ABSTRACT
The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.
Subject(s)
Coronavirus Infections/pathology , Histiocytes/pathology , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/virology , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Aged , Aged, 80 and over , Betacoronavirus , Bone Marrow/pathology , COVID-19 , Female , Humans , Hyperplasia/pathology , Hyperplasia/virology , Lung/pathology , Male , Middle Aged , Pandemics , SARS-CoV-2ABSTRACT
The current strategy for managing rheumatoid arthritis (RA) focuses on achieving clinical remission. Once remission is achieved and sustained over time, the most efficient strategy is dose optimization. This work describes the results of dose optimization after 2 years of follow-up in patients with RA treated with biological therapy and identifies predictive variables of response. Cohort: patients from the CREATE registry who, as of 1 November 2013, had been in clinical remission (DAS28 ≤2.6) for at least 6 months. INTERVENTION: Dose optimization was 20-50% of the standard dose. Outcome measurement were effectiveness (percentage of patients who continued to meet criteria for clinical remission) and efficiency (dose reduction and mean savings). Sixty-eight patients with RA were optimized, with initial mean DAS28 of 2.2 ± 0.7. After 2 years of follow-up, the mean DAS28 was 2.4 ± 0.7, a non-statistically significant difference. Twenty-eight patients (41.2%) continued in clinical remission with dose optimization after 2 years. Mean survival time was 14.2 months (95% CI 12.0-16.5). Of the 40 patients who needed to return to a standard dose, 57.5% managed to achieve remission again at 2 years. Mean dose reduction at 2 years was 21.17%, reaching a mean saving of 5576 ± 5099 per patient. In actual clinical practice, over 40% of patients with established RA who had been in sustained clinical remission managed to continue in remission 2 years after receiving optimized doses. The savings achieved was about 21% of the actual direct health costs for patients in the CREATE registry.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biological Products/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/economics , Arthritis, Rheumatoid/economics , Biological Products/administration & dosage , Biological Products/economics , Cost-Benefit Analysis , Drug Therapy, Combination , Female , Follow-Up Studies , Health Care Costs , Humans , Male , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Middle Aged , Registries , Remission Induction , Treatment OutcomeABSTRACT
BACKGROUND: There is little evidence of the impact of antimicrobial stewardship programmes on antimicrobial resistance. OBJECTIVES: To study the efficacy and safety of a package of educational and interventional measures to optimize linezolid use and its impact on bacterial resistance. METHODS: A quasi-experimental study was designed and carried out before and after implementation of a stewardship programme in hospitalized patients with Gram-positive infections treated with linezolid. RESULTS: The intervention reduced linezolid consumption by 76%. The risk of linezolid-resistant CoNS isolates (ORâ=â0.37; 95% CIâ=â0.27-0.49; Pâ<â0.001) and Enterococcus faecalis (ORâ=â0.44; 95% CIâ=â0.21-0.90; Pâ=â0.03) during the intervention period was lower than in the pre-intervention period. CONCLUSIONS: A programme to optimize linezolid use can contribute to reducing the resistance rate of CoNS and E. faecalis to this antibiotic.