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1.
Artigo em Inglês | MEDLINE | ID: mdl-32003065

RESUMO

Following the release of the framework for the Real-World Evidence (RWE) Program, the US Food and Drug Administration (FDA) is actively evaluating and exploring ways to optimize the utility of real-world data (RWD) and RWE to support regulatory decision making. For rare conditions, conducting traditional randomized clinical trials may not always be feasible, and RWD and RWE have played and will continue to play an important role. We use three case examples-cerliponase alfa, asfotase alfa, and uridine triacetate-to illustrate how RWD from disease registries, medical records with chart review, and literature, respectively, have been used to generate RWE to support regulatory decisions for selected rare diseases. These examples highlight the need for improving data reliability and quality in existing data to expand use of RWD and RWE beyond "hard endpoints" and standardizing data collection for outcome measures in patient registries to expand its utility. We also discuss a recent FDA guidance for using RWE in supporting rare disease drug development, including its recommendations about using natural history studies as external control groups for single-arm interventional trials. The external control group needs to be comparable with the treated group. Selection bias and confounding are major concerns because of lack of randomization and unrecognized baseline differences. Use of valid epidemiological approaches can reduce these biases. Lastly, we discuss future directions to expand the use of RWD and RWE to support orphan drug approvals, including the need for including patient experience data as an important source of RWD.

3.
JAMA Intern Med ; 176(12): 1818-1825, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27775769

RESUMO

Importance: In 2011, the US Centers for Medicare & Medicaid Services (CMS) changed its reimbursement policy for hemodialysis to a bundled comprehensive payment system that included the cost of erythrocyte-stimulating agents (ESAs). Also in 2011, the US Food and Drug Administration revised the drug label for ESAs, recommending more conservative dosing in patients with chronic kidney disease. In response to concerns that these measures could have adverse effects on patient care and outcomes, the CMS and the FDA initiated a collaboration to assess the effect. Objective: To assess the effects of the changes in reimbursement policy and the ESA drug label on patients who underwent incident hemodialysis. Design, Setting, and Participants: For this retrospective cohort study, patients 66 years or older who had undergone incident hemodialysis, and were enrolled in Medicare parts A, B, or D for at least 12 months prior to hemodialysis initiation between January 1, 2008, and December 31, 2013, were recruited from hemodialysis centers across the United States. Patients were divided into 2 cohorts based on their date of hemodialysis initiation and followed: January 1, 2008, to December 31, 2009, for the prepolicy cohort and July 1, 2011, to June 30, 2013, for the postpolicy cohort, with the exclusion of January 1, 2010, to June 30, 2011, as a transition period. Interventions: Changes in CMS reimbursement policy for dialysis and the FDA label for ESAs. Main Outcomes and Measures: Major adverse cardiovascular events (MACEs), including acute myocardial infarction (AMI), stroke, and all-cause mortality; hospitalized congestive heart failure (H-CHF); venous thromboembolism; and red blood cell transfusions. Secondary outcomes included evaluating effects on black and other patient subgroups. Results: Baseline characteristics of the 69 718 incident hemodialysis patients were similar between cohorts. Compared with the prepolicy period, the risk of MACE, death, H-CHF, and venous thromboembolism were similar in the postpolicy period, and the risk of stroke decreased (hazard ratio [HR], 0.77; 95% CI, 0.64-0.93; P = .01); the use of ESAs also decreased, and the rate of blood transfusions increased (HR, 1.09; 95% CI, 1.07-1.12; P < .001). In the post-postpolicy period, black patients had a significant reduction in risk of MACE (HR, 0.82; 95% CI, 0.73-0.92; P < .001) and all-cause mortality (HR, 0.82; 95% CI, 0.73-0.93; P = .002). Conclusions and Relevance: After the bundling policy and ESA labeling changes in 2011, the risks of MACE and death for patients 66 years or older and covered by fee-for-service Medicare who had undergone incident hemodialysis did not change; the risk of stroke was reduced, and the rate of blood transfusions modestly increased. Black patients had substantial reductions in the risks of MACE and death.


