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1.
N Engl J Med ; 385(10): 885-895, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34469646

RESUMO

BACKGROUND: Immune thrombocytopenia is a rare autoimmune disorder with associated bleeding risk and fatigue. Recommended first-line treatment for immune thrombocytopenia is high-dose glucocorticoids, but side effects, variable responses, and high relapse rates are serious drawbacks. METHODS: In this multicenter, open-label, randomized, controlled trial conducted in the United Kingdom, we assigned adult patients with immune thrombocytopenia, in a 1:1 ratio, to first-line treatment with a glucocorticoid only (standard care) or combined glucocorticoid and mycophenolate mofetil. The primary efficacy outcome was treatment failure, defined as a platelet count of less than 30×109 per liter and initiation of a second-line treatment, assessed in a time-to-event analysis. Secondary outcomes were response rates, side effects, occurrence of bleeding, patient-reported quality-of-life measures, and serious adverse events. RESULTS: A total of 120 patients with immune thrombocytopenia underwent randomization (52.4% male; mean age, 54 years [range 17 to 87]; mean platelet level, 7×109 per liter) and were followed for up to 2 years after beginning trial treatment. The mycophenolate mofetil group had fewer treatment failures than the glucocorticoid-only group (22% [13 of 59 patients] vs. 44% [27 of 61 patients]; hazard ratio, 0.41; range, 0.21 to 0.80; P = 0.008) and greater response (91.5% of patients having platelet counts greater than 100×109 per liter vs. 63.9%; P<0.001). We found no evidence of a difference between the groups in the occurrence of bleeding, rescue treatments, or treatment side effects, including infection. However, patients in the mycophenolate mofetil group reported worse quality-of-life outcomes regarding physical function and fatigue than those in the glucocorticoid-only group. CONCLUSIONS: The addition of mycophenolate mofetil to a glucocorticoid for first-line treatment of immune thrombocytopenia resulted in greater response and a lower risk of refractory or relapsed immune thrombocytopenia, but with somewhat decreased quality of life. (Funded by the U.K. National Institute for Health Research; FLIGHT ClinicalTrials.gov number, NCT03156452; EudraCT number, 2017-001171-23.).


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Fadiga/induzido quimicamente , Feminino , Glucocorticoides/efeitos adversos , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/complicações , Qualidade de Vida , Adulto Jovem
2.
J Am Podiatr Med Assoc ; 111(4)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478539

RESUMO

Triamcinolone acetonide is a synthetic glucocorticoid used to treat numerous acute and chronic inflammatory conditions. The various side effects of this drug from parenteral administration are well documented in the literature. In this study, three patients present with a rare side effect of violaceous dermal pigmentation. To the best of the authors' knowledge, this finding is rarely presented in the current literature. The purpose of this study is to provide awareness of a less-documented, delayed side effect from triamcinolone acetonide administration. Although all patients presenting in this study had a known history of autoimmune disease (eg, lupus, psoriatic arthritis) further research is needed to suggest a possible association between dermal violaceous change and the use of triamcinolone.


Assuntos
Doenças Autoimunes , Triancinolona Acetonida , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Glucocorticoides/efeitos adversos , Humanos , Triancinolona Acetonida/efeitos adversos
3.
Int J Chron Obstruct Pulmon Dis ; 16: 2419-2431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471349

RESUMO

Background: Clinicians' selection of glucocorticoids during hospitalization of COPD patients is often based on the medical staff's judgment of the patient's condition, and there is no objective judgment standard. The purpose of this study was to investigate the outcome of severe COPD deterioration in patients treated with glucocorticoid and without glucocorticoid during hospitalization. Methods: This study was an observational cohort study. Data on hospitalization with severe COPD deterioration were collected and followed up for 1 year. One year after discharge, the re-hospitalization due to COPD was collected retrospectively. The patients were divided into glucocorticoid group and control group according to whether the patients were given glucocorticoid therapy or not when they were admitted to hospital for the first time. The primary outcome was rate of future COPD exacerbations, while the secondary outcome was hospital stay, treatment cost and COPD-related readmission time. These results are analyzed by using Poisson model and Cox regression model. Results: A total of 91 patients were enrolled in the study, including 39 in the control group and 52 in the glucocorticoid group. The annual rate of future COPD exacerbations in the glucocorticoid group was significantly lower than that in the control group (RR,0.50 [95% CI, 0.26-0.98]; P = 0.045). The risk of COPD recurrence in the glucocorticoid group was lower than that in the control group, as assessed in a time-to-first-event analysis (HR,0.46[95% CI 0.22-0.97]; P = 0.042). Subgroup analysis found that in patients with blood eosinophil <100 cells/µ l, the future annual severe exacerbation rate of glucocorticoid group was significantly lower than that in the control group (adjusted RR,0.37 [95% CI 0.17-0.83]; P = 0.016). Conclusion: The use of glucocorticoids during hospitalization in COPD can more effectively reduce the severe deterioration of COPD than without glucocorticoids.


