RESUMO
BACKGROUND: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. METHODS: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. RESULTS: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. CONCLUSION: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Triagem/métodos , Serviço Hospitalar de Emergência , Hospitalização , Unidades de Terapia IntensivaRESUMO
Systemic sclerosis is classed as a diffuse (systemic) disease of connective tissue. It is a heterogeneous disease significantly shortening life expectancy. Its etiology is unknown. Pathogenetic interplay is assumed to involve a triad of pathological autoimmune inflammation, vasculopathy and fibrosis. Clinical manifestations can be classed based on the preponderant pathogenetic process. Vasculopathy is manifested by secondary Raynauds phenomenon with abnormal findings on the nailfold capillaroscopy, skin telangiectasias, gastric antral vascular ectasia, life threatening scleroderma renal crisis, digital ulcerations and prognostically severe pulmonary arterial hypertension. The treatment of vascular manifestations uses medicines with vasodilation effect. The manifestation of inflammation is accentuated by pleurisy, pericarditis, myositis, synovitis/arthritis and alveolitis. Finally, the manifestation of fibrosis predominates in association with dermatosclerosis, interstitial lung disease and fibrotic impairment of the gastrointestinal tract. Medicines with immunomodulatory or immunosupressive effects are used to affect the inflammation and fibrosis. Despite the aforementioned, there is still no universally effective treatment available. The pharmacological therapy of this disease is organ specific and symptomatic.Key words: capillaroscopy - digital ulcers - interstitial lung disease - pulmonary arterial hypertension - scleroderma renal crisis - systemic sclerosis.
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Escleroderma Sistêmico , Humanos , Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Angioscopia Microscópica , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia , Telangiectasia/etiologiaRESUMO
RE-VERSE AD, a prospective multicentric cohort study, examined the effect of idarucizumab on 2 cohorts of patients anticoagulated with dabigatran - in cohort A in patients with uncontrollable or life threatening bleeding, in cohort B in patients who undergo acute surgery. Within the study patients were intravenously administered 5 g antidote divided into 2 doses per 2.5 g within 15 min to eliminate the anticoagulation effect of dabigatran. A series of case studies is presented to describe the use of idarucizumab within the RE-VERSE AD study and in clinical practice in the period of 2015-2016 at the University Hospital Hradec Králové. The included examples illustrate the benefit of dabigatran as the only drug so far from the group of direct oral anticoagulants which has an antidote.Key words: antidote - bleeding - dabigatran - direct oral anticoagulants - DOAC - high risk of bleeding - idarucizumab - intervention.
Assuntos
Anticorpos Monoclonais Humanizados , Anticoagulantes , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Estudos de Coortes , Dabigatrana/uso terapêutico , Humanos , Estudos ProspectivosRESUMO
Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene are predictive of MTX response. Comparison was made using EULAR response criteria and according to the change of DAS28 (∆DAS28) after a 6-month MTX treatment in RA patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been genotyped. A total of 120 patients were enrolled in the study, and all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η (2) = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/efeitos adversos , Antirreumáticos/metabolismo , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Estudos Transversais , República Tcheca , Feminino , Heterozigoto , Homozigoto , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Metotrexato/efeitos adversos , Metotrexato/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Farmacogenética , Fenótipo , Reação em Cadeia da Polimerase , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Aim: We studied the influence of coffee consumption on the therapeutic effect of methotrexate (MTX) in patients with rheumatoid arthritis (RA) sorted according to ADORA2A genotypes. Patients & methods: 82 RA patients were dichotomized according to caffeine intake with a threshold of 700 mg/week. Disease activity score 28 (DAS28) was applied (>3.2: high; <3.2: low or remission). Patients were genotyped using quantitative PCR allelic discrimination. Results: We found significantly higher risk of RA in patients with higher caffeine intake and the CT genotype of ADOARA2A rs2298383, rs3761422 and rs2267076 SNPs. The CC genotype of ADORA2A rs2236624 SNP in patients with lower caffeine intake treated with MTX is significantly protective. Conclusion:ADORA2A genotypes and coffee intake influence risk of RA and efficacy of it MTX treatment.
Assuntos
Adenosina/genética , Adenosina/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Café/metabolismo , Receptor A2A de Adenosina/genética , Adulto , Antirreumáticos/metabolismo , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Café/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Metotrexato/metabolismo , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases. Glucocorticoids (GCs) are first-choice drugs for PMR and GCA, although some patients show poor responsiveness to the initial GC regimen or experience flares after GC tapering. To date, no valid biomarkers have been found to predict which patients are at most risk for developing GC resistance. In this review, we summarize PMR- and GCA-related gene polymorphisms and we associate these gene variants with GC resistance and therapeutic outcomes. A limited number of GC resistance associated-polymorphisms have been published so far, mostly related to HLA-DRB1*04 allele. Other genes such ICAM-1, TLR4 and 9, VEGF, and INFG may play a role, although discrepancies are often found among different populations. We conclude that more studies are required to identify reliable biomarkers of GC resistance. Such biomarkers could help distinguish non-responders from responders to GC treatment, with concomitant consequences for therapeutic strategy.
RESUMO
Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).