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BACKGROUND AND AIMS: Cenicriviroc (CVC) is a novel, orally administered, chemokine receptor type 2 and 5 antagonist that showed antifibrotic potential in preclinical and phase IIb studies of nonalcoholic steatohepatitis (NASH). Herein, we report efficacy and safety results from the phase III study. METHODS: The AURORA (A Study for the Efficacy and Safety of CVC for the Treatment of Liver Fibrosis in Adults With NASH) study was a phase III, randomized, double-blind, placebo-controlled, 2-part study of patients with NASH and stage 2/3 liver fibrosis. Adults, 18-75 years of age, were randomized to CVC 150 mg or placebo once daily for 12 months (part 1) or 60 months (part 2). Liver biopsies were performed at screening, month 12, and early study discontinuation or termination. The primary efficacy endpoint was the proportion of patients with fibrosis improvement ≥1 stage without worsening of steatohepatitis at month 12 relative to screening. Adverse events were assessed throughout the study. RESULTS: A total of 1778 patients were randomized and discontinued (part 1: n = 1293; part 2: n = 485). In part 1, at month 12, a similar proportion of patients receiving CVC or placebo achieved the primary endpoint (22.3% vs 25.5%; odds ratio, 0.84; 95% confidence interval, 0.63-1.10; P = .21) and complete resolution of steatohepatitis without worsening of fibrosis (23.0% vs 27.2%; P = .21). The safety profile was generally comparable across treatment groups. CONCLUSIONS: This study did not demonstrate the efficacy of CVC for treating liver fibrosis assessed by histology in adults with NASH; however, CVC was safe and well tolerated in patients with NASH and liver fibrosis. (ClinicalTrials.gov, Number: NCT03028740).
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Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Niño , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Imidazoles , Fibrosis , Método Doble Ciego , Hígado/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Acute myeloid (AML) and promyelocytic (APL) leukemia patients are at high risk for infection and mortality. While guidance for infection prevention is provided by the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), each institution may vary in antimicrobial prophylaxis prescribing practices. The discrepancy may be explained by medication intolerance, cost, and low incidence of mold infections in leukemia patients. A recent meta-analysis demonstrated mortality benefits with the use of posaconazole, which was adopted by the NCCN. Despite known risks, it is unclear whether universal mold-active coverage is indicated for all AML and APL patients. OBJECTIVE: To assess the incidence of breakthrough infections in AML and APL patients. METHODS: This was a single-center, retrospective chart review of AML and APL patients receiving induction therapy at Baylor St Luke's Medical Center (BSLMC) between January 2019 and October 2021. The primary outcome assessed the incidence of breakthrough infections. Descriptive statistics were used to summarize the data. RESULTS: A total of 55 patients were included and 54 (98%) had prolonged neutropenia with a median duration of 30 days. Five patients (9.3%) experienced breakthrough infections during induction while 21 individuals (38.9%) during the follow-up period. Aspergillus infections occurred in three patients receiving nonmold coverage compared to none on mold-active agents (p = 1.0) with no statistical difference in mortality. CONCLUSION: Despite the majority of patients not receiving mold-active prophylaxis, nonmold-active prophylaxis may be sufficient with consideration of low aspergillosis incidence.
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BACKGROUND: The impact of the United States Prospective Payment System (PPS) "bundle payment system" on anemia management within small dialysis organizations (SDOs) was studied to evaluate the financia burden on SDOs. METHODS: Facilities enrolled in the original study on SDOs were grouped into three hemoglobin (Hb) categories by subject-months: > 25% of subjectmonths with Hb < 10 g/dL (sub-10); > 25% of subject-months with Hb > 12 g/dL (super-12); remaining facilities (10 - 12 group). Subjectlevel data aggregated to facility level for Hb concentration, intravenous (IV) epoetin ± (EA) dose per administration, dose titration, and EA administration frequency during the baseline and follow-up periods were described. RESULTS: Baseline demographic characteristics were imbalanced between the sub-10 (n = 7) and super-12 facilities (n = 5). Mean (SD) Hb concentrations were similar for sub-10 (11.1 (3.0) g/dL) and super-12 (11.6 (2.2) g/dL) facilities during the baseline period, but differed during the follow-up period (10.4 (2.7) vs. 11.4 (2.3) g/dL). The median (Q1, Q3) EA IV dose per administration during follow-up was 3,726 (3,467, 3,961) and 5,712 (4,816, 7,324) units in the sub-10 and super-12 facilities, respectively. A small trend toward upward titration was seen. CONCLUSIONS: Results suggest a difference in anemia management between sub-10 and super-12 facilities during the first year of PPS implementation. Future analyses evaluating patterns of reimbursement and shifts in clinical practice guidelines are warranted globally.
