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PURPOSE: The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need. METHODS: We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay. RESULTS: We observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0-25 may omit chemotherapy without compromising outcomes. CONCLUSION: These data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Pronóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Quimioterapia Adyuvante , Perfilación de la Expresión Génica/métodosRESUMEN
BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR I) study demonstrated high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treatment. OBJECTIVE: We sought to determine the long-term natural history of disease and outcomes in patients in TENOR I after more than a decade. METHODS: TENOR I was a multicenter observational study (2001-2004) of 4756 patients with severe or difficult-to-treat asthma. TENOR II was a follow-up study of TENOR I patients using a single cross-sectional visit in 2013/2014. Overall, the sites participating in TENOR II originally enrolled 1230 patients in TENOR I. Clinical and patient-reported outcomes were assessed, including very poorly controlled asthma based on National Heart, Lung, and Blood Institute guidelines. RESULTS: A total of 341 (27.7%) patients were enrolled in TENOR II and were representative of the TENOR I cohort. The most frequent comorbidities were rhinitis (84.0%), sinusitis (47.8%), and gastroesophageal reflux disease (46.3%). Mean percent predicted prebronchodilator and postbronchodilator FEV1 were 72.7% (SD, 21.4%) and 78.2% (SD, 20.7%), respectively. A total of 231 (72.9%) of 317 patients had positive test responses to 1 or more allergen-specific IgEs. The mean blood eosinophil count was 200/µL (SD, 144/µL). Eighty-eight (25.8%) patients experienced an asthma exacerbation in the prior 3 months requiring hospital attention, oral corticosteroids, or both. More than half (197/339 [58.1%]) had very poorly controlled asthma. Medication use suggested undertreatment. CONCLUSION: TENOR II provides longitudinal data to characterize disease progression, heterogeneity, and severity in patients with severe or difficult-to-treat asthma. Findings show continued morbidity, including a high degree of comorbid conditions, allergic sensitization, exacerbations, and very poorly controlled asthma, including reduced lung function.
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Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/epidemiología , Corticoesteroides/inmunología , Adulto , Asma/inmunología , Protocolos Clínicos , Estudios de Cohortes , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/inmunología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted.
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Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Pautas de la Práctica en Medicina , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Biopsia , Médula Ósea/patología , Comorbilidad , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide de Fase Crónica/diagnóstico , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To evaluate several alternative measures of forced expiratory volume in 1 second percent predicted (FEV1 %pred) variability as potential predictors of future FEV1 %pred decline in patients with cystic fibrosis. STUDY DESIGN: We included 13,827 patients age ≥6 years from the Epidemiologic Study of Cystic Fibrosis 1994-2002 with ≥4 FEV1 %pred measurements spanning ≥366 days in both a 2-year baseline period and a 2-year follow-up period. We predicted change from best baseline FEV1 %pred to best follow-up FEV1 %pred and change from baseline to best in the second follow-up year by using multivariable regression stratified by 4 lung-disease stages. We assessed 5 measures of variability (some as deviations from the best and some as deviations from the trend line) both alone and after controlling for demographic and clinical factors and for the slope and level of FEV1 %pred. RESULTS: All 5 measures of FEV1 %pred variability were predictive, but the strongest predictor was median deviation from the best FEV1 %pred in the baseline period. The contribution to explanatory power (R(2)) was substantial and exceeded the total contribution of all other factors excluding the FEV1 %pred rate of decline. Adding the other variability measures provided minimal additional value. CONCLUSIONS: Median deviation from the best FEV1 %pred is a simple metric that markedly improves prediction of FEV1 %pred decline even after the inclusion of demographic and clinical characteristics and the FEV1 %pred rate of decline. The routine calculation of this variability measure could allow clinicians to better identify patients at risk and therefore in need of increased intervention.
