Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study

Introduction

Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA.

Methods

Utilization of Metoject^® in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient’s clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration.

Result

Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three.

Conclusion

The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

     

The impacts of abnormal color vision on people's life: an integrative review

Quality of Life Research - This article shows an integrative review on the impact that abnormal color vision may have on the daily routine of individuals. We followed the PRISMA guidelines for...     

Fibrous dysplasia and McCune-Albright syndrome: case-report and differential diagnose with Paget bone disease

Fibrous dysplasia of bone or Jaffe Lischtenstein's disease is a genetic, non-inheritable disease of bone development, characterized by bone pain, deformities and fracture, mainly observed in yo ung adults. The frequency is equal between sexes. Mutations in the gene coding the Gsα, GNAS complex, results in osteoblastic differentiation defects, and bone resorption. The disease can have a monostotic or polyostotic form, or be associated with café-au-lait skin spots and precocious puberty (McCune-Al bright syndrome). The normal bone and bone marrow is replaced with abnormal benign intramedullary fibro-osseous tissue, and can involve any bone in the body. The vertebral involvement is rare. Radiological and pathological findings can be diagnostic. Biphosphonates and calcium, vitamin D and phosphorus supplements have been used in fibrous dysplasia treatment. Osteosarcoma is a rare, but serious malignant complication. We report the case of a 68 year old woman with a history of hypofisectomy, with a progressive low back pain, without systemic or neurological symptoms. The bone scan, the ra di o graphs and the computed tomography findings revealed polyostotic fibrous dysplasia, with vertebral and mandibular involvement. In this paper we compared fibrous dysplasia of bone with Paget bone disease.     

Structural isomerization of synephrine influences its uptake and ensuing glutathione depletion in rat-isolated cardiomyocytes

Synephrine is a natural compound, frequently added to ephedra-free dietary supplements for weight-loss, due to its effects as a nonspecific adrenergic agonist. Though only p-synephrine has been documented in plants, the presence of m-synephrine has also been reported in weight-loss products. The use of synephrine in dietary supplements was accompanied by reports of adverse effects, especially at the cardiovascular level. It is well known that the imbalance in cardiac glutathione levels can increase the risk of cardiomyopathy. The present work aimed to study the role of organic cation-mediated transport of m- and p-synephrine and the possibility that p- and m-synephrine induce intracellular changes in glutathione levels in calcium-tolerant freshly isolated cardiomyocytes from adult rat. After a 3 h incubation with 1 mM p- or m-synephrine, the intracellular content of synephrine was measured by gas chromatography/ion trap-mass spectrometry (GC/IT-MS); cell viability and intracellular glutathione levels were also determined. To evaluate the potential protective effects of antioxidants against the adverse effects elicited by m-synephrine, cells were pre-incubated for 30 min with Tiron (100 μM) or N-acetyl-cysteine (NAC) (1 mM). To assess the influence of α₁-adrenoceptors activation in glutathione depletion, a study with prazosin (100 nM) was also performed. The results obtained provide evidence that organic cation transporters OCT3 and OCT1 play a major role in m- and p-synephrine-mediated transport into the cardiomyocytes. The importance of these transporters seems similar for both isomers, although p-synephrine enters more into the cardiomyocytes. Furthermore, only m-synephrine induced intracellular total glutathione (GSHt) and reduced glutathione (GSH) depletion. NAC and Tiron were able to counteract the m-synephrine-induced GSH and GSHt decrease. On the other hand, the incubation with prazosin was not able to change m-synephrine-induced glutathione depletion showing that this effect is independent of α₁-adrenoceptor stimulation. In conclusion, both positional isomers require OCT3 and OCT1-mediated transport to enter into the cardiomyocytes; however, the hydroxyl group in the p-position favours the OCT-mediated transport into cardiomyocytes. Furthermore, the structural isomerization of synephrine influences its toxicological profile since only m-synephrine caused GSH depletion.     

Costs of illness and care in Parkinson's Disease: An evaluation in six countries

We investigated the costs of Parkinson's Disease (PD) in 486 patients based on a survey conducted in six countries. Economic data were collected over a 6-month period and presented from the societal perspective. The total mean costs per patient ranged from EUR 2620 to EUR 9820. Direct costs totalled about 60% to 70% and indirect costs about 30% to 40% of total costs. The proportions of costs components of PD vary notably; variations were due to differences in country-specific health system characteristics, macro economic conditions, as well as frequencies of resource use and price differences. However, inpatient care, long-term care and medication were identified as the major expenditures in the investigated countries.     

Surgical treatment of oral lymphangiomas with CO₂ laser: report of two uncommon cases

This paper reports the treatment of oral lymphangiomas with carbon dioxide CO? Laser. Lymphangiomas are rare congenital lymphatic malformations. These lesions are most frequently diagnosed during childhood, are most commonly located in the head and neck region, and are extremely rare in the oral cavity. Oral lymphangiomas are of complex treatment due to the difficulty in performing a complete excision. CO? laser is the most often used laser in the oral cavity due to its affinity with water and high absorption by the oral mucosa. Several benefits of the use of CO? laser have been reported for surgical oral procedures. The cases reported herein were biopsy-proven lymphangiomas of the oral cavity. The surgical procedures were carried out under local anesthesia and a focused CO? laser beam (λ10.600 nm, Φ ~2 mm, CW/RSP) was used. At the end of the surgery, the laser beam was used on a defocused mode to promote better hemostasis. Neither sutures nor dressings were used after surgery. No medication and only mouthwashes were prescribed to all patients on the postoperative period. There were no postsurgical complaints from the patients and no relapses of the conditions were observed after follow-up periods of 12 and 18 months. The use of CO? laser was practical, easy to carry out and effective on the treatment of oral lymphangiomas, with no lesion recurrence.