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1.
PLoS Med ; 17(3): e1003058, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32231363

RESUMO

BACKGROUND: Evidence and guidelines do not support use of systemic steroids for acute respiratory tract infections (ARTIs), but such practice appears common. We aim to quantify such use and determine its predictors. METHODS AND FINDINGS: We conducted a cohort study based on a large United States national commercial claims database, the IBM MarketScan, to identify patients aged 18-64 years with an ARTI diagnosis (acute bronchitis, sinusitis, pharyngitis, otitis media, allergic rhinitis, influenza, pneumonia, and unspecified upper respiratory infections) recorded in ambulatory visits from 2007 to 2016. We excluded those with systemic steroid use in the prior year and an extensive list of steroid-indicated conditions, including asthma, chronic obstructive pulmonary disease, and various autoimmune diseases. We calculated the proportion receiving systemic steroids within 7 days of the ARTI diagnosis and determined its significant predictors. We identified 9,763,710 patients with an eligible ARTI encounter (mean age 39.6, female 56.0%) and found 11.8% were prescribed systemic steroids (46.1% parenteral, 47.3% oral, 6.6% both). All ARTI diagnoses but influenza predicted receiving systemic steroids. There was high geographical variability: the adjusted odds ratio (aOR) of receiving parenteral steroids was 14.48 (95% confidence interval [CI] 14.23-14.72, p < 0.001) comparing southern versus northeastern US. The corresponding aOR was 1.68 (95% CI 1.66-1.69, p < 0.001) for oral steroids. Other positive predictors for prescribing included emergency department (ED) or urgent care settings (versus regular office), otolaryngologist/ED doctors (versus primary care), fewer comorbidities, and older patient age. There was an increasing trend from 2007 to 2016 (aOR 1.93 [95% CI 1.91-1.95] comparing 2016 to 2007, p < 0.001). Our findings are based on patients between 18 and 64 years old with commercial medical insurance and may not be generalizable to older or uninsured populations. CONCLUSIONS: In this study, we found that systemic steroid use in ARTI is common with a great geographical variability. These findings call for an effective education program about this practice, which does not have a clear clinical net benefit.

2.
Am J Med ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147448

RESUMO

BACKGROUND: Systemic corticosteroids are not indicated for acute respiratory tract infections yet are nonetheless prescribed in outpatient care. Acute respiratory tract infections are the most common diagnosis in direct-to-consumer telemedicine. The objective of this study was to characterize use of corticosteroids for acute respiratory tract infections in this setting and to assess the association between corticosteroid receipt and patient satisfaction. METHODS: Encounters with acute respiratory tract infection patients 18 years and older on a nationwide direct-to-consumer telemedicine platform were conducted by physicians between July 2016 and July 2018. Mixed-effects logistic regression was used to assess differences in the odds of corticosteroid prescription. A second mixed-effects model assessed differences in patient satisfaction by corticosteroid or antibiotic receipt. Adjusted prescribing rates for individual physicians were estimated. Models included diagnoses, patient age and geographic region, physician specialty and geographic region, and antibiotic prescription. RESULTS: Of the 85,972 encounters with 465 physicians, 11% resulted in the physician prescribing corticosteroids. The median physician prescribing rate was 4.0% (range: <1%-81%). Corticosteroid receipt was associated with higher satisfaction versus receiving nothing (odds ratio: 2.54; 95% confidence interval: 2.25-2.87). Patients who received both an antibiotic and a corticosteroid reported the highest satisfaction (odd ratio: 3.91; 95% confidence interval: 3.27-4.68). There was no correlation between individual physicians' corticosteroid and antibiotic prescribing rates. CONCLUSIONS: Corticosteroid receipt was associated with patient satisfaction. Most physicians rarely prescribed corticosteroids, yet a small number prescribed them frequently. Identification of high-prescribing physicians for educational interventions could reduce use of corticosteroids for acute respiratory tract infections.