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Fibrosis Quística/fisiopatología , Volumen Espiratorio Forzado , Pulmón/fisiopatología , Niño , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare but important cause of morbidity and mortality in children. METHODS AND RESULTS: We analyzed data from 216 patients ≤18 years of age at diagnosis who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Median age at diagnosis and enrollment was 7 and 15 years, respectively. The most frequent presenting symptom was dyspnea (idiopathic/familial PAH, 53%; PAH associated with congenital heart disease, 30%). Presyncope/syncope was more frequent in patients with idiopathic PAH/familial PAH (36%) than in those with PAH associated with congenital heart disease (4%). At diagnosis, mean pulmonary artery pressure and pulmonary vascular resistance index were 56 mm Hg and 17 Wood units · m(2), respectively. Five-year survival from diagnosis for the overall cohort was 74±6%, with no significant difference between the idiopathic PAH/familial PAH (n=122, 75±7%) and PAH associated with congenital heart disease (n=77, 71±13%) cohorts (P=0.53). Older age at diagnosis was the only variable significantly associated with decreased survival from diagnosis. Variables at enrollment that were significantly associated with decreased survival from enrollment included higher pulmonary vascular resistance index, lower-weight z scores, and familial PAH. Additional variables at enrollment, identified in a secondary analysis, that were marginally associated with increased survival from enrollment included acute vasoreactivity (adaptation of conventional pediatric definition; P=0.087) and lower brain natriuretic peptide (P=0.060). None of the 22 patients who were acute responders treated with high-dose calcium channel blockade as monotherapy or combination therapy died within 5 years of diagnosis. CONCLUSION: Using REVEAL, we identified key predictors of survival in childhood PAH. Refining these prognostic parameters should help clinicians improve outcomes. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00370214.
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Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/terapia , Sistema de Registros , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Manejo de la Enfermedad , Diagnóstico Precoz , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Lactante , Masculino , Tasa de Supervivencia/tendenciasRESUMEN
Purpose: The objective of this study was to assess the association between the Oncotype DX Genomic Prostate Score (GPS) assay and long-term outcomes in men with localized prostate cancer (PCa) after radiation therapy (RT). We hypothesized that the GPS assay is prognostic for biochemical failure (BCF), along with distant metastasis (DM) and PCa-specific mortality in patients with PCa receiving RT. Methods and Materials: We retrospectively studied men with localized PCa treated with definitive RT at Georgia Urology from 2010 to 2016. The primary objective was to assess the association between GPS results and time to BCF per the Phoenix criteria; we also assessed time to DM and PCa-specific mortality. We used Cox proportional hazards regression models for all analyses, with clinicopathologic covariates determined a priori for multivariable modeling. Results: A total of 450 patients (median age, 65 years; 35% Black) met eligibility criteria. There was a strong univariable association between GPS result and time to BCF (hazard ratio [HR] per 20-unit increase = 3.08; 95% confidence interval [CI], 2.11-4.46; P < .001), which persisted after adjusting for clinicopathologic characteristics in multivariable analyses. We also observed this association for time to DM (HR = 5.19; 95% CI, 3.06-8.77; P < .001) and PCa-specific mortality (HR = 13.07; 95% CI, 4.42-49.39; P < .001). Race was not a predictor of time to BCF or DM, and the GPS assay was strongly prognostic for all endpoints in Black and White patients. Conclusions: In a community-based cohort, the GPS assay was strongly prognostic for time to BCF as well as long-term outcomes in men treated with RT for localized PCa.
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BACKGROUND: Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use. METHODS AND RESULTS: Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique. CONCLUSIONS: We identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.
