Patrones de tratamiento con agentes biológicos, eficacia y sobrevida a largo plazo en pacientes con espondiloartritis axial: Impacto de los factores sociodemográficos en Latinoamérica / Patterns of treatment with biological agents, efficacy and long-term survival in patients with axial spondyloarthritis: Impact of sociodemographic factors in Latin America

Objetivos: Evaluar y comparar la eficacia y la sobrevida a largo plazo de las Drogas Modificadoras de la Enfermedad-biológicas (DME-b) en Espondiloartritis Axial (EsPax) mediante el índice LUNDEX y determinar las variables asociadas a la discontinuación de las mismas. Material y métodos: Estudio multicéntrico de corte transversal. Se incluyeron pacientes con EsPax en tratamiento con DME-b. Se registraron variables sociodemográficas, terapéuticas y clínicas. Se consignaron fechas de inicio del tratamiento con DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y causas de suspensión. La eficacia terapéutica se definió según BASDAI a los 6, 12 meses y luego anualmente a partir del inicio de la DME-b. Se calculó el índice LUNDEX en estos períodos. Análisis estadístico: Estadística descriptiva. Test de Student y test Chi² o test exacto de Fisher. Curvas de Kaplan-Meier y Log-Rank. Análisis de regresión proporcional de Cox. Resultados: Se estudiaron 101 pacientes con EsPax, 80,2% varones, con una edad mediana de 42 años (RIC 35-54,5) y un tiempo mediano de evolución de la enfermedad de 19,3 años (RIC 9,4-28,8). El 26,7% de los pacientes no tenían seguro de salud. Los agentes anti-TNFα utilizados como 1º DME-b en orden de frecuencia fueron: Etanercept (ETN) 44,6%, Adalimumab (ADA) 41,6%, Infliximab 7,9% y Certolizumab 5,9%. En el 32,7% de los casos, la DME-b se administró en combinación con una droga modificadora de enfermedad convencional. La sobrevida media fue de 66,2 meses (IC 95%: 51,8-80,5). Debido a que ETN y ADA se utilizaron en el 85% de los pacientes estudiados, se realizaron comparaciones solamente entre estos agentes. El tiempo medio de supervivencia acumulada fue significaticamente menor para ETN versus ADA (X 53,18±8,8 vs X 74,8±8,9, Log-Rank p=0,02), siendo la causa principal de suspensión, la falta de provisión de la medicación. El tiempo promedio de supervivencia para aquellos que no tenían seguro de salud fue significativamente menor X 31,9 meses (IC 95%: 19-45) con respecto a aquellos pacientes con dicho seguro X 72,3 meses (IC 95%: 55,3-89,3), p=0,03. Luego de ajustar por factores confundidores, la falta de un seguro de salud fue la única variable asociada en forma independiente con menor supervivencia del DME-b (HR 2,54, IC 95%: 1,18-5,75). El LUNDEX global fue del 52,7% a los 6 meses y del 46,9% a los 12 meses. Conclusiones: La sobrevida promedio del 1º DME-b fue de 5,5 años. La falta de cobertura de salud fue la única variable que influyó negativamente en la sobrevida del tratamiento con el 1º DME-b en pacientes con EsPax.

