RESUMO
STUDY OBJECTIVE: Identification of HIV remains a critical health priority for which emergency departments (EDs) are a central focus. The comparative cost-effectiveness of various HIV screening strategies in EDs remains largely unknown. The goal of this study was to compare programmatic costs and cost-effectiveness of nontargeted and 2 forms of targeted opt-out HIV screening in EDs using results from a multicenter, pragmatic randomized clinical trial. METHODS: This economic evaluation was nested in the HIV Testing Using Enhanced Screening Techniques in Emergency Departments (TESTED) trial, a multicenter pragmatic clinical trial of different ED-based HIV screening strategies conducted from April 2014 through January 2016. Patients aged 16 years or older, with normal mental status and not critically ill, or not known to be living with HIV were randomized to 1 of 3 HIV opt-out screening approaches, including nontargeted, enhanced targeted, or traditional targeted, across 4 urban EDs in the United States. Each screening method was fully integrated into routine emergency care. Direct programmatic costs were determined using actual trial results, and time-motion assessment was used to estimate personnel activity costs. The primary outcome was newly diagnosed HIV. Total annualized ED programmatic costs by screening approach were calculated using dollars adjusted to 2023 as were costs per patient newly diagnosed with HIV. One-way and multiway sensitivity analyses were performed. RESULTS: The trial randomized 76,561 patient visits, resulting in 14,405 completed HIV tests, and 24 (0.2%) new diagnoses. Total annualized new diagnoses were 12.9, and total annualized costs for nontargeted, enhanced targeted, and traditional targeted screening were $111,861, $88,629, and $70,599, respectively. Within screening methods, costs per new HIV diagnoses were $20,809, $23,554, and $18,762, respectively. Enhanced targeted screening incurred higher costs but with similar annualized new cases detected compared with traditional targeted screening. Nontargeted screening yielded an incremental cost-effectiveness ratio of $25,586 when compared with traditional targeted screening. Results were most sensitive to HIV prevalence and costs of HIV tests. CONCLUSION: Nontargeted HIV screening was more costly than targeted screening largely due to an increased number of HIV tests performed. Each HIV screening strategy had similar within-strategy costs per new HIV diagnosis with traditional targeted screening yielding the lowest cost per new diagnosis. For settings with budget constraints or very low HIV prevalences, the traditional targeted approach may be preferred; however, given only a slightly higher cost per new HIV diagnosis, ED settings looking to detect the most new cases may prefer nontargeted screening.
Assuntos
Análise Custo-Benefício , Serviço Hospitalar de Emergência , Infecções por HIV , Programas de Rastreamento , Humanos , Serviço Hospitalar de Emergência/economia , Infecções por HIV/diagnóstico , Infecções por HIV/economia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Feminino , Adulto , Masculino , Estados Unidos , Pessoa de Meia-Idade , Teste de HIV/economia , Teste de HIV/métodos , Adulto JovemRESUMO
In the present study, we examined the growth parameters of Bacillus licheniformis in solid-state fermentation (SSF) and evaluated the effects of Bacillus licheniformis-fermented products on Clostridium perfringens-challenged broilers. During four and six days of SSF, the highest viable biomass was observed at 5% glucose, 10% soybean meal, 3% yeast, and 50% initial moisture content. The Bacillus licheniformis SSF products were heat- and acid-resistant. Furthermore, the fermented products were able to inhibit the growth of Clostridium perfringens and Staphylococcus aureus in vitro. In feeding experiments, in a similar manner to the antibiotic treatment group, dietary supplementation of Bacillus licheniformis-fermented products significantly improved intestinal morphology and necrotic lesions under Clostridium perfringens challenge, accompanied by increased IFN-γ mRNA expression in the spleen and bursa of Fabricius. These results together suggest that Bacillus licheniformis-fermented products have potential for development as feed additives and use as possible substitutes for antibiotics to treat Clostridium perfringens in the poultry industry.(AU)
Assuntos
Animais , Galinhas/microbiologia , Clostridium perfringens/fisiologia , Probióticos/efeitos adversos , Fermentação/fisiologia , Bacillus licheniformis/enzimologia , Enterite/diagnósticoRESUMO
The objective of the present study was to investigate the effect of single nucleotide polymorphism (SNP) of the melanocortin 1 receptor (MC1R) gene on plumage coloration in mule ducks. PCR-high-resolution melting analysis (PCR-HRM) and DNA sequencing were used to identify the SNP variability of the MC1R gene in white common ducks. Three non-synonymous SNP (MC1R gene exon 1, c.52G>A, c.376G>A, and c.409G>A) were identified in white Tsaiya ducks. Mating test (white Tsaiya ducks × white Muscovy drakes) in combination with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to investigate the effect of non-synonymous SNP of different maternal lines on plumage coloration in mule ducks. Genotyping results from 58 white Tsaiya ducks revealed the significant associations between genetic variations (c.52G>A, c.376A>G, and c.409G>A) and plumage color in two maternal populations. After genotyping of 266 mule ducks, these three non-synonymous SNP identified in white Tsaiya ducks were significantly associated with plumage color of mule ducks. Therefore, the polymorphisms of MC1R gene at c.52G>A, c.376A>G, and c.409G>A in white Tsaiya duck could be used in marker-assisted selection to improve the plumage color of mule ducks.(AU)