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Hipertensión Pulmonar/mortalidad , Sistema de Registros , Insuficiencia Renal/mortalidad , Resistencia Vascular , Adulto , Anciano , Presión Sanguínea , Monóxido de Carbono/sangre , Supervivencia sin Enfermedad , Femenino , Frecuencia Cardíaca , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/sangre , Estudios Prospectivos , Insuficiencia Renal/sangre , Insuficiencia Renal/fisiopatología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Six-minute walk distance (6MWD) is used in the REVEAL equation to predict 1-year survival for patients with pulmonary arterial hypertension. We sought to determine whether exercise treadmill testing (ETT) could be used in its place. METHODS: This was a single-center study in which 449 patients were enrolled. The variables predictive of survival in the REVEAL equation were evaluated and compared with survival predicted by the REVEAL equation without an exercise measure and a revised equation using ETT. RESULTS: The addition of ETT to the equation improved the predictive ability of the REVEAL equation in the high- and low-risk patient groups. CONCLUSION: The study findings suggest that the addition of ETT parameters to the REVEAL prognostic equation improves the predictive value of the equation when 6-minute walk distance is unavailable.
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Prueba de Esfuerzo , Hipertensión Pulmonar/mortalidad , Adulto , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Valor Predictivo de las Pruebas , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/Respiratory Society guideline-derived risk assessment strategies. METHODS: A subpopulation from the US-based registry REVEAL that survived ≥ 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk. RESULTS: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed ≥ 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk. CONCLUSIONS: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00370214; URL: www.clinicaltrials.gov.
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Hipertensión Arterial Pulmonar/mortalidad , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sistema de Registros , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes. METHODS: To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na+] < 135 mEq/L within 24 hours of admission value. RESULTS: Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 +/- 15.7 vs. 68.0 +/- 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 +/- 1.7 vs. 1.6 +/- 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 +/- 5.6 vs. 5.3 +/- 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 +/- 5.3 vs. 7.0 +/- 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20-2.08), MV (OR 1.75 95% CI 1.13-2.69), and hospital death (OR 1.3, 95% CI 0.90-1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs. CONCLUSION: Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na+] may impact these outcomes.
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Hiponatremia/epidemiología , Neumonía/epidemiología , Anciano , Anciano de 80 o más Años , Infecciones Comunitarias Adquiridas , Comorbilidad , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
RATIONALE: Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. OBJECTIVES: To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. METHODS: We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. RESULTS: We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2.04) during the corresponding 2-year period, a 37.5% slower decline among users compared with nonusers (95% confidence interval; 0.4%, 71.3%; P = 0.046). The users had better subsequent survival (P < 0.001): the unadjusted and adjusted hazard ratios for mortality (high-dose ibuprofen/non-high-dose ibuprofen) (95% confidence interval) were 0.75 (0.64, 0.87) and 0.82 (0.69, 0.96). CONCLUSIONS: In a propensity-score matched cohort study of children with cystic fibrosis, we observed an association between high-dose ibuprofen use and both slower lung function decline and improved long-term survival. These results are consistent with the hypothesis that treatment-associated reduction of lung function decline in children with cystic fibrosis leads to improved survival.
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Antiinflamatorios no Esteroideos/administración & dosificación , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/mortalidad , Ibuprofeno/administración & dosificación , Adolescente , Niño , Relación Dosis-Respuesta a Droga , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Puntaje de Propensión , Estudios Prospectivos , Sistema de Registros , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. METHODS: Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. RESULTS: Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. CONCLUSIONS: Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications.
