiología , Imagen por Resonancia Magnética , Lupus Eritematoso Sistémico/complicacionesRESUMEN
OBJECTIVE: The SLICC frailty index (SLICC-FI) was recently developed as a measure of susceptibility to adverse outcomes in SLE. We aimed to externally validate the SLICC-FI in a prevalent cohort of individuals with more long-standing SLE. METHODS: This secondary analysis included data from a single-centre prospective cohort of adult patients with established SLE (disease duration >15 months at enrolment). The baseline visit was the first at which both SLICC/ACR Damage Index (SDI) and 36-item Short Form data were available. Baseline SLICC-FI scores were calculated. Cox regression models estimated the association between baseline SLICC-FI values and mortality risk. Negative binomial regression models estimated the association of baseline SLICC-FI scores with the rate of change in SDI scores during follow-up. RESULTS: The 183 eligible SLE patients were mostly female (89%) with a mean age of 45.2 years (s.d. 13.2) and a median disease duration of 12.4 years (interquartile range 7.8-17.4) at baseline. The mean baseline SLICC-FI score was 0.17 (s.d. 0.09), with 54 patients (29.5%) classified as frail (SLICC-FI >0.21). Higher baseline SLICC-FI values (per 0.05 increase) were associated with an increased mortality risk [hazard ratio 1.31 (95% CI 1.01, 1.70)] after adjusting for age, sex, education, SLE medication use, disease duration, smoking status and baseline SDI. Higher baseline SLICC-FI values (per 0.05 increase) were associated with increased damage accrual over time [incidence rate ratio 1.18 (95% CI 1.07, 1.29)] after adjusting for potential confounders. CONCLUSION: Frailty, measured using the SLICC-FI, predicts organ damage accrual and mortality risk among individuals with established SLE.
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Fragilidad , Lupus Eritematoso Sistémico , Adulto , Femenino , Fragilidad/complicaciones , Fragilidad/epidemiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Using a novel isotemporal substitution paradigm, this study aimed to estimate the cross-sectional associations of objectively measured sedentary behaviour and physical activity (PA) with cardiovascular risk factors among patients with SLE. METHODS: This was a cross-sectional study of adult SLE patients without documented cardiovascular disease (CVD). Cardiovascular risk factors were measured, including BMI, blood pressure, fasting glucose and lipid profile. Ten-year CVD risk was estimated using the American College of Cardiology/American Heart Association risk assessment tool. Time in sedentary behaviour, light PA, and moderate-vigorous PA (MVPA) was measured by accelerometry. We used three linear regression models-single-activity models, partition models, and isotemporal substitution models-to evaluate the associations of time spent at each movement intensity with each CVD risk variable. RESULTS: There were 100 SLE patients [92% female; mean (s.d.) age 52.4 (14.4) years]. Only 11 participants adhered to current PA recommendations (⩾150 MVPA min/week in ⩾10-min bouts). In isotemporal substitution, reallocating 10 min from sedentary behaviour to MVPA was associated with lower systolic (ß = -2.15 mmHg; P = 0.01) and diastolic blood pressure (ß = -1.56 mmHg; P = 0.01), as well as lower estimated 10-year CVD risk (RR 0.81, 95% CI 0.70, 0.93). Time reallocation from light PA to MVPA was associated with lower diastolic blood pressure (ß = -1.45 mmHg; P = 0.01) and lower 10-year CVD risk estimates (RR 0.80, 95% CI 0.69, 0.94). CONCLUSION: Given that reallocating time from other movement intensities to MVPA is associated favourably with lower cardiovascular risk, PA interventions are needed to address suboptimal MVPA levels among SLE patients.