Assuntos
/organização & administração , Rotulagem de Medicamentos , Hematínicos/administração & dosagem , Falência Renal Crônica/terapia , Mecanismo de Reembolso/organização & administração , Diálise Renal , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Planos de Pagamento por Serviço Prestado , Feminino , Reforma dos Serviços de Saúde , Hematínicos/economia , Humanos , Falência Renal Crônica/mortalidade , Masculino , Infarto do Miocárdio/epidemiologia , Mecanismo de Reembolso/economia , Reembolso de Incentivo/economia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Estados Unidos/epidemiologia
6.
Pharmacoepidemiol Drug Saf ; 25(5): 590-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26530380

RESUMO

PURPOSE: The goal of this study is to summarize trends in rates of adverse events attributable to acetaminophen use, including hepatotoxicity and mortality. METHODS: A comprehensive analysis of data from three national surveillance systems estimated rates of acetaminophen-related events identified in different settings, including calls to poison centers (2008-2012), emergency department visits (2004-2012), and inpatient hospitalizations (1998-2011). Rates of acetaminophen-related events were calculated per setting, census population, and distributed drug units. RESULTS: Rates of poison center calls with acetaminophen-related exposures decreased from 49.5/1000 calls in 2009 to 43.5/1000 calls in 2012. Rates of emergency department visits for unintentional acetaminophen-related adverse events decreased from 58.0/1000 emergency department visits for adverse drug events in 2009 to 50.2/1000 emergency department visits in 2012. Rates of hospital inpatient discharges with acetaminophen-related poisoning decreased from 119.8/100 000 hospitalizations in 2009 to 108.6/100 000 hospitalizations in 2011. After 2009, population rates of acetaminophen-related events per 1 million census population decreased for poison center calls and hospitalizations, while emergency department visit rates remained stable. However, when accounting for drug sales, the rate of acetaminophen-related events (per 1 million distributed drug units) increased after 2009. Prior to 2009, the rates of acetaminophen-related hospitalizations had been slowly increasing (p-trend = 0.001). CONCLUSIONS: Acetaminophen-related adverse events continue to be a public health burden. Future studies with additional time points are necessary to confirm trends and determine whether recent risk mitigation efforts had a beneficial impact on acetaminophen-related adverse events. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Hospitalização/estatística & dados numéricos , Acetaminofen/administração & dosagem , Acetaminofen/envenenamento , Adolescente , Adulto , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/envenenamento , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Overdose de Drogas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Centros de Controle de Intoxicações , Estados Unidos/epidemiologia , Adulto Jovem
7.
JAMA ; 314(19): 2062-8, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26575062

RESUMO

IMPORTANCE: All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. OBJECTIVE: To compare the risk of anaphylaxis among marketed IV iron products. DESIGN, SETTING, AND PARTICIPANTS: Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. EXPOSURES: Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. MAIN OUTCOMES AND MEASURES: Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. RESULTS: A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100,000 persons for iron dextran (95% CI, 57.8-78.7 per 100,000) and 24 per 100,000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100,000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P < .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100,000 persons, 95% CI, 15.3- 26.4). CONCLUSIONS AND RELEVANCE: Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.


Assuntos
Anafilaxia/etiologia , Compostos Férricos/efeitos adversos , Óxido Ferroso-Férrico/efeitos adversos , Ácido Glucárico/efeitos adversos , Gluconatos/efeitos adversos , Complexo Ferro-Dextran/efeitos adversos , Idoso , Anafilaxia/epidemiologia , Feminino , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado , Óxido Ferroso-Férrico/administração & dosagem , Ácido Glucárico/administração & dosagem , Gluconatos/administração & dosagem , Humanos , Incidência , Injeções Intravenosas , Complexo Ferro-Dextran/administração & dosagem , Masculino , Medicare Part A/estatística & dados numéricos , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia
8.
J Hum Lact ; 30(1): 62-72; quiz 110-2, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24166052

RESUMO

BACKGROUND: Benefits of using a breast pump are well documented, but pump-related problems and injuries and the associated risk factors have not been reported. OBJECTIVES: This study aimed to describe breast pump-related problems and injuries and identify factors associated with these problems and injuries. METHODS: Data were from the Infant Feeding Practices Study II; mothers were recruited from a nationally distributed consumer opinion panel. Mothers were asked about breast pump use, problems, and injuries at infant ages 2, 5, and 7 months. Survival analysis was used to identify factors associated with pump-related problems and injuries. RESULTS: The sample included 1844 mothers. About 62% and 15% of mothers reported pump-related problems and injuries, respectively. The most commonly reported problem was that the pump did not extract enough milk and the most commonly reported injury was sore nipples. Using a battery-operated pump and intending to breastfeed less than 12 months were associated with higher risks of pump-related problems and injury. Learning from a friend to use the pump was associated with lower risk of pump-related problems, and using a manual pump and renting a pump were associated with a higher risk of problems. CONCLUSION: Our results suggest that problems and injuries associated with breast pump use can happen to mothers of all socioeconomic characteristics. Breastfeeding mothers may reduce their risks of problems and injury by not using battery-operated pumps and may reduce breast pump problems by not using manual pumps and by learning breast pump skills from a person rather than following written or video instructions.


