Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis.

MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.

Impacto del uso de remedios no convencionales en una población de enfermos reumáticos / Impact of the non conventional remedies in a rheumatic population

Objetivos: investigar la frecuencia y el impacto económico del uso de remedios no convencionales (RNC) en una población de enfermos reumáticos. Pacientes y métodos: Se encuestaron 275 pacientes con diferentes enfermedades reumáticas, que incluyeron variables de uso, características, costos y satisfacción de los RNC, apego al tratamiento formal, educación, estado laboral y estado funcional. Se excluyeron 4 por falta de consistencia en las respuestas. Resultados principales: Los pacientes encuestados provinieron de 8 consultorios de Reumatología de 2 hospitales de alta referencia, 2 hospitales de segundo nivel de atención y de 2 consultas privadas. El 84 por ciento fueron mujeres, la edad promedio fue de 40.7 años (ñ 14.1 DS) y la escolaridad fue de 8.4 años (ñ 4.7 DS). El 85.6 por ciento de los encuestados admitió haber utilizado RNC; el promedio fue de 3.4 RNC por paciente (rango 0-15). El 40 por ciento de los pacientes suspendió por lo menos una vez el tratamiento formal mientras que utilizaban RNC. El 31 por ciento de los RNC utilizados fueron percibidos por el paciente como de mucha utilidad. Sólo el 36.2 por ciento (n=98) de los encuestados refirió el costo de los RNC usados, siendo un total de N$70,137.62, o el equivalente a 48 días de salario mínimo en el área, por paciente. Conclusiones: El uso de RNC es frecuente en nuestra población de enfermos reumáticos y el impacto económico es importante. Desafortunadamente, la frecuencia de suspensión del tratamiento formal al utilizar RNC es elevada. Aunque es obvio el daño, queda por determinar el papel de los RNC en la morbimortalidad de los pacientes con enfermedades reumáticas