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Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico/fisiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Conducta Sedentaria , Acelerometría/métodos , Adulto , Presión Sanguínea/fisiología , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Prevención Primaria/métodos , Medición de Riesgo , Estados UnidosAsunto(s)
Enfermedades Cardiovasculares , Lupus Eritematoso Sistémico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Ejercicio Físico , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Factores de Riesgo , Conducta SedentariaRESUMEN
BACKGROUND: There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We determined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes. METHODS: We used a population-based perinatal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included women who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes between vaccinated and unvaccinated women using logistic regression analysis. RESULTS: Overall, 1958 (16.0%) of 12,223 women in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.94). The rate of low-birth-weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56-0.95). INTERPRETATION: Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy.
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Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Femenino , Humanos , Recién Nacido , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Estado Civil , Nueva Escocia/epidemiología , Paridad , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Características de la Residencia , Estudios Retrospectivos , Medición de Riesgo , Fumar/epidemiologíaRESUMEN
OBJECTIVE: To examine the effect of body mass index on gonadotropin dose requirements for ovarian stimulation, as well as other clinical outcomes in women undergoing in vitro fertilization. METHODS: We performed a retrospective cohort study involving 752 women undergoing a total of 951 IVF or IVF-ICSI cycles at a private fertility clinic between January 2007 and May 2011. The 951 treatment cycles were divided into three groups according to the weight of the women involved: normal weight (BMI < 25 kg/m², 461 cycles), overweight (25 ≤ BMI < 30 kg/m², 277 cycles), and obese (BMI ≥ 30 kg/m², 179 cycles). Total gonadotropin dose requirements and clinical IVF cycle outcomes (cycle cancellation, clinical pregnancy, and live birth) were compared between the three BMI groups. We performed multivariable analyses, adjusting for potential confounders such as age at cycle start, day 3 serum FSH level, smoking, presence of polycystic ovary syndrome, and duration of infertility. RESULTS: There were no significant differences between the three BMI groups for any of the IVF cycle outcomes measured, including the total FSH dose required for ovarian stimulation. The likelihood of cycle cancellation, clinical pregnancy, and live birth were not significantly different between normal weight, overweight, and obese women. CONCLUSION: Obese women did not require significantly higher doses of gonadotropins for ovarian stimulation than normal weight individuals. At our centre, female obesity did not significantly affect the clinical outcomes of IVF treatment. However, given the conflicting results of existing studies, the effect of maternal obesity on IVF outcomes remains unclear.
Objectif : Examiner l'effet de l'indice de masse corporelle sur les doses de gonadotrophine requises aux fins de la stimulation ovarienne, ainsi que sur d'autres issues cliniques chez les femmes ayant recours à la fécondation in vitro. Méthodes : Nous avons mené une étude de cohorte rétrospective mettant en jeu 752 femmes qui ont subi, au total, 951 cycles de FIV ou de FIV-IICS au sein d'une clinique de fertilité privée entre janvier 2007 et mai 2011. Ces 951 cycles de traitement ont été répartis en trois groupes, en fonction du poids des participantes : poids normal (IMC < 25 kg/m2, 461 cycles), surcharge pondérale (25 ≤ IMC < 30 kg/m2, 277 cycles) et obèse (IMC ≥ 30 kg/m2, 179 cycles). Les doses totales de gonadotrophine requises et les issues cliniques des cycles de FIV (annulation de cycle, grossesse clinique, et naissance vivante) constatées au sein des trois groupes d'IMC ont été comparées. Nous avons mené des analyses multivariées, en neutralisant l'effet de facteurs parasites potentiels comme l'âge au début du cycle, le taux sérique de FSH au jour 3, le tabagisme, la présence du syndrome des ovaires polykystiques et la durée de l'infertilité. Résultats : Aucune différence significative n'a été constatée entre les trois groupes d'IMC pour ce qui est de l'une ou l'autre des issues de cycle de FIV qui ont été mesurées, y compris la dose totale de FSH requise aux fins de la stimulation ovarienne. Aucune différence significative n'a également été constatée entre les femmes de poids normal, les femmes présentant une surcharge pondérale et les femmes obèses pour ce qui est de la probabilité de constater une annulation de cycle, une grossesse clinique et une naissance vivante. Conclusion : Les femmes obèses n'ont pas nécessité des doses considérablement accrues de gonadotrophines aux fins de la stimulation ovarienne, par comparaison avec les femmes de poids normal. Au sein de notre centre, l'obésité féminine n'a pas affecté de façon significative les issues cliniques du traitement de FIV. Toutefois, compte tenu des résultats contradictoires obtenus par les études existantes, l'effet de l'obésité maternelle sur les issues de la FIV reste encore à élucider.