3.
Am Fam Physician ; 101(2): 89-94, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31939645

RESUMO

Short-term systemic corticosteroids, also known as steroids, are frequently prescribed for adults in the outpatient setting by primary care physicians. There is a lack of supporting evidence for most diagnoses for which steroids are prescribed, and there is evidence against steroid use for patients with acute bronchitis, acute sinusitis, carpal tunnel, and allergic rhinitis. There is insufficient evidence supporting routine use of steroids for patients with acute pharyngitis, lumbar radiculopathy, carpal tunnel, and herpes zoster. There is evidence supporting use of short-term steroids for Bell palsy and acute gout. Physicians might assume that short-term steroids are harmless and free from the widely known long-term effects of steroids; however, even short courses of systemic corticosteroids are associated with many possible adverse effects, including hyperglycemia, elevated blood pressure, mood and sleep disturbance, sepsis, fracture, and venous thromboembolism. This review considers the evidence for short-term steroid use for common conditions seen by primary care physicians.


Assuntos
Doença Crônica/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Esteroides/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Humanos , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico
5.
BMJ ; 333(7581): 1248, 2006 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-17060338

RESUMO

OBJECTIVE: To examine the accessibility of absolute risk in articles reporting ratio measures in leading medical journals. DESIGN: Structured review of abstracts presenting ratio measures. SETTING: Articles published between 1 June 2003 and 1 May 2004 in Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Journal of the National Cancer Institute, Lancet, and New England Journal of Medicine. PARTICIPANTS: 222 articles based on study designs in which absolute risks were directly calculable (61 randomised trials, 161 cohort studies). MAIN OUTCOME MEASURE: Accessibility of the absolute risks underlying the first ratio measure in the abstract. RESULTS: 68% of articles (150/222) failed to report the underlying absolute risks for the first ratio measure in the abstract (range 55-81% across the journals). Among these articles, about half did report the underlying absolute risks elsewhere in the article (text, table, or figure) but half did not report them anywhere. Absolute risks were more likely to be reported in the abstract for randomised trials compared with cohort studies (62% v 21%; relative risk 3.0, 95% confidence interval 2.1 to 4.2) and for studies reporting crude compared with adjusted ratio measures (62% v 21%; relative risk 3.0, 2.1 to 4.3). CONCLUSION: Absolute risks are often not easily accessible in articles reporting ratio measures and sometimes are missing altogether-this lack of accessibility can easily exaggerate readers' perceptions of benefit or harm.


Assuntos
Publicações Periódicas como Assunto/estatística & dados numéricos , Distribuição de Qui-Quadrado , Estudos de Coortes , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Medição de Risco
6.
J Heart Valve Dis ; 12(5): 617-24, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14565715

RESUMO

BACKGROUND AND AIM OF THE STUDY: Histopathological studies of rejected orthotopic heart transplants suggest that cardiac valve endothelium is spared the inflammatory cell infiltration and tissue damage that occurs in the myocardium. To test whether this apparent protection from leukocyte invasion might be an inherent feature of the valve endothelium, leukocyte adhesion molecule expression and function were analyzed in human pulmonary valve endothelial cells (HPVEC). Use of cultured HPVEC allowed delineation of the potential contribution of functional adhesion molecules from the contribution of hemodynamic forces exerted on the leaflet surface in vivo METHODS AND RESULTS: HPVEC express E-selectin, ICAM-1, and VCAM-1 in response to the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) similarly to other types of cultured human endothelial cells. In a static cell adhesion assay, E-selectin-mediated adhesion of HL-60 cells, a human promyelocytic leukemia cell line, and U937 cells, a human monocytic cell line, was determined in cells treated with TNF-alpha for 5 h. After 24 h of TNF-alpha, adhesion of U937 cells to HPVEC was mediated primarily by VCAM-1, consistent with the high expression of VCAM-1 and diminished expression of E-selectin at 24 h. CONCLUSION: These results demonstrate that HPVEC express functional leukocyte adhesion molecules in vitro and suggest that cardiac valve endothelium is competent to initiate leukocyte adhesion. Thus, other factors, such as the hemodynamic forces exerted on the valve, may contribute to the apparent protection from inflammatory cell infiltration in vivo.