Assuntos
Extração de Leite/efeitos adversos , Mama/lesões , Adulto , Extração de Leite/instrumentação , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Estudos Longitudinais , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários
9.
JAMA Intern Med ; 173(6): 435-41, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-23420484

RESUMO

IMPORTANCE: The role of sex in relationship to implant failure after total hip arthroplasty (THA) is important for patient management and device innovation. OBJECTIVE: To evaluate the association of sex with short-term risk of THA revision after adjusting for patient, implant, surgery, surgeon, and hospital confounders. DESIGN AND SETTING: A prospective cohort of patients enrolled in a total joint replacement registry from April 1, 2001, through December 31, 2010. PARTICIPANTS: Patients undergoing primary, elective, unilateral THA. MAIN OUTCOME MEASURES: Failure of THA, defined as revision procedure for (1) any reason, (2) septic reason, or (3) aseptic reason after the index procedure. RESULTS: A total of 35,140 THAs with 3.0 years of median follow-up were identified. Women constituted 57.5% of the study sample, and the mean (SD) patient age was 65.7 (11.6) years. A higher proportion of women received 28-mm femoral heads (28.2% vs 13.1%) and had metal on highly cross-linked polyethylene-bearing surfaces (60.6% vs 53.7%) than men. Men had a higher proportion of 36-mm or larger heads (55.4% vs 32.8%) and metal on metal-bearing surfaces (19.4% vs 9.6%). At 5-year follow-up, implant survival was 97.4% (95% CI, 97.2%-97.6%). Device survival for men (97.7%; 95% CI, 97.4%-98.0%) vs women (97.1%; 95% CI, 96.8%-97.4%) was significantly different (P = .01). After adjustments, the hazards ratios for women were 1.29 (95% CI, 1.11-1.51) for all-cause revision, 1.32 (95% CI, 1.10-1.58) for aseptic revision, and 1.17 (95% CI, 0.81-1.68) for septic revision. CONCLUSIONS: After considering patient-, surgery-, surgeon-, volume-, and implant-specific risk factors, women had a 29% higher risk of implant failure than men after THA in this community-based sample.


Assuntos
Artroplastia de Quadril , Desenho de Prótese , Falha de Prótese/etiologia , Reoperação/estatística & dados numéricos , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Estudos de Coortes , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese/métodos , Desenho de Prótese/estatística & dados numéricos , Sistema de Registros , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Resultado do Tratamento , Estados Unidos
10.
J Bone Joint Surg Am ; 94(21): 1929-35, 2012 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-23138235