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Anemia/tratamiento farmacológico , Fallo Renal Crónico/terapia , Sistema de Pago Prospectivo , Diálisis Renal , Adulto , Anciano , Anemia/sangre , Eritropoyetina/uso terapéutico , Femenino , Hemoglobinas/análisis , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Estudios ProspectivosRESUMEN
Statistical analysis plays a critical role in data interpretation in all fields and particularly so for clinical data where important treatment decisions are made. We provide here an in-depth and illustrative analysis to examine patterns and radiographic scores in an early disease rheumatoid arthritis cohort over a 3-year follow-up period. The total Sharp radiographic scores were interpolated from the rates at 6 months, 1, 2, and 3 years and were transformed to count data after rounding. The generalized estimating equations approach and two-part models were applied to analyze the longitudinal radiographic scores using the clinical, demographic, and therapeutic characteristics of the patients after adjusting for the pattern outcomes. Total Sharp scores were modeled, assuming that they were Poisson distributed or had a negative binomial distribution with either an AR(1) working correlation matrix or an exchangeable working correlation matrix. To account for the excessive zero counts, we used two-part models that include the zero-inflated Poisson and the zero-inflated negative binomial to fit the data. This is an innovation because two-part models have not been used in rheumatology even though they are highly appropriate for analyzing data from rheumatic studies. In addition, we analyzed data using generalized estimating equations and compared results from different models using formal statistical goodness-of-fit criteria and arrive at the best model for predicting purposes.
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Artritis Reumatoide/diagnóstico por imagen , Artrografía , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artrografía/estadística & datos numéricos , Interpretación Estadística de Datos , Humanos , Modelos Estadísticos , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Cenicriviroc (CVC) is a novel, orally administered antagonist of chemokine receptor types 2/5 that has demonstrated antifibrotic activity in a phase 2b study of patients with NASH. This phase 2, open-label, rollover study investigated the long-term safety and tolerability of CVC in patients with NASH and stage 0-4 liver fibrosis. METHODS: Eligible patients who completed the phase 2 CENTAUR study or reached a predefined endpoint in the phase 3 AURORA study were rolled over and received open-label CVC 150 mg once daily. Safety assessments were conducted at the start of the study, and patients were seen in the clinic every 3 months until the study sponsor terminated CVC development. Safety endpoints included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, adverse event severity, and clinical laboratory assessments. RESULTS: A total of 167 patients were enrolled, with a median treatment duration of 33.6 months. Before study termination, 36 patients (21.6%) prematurely discontinued the study. Treatment-related TEAEs were reported in 28 patients (16.8%). The most common treatment-related TEAEs were 4 cases of diarrhea (2.4%) and 2 cases each (1.2%) of abdominal pain, nausea, alanine aminotransferase increased, aspartate aminotransferase increased, hypertriglyceridemia, myalgia, pruritus, and rash. The majority of these treatment-related events were mild in intensity, and none were life-threatening. There were no clinically meaningful changes in hepatic function, chemistry, or liver parameters from baseline to the end of the study. CONCLUSIONS: In this rollover study, CVC 150 mg once daily was well tolerated in patients with NASH and stage 0-4 liver fibrosis. No new safety signals were reported, and these data further support the safety and tolerability of CVC.