Objectives: To evaluate and compare the efficacy and long-term survival of biological disease-modifying drugs (b-DMARDs) in Axial Spondyloarthritis (axSpA) using the LUNDEX index and to determine the variables associated with the discontinuation of these drugs. Material and methods: Cross-sectional multicenter study. Patients with axSpA in treatment with b-DMARDs were included. Sociodemographic, therapeutic and clinical variables were recorded. The dates of initiation of treatment with b-DMARDs, concomitant treatment, suspension or change of treatment, and causes of suspension were recorded. Therapeutic efficacy was defined according to BASDAI at 6, 12 months and then annually from the initiation of b-DMARDs. The LUNDEX index was calculated in these periods. Statistical analysis: Descriptive statistics. Student's test and Chi² test or Fisher's exact test. Curves of Kaplan-Meier and Log-Rank. Proportional regression analysis of Cox. Results: 101 patients with axSpA were studied, 80.2% men, with a median age of 42 years (IQR 35-54.5) and a median disease duration of 19.3 years (IQR 9.4-28.8). 26.7% of patients didn´t have health insurance. The frequency of the anti-TNFα agent used as 1st b-DMARD was: Etanercept (ETA) 44.6%, Adalimumab (ADA) 41.6%, Infliximab 7.9%, and Certolizumab 5.9%. In 32.7% of the cases, the b-DMARD was administered in combination with a c-DMARD (conventional disease-modifying drug). The mean survival was 66.2 months (95% CI: 51.8-80.5). As ETA and ADA were used in 85% of the patients, comparisons were made only between these two agents. The mean survival time was significantly lower for ETA vs ADA (X 53.18 ±8.8 vs X 74.8±8.9, Log-Rank p=0.02), being the main cause of suspension, the lack of drug provision. The average survival time for those who didn´t have health insurance was significantly lower X 31.9 months (95% CI: 19-45) in comparison to those patients who had health insurance X 72.3 months (95% CI: 55.3-89.3), p=0.03. After adjusting for confounding factors, the lack of health insurance was the only variable independently associated with a lower survival of the b-DMARD (HR 2.54, 95% CI: 1.18 to 5.75). The global LUNDEX was 52.7% at 6 months and 46.9% at 12 months. Conclusions: The average survival of the 1st b-DMARD was 5.5 years. The lack of health insurance was the only variable that negatively influenced the survival of the treatment with the 1st b-DMARD in patients with axSpA.

Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy.

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi2 test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis.

Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the different WS states, to the changes in the WS states observed when body homeostasis is challenged by the external environment and when the return to normal ambient conditions allows sleep homeo- stasis to run without apparent physiological restrictions. The data summarized in this review suggest that an approach to the dichotomy between NREM and REM sleep based on physiological regulations may offer a framework within which observations that a traditional behavioral approach may overlook can be interpreted. The study of the interplay between body and sleep homeostasis appears, therefore, to be a way to understand the function of complex organisms beyond that of the specific regulations.

[Impact of left ventricular patterns and diastolic dysfunction on hemodialysis patients]. / Pattern cardiaci geometrici e disfunzione diastolica nel paziente uremico: quale l'impatto sul trattamento dialitico?

BACKGROUND: Left ventricular hypertrophy is the main manifestation of uraemic cardiomyopathy and predicts both cardiovascular events and death independently of conventional risk factors. Diastolic dysfunction is often associated with left ventricular hypertrophy, and accounts for up to 30% of heart failure. The aim of this study was to estimate the impact and the prevalence of left ventricular hypertrophy, its geometric models and diastolic dysfunction on haemodialysis patients, as well as the relationship with cardiac troponin, a specific marker for myocardial damage. METHODS: We enrolled in the study 31 patients (26 on haemodialysis, 5 on peritoneal dialysis) and 31 normal healthy subjects as the control group. Echocardiographic measurements were carried out according to the recommendations of the American Society of Echocardiography. Left ventricular mass was calculated according to the Devereux formula and indexed to height 2.7 We carried out Doppler echocardiography to study the diastolic function by measurements of isovolumic relaxation period (IVRT), E-wave deceleration time (DTE) and E/A ratio. We measured cardiac troponin using a third generation electrochemiluminescence immunoassay. We did the statistical analysis with the t test for comparison among groups, and we established correlations using the Pearson and Spearman correlation test. We considered values of p<0.05 to be statistically significant. RESULTS: Eccentric hypertrophy was the most frequent pattern (n=17; 55%), followed by normal cardiac geometry (n=7; 23%) and concentric hypertrophy (n=5; 16%). Only a minority of patients (n=2; 6%) showed concentric remodelling. Systolic dysfunction was present in 3 patients (EF<50%). Diastolic dysfunction was present in 24 out of 31 HD patients, that had abnormal relaxation pattern, characterised by prolonged IVRT, prolonged DTE and E/A ratio <1. Only one patient had restrictive filling pattern with reduced DTE and E/A ratio >2. Fourteen patients (45%) had E/A ratio < or =0.5, 10 patients (32%) had E/A ratio >0.5<1 and 7 patients (13%) had E/A ratio > or =1. DTE was prolonged in 14 patients (45%) and IVRT was prolonged in 6 patients (19%). The patients with E/A ratio < or =0.5 (n=14; 45%) suffered major hypotensive episodes during dialytic sessions compared to patients with E/A ratio >0.5, we found this difference to be statistically significant (p < 0.01). We observed the E/A ratio to be negatively correlated with age (r = -0.41; p=0.02) whereas DTE was positively correlated with posterior wall thickness (r =0.36; p= 0.05) and interventricular septum thickness (r =0.45; p=0.01). Cardiac troponin was positively correlated with age (r =0.50; p=0.00), left ventricular mass (r =0.41; p=0.02), posterior wall thickness (r =0.41; p=0.02) and interventricular septum thickness (r =0.39; p=0.03) but not with diastolic dysfunction parameters. Serum cardiac troponin was elevated (> or =0.10 micro g/L) in 12 patients (38.7%) and was associated with eccentric hypertrophy in all the cases. We detected no significant differences among groups with normal left ventricular geometry and left ventricular hypertrophy in the duration of the dialytic treatment, but we noted a statistically significant difference in relationship to age (p=0.03). CONCLUSIONS: Left ventricular hypertrophy is associated with diastolic dysfunction, both cause of hypotensive episodes during dialytic treatments and heart failure in patients with normal systolic function. The non invasive assessment of left ventricular diastolic function would represent an important advancement in the diagnosis and prevention of heart failure in haemodialysis patients.