RESUMO

BACKGROUND: Mobile-bearing total knee arthroplasty prostheses were developed to reduce wear and revision rates; however, these benefits remain unproven. The purposes of this study were to compare the short-term survivorship and to determine risk factors for revision of mobile-bearing and fixed-bearing total knee replacements. METHODS: A prospective cohort study of primary total knee arthroplasties performed from 2001 to 2009 was conducted with use of a community total joint replacement registry. Patient characteristics and procedure details were identified. Cox regression models were used. Bearing type was investigated as a risk factor for revision while adjusted for other risk factors such as age, American Society of Anesthesiologists (ASA) score, body mass index, sex, race, diagnosis, bilateral procedures, cruciate-retaining versus posterior-stabilized components, surgical approach, fixation, patellar resurfacing, hospital and surgeon volumes, and fellowship training. RESULTS: The study cohort consisted of 47,339 total knee arthroplasties, with 62.6% of the procedures in women. Fixed bearings were used in 41,908 knees (88.5%) and mobile bearings in 4830 (10.2%). Rotating-platform designs were used in all mobile-bearing total knee arthroplasties (3112 had a Rotating-Platform Press-Fit Condylar posterior-stabilized design; 1053, a Low Contact Stress [LCS] design; and 665, a Rotating-Platform Press-Fit Condylar cruciate-retaining design). Patients who received fixed-bearing total knee arthroplasty systems were older (mean age, 68.1 years) than those who received mobile-bearing total knee arthroplasty systems (mean age, 62.2 years); the difference was significant (p < 0.001). Overall, 515 knees (1.1%) were revised for reasons other than infection. The survival rate was 97.8% (95% confidence interval [CI], 97.4% to 98.0%) at 6.7 years. The adjusted risk of aseptic revision for the LCS total knee replacements was 2.01 times (95% CI, 1.41 to 2.86) higher than that for fixed-bearing total knee replacements (p < 0.001).There was no significant revision risk for the other mobile-bearing total knee arthroplasty systems. There was no association with surgeon and hospital case volumes and the risk of revision total knee arthroplasty. CONCLUSIONS: Our study suggests the benefit of potential long-term wear reduction with the LCS implant may not be realized in a community-based setting, where a variety of surgical skills, surgical experience, and diverse patient demographic factors may affect early outcomes. LEVEL OF EVIDENCE: Therapeutic Level II.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Idoso , Artroplastia do Joelho/efeitos adversos , Feminino , Humanos , Prótese do Joelho/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Reoperação , Fatores de Risco
11.
Pediatrics ; 126(2): 247-59, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20660543

RESUMO

OBJECTIVES: The purposes of this study were to provide national estimates of emergency department (ED) visits for medical device-associated adverse events (MDAEs) in the pediatric population and to characterize these events further. METHODS: ED medical record reports from the National Electronic Injury Surveillance System All Injury Program database from January 1, 2004, through December 21, 2005, were reviewed. MDAEs among pediatric patients were identified, and data were abstracted. National estimates for pediatric MDAEs were determined according to medical specialty, device category and class, injury diagnosis, and patient characteristics and outcome. RESULTS: The total estimated number of pediatric MDAEs during the 24-month period was 144,799 (95% confidence interval: 113,051-183,903), involving devices from 13 medical specialties. Contact lenses accounted for most MDAEs (23%), followed by hypodermic needles (8%). The distribution of MDAEs according to medical specialty varied according to age subgroup. The most-prevalent types of injuries included contusions/abrasions, foreign-body intrusions, punctures, lacerations, and infections. The most-frequently affected body parts were the eyeball, pubic region, finger, face, and ear. The majority of pediatric MDAEs involved class II (moderate-risk) devices. The incidence of pediatric MDAEs decreased with increasing age from early to late childhood and then spiked after 10 years of age. More girls than boys were affected at older ages (16-21 years) and more boys than girls at younger ages (< or =10 years). Hospitalizations were more likely to involve invasive or implanted devices. CONCLUSIONS: This study provides national estimates of pediatric MDAEs resulting in ED visits and highlights the need to develop interventions to prevent pediatric device-related injuries.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Falha de Equipamento/estatística & dados numéricos , Segurança de Equipamentos/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/reabilitação , Adolescente , Criança , Processamento Eletrônico de Dados , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Distribuição por Sexo , Resultado do Tratamento , Ferimentos e Lesões/classificação , Adulto Jovem
12.
AIDS Care ; 22(2): 246-52, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20390503

RESUMO

Males who seek commercial sex have been identified as an important "bridging population" in the transmission of HIV. There is little information on the HIV-related risk perceptions and behaviors among commercial sex male clients (CSMCs) in China. This study reports qualitative findings from six focus groups and 41 in-depth interviews with CSMCs in Sichuan Province, China. Commercial sex visits were described as a group activity and associated with patterns of social-network specific interactions and norms. Primary motivations for visiting female sex workers included peer pressure, stress reduction, and fulfilling a need for an intimate and emotional support. Male clients' decisions about condom use were influenced by their perceived norms of condom use, susceptibility of HIV infection, and the condom policy and availability in the establishments. Implications of these findings for further research and interventions are discussed.