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Imidazoles , Enfermedad del Hígado Graso no Alcohólico , Sulfóxidos , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Resultado del Tratamiento , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
BACKGROUND: With aging, repetitive contraction of the platysma leads to an increase in platysma prominence (PP) characterized by the accentuation of vertical neck bands and blunting of the jawline's contour. METHODS: This multicenter, double-blind, phase 2 study evaluated onabotulinumtoxinA (onabotA) treatment in adults with Moderate to Severe PP. Participants were randomized to receive 1 treatment of onabotA low dose (LD), onabotA high dose (HD), or placebo, and were followed for 4 months. Efficacy endpoints were the achievement of a ≥ 1-grade improvement on both the left and right sides at Day 14 at maximum contraction as assessed by the investigator (primary) or by participants (secondary) using validated scales. Safety was evaluated throughout. RESULTS: Participants in the modified intent-to-treat population (N = 164) had a mean age of 50 years; 95.1% were female and 93.9% were White. The primary endpoint was met for both onabotA groups, with investigator-assessed ≥ 1-grade improvement in 77.8% (LD) and 88.2% (HD) vs 12.0% (placebo) of participants on Day 14 (P < 0.0001 vs placebo). Based on participant self-assessment, 75.9% (LD) and 88.2% (HD) vs 18.0% (placebo) achieved ≥ 1-grade improvement on Day 14 (P < 0.0001 vs placebo). Most treatment-related adverse events (AEs) were procedure-related, transient, and mild in severity. The most frequent onabotA-related AE was neck muscle weakness, reported in the HD group. CONCLUSIONS: OnabotA was effective in improving the appearance of PP based on both investigators' and participants' ratings. Treatment was well tolerated.
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BACKGROUND: Launched in January 2011, the prospective payment system (PPS) for the US Medicare End-Stage Renal Disease Program bundled payment for services previously reimbursed independently. Small dialysis organizations may be particularly susceptible to the financial implications of the PPS. The ongoing Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS) was designed to describe trends in care and outcomes over the period of PPS implementation. This report details early results between October 2010 and June 2011. STUDY DESIGN: Prospective observational cohort study of patients from a sample of 51 small dialysis organizations. SETTING & PARTICIPANTS: 1,873 adult hemodialysis and peritoneal dialysis patients. OUTCOMES: Secular trends in processes of care, anemia, metabolic bone disease management, and red blood cell transfusions. MEASUREMENTS: Facility-level data are collected quarterly. Patient characteristics were collected at enrollment and scheduled intervals thereafter. Clinical outcomes are collected on an ongoing basis. RESULTS: Over time, no significant changes were observed in patient to staff ratios. There was a temporal trend toward greater use of peritoneal dialysis (from 2.4% to 3.6%; P = 0.09). Use of cinacalcet, phosphate binders, and oral vitamin D increased; intravenous (IV) vitamin D use decreased (P for trend for all <0.001). Parathyroid hormone levels increased (from 273 to 324 pg/dL; P < 0.001). Erythropoiesis-stimulating agent doses decreased (P < 0.001 for IV epoetin alfa and IV darbepoetin alfa), particularly high doses. Mean hemoglobin levels decreased (P < 0.001), the percentage of patients with hemoglobin levels <10 g/dL increased (from 12.7% to 16.8%), and transfusion rates increased (from 14.3 to 19.6/100 person-years; P = 0.1). Changes in anemia management were more pronounced for African American patients. LIMITATIONS: Limited data were available for the prebundle period. Secular trends may be subject to the ecologic fallacy and are not causal in nature. CONCLUSIONS: In the period after PPS implementation, IV vitamin D use decreased, use of oral therapies for metabolic bone disease increased, erythropoiesis-stimulating agent use and hemoglobin levels decreased, and transfusion rates increased numerically.