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Índice de Masa Corporal , Fertilización In Vitro , Gonadotropinas/administración & dosificación , Inducción de la Ovulación , Adulto , Estudios de Cohortes , Femenino , Humanos , Obesidad , Sobrepeso , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.
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Comités Consultivos , Consenso , Ejercicio Físico , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/terapia , Terapia por Ejercicio/métodos , Técnica DelphiAsunto(s)
Aterosclerosis/etiología , Enfermedades Cardiovasculares/etiología , Inflamación/complicaciones , Antiinflamatorios/uso terapéutico , Aterosclerosis/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Enfermedad Crónica , Manejo de la Enfermedad , Humanos , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Factores de RiesgoRESUMEN
Background: Admission to a neonatal intensive care unit (NICU) for prematurity or illness is necessary for approximately 20% of newborns in Australia, resulting in parent-infant separation. Web cameras in the NICU provide a virtual link for parents to remain remotely connected to their infant during admission. Web camera use is increasing; however, there is limited evidence on the impact of web cameras on parents, infants, and neonatal staff. Objective: There were two objectives: (1) to determine the attitudes of parents and staff toward web cameras in the NICU and (2) to compare parental depression, anxiety, and stress levels using validated scales before and after web camera implementation in the NICU. Methods: A pre- and postevaluation survey was administered before and after implementation of the NICVIEW camera system in a tertiary NICU in Sydney, Australia. The NICVIEW camera system provides secure real-time viewing of infants and can be accessed from any device with an internet connection. Surveys were administered to parents of inpatients and staff, and included open- and closed-ended questions and Likert scales. Survey questions aimed to determine parent and staff attitudes and use of web cameras before and after implementation. In addition, pre- and postimplementation parental levels of depression, anxiety, and stress, as measured by the 21-item version of the Depression Anxiety Stress Scale (DASS-21) and Parental Stressor Scale: Neonatal Intensive Care Unit, were recorded. Results: In total, 94 parents and 109 staff members completed the pre- and postimplementation surveys. Post implementation, 43 of 44 (98%) parents supported web cameras, and 40 of 42 (95%) parents stated that they used web cameras. The most common reasons for support from parents included web cameras making parents feel more at ease, facilitating parent-infant bonding, increasing parental confidence in staff, and allowing others to see infants. There was no significant difference between the parental groups for the depression, anxiety, or stress scales measured by DASS-21. Staff support for web cameras increased significantly from 34 of 42 (81%) participants before to 64 of 67 (96%) participants after implementation (P=.01). Following implementation, there was a resolution in staff concerns about web cameras having an adverse impact on staff roles and privacy and security concerns. Conclusions: Web camera use in a tertiary Australian NICU was strongly supported by parents and staff and may reduce parental stress, facilitate parent-infant bonding, and encourage positive parent-staff engagement. Web cameras are a feasible method of providing continuity of care for families and should be considered as a standard of care in similarly resourced settings.