Assuntos
Infecções por HIV , Trabalho Sexual , Comportamento Sexual , Adulto , China , Preservativos , Comportamento Contraceptivo , Grupos Focais , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Assunção de Riscos , Responsabilidade Social , Apoio Social , Adulto Jovem
13.
Int J Cancer ; 125(5): 1186-92, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19444920

RESUMO

Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces apoptosis in cancer cells. This study evaluated tumor inhibitory effects of a protein made by fusion E4orf4 and human epidermal growth factor (EGF). EGF was used to ensure the selective targeting of EGF receptor (EGFR)-overexpressing tumor cells. Results showed that EGF-E4orf4 stimulated EGFR phosphorylation in a time- and dose-dependent manner. Confocal microscopy analysis showed both EGF-E4orf4 and EGF could be internalized via EGFR but they had different intercellular trafficking pathways. In vitro study showed that EGF-E4orf4 significantly inhibited the proliferation of BGC823 and in vivo study showed EGF-E4orf4 suppressed tumor growth in a dose-dependent fashion with an inhibition rate of 79% for MDA-MB-231 and 49% for BGC 823 (p < 0.05). No toxic effects were observed in the nude mice with a dose as high as 10 mg/kg of EGF-E4orf4. These results indicated that EGF-E4orf4 could be a potential drug for cancer therapy.


Assuntos
Adenocarcinoma/prevenção & controle , Neoplasias da Mama/prevenção & controle , Fator de Crescimento Epidérmico/genética , Receptores ErbB/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Neoplasias Gástricas/prevenção & controle , Proteínas Virais/genética , Adenocarcinoma/metabolismo , Animais , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Feminino , Citometria de Fluxo , Humanos , Immunoblotting , Imunoprecipitação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 31(6): 674-8, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20078933

RESUMO

OBJECTIVE: To investigate the intracellular trafficking pathway of fusion protein epidermal growth factor-adenovirus early region 4 open reading frame 4 protein (EGF-E4orf4) internalized via epidermal growth factor (EGF) receptor and its affectivity on extracellular signal-regulated kinase (ERK) phosphorylation. METHODS: MDA-MB-231 and BGC823 cells were incubated with fluorescein isothiocyanate-EGF-E4orf4 or EGF at different time points. The specific molecular mark of early endosome or late lysosome was labeled by indirect immunofluorescence, and then colocalization staining was observed using confocal laser microscopy. The levels of ERK phosphorylation were detected by Western blot. RESULTS: The fluorescent signal of fusion protein EGF-E4orf4 accumulated within the cells and congregated to the perinuclear region. A nucleus localization of the fusion protein was only at MDA-MB-231 cell. Colocalization of EGF-E4orf4 with early endosome/late lysosome was observed. EGF-E4orf4 stimulated ERK phosphorylation, which was most obvious 10 minutes after stimulation, and then gradually attenuated, which was similar to EGF stimulation but with a less decrease. CONCLUSIONS: Internalized EGF-E4orf4 can be slowly degraded via endosome-lysosome pathway. The action features of EGF-E4orf4 are remarkably different between MDA-MB-231 and BGC823 cells, which may help explain the differences in its anti-tumor potency and in the special selectivity toward different tumor cells.


Assuntos
Proteínas E4 de Adenovirus/farmacocinética , Fator de Crescimento Epidérmico/farmacocinética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Virais/farmacocinética , Linhagem Celular Tumoral , Humanos , Fosforilação/efeitos dos fármacos , Transporte Proteico , Proteínas Recombinantes de Fusão/farmacocinética
15.
Pediatrics ; 122 Suppl 2: S63-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18829833

RESUMO

OBJECTIVES: Our goal was to describe the prevalence of any, occasional, and regular breast milk expression, mothers' reasons for expressing their milk, and sociodemographic factors associated with breast milk expression. PARTICIPANTS AND METHODS: Breastfeeding mothers participating in the 2005-2007 Infant Feeding Practices Study II formed the cohort for these analyses, which were conducted among those with infants in 3 age groups: 1.5 to 4.5 months (n = 1564); >4.5 to 6.5 months (n = 1128); and >6.5 to 9.5 months (n = 914). For the analyses we used frequency and stepwise multiple logistic regression procedures. RESULTS: Eighty-five percent of breastfeeding mothers of infants in the youngest age group had successfully expressed milk at some time since their infant was born. When asked only about the previous 2-week period, 68% of the breastfeeding mothers of infants in this youngest age group had expressed milk, with 43% having done so occasionally and 25% on a regular schedule. Approximately one quarter of breastfeeding mothers of infants in the 2 older infant age groups also expressed milk on a regular schedule. The percentage of mothers expressing milk decreased with increasing infant age. Mothers expressed milk for various reasons. The most frequently cited reason was to get breast milk for someone else to feed their infant. In all 3 age groups, reporting any breast milk expression, compared with none, was positively associated with maternal employment, higher income, lack of previous breastfeeding experience, and living in the Midwest versus the West. In all 3 age groups, expressing milk on a regular schedule, compared with occasionally, was positively associated with maternal employment and the use of an electric versus manual breast pump. CONCLUSIONS: Breast milk expression is a very common practice. It is associated most strongly with maternal employment, a recognized barrier to breastfeeding.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Comportamento Materno , Mulheres Trabalhadoras/estatística & dados numéricos , Comportamento de Escolha , Emprego , Feminino , Humanos , Lactente , Recém-Nascido , Leite Humano , Prevalência , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos/epidemiologia
17.
Ther Clin Risk Manag ; 3(6): 1097-104, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18516268