[The measurement of vascular access recirculation and intra-access pressure in arteriovenous fistula monitoring in hemodialysis]. / La misura del ricircolo e delle pressioni statiche dell'accesso vascolare nel monitoraggio delle fistole artero-venose in emodialisi.

BACKGROUND: The main objective of monitoring vascular access flow in haemodialysis is maintenance of adequate access blood flow (Qac ) to prevent underdialysis and detection of haemodynamically significant stenosis prior to thrombosis. METHODS: Recirculation and intra-access pressure were measured to monitor arteriovenous fistulae in a group of haemodialysed patients, for a period of six months. Vascular access blood flow measurements were taken at the first (t0), second (t1) and sixth month (t2) by recirculation measurements using the thermodilution technique (BTM) consistent with Krivitsky's theory. Intra-access pressure measurements were made using the simplified Besarab's method. RESULTS: No statistically significant differences were noted in recirculation, vascular access blood flow, cardiac output and intra-access measurements during the three periods of the study. Vascular access blood flow was significantly and positively correlated with the arterial blood pressure measured at the same time, but not with the intra-access and venous pressures. Data indicate that mean Qac values = 300 mL/m. and induced recirculation values (Rp) = 45 and = 50 are correlated with angiographic findings of vascular access dysfunction. We observed that patients with mean Qac values between 300 and 650 mL/m had negative angiograms. CONCLUSIONS: We conclude that calculation of access flow by the double recirculation technique is a better and earlier predictor of access dysfunction whereas intra-access pressure measurements are not as useful for this purpose.

[Use of ergometry for evaluating left ventricular function in chronic aortic insufficiency]. / Utilidad de la ergometría para valorar la función ventricular izquierda en la insuficiencia aórtica crónica.

Fourteen patients with chronic aortic regurgitation (AR) underwent radionuclide angiography at rest and during supine exercise with ergometric controls. Ten subjects without evidence of heart disease were taken as controls. The behavior of heart rate, ST segment and R wave amplitude were analyzed at peak exercise in relationship with ejection fraction (EF) changes. Abnormal EF, (defined by an increase less than 10%, no change or decrease respect EF control), was present in 9 of 14 patients. Five of 14 patients had normal EF response to exercise defined by an increase of 10% or more than control value. Sensitivity and specificity of heart rate changes at exercise (abnormal: less than 10 beats to MET) to identify abnormal EF were 10% and 100%, respectively. The analysis of ST segment alterations at peak exercise (abnormal more than 2 mm ST depression) to the same objective showed 33% of sensitivity and 80% of specificity. Changes in R wave amplitude (abnormal: increase, no change or decrease less than 22% R wave amplitude at control) at peak exercise had 100% sensitivity and 80% of specificity to identify abnormal EF. Our results suggest that exercise test could be useful to analyze the response to left ventricular function during stress in patients with AR. Changes in R. wave amplitude at peak exercise appeared the best parameter.