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Instituciones de Atención Ambulatoria/economía , Fallo Renal Crónico/economía , Medicare/economía , Sistema de Pago Prospectivo/economía , Diálisis Renal/economía , Adulto , Anciano , Anciano de 80 o más Años , Anemia/tratamiento farmacológico , Anemia/economía , Conservadores de la Densidad Ósea/economía , Conservadores de la Densidad Ósea/uso terapéutico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/tratamiento farmacológico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/economía , Estudios de Cohortes , Transfusión de Eritrocitos/economía , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Hematínicos/economía , Hematínicos/uso terapéutico , Hemodiálisis en el Domicilio/economía , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/economía , Diálisis Peritoneal/tendencias , Sistema de Pago Prospectivo/tendencias , Estudios Prospectivos , Diálisis Renal/tendencias , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVES: To assess, in a randomised controlled trial (RCT) and in clinical practice, an association of time to remission and baseline disease activity with both induction of remission and sustained remission in etanercept-treated patients with rheumatoid arthritis (RA). METHODS: Data from an RCT (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes [TEMPO]; n=682) and an observational registry (Rheumatoid Arthritis DMARD Intervention and Utilization Study [RADIUS II]; n=4341) were used to evaluate disease activity (Clinical Disease Activity Index [CDAI] score) over time in patients initiating etanercept (monotherapy or with methotrexate). CDAI remission (CDAI≤2.8) and sustained remission (≥6 months) were determined through year 3 by treatment group, study, time to remission, and disease severity. RESULTS: Patients from TEMPO and RADIUS II who received etanercept monotherapy showed similar CDAI remission rates (39% and 35%, respectively, at 3 years). Among patients who received etanercept with methotrexate, remission rates were 54% and 36%, respectively. Remission occurred more rapidly in TEMPO than RADIUS II perhaps from differences in compliance, patient populations, or sequence of combination therapy initiation. Generally, more patients with lower baseline CDAI scores achieved remission than those with higher scores. Continued remission appeared more likely in patients achieving remission earlier in the course of their therapy (0-6 months). CONCLUSIONS: Remission by year 3 in etanercept-treated (with and without methotrexate) patients with RA occurred in ≥35% of patients in both an RCT (TEMPO) and a clinical practice setting (RADIUS II), and more frequently in those with lower baseline disease severity. Patients with lower RA disease activity were more likely to reach remission. Continued remission may be more likely in patients who achieved remission earlier.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Australia , Distribución de Chi-Cuadrado , Quimioterapia Combinada , Etanercept , Europa (Continente) , Femenino , Humanos , Israel , Estimación de Kaplan-Meier , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Inducción de Remisión , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To derive and validate decision trees to categorise rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted not to achieve LDA at 1 year and patients who needed additional time on therapy to be categorised. METHODS: Data from RA patients enrolled in the TEMPO trial were analysed. Classification and regression trees were used to develop and validate decision tree models with week 12 and earlier assessments that predicted long-term LDA. LDA, defined as disease activity score in 28 joints (DAS28) ≤3.2 or clinical disease activity index ≤10.0, was measured at 52 or 48 weeks. Demographics, laboratory data and clinical data at baseline and to week 12 were analysed as predictors of response. RESULTS: 39% (67/172) of patients receiving etanercept and 60% (115/193) of patients receiving etanercept plus methotrexate achieved LDA at week 52. For patients receiving etanercept, 53% were predicted to have LDA, 39% were predicted not to have LDA and 8% could not be categorised using DAS28 criteria at week 12. For patients receiving etanercept plus methotrexate, 63% were predicted to have LDA, 25% were predicted not to have LDA and 12% could not be categorised. CONCLUSION: Most (80-90%) patients in TEMPO initiating etanercept with or without methotrexate could be predicted within 12 weeks of starting therapy as likely to have LDA or not at week 52. However, approximately 10-20% of patients needed additional time on therapy to decide whether to continue treatment.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Árboles de Decisión , Método Doble Ciego , Quimioterapia Combinada , Etanercept , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Dolor/etiología , Dimensión del Dolor/métodos , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
To evaluate the therapeutic potential of an apolipoprotein A-1 (apoA-1) mimetic peptide, D-4F, in combination with pravastatin in collagen-induced arthritis (CIA), syngeneic Louvain rats were immunized with type II collagen and randomized to vehicle control, D-4F monotherapy, pravastatin monotherapy, or D-4F + pravastatin combination therapy. Clinical arthritis activity was evaluated and radiographs, type II collagen antibody titers, cytokine/chemokine levels, and HDL function analysis were obtained. There was significant reduction in clinical severity scores in the high and medium dose D-4F + pravastatin groups compared to controls (p< or =0.0001). Reduction in erosive disease occurred in the medium/high dose combination groups compared to non-combination groups (p< or =0.01). Favorable changes in cytokines/chemokines were noted with treatment, and response to combination D-4F/pravastatin therapy was associated with improvement in HDL's anti-inflammatory properties. Combination D-4F/pravastatin significantly reduced clinical disease activity in CIA, and may have dual therapeutic potential in other autoimmune diseases with increased cardiovascular morbidity and mortality.