RESUMO

Highly active antiretroviral therapy has significantly reduced HIV-related morbidity and mortality. Increasingly, fixed-dose antiretroviral combinations with equal or greater potency than traditional antiretrovirals, along with fewer side effects, reduced toxicity, and simplified dosing convenience are being utilized. Tenofovir-emtricitabine (TDF-FTC) represents one of the more recent fixed-dose combinations. In combination with either a ritonavir-boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, TDF-FTC is a preferred choice in recent treatment guidelines on the basis of demonstrated potency in randomized clinical trials, one-pill-a-day dosing convenience, and relatively low toxicity. In addition, the drug is active against hepatitis B virus. Caution must be exercised in patients with renal insufficiency, or when the drug is used with certain other drugs. This manuscript reviews the use of TDF-FTC in the treatment of HIV.

19.
Am J Kidney Dis ; 47(5): 848-55, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16632024

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is increasing in incidence in persons with human immunodeficiency virus (HIV). It is not known whether the morbidity and mortality rate of ASCVD is similarly increasing among patients with HIV end-stage renal disease (ESRD), who are living longer since the initiation of newer therapeutic regimens in 1997. METHODS: We conducted a population-based study of 8,312 HIV ESRD patients enrolled in the US Renal Data System from 1987 to 2001. We determined the incidence of fatal and nonfatal ASCVD events stratified by date of dialysis therapy initiation. RESULTS: There were 3,112 HIV ESRD patients (77.9% men; mean age, 39.6 +/- 9.6 years) who initiated dialysis therapy before 1997 and 2,371 patients (71.5% men; mean age, 41.3 +/- 9.7 years) who initiated dialysis therapy after 1997. Cumulative incidences of ASCVD for those initiating dialysis therapy before 1997 compared with after 1997 were 10.6% versus 13.5% at 12 months, 18.8% versus 27.6% at 24 months, 26.2% versus 42.4% at 36 months, and 33.7% versus 65.9% at 48 months (P < 0.0001 by log rank). Those who initiated dialysis therapy after 1997 had a greater risk for developing ASCVD (adjusted hazard ratio, 1.57; 95% confidence interval, 1.29 to 1.92) than those who initiated dialysis therapy before 1997 after adjusting for demographics and ASCVD risk factors. CONCLUSION: There is an increased risk for ASCVD in patients with HIV who initiated dialysis therapy after 1997. This may reflect the long-term complications of multidrug regimens, as well as improved survival from these regimens leading to prolonged exposure to ASCVD risk factors.


Assuntos
Aterosclerose/epidemiologia , Aterosclerose/etiologia , Infecções por HIV/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino
20.
Curr HIV/AIDS Rep ; 3(2): 66-73, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16608662

RESUMO

The current literature is controversial in providing evidence to determine the optimal time to initiate therapy among patients with HIV. However, there is evidence that initiating early treatment might provide benefits by treating primary HIV infection, preserving normal immune function, suppressing HIV viral replication, deferring clinical progression, and reducing HIV transmission. The biggest challenges in initiating treatment early are issues related with long-term management, including toxicities, adherence, and drug resistance. However, the availability of superior new antiretroviral drugs and simplified regimens, the development of effective treatment strategy, and further improvement of adherence through directly observed treatment are addressing the issues and changing the balance towards earlier treatment.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Contagem de Linfócito CD4 , Estudos de Coortes , Esquema de Medicação , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepatite C/complicações , Humanos , Abuso de Substâncias por Via Intravenosa/complicações , Carga Viral
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