Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up

ABSTRACT Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objective: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). Conclusion: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

Uso de medicina complementaria y alternativa y su asociación con la relación médico-paciente en enfermos con artritis reumatoide / Association between physician-patient relationship and the use of complementary and alternative medicine in patients with rheumatoid arthritis

RESUMEN Introducción: El uso de medicina complementaria y alternativa (MCA) en pacientes con enfermedades reumáticas es prevalente pero la comunicación con el reumatólogo suele ser deficiente, lo cual afecta la relación médico-paciente (RMP). Objetivos: Evaluar la asociación entre el uso de MCA y la RMP en enfermos con artritis reumatoide. Como objetivos adicionales, describir la percepción del paciente sobre la comunicación con su reumatólogo respecto al uso de MCA y el patrón de uso de las diferentes modalidades terapéuticas. Materiales y métodos: Estudio descriptivo de corte transversal. El uso de MCA y la RMP se evaluaron mediante la autoaplicación de cuestionarios validados (I-CAM-Q y PDRQ-9 respectivamente). Resultados: Se incluyó a 246 pacientes ambulatorios de una institución de tercer nivel de atención. Se encontró asociación entre una mayor satisfacción con el tratamiento y el no usar MCA, y entre el hecho de informar al reumatólogo sobre el uso de MCA con un mayor grado de acuerdo con el médico sobre el origen de los síntomas y mayor satisfacción con el tratamiento. Las modalidades más frecuentemente utilizadas fueron: quiropraxia, acupuntura y productos herbales. El 78,5% afirmaron estar de acuerdo con comunicar el uso de este tipo de medicación al reumatólogo, sin embargo, solo el 31,3% lo notificó, por temor a represalias (54,4%). Conclusiones: Pese a la alta prevalencia de uso de MCA en nuestros pacientes, la mayoría no lo comunicó al reumatólogo. Se encontró asociación entre el uso de MCA y una menor satisfacción del paciente con el tratamiento y entre la comunicación médico-paciente sobre la práctica de MCA y una mejor satisfacción con el tratamiento.

ABSTRACT Introduction: Although complementary and alternative medicine (CAM) use among patients with rheumatic diseases is extensive, discussions regarding these treatments occur rarely in the rheumatology setting, directly affecting the physician-patient relationship (PPR). Objectives: The aim of this study was to evaluate the association between patient-physician relationship and complementary and alternative medicine use. As secondary objectives, to describe the patient's perspective towards CAM use and estimate the prevalence of CAM treatments used in patients with rheumatoid arthritis. Methods and materials: A descriptive cross-sectional survey was conducted, in which CAM use and physician-patient relationship were assessed by self-reported validated questionnaires (I-CAM-Q and PDRQ-9, respectively). Results: The study included a total of 246 outpatients of a tertiary care hospital. There were no significant differences between CAM users vs. non-users, or informers vs. non-informers in terms of physician-patient relationship measured by PDQR. The most frequent used CAM treatments were: chiropractice, acupuncture, and herbal products. A large majority (78.5%) of the patients expressed agreement to the discussion of CAM use with the rheumatologist, but only 31.3% of total CAM users did so because of fear of retaliation (54.4%). Conclusion: Despite the extensive practice of CAM among patients with rheumatoid arthritis, most patients did not discuss these treatments with their physicians. Associations were found between MCA use and a lower patient's treatment satisfaction and between physician-patient communication about CAM practice and a higher patient's treatment satisfaction.

III. The role of the Research Ethics Committees in the regulation of Pharma-Sponsored studies

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects’ first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.