Assuntos
Moléculas de Adesão Celular/fisiologia , Células Endoteliais/fisiologia , Valva Pulmonar/citologia , Adolescente , Adulto , Anticorpos Monoclonais/farmacologia , Boston , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Moléculas de Adesão Celular/efeitos dos fármacos , Criança , Bem-Estar da Criança , Pré-Escolar , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Selectina E/biossíntese , Selectina E/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Citometria de Fluxo , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/fisiopatologia , Células HL-60/efeitos dos fármacos , Células HL-60/fisiologia , Transplante de Coração , Humanos , Lactente , Bem-Estar do Lactente , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Selectina-P/biossíntese , Selectina-P/efeitos dos fármacos , Pele/citologia , Falha de Tratamento , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos
7.
Tissue Eng ; 9(3): 487-93, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12857416

RESUMO

Three-dimensional scaffolds made of bioabsorbable polymeric constituents are currently being tested for use in tissue engineering of various tissues. A composite scaffold of poly-glycolic acid (PGA) non-woven mesh dip-coated in a 1% solution of poly-4-hydroxybutyrate (P4HB) was shown to be suitable as a scaffold for creation of tissue-engineered trileaflet pulmonic valve replacements in sheep [Hoerstrup, S.P., et al., Circulation 102(Suppl. 3), III44, 2000]. However, little is known about how cells seeded on PGA/P4HB respond in vitro to soluble factors supplied in the culture medium. To optimize tissue development in vitro, before implantation, we set out to develop quantitative biochemical assays to measure how cells seeded on PGA/P4HB respond to growth and differentiation factors. Herein we show that ovine aortic valvular endothelial cells and circulating endothelial progenitor cells (EPCs) seeded onto PGA/P4HB proliferate in response to vascular endothelial growth factor and transdifferentiate to a mesenchymal phenotype in response to transforming growth factor beta(1). Transdifferentiation from an endothelial to mesenchymal phenotype is a critical step during embryonic development of cardiac valves. Our results demonstrate that valvular endothelial cells and EPCs isolated from peripheral blood can recapitulate critical developmental steps on PGA/P4HB. These results demonstrate that PGA/P4HB provides a conducive environment for cellular proliferation, differentiation, and tissue development.


Assuntos
Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Células Endoteliais , Células-Tronco , Fator de Crescimento Transformador beta/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Valvas Cardíacas , Hidroxibutiratos , Ácido Poliglicólico , Engenharia Tecidual/métodos
8.
J Biol Chem ; 277(23): 20711-6, 2002 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-12042327

RESUMO

Human AC133 antigen, also called CD133, was recently identified as a hematopoietic stem cell marker. However, the molecular structure and function of this protein has remained unclear. Here we cloned and identified a novel isoform of AC133, which we named AC133-2. In comparison to the reported AC133 cDNA, which is referred to herein as AC133-1, a small exon of 27 nucleotides is deleted in AC133-2 by alternative mRNA splicing. Similar to the previously characterized AC133 antigen, recombinant AC133-2 expressed in 293 cells was glycosylated and transported to plasma membrane. AC133-2 mRNA was found predominant in a variety of human fetal tissue, adult tissues, and several carcinomas. In contrast, AC133-1 mRNA was more prominent in fetal brain and adult skeletal muscle but was not detected in fetal liver and kidney, adult pancreas, kidney, and placenta, suggesting different roles for the two isoforms in fetal development and mature organ homeostasis. Here, we demonstrate that AC133-2 is the isoform expressed on hematopoietic stem cells derived from fetal liver, bone marrow, and peripheral blood. The results indicate that AC133-2, not AC133-1, has been the cell surface antigen recognized by anti-AC133 monoclonal antibodies that are used for isolation of hematopoietic stem cells. To further investigate its expression in other stem cell populations, we found that AC133-2 co-expressed with beta(1) integrin in the basal layer of human neonatal epidermis. AC133-2(+)/beta(1) integrin(+) cells proliferated and differentiated in culture, which coincided with a loss of AC133-2 and gain in a terminal differentiation marker involucrin. Taken together, these results suggest that AC133-2 is expressed in multiple stem cell niches and may provide a means to isolate specific stem cell subpopulations from human tissues.


Assuntos
Glicoproteínas/isolamento & purificação , Peptídeos/isolamento & purificação , Isoformas de Proteínas/isolamento & purificação , Células-Tronco/imunologia , Antígeno AC133 , Sequência de Aminoácidos , Antígenos CD , Sequência de Bases , Clonagem Molecular , DNA Complementar , Regulação para Baixo , Glicoproteínas/química , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/genética , Peptídeos/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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