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Manejo de la Enfermedad , Hemodinámica/fisiología , Hipertensión Pulmonar/terapia , Sistema de Registros , Medición de Riesgo/métodos , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Uncorrected congenital heart disease (CHD) frequently leads to pulmonary arterial hypertension (PAH), the most severe form of which is Eisenmenger syndrome (ES). We compared patients with idiopathic or heritable PAH (IPAH or HPAH; n = 1,626) against those with CHD-associated PAH (n = 353) who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL Registry). Of patients with CHD-associated PAH, 151 had ES. Compared with the IPAH or HPAH cohort, the ES cohort had greater systemic blood flow (2 ± 1 vs 3 ± 2 L/min/m(2), p <0.001), lower mean right atrial pressure (10 ± 6 vs 7 ± 4 mm Hg, p <0.001), higher mean pulmonary artery pressure (53 ± 14 vs 65 ± 17 mm Hg, p <0.001), higher pulmonary vascular resistance index (22 ± 12 vs 32 ± 31 Wood units × m(2), p <0.001), and lower systemic arterial oxygen saturation at rest (92 ± 11% vs 84 ± 13%, p <0.001). At 4 years from enrollment and 7 years from diagnosis, survival rate was similar between IPAH or HPAH and CHD-associated PAH cohorts. For the overall CHD-associated PAH cohort, longer 6-minute walk distance, lower mean right atrial pressure, brain natriuretic peptide level <50 pg/ml, and the presence of acute vasoreactivity were predictors of survival at 4 years from enrollment; younger age and lower mean right atrial pressure were predictors of survival at 7 years from diagnosis. In conclusion, these observations support predicted physiologic differences (e.g., hemodynamics) between patients with IPAH or HPAH and patients with CHD-associated PAH, with or without a systemic-pulmonary shunt. These differences, however, did not translate into significantly improved 4- and 7-year survival rates in patients with ES versus IPAH or HPAH and CHD-associated PAH.
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Cardiopatías Congénitas/complicaciones , Hemodinámica/fisiología , Hipertensión Pulmonar/etiología , Sistema de Registros , Adulto , Cateterismo Cardíaco , Hipertensión Pulmonar Primaria Familiar , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/epidemiología , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/fisiopatología , Incidencia , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: In pulmonary arterial hypertension (PAH), survival predictions can be important for optimization of therapeutic strategies. The present study aimed to validate a quantitative algorithm for predicting survival derived from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) and develop a simplified calculator for everyday clinical use. METHODS: Prospectively collected data from patients with newly diagnosed (< 3 months) World Health Organization group I pulmonary hypertension enrolled in the REVEAL Registry were used to validate a predictive algorithm for 1-year survival. Model calibration was evaluated by comparing algorithm-predicted survival with observed Kaplan-Meier estimates for the overall validation cohort and for five risk groups. Similarly, the risk discriminators for the simplified calculator were compared with those of the quantitative algorithm. RESULTS: The validation cohort comprised 504 individuals with mean ± SD 6-min walk distance 308 ± 128 m, and 61.5% were functional class III. The proportion of patients surviving 1 year fell within the range predicted by the model (95.1%, 91.5%, 84.6%, 76.3%, and 58.2%, respectively) among patients in the low (predicted survival ≥ 95%), average (90% to < 95%), moderate (85% to < 90%), high (70% to < 85%), and very high (< 70%) risk strata. Predicted and observed 1-year survival were similar across risk stratum, and the c-index indicated good discrimination for both the full equation (0.726) and the simplified risk calculator (0.724). CONCLUSIONS: The REVEAL Registry predictive algorithm and simplified risk score calculator are well calibrated and demonstrate good discriminatory ability in patients with newly or previously diagnosed PAH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.