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OBJECTIVE: To externally validate the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) in a prevalent systemic lupus erythematosus (SLE) cohort and to assess the ability of the SLICC-FI to predict organ damage accrual among individuals with longstanding SLE. METHODS: This was a secondary analysis of data from the Study of Lupus Vascular and Bone Long-Term Endpoints (SOLVABLE) cohort, which consists of adult women from the Chicago Lupus Database who met the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE. There were 185 patients with SLE enrolled, of whom 149 patients were included in a 5-year follow-up analysis. The SLICC-FI and SLICC/ACR Damage Index (SDI) scores were calculated at baseline and 5-year follow-up. Unadjusted and adjusted logistic regression models estimated the association of baseline SLICC-FI scores (per 0.05 increase) with damage accrual at 5-year follow-up. RESULTS: At enrollment the mean ± SD age of the 149 patients was 43.30 ± 10.15 years, the mean ± SD disease duration was 11.93 ± 8.46 years, and the mean ± SD SDI score was 1.64 ± 1.83. At baseline, the mean ± SD SLICC-FI score was 0.18 ± 0.08, and 36% of participants were categorized as frail (SLICC-FI score >0.21). In a model adjusted for age, race, and disease duration, each 0.05-unit increase in the baseline SLICC-FI score was associated with 28% higher odds of subsequent damage accrual (odds ratio 1.28, 95% confidence interval 1.01-1.63). CONCLUSION: In a prevalent cohort of women with established SLE, higher baseline SLICC-FI scores were associated with a higher risk of subsequent damage accrual at 5-year follow-up.
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Fragilidad , Lupus Eritematoso Sistémico , Reumatología , Adulto , Humanos , Femenino , Persona de Mediana Edad , Fragilidad/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Factores de Riesgo , Oportunidad Relativa , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
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Antirreumáticos , Enfermedades Musculoesqueléticas , Reumatología , Niño , Humanos , Estados Unidos , Antirreumáticos/uso terapéutico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , VacunaciónRESUMEN
OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
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Antirreumáticos , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Reumatología , Niño , Humanos , Estados Unidos , Antirreumáticos/uso terapéutico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Vacunación , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. METHODS: We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. RESULTS: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. CONCLUSION: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.
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Lupus Eritematoso Sistémico , Reumatología , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Cognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood-brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage. METHODS: Consecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers. RESULTS: There were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8-24 years) vs 15 (2-16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage. CONCLUSIONS: Extensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.
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Disfunción Cognitiva , Lupus Eritematoso Sistémico , Adulto , Autoanticuerpos , Biomarcadores , Barrera Hematoencefálica , Disfunción Cognitiva/complicaciones , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
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Fragilidad , Lupus Eritematoso Sistémico , Adulto , Femenino , Fragilidad/complicaciones , Fragilidad/diagnóstico , Fragilidad/epidemiología , Hospitalización , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/terapia , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma. Oncogenesis occurs via Merkel cell polyomavirus-mediated (MCPyV+) and/or ultraviolet radiation-associated (MCPyV-) pathways. Advanced clinical stage and an MCPyV- status are important adverse prognostic indicators. There is mounting evidence that p63 expression is a negative prognostic indicator in MCC and that it correlates with MCPyV- status. p63 is a member of the p53 family of proteins among which complex interactions occur. It has two main isoforms (proapoptotic TAp63 and oncogenic ΔNp63). Paradoxically, TAp63 predominates in MCC. To explore this quandary, we examined relationships between p63 and p53 expression and corresponding abnormalities in the TP63 and TP53 genes in MCC. A cohort of 26 MCCs (12 MCPyV+ and 14 MCPyV-) was studied. Comparative immunohistochemical expression of p63 and p53 was evaluated semiquantitatively (H scores) and qualitatively (aberrant patterns). The results were compared with genetic abnormalities in TP63 and TP53 via next-generation sequencing. p63 was positive in 73% of cases. p53 showed "wild-type" expression in 69%, with "aberrant" staining in 31%. TP63 mutations (predominantly low-level copy gains; 23% of cases) and mainly pathogenic mutations in TP53 (50% of cases) featured in the MCPyV- subset of cases. p63 expression correlated quantitatively with p53 expression and qualitatively with aberrant patterns of the latter. Increased expression of p63 and p53 and aberrant p53 staining correlated best with TP53 mutation. We propose that p63 expression (ie, proapoptotic TAp63) in MCC is most likely functionally driven as a compensatory response to defective p53 tumor suppressor activity.
Asunto(s)
Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/patología , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genética , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Isoformas de Proteínas , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismoRESUMEN
OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. CONCLUSION: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.