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Anticolesterolemiantes/farmacología , Apolipoproteína A-I/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Pravastatina/farmacología , Animales , Anticuerpos/sangre , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/inmunología , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/inmunología , Quimiotaxis , HDL-Colesterol/sangre , Colágeno Tipo II/inmunología , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Histocitoquímica , Humanos , Articulaciones/patología , Monocitos/inmunología , Radiografía , Distribución Aleatoria , Ratas , Análisis de RegresiónRESUMEN
The objective of this study is to characterize stability and clinical features of patients with rheumatoid arthritis (RA) in sustained remission. Combination therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has increased remission rates in RA but optimal regimens to maintain remission are unknown. We describe Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run-in period of longitudinal observation. Patients in Simplified Disease Activity Index (SDAI) remission (score ≤ 3.3) receiving etanercept and methotrexate were screened and had to maintain remission over 3 run-in visits/24 weeks before randomization to combination therapy or withdrawal of etanercept or methotrexate. Baseline characteristics were examined for predictive factors for maintaining remission. As of November 2016, 141 patients have enrolled; of these, 64 have been randomized, 34 were ineligible after run-in, and 43 are in run-in period; 70% have completed run-in. Enrolled and randomized patients, respectively, had mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years; mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD) methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores 1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission based on 28 joints and 66/68 joints, respectively. No enrollment characteristic predicted successful completion of run-in. Two-thirds of patients considered to be in remission at enrollment sustained remission through 24 weeks. Baseline characteristics of enrolled patients and those who completed run-in were comparable.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Etanercept/uso terapéutico , Metotrexato/uso terapéutico , Inducción de Remisión/métodos , Anciano , Artritis Reumatoide/diagnóstico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate concordance and agreement of the original DAS44/ESR-4 item composite disease activity status measure with nine simpler derivatives when classifying patient responses by European League of Associations for Rheumatology (EULAR) criteria, using an early rheumatoid factor positive (RF+) rheumatoid arthritis (RA) patient cohort. METHODS: Disease-modifying anti-rheumatic drug-naïve RF+ patients (n = 223; mean duration of symptoms, 6 months) were categorised as ACR none/20/50/70 responders. One-way analysis of variance and two-sample t tests were used to investigate the relationship between the ACR response groups and each composite measure. EULAR reached/change cut-point scores were calculated for each composite measure. EULAR (good/moderate/none) responses for each composite measure and the degree of agreement with the DAS44/ESR-4 item were calculated for 203 patients. RESULTS: Patients were mostly female (78%) with moderate to high disease activity. A centile-based nomogram compared equivalent composite measure scores. Changes from baseline in the composite measures in patients with ACRnone were significantly less than those of ACR20/50/70 responders, and those for ACR50 were significantly different from those for ACR70. EULAR reached/change cut-point scores for our cohort were similar to published cut-points. When compared with the DAS44/ESR-4 item, EULAR (good/moderate/none) percentage agreements were 92 with the DAS44/ESR-3 item, 74 with the Clinical Disease Activity Index, and 80 with the DAS28/ESR-4 item, the DAS28/CRP-4 item and the Simplified Disease Activity Index. CONCLUSION: The relationships of nine different RA composite measures against the DAS44/ESR-4 item when applied to a cohort of seropositive patients with early RA are described. Each of these simplified status and response measures could be useful in assessing patients with RA, but the specific measure selected should be pre-specified and described for each study.