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Algoritmos , Hipertensión Pulmonar/fisiopatología , Medición de Riesgo/métodos , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Pruebas de Función Respiratoria , Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is common in patients with left heart failure (HF), especially those with HF and preserved ejection fraction (HFpEF). However, there is limited data on risk stratification in these patients. METHODS: Baseline clinical and hemodynamic variables of 339 patients with World Health Organization (WHO) Group 2 PH, 90% of whom had HFpEF, were studied to derive a multivariate Cox proportional hazards model. A simplified prognostic risk score was created based on the outcome of all-cause mortality. Nine predictors, significant after stepwise multivariable regression (p < 0.05), were used to create the risk score. Components of the risk score were functional class, diastolic blood pressure, pulmonary artery saturation, interstitial lung disease, hypotension on initial presentation, right ventricular hypertrophy, diffusion capacity of the lung for carbon monoxide, and 2 serum creatinine variables (≤ 0.9 mg/dl and ≥ 1.4 mg/dl). RESULTS: Overall 2-year survival was 73.8% ± 2.4% in the derivation cohort, and 87.5% ± 2.3%, 66.4% ± 4.9%, and 24.4% ± 6.7% for risk scores of 0 to 2, 3 to 4, and 5+, respectively (p < 0.0001 for the trend), with a C-index of 0.76 (95% confidence interval [CI], 0.71-0.81). The risk score was validated in 2 independent PH-HFpEF cohorts: 179 patients with a C-index of 0.68 (95% CI, 0.55-0.80) and 117 patients with a C-index of 0.68 (95% CI, 0.53-0.83). For the 3 cohorts combined (N = 635), the overall C-index was 0.72 (95% CI 0.68-0.76). In all 3 cohorts individually and in the 3 cohorts combined, the risk score predicted death (hazard ratio, 1.4-1.6; p < 0.01). CONCLUSIONS: Several clinical factors independently predict death in PH-HFpEF confirmed by validation. A novel risk score composed of these factors can be used to determine prognosis and may be useful in making therapeutic decisions.
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Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/fisiopatología , Volumen Sistólico/fisiología , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión Pulmonar/mortalidad , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , UltrasonografíaRESUMEN
Cardiopulmonary hemodynamics are estimated by Doppler echocardiogram (ECHO) and measured by right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH). Whether there is a correlation between these measurements is controversial. The authors investigated ECHO and RHC in patients enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL), a multicenter, observational, US-based study designed to provide current information about patients with PAH. Patients with PAH who had an ECHO and RHC within 12 months of each other were included. Correlation between subsequent ECHO and RHC was also investigated. Of 2967 patients, 2838 were 18 years and older at enrollment and 1883 had an RHC within 12 months of an ECHO. Correlations between ECHO-estimated and RHC-measured pulmonary artery systolic pressures (PASPs) and mean right atrial pressures did not change based on temporal proximity of the two baseline studies, whether they occurred on the same day or were separated by up to 12 months. In contrast, there was little correlation of serial measurements between ECHO and RHC. Although there is good correlation in PASP between ECHO and RHC at baseline, repeat ECHO measurements alone are not sufficient to monitor change in PASP or progression of PAH.
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Cateterismo Cardíaco/métodos , Ecocardiografía/métodos , Hipertensión Pulmonar/diagnóstico , Arteria Pulmonar/diagnóstico por imagen , Función Ventricular Derecha/fisiología , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/cirugía , Masculino , Persona de Mediana Edad , SístoleRESUMEN
OBJECTIVE: To investigate the correlation between body mass index (BMI) and pulmonary artery systolic pressure in a large population of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: The BMI of patients with group 1 PAH enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) was compared with that of age- and sex-matched controls in the National Health and Nutrition Examination Survey (NHANES) to clarify whether obesity is linked with PAH. The diagnosis of PAH was defined in REVEAL by right-sided heart catheterization. Differences in BMI and the percentage of patients considered obese (BMI ≥30) and underweight (BMI <18.5) in various subgroups of patients enrolled in REVEAL from March 30, 2006, through September 11, 2007, were determined. RESULTS: Mean BMI was no different for patients with PAH (n=2141) than for the NHANES normal comparison group; however, the proportion of obese and underweight patients was increased in patients with PAH. Subgroup analysis demonstrated that subgroups with idiopathic PAH and those with PAH associated with drugs and toxins had both higher BMI and percentage of obese patients, whereas 3 other subgroups (those with PAH associated with congenital heart disease, connective tissue disease, and human immunodeficiency virus) had lower mean BMI. CONCLUSION: Mean BMI of the REVEAL patients was the same as that of the NHANES normal comparison group; however, there were higher percentages of obese and underweight patients in REVEAL. This discrepancy can be explained by the balancing effect of more overweight and underweight patients in different PAH subgroups. The reason for the increased frequency of obesity in idiopathic PAH is unknown, and additional study is needed.