Assuntos
Glucocorticoides , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Eosinófilos , Glucocorticoides/efeitos adversos , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos
4.
Respir Res ; 22(1): 245, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526033

RESUMO

BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/virologia , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal , Irã (Geográfico) , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
5.
Z Rheumatol ; 80(7): 670-687, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34357436

RESUMO

BACKGROUND: Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use. OBJECTIVE: To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. METHODS: A systematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in a structured group consensus process. RESULTS: Recommendations include supplementation with calcium and vitamin D under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3-5 years or after termination of long-term GC treatment. CONCLUSION: This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Reumatologia , Adulto , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Glucocorticoides/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(7): 704-710, 2021 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34382586

RESUMO

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.


Assuntos
Pacientes Internados , Lúpus Eritematoso Sistêmico , Idoso , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Prednisona , Fatores de Risco
8.
Arch Osteoporos ; 16(1): 108, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34347188

RESUMO

Glucocorticoid-induced osteoporosis (GIOP) is a common condition associated with increased risk for fracture. Many patients receive suboptimal care. We created a novel GIOP clinic model which successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. INTRODUCTION: This study characterizes the patient population referred to our novel glucocorticoid-induced osteoporosis (GIOP) clinic and evaluates how well the clinic performed in addressing key components of GIOP preventive care. METHODS: This population-based prospective cohort study derives data from patients reviewed at the University of Alberta Multidisciplinary Bone Health Clinic from January 2017 to September 2019. To create our clinic model, key components of GIOP preventive care were summarized based on current guidelines, and clear responsibilities were delegated to each multidisciplinary team member. A REDCap database was constructed, and each patient's multidisciplinary assessment was entered at each visit. Demographic and treatment data was extracted from our database. RESULTS: The clinic was able to achieve optimal GIOP preventive care in 60.1% of patients and in 78.7% of patients when excluding wait time. Of the 245 GIOP patients assessed, over half were females (56.7%) and the mean age was 56.7 years (range 16-95 years). Referrals were primarily made by specialists. Low-trauma fractures were reported in 24.9% of patients and 95.5% of patients had a baseline dual-energy X-ray absorptiometry (DXA). The mean current daily prednisone-equivalent dose was 14.1 mg. All patients received a recommendation for pharmacotherapy (100%) and the majority received counseling on vitamin D (98.8%), calcium (97.8%), smoking cessation (98.8%), alcohol reduction (98.4%), falls prevention (88.6%), and exercise (85.3%). CONCLUSION: Our novel GIOP clinic model successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. Further studies are required to assess the real-world long-term outcomes of our model.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Estudos Prospectivos , Adulto Jovem
9.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360594

RESUMO

Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11ß-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11ß-HSD1 activity ex vivo. Using the TNF-α-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11ß-HSD1 global knock-out (11ßKO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11ß-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg11ßKO mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg11ßKO mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg11ßKO compared to TNF-tg mice. In summary, 11ß-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11ß-HSD1 may offer a strategy to refine the safety of glucocorticoids.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Artrite Reumatoide/tratamento farmacológico , Deleção de Genes , Glucocorticoides/efeitos adversos , Atrofia Muscular/prevenção & controle , Osteoartrite do Quadril/tratamento farmacológico , Animais , Artrite Reumatoide/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/genética , Atrofia Muscular/patologia , Osteoartrite do Quadril/patologia
10.
Medicine (Baltimore) ; 100(30): e26811, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397740

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common refractory disease in orthopedics. Overdose glucocorticoid application is a common trigger for ONFH. Traditional Chinese medicine (TCM), as a treatment for ONFH, has been shown to be effective in treating steroid-induced ONFH (SONFH). However, a systematic review and meta-analysis of them is lacking. We aim to systematically review the effectiveness and safety of TCM in the treatment of SONFH. METHODS: We will search the following databases: PubMed, Embase, the Cochrane Library, MEDLINE, the Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, and Wanfang Data (since the inception of the databases to the present). In addition, we will look for clinical trial registrations, prospective grey literature, relevant conference papers, and established study reference lists. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. We will evaluate the quality of the evidence using a hierarchy of recommendation assessment, development, and evaluation. RESULTS: This study will systematically evaluate the efficacy and safety of TCM in the treatment of SONFH. CONCLUSION: This systematic review to evaluate the effectiveness and safety of TCM in the treatment of SONFH will provide updated evidence for clinical application. INPLASY REGISTRATION NUMBER: INPLASY202170015.