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Artritis Reumatoide/diagnóstico , Adulto , Análisis de Varianza , Artritis Reumatoide/sangre , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor Reumatoide/análisis , Reumatología/métodos , Índice de Severidad de la EnfermedadRESUMEN
Various methods are used to measure radiographic joint damage in patients with rheumatoid arthritis (RA), but determining proportions of responsive patients is difficult. A key problem in observational studies when assessing damage outcomes is incorporating time to treatment initialization and adjusting for observed baseline differences. We examined five different definitions to select an appropriate index to classify radiographic damage in RA patients as progressive or nonprogressive. In addition, we compared different times from symptom onset to treatment and their effects on patient radiographic categorization. Propensity scores to adjust for baseline differences, including time since symptom onset, were used to match those treated early with those treated later using the stratification, radius, nearest neighbor and kernel methods. The mean effect of treatment on the treated was computed for each matching method. Observational data were analyzed for 185 early RA patients from the Western Consortium study followed six to sixty months (mean thirty-one months). For the selected index, 75 patients were categorized as nonprogressors; they had significantly lower disease activity, more clinical improvement and were treated earlier than the progressors. Of those treated within three months of symptom onset, 57% were classified as radiographically progressive versus 35% of those treated later (P = 0.0058). However, after propensity score adjustment for baseline differences, we noticed nonsignificant (P > 0.05) nonprogression in patients given earlier treatment. We conclude that propensity score analysis reduced but did not remove all bias.
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Artritis Reumatoide/clasificación , Artritis Reumatoide/diagnóstico por imagen , Adulto , Artritis Reumatoide/fisiopatología , Interpretación Estadística de Datos , Diagnóstico por Imagen/estadística & datos numéricos , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Radiografía , Estados UnidosRESUMEN
BACKGROUND: This study assessed the impact of follow-up reminder phone calls on response rates to a mailed consent form packet. METHODS: Patients with rheumatoid arthritis were invited to enroll in a study by signing and returning consent forms by mail. Patients not returning completed study consent forms were called and reminded to return the signed consent forms. RESULTS: Among 724 mailed consent form packets, 376 (52%) were returned without further follow-up. Follow-up reminder calls were made to 220 of the 348 patients who did not return signed consent forms. Among subjects contacted by phone, 67 (31% of those called) returned signed consent forms. CONCLUSION: Follow-up reminder phone calls raised the overall consent rate of 52 to 61%, suggesting that they can be an effective technique in increasing response rates.
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Artritis Reumatoide/psicología , Consentimiento Informado , Sistemas Recordatorios , Teléfono , Actitud Frente a la Salud , Humanos , Negativa a ParticiparRESUMEN
Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.