Assuntos
Animais , Polimorfismo Genético , Receptor Tipo 1 de Melanocortina/genética , Patos/fisiologia , Reação em Cadeia da Polimerase/métodosRESUMO
Obesity and adipokines are associated with development of type 2 diabetes. However, limited longitudinal studies have examined their roles on declining ß-cell function over time. This report assessed three adiposity measures (BMI, percent body fat, trunk fat), insulin resistance, and fifteen adipokines in relationship to longitudinal change in ß-cell function measured by disposition index (DI) from frequently-sampled-intravenous-glucose-tolerance testing. The results showed that three factors were significantly and independently associated with rate of change in DI over time: rate of change in BMI (negative), rate of change in IL-6 (negative), and baseline adiponectin (positive). The association was the strongest for changing BMI and was largely explained by changing insulin resistance; the association with changing IL-6 was also largely explained by changing insulin resistance. Baseline adiponectin remained positively associated after adjustment for changing insulin resistance, suggesting an independent effect of adiponectin to preserve or improve ß-cell function. These findings provide evidence and potential mechanisms for the role of obesity in promoting ß-cell dysfunction, highlighting the potential importance of mitigating obesity and its metabolic effects in preventing and treating type 2 diabetes.
Assuntos
Adipocinas/sangue , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , Aumento de Peso , Adulto , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , Masculino , Americanos Mexicanos , ObesidadeRESUMO
OBJECTIVE: Limited studies have assessed the relationship between longitudinal changes in adiposity and changes in multiple adipokines over time. This study examined changes in BMI, total body fat, and trunk fat associated with changes in 16 circulating adipokines in Mexican Americans at risk for type 2 diabetes. METHODS: Participants included 1,213 individuals with cross-sectional data and a subset of 368 individuals with follow-up measures (mean 4.6 ± 1.5 years from baseline). Joint multivariate associations between 3 adiposity measures and 16 adipokines were assessed by canonical correlation analysis. RESULTS: Longitudinal increases in adiposity were most strongly associated with increasing leptin, C-reactive protein (CRP), and interleukin 1 receptor antagonist (IL-1Ra) and decreasing adiponectin and secreted frizzled protein 5 (SFRP5) over time. Participants with BMI ≥ 30 kg/m2 at baseline had greater increases in leptin, CRP, IL-1Ra, and interleukin 6 (IL-6) and greater decreases in adiponectin and SFRP5, associated with increasing adiposity over follow-up, than those with BMI < 30 kg/m2 . Associations between adiposity and adipokines were most accounted for by leptin; adjustment for leptin greatly reduced the magnitude of all associations between adiposity and remaining adipokines. CONCLUSIONS: Increasing adiposity contributes to a worsening imbalance of pro- and anti-inflammatory adipokines over time, in which leptin may have an important role as a key mediator of metabolic disease risk in Mexican Americans.
Assuntos
Adipocinas/metabolismo , Adiposidade/fisiologia , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Interleucina-6/metabolismo , Leptina/metabolismo , Adulto , Feminino , Humanos , Masculino , Americanos MexicanosRESUMO
The lack of breast cancer screening in low and middle-income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogotá, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm. Physicians in intervention clinics were instructed to perform clinical breast examination on all women aged 50-69 years attending clinics for non-breast health issues, and then refer them for mammographic screening. Physicians in control clinics were not explicitly instructed to perform breast screening or mammography referrals, but could do so if they thought it indicated ("usual care"). Women were followed for 2-years postrandomization. 7,436 women were enrolled and 7,419 (99.8%) screened in intervention clinics, versus 8,419 enrolled and 1,108 (13.1%) screened in control clinics. Incidence ratios (IR) of early, advanced and all breast cancers were 2.9 (95% CI 1.1-9.2), 1.0 (0.3-3.5) and 1.9 (0.9-4.1) in the first (screening) year of the trial, and the cumulative IR for all breast cancers converged to 1.4 (0.7-2.8) by the end of follow-up (Year 2). Eighteen (69.2%) of 26 women with early stage disease had breast conservation surgery (BCS) versus 6 (42.5%) of 14 women with late-stage disease (p = 0.02). Fifteen (68.2%) of 22 women with breast cancer in the intervention group had BCS versus nine (50.0%) of 18 women in the control group (p = 0.34). Well-designed opportunistic clinic-based breast cancer screening programs may be useful for early breast cancer detection in LMICs.
Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Exame Ginecológico , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.
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Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Nanopartículas , Platina/farmacocinética , Platina/toxicidade , Nanomedicina Teranóstica , Animais , Disponibilidade Biológica , Química Farmacêutica , Ácido Hialurônico/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nanopartículas/química , Polímeros/química , Ratos , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologiaRESUMO
Hyperglycemia is associated with advanced glycation end products (AGEs). Recently, AGEs were found to cause pancreatic damage, oxidative stress, and hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but whether it induces pancreatic dysfunction remains unclear. Graptopetalum paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and is an antioxidant that protects against liver damage. We investigated the protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML-induced pancreatic damage. The results indicated that resveratrol, GPE, and gallic acid (the active compound of GPE) increased insulin synthesis via upregulation of pancreatic peroxisome proliferator activated-receptor-γ (PPARγ) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the expression of CML-mediated CCAAT/enhancer binding protein-ß (C/EBPß), a negative regulator of insulin production. Moreover, resveratrol and GPE also strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to attenuate oxidative stress and improve insulin sensitivity in the liver and muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels. Taken together, these findings suggested that GPE and gallic acid could potentially be used as a food supplement to protect against pancreatic damage and the development of diabetes.
Assuntos
Crassulaceae/química , Hiperglicemia/tratamento farmacológico , Lisina/análogos & derivados , Pâncreas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Ácido Gálico/análise , Ácido Gálico/farmacologia , Proteínas de Homeodomínio/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisina/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Pâncreas/fisiopatologia , Resveratrol , Taiwan , Transativadores/metabolismoRESUMO
Role of inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airways diseases has received increasing attention in recent years. Nuclear factor erythroid 2-related factor 2 is the primary transcription factor that regulates the expression of antioxidant and detoxifying enzymes. Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury through elevating antioxidation. Recently, we found that gallic acid is an active compound of Graptopetalum paraguayense E. Walther, which has been reported to inhibit T-helper 2 cytokines. Currently, we assumed that Graptopetalum paraguayense E. Walther may potentially protect against ovalbumin-induced allergy and airway inflammation. Results demonstrated that Graptopetalum paraguayense E. Walther ethanolic extracts (GPE) clearly inhibited airway inflammation, mucus cell hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, GPE also prevented T-cell infiltration and Th2 cytokines, including interleukin- (IL-)4, IL-5, and IL-13 generations in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1 and VCAM-1 were substantially reduced by GPE treatment mediated by Nrf2 activation. Moreover, GPE attenuated GATA3 expression and inhibited Th2 signals of the T cells. These findings suggested that GPE ameliorated the development of airway inflammation through immune regulation.
RESUMO
CONTEXT: Acid phosphatase locus 1 (ACP1) is a low molecular weight tyrosine phosphatase that has been shown to be an important regulator of insulin receptor signaling. OBJECTIVE: We tested whether variation in ACP1 is associated with type 2 diabetes-related traits in 1035 individuals in 339 Mexican-American families of probands with or without a previous diagnosis of gestational diabetes mellitus (GDM). DESIGN: Study participants were phenotyped by oral glucose tolerance test (for glucose and insulin level) and iv glucose tolerance test (for insulin sensitivity and acute insulin response) and had dual-energy x-ray absorptiometry scans to assess body composition. Six tag single nucleotide polymorphisms (SNPs) were identified from among 15 SNPs genotyped across the ACP1 region. SNPs were tested for association with phenotypes using a likelihood ratio test under a variance components framework. RESULTS: After Bonferroni correction, none of the SNPs were associated with type 2 diabetes mellitus-related phenotypes. However, we observed a significant sex-specific effect of rs3828329. Among males, rs3828329 was significantly associated with fasting insulin (Bonferroni P = 0.007) and insulin sensitivity (Bonferroni P = 0.019) and marginally associated with 2-h insulin (Bonferroni P = 0.058) and percentage body fat (Bonferroni P = 0.09). CONCLUSIONS: There were no significant associations in females. We conclude that variation in ACP1 is associated with fasting insulin and insulin sensitivity in a sex-specific manner.