Assuntos
Necrose da Cabeça do Fêmur/terapia , Medicina Tradicional Chinesa , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
11.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360821

RESUMO

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1ß/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.


Assuntos
Benzofuranos/farmacologia , Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Inflamassomos/efeitos dos fármacos , Atrofia Muscular , Piroptose/efeitos dos fármacos , Animais , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia
12.
BMC Pediatr ; 21(1): 339, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384372

RESUMO

BACKGROUND: Perthes disease (Legg-Calvé-Perthes, LCP) is a self-limited and non-systemic disease occurring in the femoral heads of children, which is mainly manifested as an ischemic necrosis of the femoral head epiphysis, leading to subchondral ossification injury of the femoral head. CASE PRESENTATION: Here we report a case of 11-year-old child with long-term use of high-dose glucocorticoids. With MRI examination finding the epiphyseal necrosis of right humeral head, femur and tibia, and X-ray examination finding bilateral femoral head necrosis, the child was diagnosed as Perthes disease based on his clinical and imaging data. CONCLUSIONS: Long-term and high-dose glucocorticoids may be one of the causes of Perthes disease.


Assuntos
Glucocorticoides , Doença de Legg-Calve-Perthes , Criança , Epífises , Cabeça do Fêmur/diagnóstico por imagem , Glucocorticoides/efeitos adversos , Humanos , Doença de Legg-Calve-Perthes/diagnóstico , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Radiografia
13.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445056

RESUMO

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Musculoesqueléticas/etiologia , Sarcopenia/etiologia , Fatores Etários , Composição Corporal , Remodelação Óssea , Colite Ulcerativa/sangue , Colite Ulcerativa/fisiopatologia , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Citocinas/sangue , Glucocorticoides/efeitos adversos , Humanos , Mediadores da Inflamação/sangue , Doenças Musculoesqueléticas/sangue , Doenças Musculoesqueléticas/fisiopatologia , Estado Nutricional , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/fisiopatologia , Medição de Risco , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/fisiopatologia
15.
Arthritis Res Ther ; 23(1): 176, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215316

RESUMO

OBJECTIVE: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs). METHODS: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations. RESULTS: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm2, P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group. CONCLUSION: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704 .


Assuntos
Artrite Reumatoide , Doenças Ósseas Metabólicas , Osteoporose Pós-Menopausa , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea , Remodelação Óssea , Feminino , Glucocorticoides/efeitos adversos , Humanos , Indóis , Vértebras Lombares
16.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220705

RESUMO

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/efeitos adversos , Insulina/uso terapêutico , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/prevenção & controle , COVID-19/complicações , Cuidados Críticos/métodos , Estado Terminal/terapia , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Doenças Metabólicas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/mortalidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
17.
Biomed Pharmacother ; 139: 111711, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243617

RESUMO

Platelet Rich Plasma (PRP) can activate angiogenic and osteogenic pathways, making it a highly promising therapeutic agent for bone growth. Super active platelet lysate (sPL) is derived from platelet-rich plasma (PRP) through ultra-low temperature freeze-thawing. The aim of this study was to evaluate the potential therapeutic effect of sPL on glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). sPL increased the proliferation of GC-treated osteoblasts and endothelial cells, and inhibited apoptosis in vitro. Furthermore, sPL promoted healing of necrotic bone tissues in a rat ONFH model by restraining GC-induced apoptosis and increase autophagy of the osteoblasts. Overall, the results of this study provide a theoretical basis for the clinical application of sPL in ONFH.


Assuntos
Autofagia/efeitos dos fármacos , Plaquetas/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/prevenção & controle , Cabeça do Fêmur/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Plasma Rico em Plaquetas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
18.
BMJ ; 374: n1380, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253540

RESUMO

Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing's syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Síndrome de Abstinência a Substâncias , Doença Aguda , Insuficiência Adrenal/tratamento farmacológico , Doença Crônica , Síndrome de Cushing/induzido quimicamente , Aconselhamento Diretivo , Humanos , Sistema Hipotálamo-Hipofisário , Educação de Pacientes como Assunto , Fatores de Risco , Síndrome de Abstinência a Substâncias/tratamento farmacológico
19.
Arthritis Care Res (Hoboken) ; 73(8): 1071-1087, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235871

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.


Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Reumatologia/normas , Arterite de Takayasu/tratamento farmacológico , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/imunologia , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/imunologia , Resultado do Tratamento
20.
Arthritis Care Res (Hoboken) ; 73(8): 1061-1070, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235889

RESUMO

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Poliarterite Nodosa/tratamento farmacológico , Reumatologia/normas , Tomada de Decisão Clínica , Consenso , Ciclofosfamida/efeitos adversos , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Medicina Baseada em Evidências/normas , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
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