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Registros Electrónicos de Salud , Eritropoyetina/administración & dosificación , Hematínicos/administración & dosificación , Hemoglobinas/metabolismo , Modelos Biológicos , Diálisis Renal , Diabetes Mellitus/sangre , Diabetes Mellitus/terapia , Epoetina alfa , Femenino , Ferritinas , Humanos , Hipertensión/sangre , Hipertensión/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Proteínas Recombinantes/administración & dosificación , Estados UnidosRESUMEN
We examine radiographic profile patterns using clustering algorithms to assess progression rates at set time intervals in a rheumatoid arthritis (RA) observational study. Hands/feet radiographic scores were analyzed for 190 early, seropositive RA patients with ≥ 3 radiographic observations from a prospective cohort. Assessments at 6 months, 1 year, and yearly thereafter were requested for demographic, therapeutic, functional, laboratory, radiographic, and clinical data. Progression rates for the total sharp scores [erosion (E)+joint space narrowing (JSN)] were interpolated for intervals of 0 to 6 months, 6 month-1 year, 1-2 years, and 2-3 years past first radiographic observation. Patients were grouped on their sets of rates by K-median clustering algorithms, and categorical group membership was regressed onto baseline characteristics using multinomial models. The number of clusters was determined using one-way MANOVA, and baseline differences across clusters by Kruskal-Wallis tests. The median RA duration was 6.1 months, mean age 52 years, median disease activity score (DAS) 4.6, mean radiographic observations 4.6 (range 3-8) for this mostly female (77%), Caucasian (78%) sample. 3 patterns were determined: increasing (n = 41; 22%), increasing then decreasing (n = 41; 22%), and flat (n = 108; 57%). High baseline C-reactive protein was associated with a worsening radiographic progression (p < 0.005), as were HAQ-DI (p = 0.07), JSN (p < 0.01), and E (p = 0.03). Our conclusions are that radiographic progression patterns graphically supplement traditional linear rates, and are flexible to use in both clinical and observational studies. The identified clusters and rates may correspond better with clinical status and treatment over the disease course than linear progression rates alone.
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Artritis Reumatoide/diagnóstico por imagen , Adulto , Anciano , Algoritmos , Artritis Reumatoide/patología , Artrografía , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Femenino , Humanos , Articulaciones/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the long-term safety and efficacy of etanercept therapy in rheumatoid arthritis (RA) patients. METHODS: Adult patients with early RA or longstanding RA received etanercept in open-label extension studies following initial double-blind trials of etanercept. RESULTS: Of 558 early RA patients and 714 longstanding RA patients who received at least 1 dose of etanercept, a total of 194 early RA patients and 217 longstanding RA patients were treated with 25 mg of etanercept twice weekly through 10 years. Five opportunistic infections were reported: in early RA, 1 Candida septicemia; in longstanding RA, 1 herpes zoster, 1 atypical mycobacterium infection, 1 meningoencephalitis (unspecified), and 1 fungal sepsis (unspecified). Twenty-nine cases of sepsis occurred (10 early RA, 19 longstanding RA). Occurrence of all malignancies was similar to that expected in the general population, but the occurrence of lymphomas was higher than expected in the general population. Fourteen lymphomas (7 early RA, 7 longstanding RA) and 2 cases of demyelinating disease (1 early RA, 1 longstanding RA) were reported. Deaths occurred in 18 early RA patients and 43 longstanding RA patients. Both patient groups showed sustained improvement in American College of Rheumatology responses, swollen joint counts, Health Assessment Questionnaire disability index scores, and C-reactive protein levels. CONCLUSION: Etanercept maintained therapeutic benefits beyond 10 years of therapy in both early RA and longstanding RA patients, suggesting that etanercept is well tolerated and effective as a long-term, continuous therapy for the treatment of RA, with a favorable risk/benefit ratio.
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Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Evaluación de la Discapacidad , Método Doble Ciego , Esquema de Medicación , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , América del Norte , Infecciones Oportunistas/inducido químicamente , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Sepsis/inducido químicamente , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate responses by time to initiation of nonbiologic disease-modifying antirheumatic drugs (DMARD) in a DMARD-naive cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months, range 0.6-15.9). Subjects who started their first DMARD within 5 months of symptom onset were compared to subjects who started after 5 months. Disease Activity Scores (DAS-44) and total Sharp Score (TSS) progression rates were analyzed using Wilcoxon rank-sum and chi-square tests; multiple linear regression analysis adjusted for potential covariates. The slope of the least-squares regression line was calculated to estimate the annualized TSS progression rates. RESULTS: Of 233 RA patients, 76% were female and mean age was 50 (SD 13) years. At DMARD start, DAS-44 was similar in all subsets within the 0.6 to 15 months' duration between symptom onset and DMARD initiation. Erosion scores tended to be higher in those who started DMARD later, but Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were higher in those who started DMARD earlier. During the 2 years after DMARD initiation, improvements in HAQ-DI and DAS-44 were similar in the various duration subsets, with about 25% ever achieving DAS remission (DAS < 1.6). Radiographic progression tended to be numerically but not statistically more rapid in the earlier subsets. CONCLUSION: Following initiation of nonbiologic DMARD therapy at various times within 15 months of symptom onset, improvements of DAS-44, HAQ-DI, remission rate, and radiographic progression rate were similar, although higher baseline erosion scores were present in those with later initiation of DMARD.