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Presión Sanguínea , Índice de Masa Corporal , Hipertensión Pulmonar/epidemiología , Obesidad/epidemiología , Delgadez/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To examine trends in annual medical expenditures from 1997 to 2005 among adults with arthritis and other rheumatic conditions (denoted Arthritis group). METHODS: We analyzed annual medical expenditures (2005 US dollars) among adults with Arthritis using the Medical Expenditure Panel Survey (MEPS), a nationally representative survey of the US civilian, noninstitutionalized population. Expenditures were stratified by Arthritis and comorbidity status. RESULTS: The Arthritis population increased by 22% (36.8 to 44.9 million) during this period, attributable entirely to the subpopulation with at least one comorbid condition (31.8 to 40.3 million). The overall, inflation-adjusted annual mean medical expenditures for adults with Arthritis increased from $6,848 in 1997 to $7,854 in 2005. In 1997, inpatient care was the most expensive component of overall expenditures (mean $2,702), but beginning in 2001, mean inpatient and ambulatory expenditures were almost identical. Mean prescription expenditures increased nearly every year, almost doubling from $970 in 1997 to $1,811 in 2005. Aggregate total expenditures for the Arthritis population increased markedly during this period, from $252.0 to $353.0 billion (+40%). Most of this increase was attributable to the population increase in the Arthritis and comorbid condition subgroup. CONCLUSION: Mean annual ambulatory and prescription expenditures for adults with Arthritis increased far above the rate of medical inflation, offsetting a relative decline in inpatient expenditures. Increases in overall mean and aggregate total expenditures are attributable to the increasing number of adults with Arthritis and at least one comorbid chronic condition. Projected increases in this population suggest that these expenditures will continue to rise.
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Artritis/economía , Costos de los Medicamentos/tendencias , Costos de la Atención en Salud/tendencias , Gastos en Salud/tendencias , Enfermedades Reumáticas/economía , Adulto , Humanos , Pacientes Internos , Medicare/estadística & datos numéricos , Estados UnidosRESUMEN
OBJECTIVE: The goal of this study is to provide annual estimates for the treated prevalence and expenditures attributable to overactive bladder (OAB) in the elderly prior to Medicare Part D drug coverage. RESEARCH DESIGN AND METHODS: All Medicare claims were extracted for beneficiaries over 65 with continuous coverage for Medicare Parts A and B during 2003-2004. Two OAB definitions were created: (1) the base case included diagnosis codes that narrowly defined OAB, and (2) the sensitivity variant included additional codes indicative of OAB. Descriptive comparisons of baseline characteristics, annual expenditures, and events and procedures were performed for OAB vs. non-OAB subjects meeting the inclusion criteria. CMS expenditures (2004 US dollars) for individuals were totaled and multiple regression techniques were used to estimate costs attributable to OAB after adjusting for demographic characteristics and comorbid conditions. RESULTS: The prevalence of subjects with an OAB diagnosis ranged from 8.8 to 13.6% for the base and sensitivity definitions, respectively. While mean total annual expenditures ranged from $9331 to $9655, mean annual expenditures attributable to OAB ranged from $825 to $1184 per subject (9-12% of total medical expenditures for OAB subjects), with aggregate total OAB-attributable expenditures of $1.8-3.9 billion per year. CONCLUSIONS: The treated prevalence of individuals seeking treatment for OAB in the elderly Medicare population is comparable to some common chronic conditions in that population, and OAB-attributable CMS expenditures are considerable. However, due to study limitations this is a conservative estimate of the direct cost of OAB in the elderly population. The reported estimates exclude pharmacy and out-of-pocket costs, are extrapolated to only two-thirds of the elderly Medicare population, and do not include expenditures by Medicaid for long-term care. Additionally, claims data limits detection of chronic conditions to patients who receive treatment or consultation for OAB; diagnosis codes used were based on expert opinion rather than a review of medical records to identify OAB patients; and long-term care costs are not included.