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Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Adulto , Artritis Reumatoide/diagnóstico por imagen , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Radiografía , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Systemic sclerosis (SSc) is associated with vasculopathy and endothelial cell injury, which could potentially increase the risk of coronary atherosclerosis. Multidetector computed tomography, a noninvasive procedure, generates a coronary calcium score (CCS) as a marker for coronary atherosclerosis. Serum proinflammatory high-density lipoprotein (piHDL) is a potential novel marker of atherosclerotic risk. The objective of the pilot study was to determine 1) the prevalence of subclinical coronary atherosclerosis in SSc and 2) serum piHDL levels as a potential novel marker of atherosclerotic risk in SSc. METHODS: A cross-sectional study of 17 patients with SSc and 17 age-, sex-, and race-matched healthy controls in Cincinnati, Ohio, was conducted. Measurements included CCS; body mass index; lipid profile; and serum levels of high-sensitivity C-reactive protein, homocysteine, and piHDL. RESULTS: Patients with SSc were slightly older (mean 52.8 years) than control subjects (mean 50.6 years; P = 0.01). Coronary calcium was found in 12 participants (9 with SSc, 3 controls; P = 0.03). The mean +/- SD CCS in patients with SSc was significantly greater than the controls (126.6 +/- 251.0 versus 14.7 +/- 52.2; P = 0.003). Five patients with SSc (29%), but no controls, had detectable levels of piHDL (P = 0.06). CONCLUSION: Prevalence of subclinical coronary atherosclerosis is greater in patients with SSc compared with healthy controls. These findings should be confirmed in a larger study.
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Calcinosis/etiología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Esclerodermia Sistémica/complicaciones , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , PrevalenciaRESUMEN
INTRODUCTION: Gout is a chronic painful inflammatory arthritis. Data regarding the impact of gout on health-related quality of life, however, are limited. METHODS: We interviewed patients with chronic stable gout. Health status was measured by using the Short Form 36 (SF-36) physical component summary (PCS) and physical component summary (MCS) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Direct preference-based measures included a health rating scale (RS), the time tradeoff (TTO), and standard gamble (SG) for one's current health state with gout and current health state without gout; indirect preference-based measures included the SF-6D and the EQ-5D. Disutilities for gout were assessed by subtracting preference scores for current health states with gout from those for current health without gout and were compared between patients ranking gout as their top health concern versus the rest of the patients. RESULTS: Of the 80 interviewees, 72 (90%) were male, 55 (69%) were Caucasian, and the mean (SD) age was 60 (11) years. The mean SF-36 PCS and MCS scores were 38.9 and 48.6, respectively. The mean (SD) SF-6D score was 0.68 (0.13) and the mean (SD) EQ-5D score was 0.73 (0.23). The mean (SD) RS disutility for gout was 0.05 (0.12), the mean TTO disutility was 0.03 (0.12), and the mean SG disutility was 0.02 (0.11). The RS disutilities of subject patients who ranked gout as their top concern (n = 17) trended towards being statistically significantly larger than those of the remaining patients, P = 0.06 but their TTO and SG disutilities were similar to those of the remaining patients. CONCLUSION: Although physical functioning of patients with gout is often compromised, patients with chronic stable gout do not assign a large disutility to gout per se. Still, patients who rank their gout as their top health concern tend to assign greater RS disutility to gout than do other patients.